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Sample records for human disease infarct

  1. Orbital infarction in sickle cell disease.

    Science.gov (United States)

    Blank, J P; Gill, F M

    1981-06-01

    Bone infarction is a common occurrence in sickle cell disease. Described are three cases in which frontal headache, proptosis, and lid edema were seen with infarction of the orbital bone. Radionuclide scanning was useful in distinguished bone infarction from orbital infection in one case.

  2. DJ-1 immunoreactivity in human brain astrocytes is dependent on infarct presence and infarct age.

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    Mullett, Steven J; Hamilton, Ronald L; Hinkle, David A

    2009-04-01

    DJ-1 is a protein with anti-oxidative stress and anti-apoptotic properties that is abundantly expressed in reactive CNS astrocytes in chronic neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), and Pick's disease. Genetic mutations which eliminate DJ-1 expression in humans are sufficient to produce an early-onset form of familial PD, PARK7, suggesting that DJ-1 is a critical component of the neuroprotective arsenal of the brain. Previous studies in parkinsonism/dementia brain tissues have revealed that reactive astrocytes within and surrounding incidentally identified infarcts were often robustly immunoreactive for DJ-1, especially if the infarcts showed histological features consistent with older age. Given this, we sought to evaluate astrocytic DJ-1 expression in human stroke more extensively, and with a particular emphasis on determining whether immunohistochemical DJ-1 expression in astrocytes correlates with histological infarct age. The studies presented here show that DJ-1 is abundantly expressed in reactive infarct region astrocytes in both gray and white matter, that subacute and chronic infarct region astrocytes are much more robustly DJ-1+ than are acute infarct and non-infarct region astrocytes, and that DJ-1 staining intensity in astrocytes generally correlates with that of the reactive astrocyte marker GFAP. Confocal imaging of DJ-1 and GFAP dual-labelled human brain sections were used to confirm the localization to and expression of DJ-1 in astrocytes. Neuronal DJ-1 staining was minimal under all infarct and non-infarct conditions. Our data support the conclusion that the major cellular DJ-1 response to stroke in the human brain is astrocytic, and that there is a temporal correlation between DJ-1 expression in these cells and advanced infarct age.

  3. Space weather and myocardial infarction diseases at subauroral latitudes

    Science.gov (United States)

    Samsonov, Sergey; Kleimenova, Natalia; Petrova, Palmira

    The relationship of the number of calls for the emergency medical care in Yakutsk (subauroral latitudes) in connection with myocardial infarction diseases during years near the maximum (1992) and minimum (1998) of the 11-year geomagnetic disturbance cycle to space weather parameters has been studied. It is found that at subauroral latitudes, the increase of geomagnetic activity, namely, the occurrence of night magnetospheric substorms, plays the important role in the exacerbation of myocardial infarctions. Substorms are accompanied by Pi1 irregular geomagnetic pulsations with periods of (0.5-3.0) Hz, coinciding with heart rhythms of a human being, thus, these waves can be a biotropic factor negatively influencing on the occurrence of myocardial infarctions. The comparison of seasonal change of the number of calls for emergency medical care to patients at subauroral latitudes with a simultaneous seasonal change of fatal endings because of an infarction at low latitudes (Bulgaria) has shown their essential difference. Thus, in Bulgaria the maximum of infarctions have been marked in winter, and minimum - in summer, and in Yakutsk a few maxima coinciding with the sharp and considerable increases of the level of the planetary geomagnetic disturbances have been observed. In this case, in Bulgaria the infarctions could be connected with availability of the Pc1 geomagnetic pulsations. Thus, the stable quasi-sinusoidal Pc1 pulsations can be a biotropic factor influencing on the development of myocardial infarctions at middle latitudes and the Pi1 irregular geomagnetic pulsations, which do not propagate to the lower latitudes, could be a biotropic factor at subauroral latitudes.

  4. Nonfasting glucose, ischemic heart disease, and myocardial infarction

    DEFF Research Database (Denmark)

    Benn, Marianne; Tybjaerg-Hansen, Anne; McCarthy, Mark I

    2012-01-01

    The purpose of this study was to test whether elevated nonfasting glucose levels associate with and cause ischemic heart disease (IHD) and myocardial infarction (MI).......The purpose of this study was to test whether elevated nonfasting glucose levels associate with and cause ischemic heart disease (IHD) and myocardial infarction (MI)....

  5. Cerebellar cortical infarct cavities and vertebral artery disease

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    Cocker, Laurens J.L. de [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Kliniek Sint-Jan Radiologie, Brussels (Belgium); Compter, A.; Kappelle, L.J.; Worp, H.B. van der [University Medical Center Utrecht, Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, Utrecht (Netherlands); Luijten, P.R.; Hendrikse, J. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands)

    2016-09-15

    Cerebellar cortical infarct cavities are a newly recognised entity associated with atherothromboembolic cerebrovascular disease and worse physical functioning. We aimed to investigate the relationship of cerebellar cortical infarct cavities with symptomatic vertebrobasilar ischaemia and with vascular risk factors. We evaluated the MR images of 46 patients with a recent vertebrobasilar TIA or stroke and a symptomatic vertebral artery stenosis ≥50 % from the Vertebral Artery Stenting Trial (VAST) for the presence of cerebellar cortical infarct cavities ≤1.5 cm. At inclusion in VAST, data were obtained on age, sex, history of vertebrobasilar TIA or stroke, and vascular risk factors. Adjusted risk ratios were calculated with Poisson regression analyses for the relation between cerebellar cortical infarct cavities and vascular risk factors. Sixteen out of 46 (35 %) patients showed cerebellar cortical infarct cavities on the initial MRI, and only one of these 16 patients was known with a previous vertebrobasilar TIA or stroke. In patients with symptomatic vertebrobasilar ischaemia, risk factor profiles of patients with cerebellar cortical infarct cavities were not different from patients without these cavities. Cerebellar cortical infarct cavities are seen on MRI in as much as one third of patients with recently symptomatic vertebral artery stenosis. Since patients usually have no prior history of vertebrobasilar TIA or stroke, cerebellar cortical infarct cavities should be added to the spectrum of common incidental brain infarcts visible on routine MRI. (orig.)

  6. Sickle cell disease with orbital infarction and epidural hematoma

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    Naran, A.D.; Fontana, L. [Dept. of Diagnostic Radiology, New York Methodist Hospital, Brooklyn, NY (United States)

    2001-04-01

    Although bone infarction is a common feature in sickle cell disease, the involvement of the orbit is an unusual complication. Intracranial bleeding is another uncommon and serious complication. Few cases of orbital infarction alone have been reported. We report imaging findings (CT, bone scan, MRI) in a 16-year-old boy with sickle cell disease with orbital infarction and epidural hematoma. The precise cause of epidural hematoma is not well known, but it is probably related to vaso-occlusive episodes and the tearing of small vessels. (orig.)

  7. Orbital Infarction due to Sickle Cell Disease without Orbital Pain

    Directory of Open Access Journals (Sweden)

    Cameron L. McBride

    2016-01-01

    Full Text Available Sickle cell disease is a hemoglobinopathy that results in paroxysmal arteriolar occlusion and tissue infarction that can manifest in a plurality of tissues. Rarely, these infarcted crises manifest in the bony orbit. Orbital infarction usually presents with acute onset of periorbital tenderness, swelling, erythema, and pain. Soft tissue swelling can result in proptosis and attenuation of extraocular movements. Expedient diagnosis of sickle cell orbital infarction is crucial because this is a potentially sight-threatening entity. Diagnosis can be delayed since the presentation has physical and radiographic findings mimicking various infectious and traumatic processes. We describe a patient who presented with sickle cell orbital crisis without pain. This case highlights the importance of maintaining a high index of suspicion in patients with known sickle cell disease or of African descent born outside the United States in a region where screening for hemoglobinopathy is not routine, even when the presentation is not classic.

  8. Endogenous neurogenesis in the human brain following cerebral infarction.

    Science.gov (United States)

    Minger, Stephen L; Ekonomou, Antigoni; Carta, Eloisa M; Chinoy, Amish; Perry, Robert H; Ballard, Clive G

    2007-01-01

    Increased endogenous neurogenesis has a significant regenerative role in many experimental models of cerebrovascular diseases, but there have been very few studies in humans. We therefore examined whether there was evidence of altered endogenous neurogenesis in an 84-year-old patient who suffered a cerebrovascular accident 1 week prior to death. Using antibodies that specifically label neural stem/neural progenitor cells, we examined the presence of immunopositive cells around and distant from the infarcted area, and compared this with a control, age-matched individual. Interestingly, a large number of neural stem cells, vascular endothelial growth factor-immunopositive cells and new blood vessels were observed only around the region of infarction, and none in the corresponding brain areas of the healthy control. In addition, an increased number of neural stem cells was observed in the neurogenic region of the lateral ventricle wall. Our results suggest increased endogenous neurogenesis associated with neovascularization and migration of newly-formed cells towards a region of cerebrovascular damage in the adult human brain and highlight possible mechanisms underlying this process.

  9. Human Umbilical Cord Blood for Transplantation Therapy in Myocardial Infarction.

    Science.gov (United States)

    Acosta, Sandra A; Franzese, Nick; Staples, Meaghan; Weinbren, Nathan L; Babilonia, Monica; Patel, Jason; Merchant, Neil; Simancas, Alejandra Jacotte; Slakter, Adam; Caputo, Mathew; Patel, Milan; Franyuti, Giorgio; Franzblau, Max H; Suarez, Lyanne; Gonzales-Portillo, Chiara; Diamandis, Theo; Shinozuka, Kazutaka; Tajiri, Naoki; Sanberg, Paul R; Kaneko, Yuji; Miller, Leslie W; Borlongan, Cesar V

    2013-07-01

    Cell-based therapy is a promising therapy for myocardial infarction. Endogenous repair of the heart muscle after myocardial infarction is a challenge because adult cardiomyocytes have a limited capacity to proliferate and replace damaged cells. Pre-clinical and clinical evidence has shown that cell based therapy may promote revascularization and replacement of damaged myocytes after myocardial infarction. Adult stem cells can be harvested from different sources including bone marrow, skeletal myoblast, and human umbilical cord blood cells. The use of these cells for the repair of myocardial infarction presents various advantages over other sources of stem cells. Among these are easy harvesting, unlimited differentiation capability, and robust angiogenic potential. In this review, we discuss the milestone findings and the most recent evidence demonstrating the therapeutic efficacy and safety of the transplantation of human umbilical cord blood cells as a stand-alone therapy or in combination with gene therapy, highlighting the importance of optimizing the timing, dose and delivery methods, and a better understanding of the mechanisms of action that will guide the clinical entry of this innovative treatment for ischemic disorders, specifically myocardial infarction.

  10. Orbital wall infarction in child with sickle cell disease.

    Science.gov (United States)

    Janssens, C; Claeys, L; Maes, P; Boiy, T; Wojciechowski, M

    2015-12-01

    We present the case of a 17-year-old boy, known with homozygous sickle cell disease, who was admitted because of generalised pain. He developed bilateral periorbital oedema and proptosis, without pain or visual disturbances. In addition to hyperhydration, oxygen and analgesia IV antibiotics were started, to cover a possible osteomyelitis. Patients with sickle cell disease are at risk for vaso-occlusive crises, when the abnormally shaped red blood cells aggregate and block the capillaries. Such a crisis typically presents at a location with high bone marrow activity, as the vertebrae and long bones. At an early age, the bone marrow is still active at other sites, for example the orbital wall, and thus infarction can also occur there. Thus, in young persons with sickle cell disease, it is important to consider orbital wall infarction in the differential diagnosis, since the approach is different from osteomyelitis. If the disease is complicated by an orbital compression syndrome, corticosteroids or surgical intervention may be necessary to preserve the vision. In our patient, an MRI of the orbitae demonstrated periorbital oedema with bone anomalies in the orbital and frontal bones, confirming orbital wall infarction. Ophthalmological examination revealed no signs of pressure on the nervus opticus. The patient recovered gradually with conservative treatment.

  11. Relationship Between Periodontal Disease and Acute Myocardial Infarction

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    M Zamirian

    2008-07-01

    Full Text Available Background: Conventional risk factors for coronary artery disease and myocardial infarction do not explain all of the clinical and epidemiological features of the disease. Periodontal disease is a common bacterial and destructive disorder of oral tissues. Many studies demonstrate close association between chronic periodontitis and development of generalized inflammation, vascular endothelial injury, and atherosclesis. Periodontal disease has been convincingly emerging as an important independent risk factor for ischemic heart disease. A case - control study was carried out to assess the prevalence of periodontitis in patients with Acute myocardial Infarction (AMI and evaluate the possible relationship between AMI and chronic periodontitis. Patients and Methods: A number of 160 patients, aged 35 to 70 years old, enrolled in the study. Eighty patients (43 men, 37 women were examined four days after hospitalization due to AMI. Control group consisted of 80 persons (38 men, 42 women with normal coronary angiography. The following periodontal parameters were examined: Plaque index (PI, gingiral index (GI, bleeding on probing (BOP, probing depth (PD, clinical attachment loss (CAL and number of sites with CAL.Results: The case, compared to control showed significantly worse results for some periodontal variables studied: The mean of PD and PD > 3 mm, CAL, and number of sites with CAL, had worse results compared to control despite similar oral hygiene and frequency of brushing. The confounding factors for the present study were found to be hypertension and diabetes. Conclusion: The association between periodontitis and acute myocardial infarction was significant after adjusting for conventional risk factors for AMI.

  12. Human cord blood cells and myocardial infarction: effect of dose and route of administration on infarct size.

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    Henning, Robert J; Burgos, Jose D; Vasko, Mark; Alvarado, Felipe; Sanberg, Cyndy D; Sanberg, Paul R; Morgan, Michael B

    2007-01-01

    There is no consensus regarding the optimal dose of stem cells or the optimal route of administration for the treatment of acute myocardial infarction. Bone marrow cells, containing hematopoietic and mesenchymal stem cells, in doses of 0.5 x 10(6) to >30 x 10(6) have been directly injected into the myocardium or into coronary arteries or infused intravenously in subjects with myocardial infarctions to reduce infarct size and improve heart function. Therefore, we determined the specific effects of different doses of human umbilical cord blood mononuclear cells (HUCBC), which contain hematopoietic and mesenchymal stem cells, on infarct size. In order to determine the optimal technique for stem cell administration, HUCBC were injected directly into the myocardium (IM), or into the LV cavity with the ascending aorta transiently clamped to facilitate coronary artery perfusion (IA), or injected intravenously (IV) in rats 1-2 h after the left anterior coronary artery was permanently ligated. Immune suppressive therapy was not given to any rat. One month later, the infarct size in control rat hearts treated with only Isolyte averaged 23.7 +/- 1.7% of the LV muscle area. Intramyocardial injection of HUCBC reduced the infarct size by 71% with 0.5 x 10(6) HUCBC and by 93% with 4 x 10(6) HUCBC in comparison with the controls (p p p p < 0.05). Nevertheless, IM, IA, and IV HUCBC all produced significant reductions in infarct size in comparison with Isolyte-treated infarcted hearts without requirements for host immune suppression. The present experiments demonstrate that the optimal dose of HUCBC for reduction of infarct size in the rat is 4 x 10(6) IM, 4 x 10(6) IA, and 16 x 10(6) IV, and that the IM injection of HUCBC is the most effective technique for reduction in infarct size.

  13. Raman spectroscopy of human saliva for acute myocardial infarction detection

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    Chen, Maowen; Chen, Yuanxiang; Wu, Shanshan; Huang, Wei; Lin, Jinyong; Weng, Guo-Xing; Chen, Rong

    2014-09-01

    Raman spectroscopy is a rapidly non-invasive technique with great potential for biomedical research. The aim of this study was to evaluate the feasibility of using Raman spectroscopy of human saliva for acute myocardial infarction (AMI) detection. Raman spectroscopy measurements were performed on two groups of saliva samples: one group from patients (n=30) with confirmed AMI and the other group from healthy controls (n=31). The diagnostic performance for differentiating AMI saliva from normal saliva was evaluated by multivariate statistical analysis. The combination of principal component analysis (PCA) and linear discriminate analysis (LDA) of the measured Raman spectra separated the spectral features of the two groups into two distinct clusters with little overlaps, rendering the sensitivity of 80.0% and specificity of 80.6%. The results from this exploratory study demonstrated that Raman spectroscopy of human saliva can serve as a potentially clinical tool for rapid AMI detection and screening.

  14. Sterile subperiosteal fluid collections accompanying orbital wall infarction in sickle-cell disease.

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    Huckfeldt, Rachel M; Shah, Ankoor S

    2014-10-01

    Infarction of the orbital wall is an uncommon manifestation of sickle cell disease (SCD) that may mimic an infectious process. We report a patient with two separate orbital infarctions with different presenting symptoms involving different bones. Radiologic-guided sampling of a periosteal fluid collection in the first episode showed likely sterile inflammatory exudates. This case highlights the range of findings in orbital wall infarction in SCD as well as helpful clinical and imaging entities that may differentiate infarction from infection, allowing early diagnosis and appropriate management.

  15. Effects of chronic kidney disease on platelet response to antiplatelet therapy in acute myocardial infarction patients

    Institute of Scientific and Technical Information of China (English)

    邓捷

    2012-01-01

    Objective To elucidate the effects of dual antiplatelet therapy on platelet response in acute myocardial infarction patients with chronic kidney disease. Methods From September 2011 to June 2012,a total of 195 acute myocardial infarction patients with drug eluting stent implanting were enrolled. Among them,133 cases had normal

  16. Recurrent infarction of sphenoid bone with subperiosteal collection in a child with sickle cell disease.

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    Alsuhaibani, Adel H; Marzouk, Mohammed Abu

    2011-01-01

    Infarction of the orbital bone in patients with sickle cell disease is very rare. The authors report a young boy who presented twice with marked acute proptosis and eyelid swelling of the right eye resulting from infarction in the greater wing of the sphenoid bone accompanied by an orbital subperiosteal collection. The time interval between the 2 attacks was 3 years.

  17. Accurate detection of triple vessel disease in patients with exercise induced ST segment depression after infarction.

    OpenAIRE

    Mannering, D; Bennett, E D; Ward, D. E.; Dawkins, K; Dancy, M; Valantine, H; Mehta, N.

    1987-01-01

    The severity of coronary artery disease is an important determinant of prognosis after acute myocardial infarction. The ability of a symptom limited exercise test to predict the presence of triple vessel disease was assessed in 221 patients three weeks after infarction. Coronary angiography was performed in patients with exercise induced ST segment depression. The presence of ST segment depression alone was poorly indicative of triple vessel disease; however, some specific features of ST segm...

  18. Splenic infarction

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    Splenic infarction is the death of tissue (necrosis) in the spleen due to a blockage in blood flow. ... Common causes of splenic infarction include: Blood clots Blood diseases such as sickle cell anemia Infections such as endocarditis

  19. Acute Myocardial Infarction: The First Manifestation of Ischemic Heart Disease and Relation to Risk Factors

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    Manfroi Waldomiro Carlos

    2002-01-01

    Full Text Available OBJECTIVE: To assess the association between cardiovascular risk factors and acute myocardial infarction as the first manifestation of ischemic heart disease, correlating them with coronary angiographic findings. METHODS: We carried out a cross-sectional study of 104 patients with previous acute myocardial infarction, who were divided into 2 groups according to the presence or absence of angina prior to acute myocardial infarction. We assessed the presence of angina preceding acute myocardial infarction and risk factors, such as age >55 years, male sex, smoking, systemic arterial hypertension, lipid profile, diabetes mellitus, obesity, sedentary lifestyle, and familial history of ischemic heart disease. On coronary angiography, the severity of coronary heart disease and presence of left ventricular hypertrophy were assessed. RESULTS: Of the 104 patients studied, 72.1% were males, 90.4% were white, 73.1% were older than 55 years, and 53.8% were hypertensive. Acute myocardial infarction was the first manifestation of ischemic heart disease in 49% of the patients. The associated risk factors were systemic arterial hypertension (RR=0.19; 95% CI=0.06-0.59; P=0.04 and left ventricular hypertrophy (RR=0.27; 95% CI=0,.8-0.88; P=0.03. The remaining risk factors were not statistically significant. CONCLUSION: Prevalence of acute myocardial infarction as the first manifestation of ischemic heart disease is high, approximately 50%. Hypertensive individuals more frequently have symptoms preceding acute myocardial infarction, probably due to ventricular hypertrophy associated with high blood pressure levels.

  20. Renal infarct: a rare disease due to a rare etiology

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    Akshintala, Divya; Bansal, Saurabh K.; Emani, Vamsi Krishna; Yadav, Manajyoti

    2015-01-01

    Renal infarction is caused by profound hypoperfusion secondary to embolic/thrombotic occlusion of the renal artery or vasospasm of the renal artery. We present a case of a 54-year-old patient who presented with nausea, vomiting, and vague abdominal pain. He had frequent episodes of migraine headaches and he treated himself with as needed rizatriptan. CT scan of the abdomen showed renal cortical infarction. After extensive investigations, etiology of his renal infarct was deemed to be due to rizatriptan. PMID:26091657

  1. Renal infarct: a rare disease due to a rare etiology

    Directory of Open Access Journals (Sweden)

    Divya Akshintala

    2015-06-01

    Full Text Available Renal infarction is caused by profound hypoperfusion secondary to embolic/thrombotic occlusion of the renal artery or vasospasm of the renal artery. We present a case of a 54-year-old patient who presented with nausea, vomiting, and vague abdominal pain. He had frequent episodes of migraine headaches and he treated himself with as needed rizatriptan. CT scan of the abdomen showed renal cortical infarction. After extensive investigations, etiology of his renal infarct was deemed to be due to rizatriptan.

  2. Genetics of coronary artery disease and myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Xuming Dai; Szymon Wiernek; James P Evans; Marschall S Runge

    2016-01-01

    Atherosclerotic coronary artery disease(CAD) comprises a broad spectrum of clinical entities that include asymptomatic subclinical atherosclerosis and its clinical complications, such as angina pectoris, myocardial infarction(MI) and sudden cardiac death. CAD continues to be the leading cause of death in industrialized society. The long-recognized familial clustering of CAD suggests that genetics plays a central role in its development, with the heritability of CAD and MI estimated at approximately 50% to 60%. Understanding the genetic architecture of CAD and MI has proven to be difficult and costly due to the heterogeneity of clinical CAD and the underlying multi-decade complex pathophysiological processes that involve both genetic and environmental interactions. This review describes the clinical heterogeneity of CAD and MI to clarify the disease spectrum in genetic studies, provides a brief overview of the historical understanding and estimation of the heritability of CAD and MI, recounts major gene discoveries of potential causal mutations in familial CAD and MI, summarizes CAD and MIassociated genetic variants identified using candidate gene approaches and genome-wide association studies(GWAS), and summarizes the current status of the construction and validations of genetic risk scores for lifetime risk prediction and guidance for preventive strategies. Potential protective genetic factors against the development of CAD and MI are also discussed. Finally, GWAS have identified multiple genetic factors associated with an increased risk of in-stent restenosis following stent placement for obstructive CAD. This review will also address genetic factors associated with in-stent restenosis, which may ultimately guide clinical decision-making regarding revascularization strategies for patients with CAD and MI.

  3. A new non-human primate model of photochemically induced cerebral infarction.

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    Satoshi Ikeda

    Full Text Available BACKGROUND AND PURPOSE: Rat models of photochemically induced cerebral infarction have been readily studied, but to date there are no reports of transcranial photochemically induced infarctions in the marmoset. In this report, we used this non-human primate as a model of cerebral thrombosis and observed the recovery process. METHODS: Five common marmosets were used. Cerebral ischemia was produced via intravascular thrombosis induced by an intravenous injection of Rose Bengal and irradiation with green light. After inducing cerebral infarction, we observed the behavior of marmosets via a continuous video recording. We evaluated maximum speed, mean speed, and distance traveled in 1 min. In addition, we evaluated scores for feeding behavior, upper limb grip, and lower limb grip. We confirmed the infarct area after cerebral infarction using 2,3,5-triphenyltetrazolium chloride staining in a separate marmoset. RESULTS: We found functional decreases 2 days after creating the cerebral infarction in all measurements. Total distance traveled, average speed, upper limb score, and feeding behavior score did not recover to pre-infarction levels within 28 days. Maximum speed in 1 min and lower limb score recovered 28 days after infarction as compared to pre-infarction levels. We confirmed the infarct area of 11.4 mm × 6.8 mm as stained with 2,3,5-triphenyltetrazolium chloride. CONCLUSION: We were able to create a primate photothrombosis-induced cerebral infarction model using marmosets and observe functional recovery. We suggest that this is a useful model for basic research of cerebral infarction.

  4. Importance of chronic obstructive pulmonary disease for prognosis and diagnosis of congestive heart failure in patients with acute myocardial infarction

    DEFF Research Database (Denmark)

    Kjøller, Erik; Køber, Lars; Iversen, Kasper

    2004-01-01

    AIMS: To evaluate the importance of chronic obstructive pulmonary disease for prognosis and diagnosis of congestive heart failure in patients with acute myocardial infarction. METHOD AND RESULTS: Prospective registration of 6669 consecutive patients admitted with infarction and screened...... in patients with acute myocardial infarction without congestive heart failure, but is also a confounding factor for the diagnosis of congestive heart failure....

  5. Differentiating osteomyelitis from bone infarction in sickle cell disease.

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    Wong, A L; Sakamoto, K M; Johnson, E E

    2001-02-01

    This brief review discusses one possible approach to evaluating the sickle cell patient with bone pain. The major differential diagnoses include osteomyelitis and bone infarction. Based on previous studies, we provide an approach to assessing and treating patients with the possible diagnosis of osteomyelitis. An algorithm has been provided, which emphasizes the importance of the initial history and physical examination. Specific radiographic studies are recommended to aid in making the initial assessment and to determine whether the patient has an infarct or osteomyelitis. Differentiating osteomyelitis from infarction in sickle cell patients remains a challenge for the pediatrician. This algorithm can be used as a guide for physicians who evaluate such patients in the acute care setting.

  6. Short Telomere Length, Myocardial Infarction, Ischemic Heart Disease, and Early Death

    DEFF Research Database (Denmark)

    Weischer, Maren; Bojesen, Stig E; Cawthon, Richard M;

    2012-01-01

    OBJECTIVE: We tested the hypothesis that short telomere length is associated with increased risk of myocardial infarction, ischemic heart disease, and early death. METHODS AND RESULTS: We measured leukocyte telomere length in 2 prospective studies of 19 838 Danish general population participants...... from the Copenhagen City Heart Study and the Copenhagen General Population Study. Participants were followed for up to 19 years for incident myocardial infarction (n=929), ischemic heart disease (n=2038), and death (n=4342). Follow-up was 100% complete. Telomere length decreased linearly...... with increasing age in women and men in both studies (P=7×10(-74) to P=3×10(-125)). Multifactorially adjusted hazard ratios were 1.10 (95% CI 1.01-1.19) for myocardial infarction, 1.06 (1.00-1.11) for ischemic heart disease, and 1.09 (1.05-1.13) for early death per 1000-base pair decrease in telomere length...

  7. Nonobstructive Coronary Artery Disease and Risk of Myocardial Infarction

    Science.gov (United States)

    Maddox, Thomas M.; Stanislawski, Maggie A.; Grunwald, Gary K.; Bradley, Steven M.; Ho, P. Michael; Tsai, Thomas T.; Patel, Manesh R.; Sandhu, Amneet; Valle, Javier; Magid, David J.; Leon, Benjamin; Bhatt, Deepak L.; Fihn, Stephan D.; Rumsfeld, John S.

    2016-01-01

    IMPORTANCE Little is known about cardiac adverse events among patients with nonobstructive coronary artery disease (CAD). OBJECTIVE To compare myocardial infarction (MI) and mortality rates between patients with nonobstructive CAD, obstructive CAD, and no apparent CAD in a national cohort. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of all US veterans undergoing elective coronary angiography for CAD between October 2007 and September 2012 in the Veterans Affairs health care system. Patients with prior CAD events were excluded. EXPOSURES Angiographic CAD extent, defined by degree (no apparent CAD: no stenosis >20%; nonobstructive CAD: ≥1 stenosis ≥20% but no stenosis ≥70%; obstructive CAD: any stenosis ≥70% or left main [LM] stenosis ≥50%) and distribution (1,2, or 3 vessel). MAIN OUTCOMES AND MEASURES The primary outcome was 1-year hospitalization for nonfatal MI after the index angiography. Secondary outcomes included 1-year all-cause mortality and combined 1-year MI and mortality. RESULTS Among37 674 patients, 8384 patients (22.3%) had nonobstructive CAD and 20 899 patients (55.4%) had obstructive CAD. Within 1 year, 845 patients died and 385 were rehospitalized for MI. Among patients with no apparent CAD, the 1-year MI rate was 0.11% (n = 8, 95% CI, 0.10%–0.20%) and increased progressively by 1-vessel nonobstructive CAD, 0.24% (n = 10, 95% CI, 0.10%–0.40%); 2-vessel nonobstructive CAD, 0.56% (n = 13, 95% CI, 0.30%–1.00%); 3-vessel nonobstructive CAD, 0.59% (n = 6, 95% CI, 0.30%–1.30%); 1-vessel obstructive CAD, 1.18% (n = 101, 95% CI, 1.00%–1.40%); 2-vessel obstructive CAD, 2.18% (n = 110, 95% CI, 1.80%–2.60%); and 3-vessel or LM obstructive CAD, 2.47% (n = 137, 95% CI, 2.10%–2.90%). After adjustment, 1-year MI rates increased with increasing CAD extent. Relative to patients with no apparent CAD, patients with 1-vessel nonobstructive CAD had a hazard ratio (HR) for 1-year MI of 2.0 (95% CI, 0.8–5.1); 2-vessel

  8. Human Environmental Disease Network

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Audouze, Karine

    2017-01-01

    During the past decades, many epidemiological, toxicological and biological studies have been performed to assess the role of environmental chemicals as potential toxicants for diverse human disorders. However, the relationships between diseases based on chemical exposure have been rarely studied...... by computational biology. We developed a human environmental disease network (EDN) to explore and suggest novel disease-disease and chemical-disease relationships. The presented scored EDN model is built upon the integration on systems biology and chemical toxicology using chemical contaminants information...

  9. Proptosis, skull infarction, and retro-orbital and epidural hematomas in a child with sickle cell disease.

    Science.gov (United States)

    Mallouh, A A; Young, M; Hamdan, J; Salamah, M M

    1987-10-01

    A Saudi child with homozygous sickle cell disease (SS) presented with bilateral periorbital swelling, right-sided proptosis, skull bone infarcts, and retro-orbital and epidural hematomas. The findings of skull bone infarcts, retro-orbital and epidural hematomas are rare in patients with sickle cell disease.

  10. Myocardial infarction and transient ventricular dysfunction in an adolescent with sickle cell disease.

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    Deymann, Andreas J; Goertz, Kenneth K

    2003-02-01

    We report a case of an adolescent who had sickle cell disease and previous evidence of myocardial damage and presented with abdominal pain and rapid progression to cardiogenic shock and subsequent development of myocardial infarction. To our knowledge, this represents only the second report of a case of acute myocardial ischemia and subsequent infarction resulting transient ventricular dysfunction reported in a child with sickle cell disease successfully treated with exchange transfusion. The pathophysiology of this complication remains unclear, and cardiac complications may remain undetected as lung, bone, and brain infarcts are more common and the pain associated with sickle cell crisis may mask the ischemic symptoms. Multiple factors may contribute to ischemia in addition to the presence of a vaso-occlusive crisis or infection. Acute or chronic myocardial ischemia are probably more prevalent than currently known.

  11. Human umbilical cord-derived endothelial progenitor cells promote growth cytokines-mediated neorevascularization in rat myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    HU Cheng-heng; LI Zhi-ming; DU Zhi-min; ZHANG Ai-xia; YANG Da-ya; WU Gui-fu

    2009-01-01

    Background Cell-based vascular therapies of endothelial progenitor cells (EPCs) mediated neovascularization is still a novel but promising approach for the treatment of ischemic disease. The present study was designed to investigate the therapeutic potentials of human umbilical cord blood-derived EPCs (hUCB-EPCs) in rat with acute myocardial infarction.Methods Human umbilical cord blood (hUCB) mononuclear cells were isolated using density gradient centrifugation from the fresh human umbilical cord in healthy delivery woman, and cultured in M199 medium for 7 days. The EPCs were identified by double-positive staining with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine percholorate-labeled acetylated low-density lipoprotein (Dil-Ac-LDL) and fluorescein isothiocyanate-conjugated Ulex europaeus lectin (FITC-UEA-I). The rat acute myocardial infarction model was established by the ligation of the left anterior descending artery. The hUCB-EPCs were intramyocardially injected into the peri-infarct area. Four weeks later, left ventricular function was assessed by a pressure-volume catheter. The average capillary density (CAD) was evaluated by anti-VⅢ immunohistochemistry staining to reflect the development of neovascularization at the peri-infarct area. The graft cells were identified by double immunofluorescence staining with human nuclear antigen (HNA) and CD31 antibody,representing human origin of EPCs and vascular endothelium, respectively. Expressions of cytokines, proliferating cell nuclear angigen (PCNA), platelet endothelial cell adhesion molecule (PECAM) and vascular endothelial growth factor (VEGF) were detected to investigate the underlying mechanisms of cell differentiation and revascularization.Results The donor EPCs were detectable and integrated into the host myocardium as confirmed by double-positive immunofluorescence staining with HNA and CD31. And the anti-VⅢ staining demonstrated a higher degree of microvessel formation in EPCs transplanted

  12. Physiological Correlates of Intellectual Function in Children with Sickle Cell Disease: Hypoxaemia, Hyperaemia and Brain Infarction

    Science.gov (United States)

    Hogan, Alexandra M.; Pit-ten Cate, Ineke M.; Vargha-Khadem, Faraneh; Prengler, Mara; Kirkham, Fenella J.

    2006-01-01

    Lowered intelligence relative to controls is evident by mid-childhood in children with sickle cell disease. There is consensus that brain infarct contributes to this deficit, but the subtle lowering of IQ in children with normal MRI scans might be accounted for by chronic systemic complications leading to insufficient oxygen delivery to the brain.…

  13. Sociodemographic differences in myocardial infarction risk perceptions among people with coronary heart disease

    DEFF Research Database (Denmark)

    Aalto, Anna-Mari; Weinman, John; French, David P

    2007-01-01

    This study examines sociodemographic differences in myocardial infarction (MI) risk perceptions among people with coronary heart disease (CHD) (N = 3130). Two variables for comparative risk perceptions were computed: (1) own risk compared to that of an average person; and (2) own risk compared...

  14. Complete versus culprit-only revascularisation in ST elevation myocardial infarction with multi-vessel disease

    DEFF Research Database (Denmark)

    Bravo, Claudio A; Hirji, Sameer A; Bhatt, Deepak L

    2017-01-01

    BACKGROUND: Multi-vessel coronary disease in people with ST elevation myocardial infarction (STEMI) is common and is associated with worse prognosis after STEMI. Based on limited evidence, international guidelines recommend intervention on only the culprit vessel during STEMI. This, in turn, leav...

  15. Acute lacunar infarcts in CLIPPERS: is the chronic infiltrative lymphocytic perivascular disease process to blame?

    Science.gov (United States)

    Saigal, Gaurav; Quencer, Robert

    2013-12-01

    CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is a recently described chronic inflammatory disorder involving the brainstem with characteristic imaging findings. Since it was originally described in 2002, only a handful of cases have been reported in the literature. We describe two additional cases of CLIPPERS with characteristic clinical and radiological findings. Besides the previously described MR findings, one of the cases also demonstrated multiple basal ganglia lacunar infarcts, a finding which has not been previously reported. We hypothesize that the lacunar infarcts are caused by this chronic infiltrative perivascular disease process.

  16. Regional sympathetic denervation after myocardial infarction in humans detected noninvasively using I-123-metaiodobenzylguanidine

    Energy Technology Data Exchange (ETDEWEB)

    Stanton, M.S.; Tuli, M.M.; Radtke, N.L.; Heger, J.J.; Miles, W.M.; Mock, B.H.; Burt, R.W.; Wellman, H.N.; Zipes, D.P. (Indiana Univ. School of Medicine, IN (USA))

    1989-11-15

    Transmural myocardial infarction in dogs produces denervation of sympathetic nerves in viable myocardium apical to the infarct that may be arrhythmogenic. It is unknown whether sympathetic denervation occurs in humans. The purpose of this study was to use iodine-123-metaiodobenzylguanidine (MIBG), a radiolabeled guanethidine analog that is actively taken up by sympathetic nerve terminals, to image noninvasively the cardiac sympathetic nerves in patients with and without ventricular arrhythmias after myocardial infarction. Results showed that 10 of 12 patients with spontaneous ventricular tachyarrhythmias after myocardial infarction exhibited regions of thallium-201 uptake indicating viable perfused myocardium, with no MIBG uptake. Such a finding is consistent with sympathetic denervation. One patient had frequent episodes of nonsustained ventricular tachycardia induced at exercise testing that was eliminated by beta-adrenoceptor blockade. Eleven of the 12 patients had ventricular tachycardia induced at electrophysiologic study and metoprolol never prevented induction. Sympathetic denervation was also detected in two of seven postinfarction patients without ventricular arrhythmias. Normal control subjects had no regions lacking MIBG uptake. This study provides evidence that regional sympathetic denervation occurs in humans after myocardial infarction and can be detected noninvasively by comparing MIBG and thallium-201 images. Although the presence of sympathetic denervation may be related to the onset of spontaneous ventricular tachyarrhythmias in some patients, it does not appear to be related to sustained ventricular tachycardia induced at electrophysiologic study.

  17. Serial Ultrasonography Assessments of a Testicular Infarction Mimicking Testicular Tumor in a Behcet Disease Patient

    Directory of Open Access Journals (Sweden)

    Zeid Al-Ani

    2014-03-01

    Full Text Available Behcet disease (BD, a vasculitic disease, may present with a broad range of systemic manifestations. Urologic complications are rarely described in the literature, but when they occur, they present as epididymo-orchitis. We describe a rare case of testicular infarction in a patient with BD followed up with serial ultrasound imaging. We highlight the diagnostic challenges when presented with testicular pain in a patient with BD and the potential consequences in the management.

  18. Comparative effects of percutaneous coronary intervention for infarct-related artery only or for both infarct-and non-infarct-related arteries in patients with ST-elevation myocardial infarction and multi-vessel disease

    Institute of Scientific and Technical Information of China (English)

    HAN Ya-ling; WANG Bin; WANG Xiao-zeng; LI Yi; WANG Shou-li; JING Quan-min; WANG Geng; MA Ying-yan; LUAN Bo

    2008-01-01

    Background Rapid recanalization of infarct-related artery (IRA) has become the major target during primary percutaneous coronary intervention (PCI) for patients with ST-elevation myocardial infarction (MI),but strategy for treatment of non-IRA lesions in this setting remains unclear.This study aimed to compare long-term effects between PCI for IRA only and that for both IRA and non-IRA in ST-elevation MI patients with multi-vessel disease.Methods A total of 242 eligible patients with ST-elevation MI and at least two diseased coronary arteries (luminal narrowing≥70%) undergoing primary PCI were included.Of them,149 patients underwent primary PCI for IRA only (group 1),and 93 received primary PCI for IRA followed by elective PCI for non-IRA 7 to 15 days after acute myocardial infarction (AMI) (group 2).Drug-eluting stents (DESs) were deployed in more than 90% of the patients.Results The two groups did not differ with respect to baseline clinical and angiographic characteristics.No significant differences were observed in 12-month clinical follow-up results regarding major adverse cardiac events (11.5% vs 15.1%,P>0.05) and target lesion revascularization (8.1% vs 7.6%,P>0.05) between the two groups.However,patients in group 1 had higher rates of recurrent angina (10.1% vs 2.1%,P<0.05) and depressed left ventricular ejection fraction evaluated by echocardiography (0.56±0.22 vs 0.63±0.25,P <0.05).Conclusion With the use of DESs,complete revascularization with elective PCI for non-IRA after primary PCI may exert a beneficial effect on long-term symptomatology and left ventricular function in patients with ST-elevation MI and multi-vessel disease.

  19. Conditioned Medium From Human Amniotic Mesenchymal Stromal Cells Limits Infarct Size and Enhances Angiogenesis

    NARCIS (Netherlands)

    Danieli, Patrizia; Malpasso, Giuseppe; Cluffreda, Maria Chiara; Cervio, Elisabetta; Calvillo, Laura; Copes, Francesco; Pisano, Federica; Mura, Manuela; Kleijn, Lennaert; de Boer, Rudolf A.; Viarengo, Gianluca; Rosti, Vittorio; Spinillo, Arsenio; Roccio, Marianna; Gnecchi, Massimiliano

    2015-01-01

    The paracrine properties of human amniotic membrane-derived mesenchymal stromal cells (hAMCs) have not been fully elucidated. The goal of the present study was to elucidate whether hAMCs can exert beneficial paracrine effects on infarcted rat hearts, in particular through cardioprotection and angiog

  20. Creatinine, eGFR and association with myocardial infarction, ischemic heart disease and early death in the general population

    DEFF Research Database (Denmark)

    Sibilitz, Kirstine L; Benn, Marianne; Nordestgaard, Børge G

    2014-01-01

    OBJECTIVE: We tested the hypothesis that moderately elevated plasma creatinine levels and decreased levels of estimated glomerular filtration rate (eGFR) are associated with increased risk of myocardial infarction, ischemic heart disease, and early death in the general population. METHODS: We...... studied 10,489 individuals with a plasma creatinine measurement and calculated eGFR from the Danish general population, of which 1498 developed myocardial infarction, 3001 ischemic heart disease, and 7573 died during 32 years follow-up. RESULTS: Cumulative incidences of myocardial infarction and ischemic...... heart disease as a function of age increased with increasing levels of creatinine, and survival decreased (log-rank trends: creatinine levels

  1. Retroviruses and human disease.

    OpenAIRE

    1987-01-01

    Over the past 25 years animal retroviruses have been favoured subjects of research by virologists, oncologists, and molecular biologists. Retroviruses have given us reverse transcriptase, oncogenes, and cloning vectors that may one day be exploited for human gene therapy. They have also given us leukaemia and the acquired immune deficiency syndrome (AIDS). Kawasaki disease and tropical spastic paraparesis are thought to be associated with retrovirus infection, and other diseases such as de Qu...

  2. Cortical infarction of the right parietal lobe and neurogenic heart disease A report of three cases

    Institute of Scientific and Technical Information of China (English)

    Fang Li; Yujie Jia

    2012-01-01

    Three male patients were diagnosed with new cortical infarctions of the right parietal lobe on the basis of head magnetic resonance imaging; high-intensity signals indicating lesions in the right parietal lobe were noted on diffusion-weighted images at admission. Two of them presented with left hand weakness, and one exhibited left upper limb weakness. Treatment for improving blood supply to the brain was administered. One patient died suddenly because of ventricular fibrillation 3 days after admission. The other two patients had increased troponin levels and abnormal elec-trocardiograms, and were diagnosed with acute myocardial infarction half a month after admission. When lesions exist in field 7 of the parietal cortex (resulting in paralysis of the contralateral hand), the sympathetic center of the posterior lateral nucleus of the hypothalamus demonstrates compensatory excitement, which easily causes tachyarrhythmia and sudden death. Our experi-mental findings indicate that close electrocardiograph monitoring and cerebral infarction treatment should be standard procedures to predict and help prevent heart disease in patients with cerebral infarction in the right parietal lobe and left upper limb weakness as the main complaint.

  3. Cortical infarction of the right parietal lobe and neurogenic heart disease: A report of three cases.

    Science.gov (United States)

    Li, Fang; Jia, Yujie

    2012-04-25

    Three male patients were diagnosed with new cortical infarctions of the right parietal lobe on the basis of head magnetic resonance imaging; high-intensity signals indicating lesions in the right parietal lobe were noted on diffusion-weighted images at admission. Two of them presented with left hand weakness, and one exhibited left upper limb weakness. Treatment for improving blood supply to the brain was administered. One patient died suddenly because of ventricular fibrillation 3 days after admission. The other two patients had increased troponin levels and abnormal electrocardiograms, and were diagnosed with acute myocardial infarction half a month after admission. When lesions exist in field 7 of the parietal cortex (resulting in paralysis of the contralateral hand), the sympathetic center of the posterior lateral nucleus of the hypothalamus demonstrates compensatory excitement, which easily causes tachyarrhythmia and sudden death. Our experimental findings indicate that close electrocardiograph monitoring and cerebral infarction treatment should be standard procedures to predict and help prevent heart disease in patients with cerebral infarction in the right parietal lobe and left upper limb weakness as the main complaint.

  4. Acute myocardial infarction in a 35-year-old man with coronary artery aneurysm most probably caused by Kawasaki disease

    Institute of Scientific and Technical Information of China (English)

    Saeed Alipour Parsa; Isa Khaheshi; Koosha Paydary; Habib Haybar

    2014-01-01

    We present a 35-year-old man with history of Kawasaki disease who referred with myocardial infarction, and angiography, revealing aneurysm of left main and left anterior descending coronary arteries. The patient underwent percutaneous coronary intervention and thrombectomy and was discharged after 6 d. Coronary artery sequels of Kawasaki disease should be considered as one of the underlying causes of acute myocardial infarction in young adults.

  5. Relation between cardiovascular disease risk markers and brain infarcts detected by magnetic resonance imaging in an elderly population.

    Science.gov (United States)

    Nylander, Ruta; Lind, Lars; Wikström, Johan; Lindahl, Bertil; Venge, Per; Larsson, Anders; Ärnlöv, Johan; Berglund, Lars; Ahlström, Håkan; Johansson, Lars; Larsson, Elna-Marie

    2015-02-01

    Established cardiovascular risk markers, such as hypertension, are associated with increased risk of brain infarcts. The newer markers N-terminal pro-brain natriuretic peptide, troponin I, C-reactive protein, and cystatin C may affect the risk of cardiovascular events and potentially, thereby, also stroke. We investigated the association between established and new risk markers for cardiovascular disease and brain infarcts detected by magnetic resonance imaging (MRI) at age 75. Four hundred six randomly selected subjects from the Prospective Investigation of the Vasculature in Uppsala Seniors study were examined with MRI of the brain at age 75. Blood samples, measurements, and dedicated questionnaires at age 70 were used for analysis of risk markers. A history of diseases had been obtained at age 70 and 75. MRI was evaluated regarding lacunar and cortical infarcts. Univariate associations between outcomes and risk markers were assessed with logistic regression models. One or more infarcts were seen in 23% of the subjects (20% had only lacunar infarcts, 1% had only cortical infarcts, and 2% had both). Hypertension (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.4, 4.7) and obesity (OR 1.3; CI 1.0, 1.8) were significantly associated with increased risk of brain infarction. The newer risk markers were not significantly associated with the brain infarcts. The new markers were not associated with the predominantly lacunar infarcts in our 75-year-old population, why troponin I and NT-proBNP may be associated mainly with cardioembolic infarcts as shown recently. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  6. Vitamin D and cardiovascular disease: From atherosclerosis to myocardial infarction and stroke.

    Science.gov (United States)

    Muscogiuri, Giovanna; Annweiler, Cedric; Duval, Guillaume; Karras, Spyridon; Tirabassi, Giacomo; Salvio, Gianmaria; Balercia, Giancarlo; Kimball, Samantha; Kotsa, Kalliopi; Mascitelli, Luca; Bhattoa, Harjit Pal; Colao, Annamaria

    2017-03-01

    There continues to be interest in understanding the role of vitamin D in the pathogenesis, epidemiology and prevention of cardiovascular disease (CVD). In fact vitamin D deficiency has been associated to an increased risk of developing CVD given to the relationship between low vitamin D levels and obesity, diabetes mellitus, dyslipidaemia, endothelial dysfunction and hypertension. However, although vitamin D has been identified as a potentially important marker of CVD, the mechanisms through which vitamin D deficiency leads from endothelial dysfunction to myocardial infarction and stroke are not fully understood. Thus, the goal of this review is to provide an updated review of the literature on the basic science of how vitamin D may affect the cardiovascular system and in particular to analyze the role that vitamin D may have in the whole dynamic process from the initiation of endothelial dysfunction to the development of myocardial infarction and stroke.

  7. Trace Elements in Human Myocardial Infarction Determined by Neutron Activation Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Wester, P.O.

    1965-05-15

    By means of neutron activation analysis, injured and adjacent uninjured human heart tissue from 12 autopsy cases with myocardial infarction are investigated with respect to the concentration of 23 trace elements. The bulk elements K, Na and P are also determined. A recently developed ion-exchange technique, combined with subsequent y-spectrometry, is used. The following trace elements are determined: Ag, As, Au, Ba, Br, Ca, Cd, Ce, Co, Cr, Cs, Cu, Fe, Hg, La, Mo, Rb, Sb, Sc, Se, Sm, Zn and W. In the injured tissue compared to the uninjured, calculation on a wet weight basis showed a decrease in Co, Cs, K, Mo, P, Rb and Zn, and an increase in Br, Ca, Ce, La, Na, Sb and Sm. The differences in Ca, La, Mo, P and Zn are dependent on the age of the myocardial infarction, and the regression lines for these elements are given. The concentration of the trace elements in uninjured tissue from infarcted hearts is compared to the concentration of these elements in normal heart tissue, determined in a previous study. In the uninjured tissue from infarcted hearts a decrease is found in Cu and Mo, and an increase in As and Ce.

  8. FAMILY HISTORY OF DISEASE AS A RISK FACTOR OF ACUTE MYOCARDIAL INFARCTION

    Directory of Open Access Journals (Sweden)

    Zoran Velickovic

    2006-10-01

    Full Text Available Myocardial infarction (MI is a complex disease that begins with a lifelong interaction between genetics and environmental factors. The aim of the study was to identify family history as a risk factor of myocardial infarction in examined population in the Municipality of Nis.We used a case-control study with 100 patients with a first MI (in the period 1998-2000 and 100 controls, matched with respect to sex and age (± 2 years from the Municipality of Nis.Data was obtained from the epidemiological questionnaire. The Yates c2 test, odds ratio-OR and their 99% interval of confident were used as statistical procedures.The results showed that statistical significance for MI was present among all three degrees of relatives of subjects who have had an acute MI, and for hypertension, hypercholesterolemia and stroke among first and second - degree relatives. The subjects with family history of hypercholesterolemia had 12.43 times higher risk of disease (p = 0,000 and in the case of family history of MI before the age of 55, the risk was almost 10 times (p = 0,000 higher. Almost 4 times higher risk of disease was registered in subjects with family history of hypertension (p < 0,00001 and stroke (before 65 years of age - (p < 00005; a two-fold higher risk was registered in subjects with diagnoses of diabetes (p < 0,05 and other cardiovascular diseases (unless hypertension (p < 0,01 in the nearest relatives before the age of 55.We concluded that family history of diseases on the sample of the Municipality of Nis inhabitants was very important risk factor, mostly in the first-degree relatives. Genetic epidemiology is the future for all investigations between different population, and special attention should be paid to investigations and findings of different genes and loci which are very important for myocardial infarction occurrence, which would allow a new approach to preventive medicine.

  9. iPSC-derived human mesenchymal stem cells improve myocardial strain of infarcted myocardium.

    Science.gov (United States)

    Miao, Qingfeng; Shim, Winston; Tee, Nicole; Lim, Sze Yun; Chung, Ying Ying; Ja, K P Myu Mia; Ooi, Ting Huay; Tan, Grace; Kong, Geraldine; Wei, Heming; Lim, Chong Hee; Sin, Yoong Kong; Wong, Philip

    2014-08-01

    We investigated global and regional effects of myocardial transplantation of human induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) in infarcted myocardium. Acute myocardial infarction (MI) was induced by ligation of left coronary artery of severe combined immunodeficient mice before 2 × 10(5) iMSCs or cell-free saline were injected into peri-infarcted anterior free wall. Sham-operated animals received no injection. Global and regional myocardial function was assessed serially at 1-week and 8-week by segmental strain analysis by using two dimensional (2D) speckle tracking echocardiography. Early myocardial remodelling was observed at 1-week and persisted to 8-week with global contractility of ejection fraction and fractional area change in saline- (32.96 ± 14.23%; 21.50 ± 10.07%) and iMSC-injected (32.95 ± 10.31%; 21.00 ± 7.11%) groups significantly depressed as compared to sham control (51.17 ± 11.69%, P myocardial dilatation was observed in saline-injected animals (4.40 ± 0.62 mm, P strain analysis showed significant improved basal anterior wall strain (28.86 ± 8.16%, P strain only in saline-injected (21.50 ± 5.31%, P myocardial strain coincided with the presence of interconnecting telocytes in interstitial space of the infarcted anterior segment of the heart. Our results show that localized injection of iMSCs alleviates ventricular remodelling, sustains global and regional myocardial strain by paracrine-driven effect on neoangiogenesis and myocardial deformation/compliance via parenchymal and interstitial cell interactions in the infarcted myocardium.

  10. Functional Effects of Delivering Human Mesenchymal Stem Cell-Seeded Biological Sutures to an Infarcted Heart

    Directory of Open Access Journals (Sweden)

    Katrina J. Hansen

    2016-08-01

    Full Text Available Stem cell therapy has the potential to improve cardiac function after myocardial infarction (MI; however, existing methods to deliver cells to the myocardium, including intramyocardial injection, suffer from low engraftment rates. In this study, we used a rat model of acute MI to assess the effects of human mesenchymal stem cell (hMSC-seeded fibrin biological sutures on cardiac function at 1 week after implant. Biological sutures were seeded with quantum dot (Qdot-loaded hMSCs for 24 h before implantation. At 1 week postinfarct, the heart was imaged to assess mechanical function in the infarct region. Regional parameters assessed were regional stroke work (RSW and systolic area of contraction (SAC and global parameters derived from the pressure waveform. MI (n = 6 significantly decreased RSW (0.026 ± 0.011 and SAC (0.022 ± 0.015 when compared with sham operation (RSW: 0.141 ± 0.009; SAC: 0.166 ± 0.005, n = 6 (p  0.05; however, there was a trend toward improved function with the addition of either unseeded or seeded biological suture. Histology demonstrated that Qdot-loaded hMSCs remained present in the infarcted myocardium after 1 week. Analysis of serial sections of Masson's trichrome staining revealed that the greatest infarct size was in the infarct group (7.0% ± 2.2%, where unseeded (3.8% ± 0.6% and hMSC-seeded (3.7% ± 0.8% suture groups maintained similar infarct sizes. Furthermore, the remaining suture area was significantly decreased in the unseeded group compared with that in the hMSC-seeded group (p < 0.05. This study demonstrated that hMSC-seeded biological sutures are a method to deliver cells to the infarcted myocardium and have treatment potential.

  11. Primary percutaneous coronary intervention for acute myocardial infarction in a pediatric patient with giant coronary aneurysm due to Kawasaki disease.

    Science.gov (United States)

    Mongiovì, Maurizio; Alaimo, Annalisa; Vernuccio, Federica; Pieri, Daniele

    2014-01-01

    We report a case of acute myocardial infarction in an 8-year-old boy with a history of Kawasaki disease and giant coronary aneurysms in the right and left coronary arteries. We performed coronary angiography and percutaneous coronary intervention 4 hours after the onset of symptoms. This case suggests that primary percutaneous coronary intervention might be safe and effective in the long-term treatment of acute myocardial infarction due to coronary sequelae of Kawasaki. © 2013 Wiley Periodicals, Inc.

  12. Genetic Variation in ABCG1 and Risk of Myocardial Infarction and Ischemic Heart Disease

    DEFF Research Database (Denmark)

    Schou, Jesper; Frikke-Schmidt, Ruth; Kardassis, Dimitris

    2012-01-01

    OBJECTIVE: ATP binding cassette transporter G1 (ABCG1) facilitates cholesterol efflux from macrophages to mature high-density lipoprotein particles. Whether genetic variation in ABCG1 affects risk of atherosclerosis in humans remains to be determined. METHODS AND RESULTS: We resequenced the core...... promoter and coding regions of ABCG1 in 380 individuals from the general population. Next, we genotyped 10 237 individuals from the Copenhagen City Heart Study for the identified variants and determined the effect on lipid and lipoprotein levels and on risk of myocardial infarction (MI) and ischemic heart...

  13. Occupational exposure to particles and incidence of acute myocardial infarction and other ischaemic heart disease.

    Science.gov (United States)

    Wiebert, Pernilla; Lönn, Maria; Fremling, Karin; Feychting, Maria; Sjögren, Bengt; Nise, Gun; Kauppinen, T; Plato, Nils; Gustavsson, Per

    2012-09-01

    Ambient particulate air pollution has been linked to cardiovascular disease. Occupational particle exposure levels may be several times higher than ambient levels but has been less studied. The authors investigated the association between occupational exposure to particles and the incidence of ischaemic heart disease (IHD). The cohort included all manual workers in the Swedish national census of 1980 with information on demographic data and occupation. Information on hospital admissions for acute myocardial infarction or other IHDs and cause of death were obtained from nation-wide registers. A job-exposure matrix for exposure to small (1 μm) particles was developed. HRs were calculated with Cox regression with adjustment for sex, age, socioeconomic group and urban/rural residential area. Exposure to small particles was associated with an increased HR for acute myocardial infarction of 1.12 (95% CI 1.09 to 1.15), and HR for exposure to large particles was 1.14 (95% CI 1.10 to 1.18). The association was somewhat stronger for workers exposed to small particles for more than 5 years, 1.21 (95% CI 1.11 to 1.31), but no trend with exposure intensity was found. The risk associated with exposure to small particles was higher among women than among men, 1.30 (95% CI 1.12 to 1.51) and 1.10 (95% CI 1.07 to 1.14), respectively. Findings were essentially similar for other IHDs. This explorative study gives some support to the hypothesis that occupational exposure to particles increases the risk of acute myocardial infarction and other IHD. The findings must be interpreted cautiously due to lack of smoking data.

  14. Transplantation of genetically engineered cardiac fibroblasts producing recombinant human erythropoietin to repair the infarcted myocardium

    Directory of Open Access Journals (Sweden)

    Ruvinov Emil

    2008-11-01

    Full Text Available Abstract Background Erythropoietin possesses cellular protection properties. The aim of the present study was to test the hypothesis that in situ expression of recombinant human erythropoietin (rhEPO would improve tissue repair in rat after myocardial infarction (MI. Methods and results RhEPO-producing cardiac fibroblasts were generated ex vivo by transduction with retroviral vector. The anti-apoptotic effect of rhEPO-producing fibroblasts was evaluated by co-culture with rat neonatal cardiomyocytes exposed to H2O2-induced oxidative stress. Annexin V/PI assay and DAPI staining showed that compared with control, rhEPO forced expression markedly attenuated apoptosis and improved survival of cultured cardiomyocytes. To test the effect of rhEPO on the infarcted myocardium, Sprague-Dawley rats were subjected to permanent coronary artery occlusion, and rhEPO-producing fibroblasts, non-transduced fibroblasts, or saline, were injected into the scar tissue seven days after infarction. One month later, immunostaining identified rhEPO expression in the implanted engineered cells but not in controls. Compared with non-transduced fibroblasts or saline injection, implanted rhEPO-producing fibroblasts promoted vascularization in the scar, and prevented cell apoptosis. By two-dimensional echocardiography and postmortem morphometry, transplanted EPO-engineered fibroblasts did not prevent left ventricular (LV dysfunction and adverse LV remodeling 5 and 9 weeks after MI. Conclusion In situ expression of rhEPO enhances vascularization and reduces cell apoptosis in the infarcted myocardium. However, local EPO therapy is insufficient for functional improvement after MI in rat.

  15. Genetic Mapping in Human Disease

    OpenAIRE

    Altshuler, David; Daly, Mark J; Lander, Eric S.

    2008-01-01

    Genetic mapping provides a powerful approach to identify genes and biological processes underlying any trait influenced by inheritance, including human diseases. We discuss the intellectual foundations of genetic mapping of Mendelian and complex traits in humans, examine lessons emerging from linkage analysis of Mendelian diseases and genome-wide association studies of common diseases, and discuss questions and challenges that lie ahead.

  16. The ABCG5/8 Cholesterol Transporter and Myocardial Infarction Versus Gallstone Disease

    DEFF Research Database (Denmark)

    Stender, Stefan; Frikke-Schmidt, Ruth; Nordestgaard, Børge G

    2014-01-01

    OBJECTIVES: The study sought to test the hypothesis that genetic variation in ABCG5/8, the transporter responsible for intestinal and hepatobiliary cholesterol efflux, may simultaneously influence plasma and biliary cholesterol levels, and hence risk of myocardial infarction (MI) and gallstone...... disease in opposite directions. BACKGROUND: High plasma levels of low-density lipoprotein (LDL) cholesterol are a causal risk factor for MI, whereas high levels of biliary cholesterol promote gallstone formation. METHODS: A total of 60,239 subjects from Copenhagen were included, including 5,647 with MI...... and 3,174 with symptomatic gallstone disease. Subjects were genotyped for 6 common, nonsynonymous and functional variants in ABCG5/8, and a combined weighted genotype score was calculated. RESULTS: Combined, weighted genotype scores were associated with stepwise decreases in LDL cholesterol of up to 5...

  17. Prognosis after first-time myocardial infarction in patients with inflammatory bowel disease according to disease activity

    DEFF Research Database (Denmark)

    Kristensen, Søren Lund; Ahlehoff, Ole; Lindhardsen, Jesper

    2014-01-01

    BACKGROUND: Inflammatory bowel disease (IBD) is associated with increased cardiovascular risk. We examined the effect of active IBD on major adverse cardiovascular outcomes after myocardial infarction (MI). METHODS AND RESULTS: In nationwide registries, we identified 86 790 patients with first......-time MI from the period 2002 to 2011. A total of 1030 patients had IBD, and we categorized their disease activity stages into either flare (120 days), persistent (>120 days) activity, or remission. Short-term mortality was estimated in a logistic regression-model, whereas risk of recurrent MI, all.......61-3.15), and the composite end point (hazard ratio, 2.04; 95% CI, 1.35-3.06), whereas no increased risk was identified in remission. CONCLUSIONS: Active inflammatory bowel disease worsens prognosis after MI, in particular, in relation with flares....

  18. Large deep infarcts found in proximal middle cerebral artery steno-occlusive disease: MRI and angiographic findings

    Energy Technology Data Exchange (ETDEWEB)

    Yi, Bum Ha; Kim, Eui Jong; Choi, Woo Suk; Jang, Dae Il; Chung, Kyung Cheon; Oh, Joo Hyung; Yoon, Yup; Hong, Hoon Pyo [Kyunghee Univ. Hospital, Seoul (Korea, Republic of)

    1998-11-01

    To determine the nature of large deep-seated infarcts without cortical infarct in patients with steno-occlusive disease of the proximal middle cerebral artery (MCA) using magnetic resonance images (MRI) and angiography. By means of MRI and MR angiography (MRA), we examined 24 patients with large deep cerebral infarctions (>3cm in size) involving the basal ganglia, corona radiata and/or centrum semiovale, as well as steno-occlusive lesion of the proximal MCA. According to location, infarctions were classified into five groups, as follows:Group 1:basal ganlgia and corona radiata; 2:basal ganglia, corona radiata and centrum semiovale;3:corona radiata and centrum semiovale;4:corona radiata;5:basal ganglia only. We evaluated the topography of the lesions and correlated the results with the findings of angiography (all 24 MRA;the 13:conventional angiography). Involvement of the head of the caudate nucleus and the internal capsule were also evaluated. Fifteen of 24 cases (63%) were assigned to group 1 (4 proximal MCA(M1) occlusion and 11 stenosis), and five of 24 (21%) with M1 occlusions to group 2. Group 3 comprised only one case with M1 occlusion. Two cases with both occlusion and stenosis were included in group 4, and only one case-with M1 stenosis-in group 5. Infarctions at the caudate nucleus were seen in five cases, and at the internal capsule in two. On conventional angiography (13 cases) cortical branches of the MCA were delineated through the leptomeningeal collaterals of anterior or posterior cerebral arteries. Most large deep cerebral infarctions found in proximal MCA diseases are thought to extend cephalad to the corona radiata. When large deep-seated infarctions with proximal MCA occlusion is observed more frequently than stenosis.=20.

  19. Simultaneous occurrence of diabetic ketoacidosis, thyroid storm, and multiple cerebral infarctions due to Moyamoya disease.

    Science.gov (United States)

    Noh, Byoungho H; Cho, Sang-Won; Ahn, Sung Yeon

    2016-02-01

    Diabetic ketoacidosis (DKA) is one of the precipitating factors that can evoke a thyroid storm. Thyroid storm may cause cerebral ischemia in Moyamoya disease, which can coexist in patients with Graves' disease. A 16-year-old girl complaining of dizziness and palpitations visited the emergency department and was diagnosed with DKA combined with hyperthyroidism. A thyroid storm occurred 6 h after the start of DKA management. Her Burch and Wartofsky score was 65 points. Right hemiplegia developed during the thyroid storm, and brain magnetic resonance (MR) diffusion-weighted images revealed multiple acute infarcts in both hemispheres. MR angiography showed stenosis of both distal internal carotid arteries and both M1 portions of the middle cerebral arteries, consistent with Moyamoya disease. After acute management for the thyroid storm with methimazole, Lugol solution and hydrocortisone, the patient's neurological symptoms completely resolved within 1 month, and free T4 level normalized within 2 months. Thyroid storm may trigger cerebral ischemia in Moyamoya disease and lead to rapid progression of cerebrovascular occlusive disease. As a simultaneous occurrence of DKA, thyroid storm and cerebrovascular accident in Moyamoya disease highly elevates morbidity and mortality, prompt recognition and management are critical to save the patient's life.

  20. Percutaneous coronary intervention for acute myocardial infarction in a pediatric patient with coronary aneurysm and stenosis due to Kawasaki disease.

    Science.gov (United States)

    Drossner, David M; Chappell, Clay; Rab, Tanveer; Kim, Dennis

    2012-06-01

    We report the case of an acutely ill 3-year-old female, with a previous medical history of Kawasaki disease, who presented to care with an acute myocardial infarction. We describe the coordinated therapies employed by pediatric and adult cardiologists aimed to establish coronary revascularization.

  1. Clinical applications of non-invasive imaging techniques in suspected coronary artery disease and in acute myocardial infarction

    NARCIS (Netherlands)

    Nucifora, Gaetano

    2015-01-01

    Non-invasive cardiac imaging modalities play a crucial role in the diagnostic process and clinical management of patients without known coronary artery disease and patients with acute myocardial infarction. The first part of the thesis discusses the use of non-invasive imaging modalities (including

  2. Less use of standard guideline-based treatment of myocardial infarction in patients with chronic kidney disease

    DEFF Research Database (Denmark)

    Blicher, Thalia Marie; Hommel, Kristine; Olesen, Jonas Bjerring;

    2013-01-01

    The aim of this Danish nationwide study was to evaluate the treatment of myocardial infarction (MI) in patients with non-end-stage chronic kidney disease (CKD) and in patients requiring renal replacement therapy (RRT). Upgraded guidelines for the management of MI were implemented around 2004; hence...

  3. Cerebral infarction following intracranial hemorrhage in pediatric Moyamoya disease - A case report and brief review of literature

    Directory of Open Access Journals (Sweden)

    Soumya Patra

    2012-01-01

    Full Text Available Moyamoya disease is a clinical entity characterized by progressive cerebrovascular occlusion with spontaneous development of a collateral vascular network called Moyamoya vessels. This disease mainly manifests as cerebral ischemia. Intracranial bleeding is another major presentation of patients with Moyamoya disease. We report here a 12-year-old male child who presented with severe headache, vomiting and meningismus. Initial neuroimaging study with noncontrast computed tomography scan revealed fresh intraventricular hemorrhage in right-sided lateral ventricle. Magnetic resonance imaging with angiography of brain was done 5 days later when the child developed right-sided hemiparesis, and the diagnosis of Moyamoya disease was confirmed along with lacunar infarction of right posterior peri and paraventricular area and in the left paraventricular area and centrum semiovale. Simultaneous presence of cerebral infarction along with intraventricular hemorrhage in adult with bleeding-type Moyamoya disease is reported in literature, but it is a rare entity in a child.

  4. Benefit of clopidogrel therapy in patients with myocardial infarction and chronic kidney disease

    DEFF Research Database (Denmark)

    Blicher, Thalia Marie; Hommel, Kristine; Kristensen, Søren Lund

    2014-01-01

    BACKGROUND: The aim of the present study was to evaluate clopidogrel treatment after incident myocardial infarction (MI) in patients with and without chronic kidney disease (CKD). METHODS AND RESULTS: By linking nation-wide registries, information about patients admitted with incident MI was found....... Primary endpoints were all-cause and cardiovascular (CV) mortality, a composite of all-cause mortality and recurrent MI, and a composite of fatal and nonfatal bleedings. Effect of clopidogrel use versus clopidogrel nonuse was estimated using an adjusted Cox's regression model stratified according...... to percutaneous coronary intervention (PCI) treatment.A total of 69 082 incident MI patients in the period 2002-2011 were included. Clopidogrel treatment was associated with hazard ratios (HRs) for the combined endpoint of all-cause mortality and recurrent MI in PCI-treated patients of 0.90 (95% confidence...

  5. Increasing prevalence despite decreasing incidence of ischeamic heart disease and myocardial infarction

    DEFF Research Database (Denmark)

    Koch, Mette Bjerrum; Davidsen, Michael; Andersen, Lisbeth V.

    2015-01-01

    AIMS: Mortality from ischaemic heart disease (IHD) including acute myocardial infarction (AMI) in Denmark peaked around 1977, after which a marked decline has occurred as a result of decreasing incidence and increasing effect of treatment. IHD is a chronic, relapsing condition, and the effect...... of these changes on the prevalence of IHD is not known. METHODS AND RESULTS: Changes in incidence and prevalence in 2000-2009 are presented, using nationwide data from public registers. An incident case is defined as a subject registered with a diagnosis of IHD/AMI and without a prior diagnosis for the past 20...... years (beginning in 1980). A prevalent case is defined as a subject surviving the first year after the incident diagnosis. Regarding IHD, age-standardised incidence rates declined significantly from 2000 to 2009 for both sexes (females 445 to 340/100,000, males 822 to 678/100,000), reflecting...

  6. The Role of Echocardiography in Coronary Artery Disease and Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Maryam Esmaeilzadeh

    2015-10-01

    Full Text Available Echocardiography is a non-invasive diagnostic technique which provides information regarding cardiac function and hemodynamics. It is the most frequently used cardiovascular diagnostic test after electrocardiography and chest X-ray. However, in a patient with acute chest pain, Transthoracic Echocardiography is essential both for diagnosing acute coronary syndrome, zeroing on the evaluation of ventricular function and the presence of regional wall motion abnormalities, and for ruling out other etiologies of acute chest pain or dyspnea, including aortic dissection and pericardial effusion.Echocardiography is a versatile imaging modality for the management of patients with chest pain and assessment of left ventricular systolic function, diastolic function, and even myocardial and coronary perfusion and is, therefore, useful in the diagnosis and triage of patients with acute chest pain or dyspnea.This review has focused on the current applications of echocardiography in patients with coronary artery disease and myocardial infarction

  7. Bilateral Knee Pain Associated with Bone Infarction in a Patient with Behcet's Disease

    Directory of Open Access Journals (Sweden)

    Pelin Oktayoglu

    2012-01-01

    Full Text Available We describe a 31-years-old female patient with severe pain in both knees who had been diagnosed as Behcet’s disease (BD for 12 years. She had had a history of complications due to BD including superior vena cava thrombosis, pulmonary thromboembolism, uveitis, and erythema nodosum and has reported the administration of corticosteroid therapy irregularly. After radiologic evaluation, she has been diagnosed with bone infarction of both left and right knee with the existance of lupus anticoagulants (LA positivity. Severe joint pain without the evidence of arthritis must alert the clinician to the possibility of bone necrosis of the extremity, although those may rarely occur bilateral in BD.

  8. Myocardial Infarction and Ischemic Heart Disease in Overweight and Obesity With and Without Metabolic Syndrome

    DEFF Research Database (Denmark)

    Thomsen, Mette; Nordestgaard, Børge G

    2014-01-01

    IMPORTANCE: Overweight and obesity likely cause myocardial infarction (MI) and ischemic heart disease (IHD); however, whether coexisting metabolic syndrome is a necessary condition is unknown. OBJECTIVE: To test the hypothesis that overweight and obesity with and without metabolic syndrome...... syndrome. MAIN OUTCOMES AND MEASURES: Hazard ratios for incident MI and IHD according to combinations of BMI category and absence or presence of metabolic syndrome. RESULTS: During a median of 3.6 years' follow-up, we recorded 634 incident MI and 1781 incident IHD events. For MI, multivariable adjusted...... hazard ratios vs normal weight individuals without metabolic syndrome were 1.26 (95% CI, 1.00-1.61) in overweight and 1.88 (95% CI, 1.34-2.63) in obese individuals without metabolic syndrome and 1.39 (95% CI, 0.96-2.02) in normal weight, 1.70 (95% CI, 1.35-2.15) in overweight, and 2.33 (95% CI, 1...

  9. [The effect of myosin from the human myocardium on quantitative T-lymphocyte values--active rosettes in patients with myocardial infarct and stenocardia].

    Science.gov (United States)

    Manev, V; Penkova, K; Ivanov, G; Ivanova, I; Grigorov, M; Nedialkova, V

    1990-01-01

    The aim of the investigation is to study the influence of human myocardium myosin on the quantitative values of T-lymphocytes examined as active rosettes [correction of rosellae] in patients with ischemic heart disease. The study included 99 patients with ischemic heart disease, 49 of them with myocardial infarction and 50--with stenocardia. The controls were 61 clinically healthy donors. It was established that the active rosettes [correction of rosellae] in the patients with myocardial infarction were significantly less than in the controls (p less than 0.05). A significant inhibiting action of the human myocardium myosin on the active rosettes [correction of rosellae] was manifested (p less than 0.002). This action in the patients with stenocardia was less expressed (p less than 0.05). Myosin from a striated muscle did not exert an inhibiting action (p greater than 0.1). The results prove the participation of human myocardium myosin in the pathogenetic mechanism of T-lymphocytes suppression in patients with ischemic heart disease.

  10. Transplanted human umbilical cord blood mononuclear cells improve left ventricular function through angiogenesis in myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    HU Cheng-heng; WU Gui-fu; WANG Xiao-qing; YANG Yan-hua; DU Zhi-min; HE Xiao-hong; XIANG Peng

    2006-01-01

    Background Human umbilical cord blood contains an abundance of immature stem/progenitor cells, which may participate in the repair of hearts that have been damaged by myocardial infarction (MI). This study aimed to evaluate the effects of human umbilical cord blood mononuclear cells (hUCBC) transplantation on cardiac function and left ventricular remodeling in rat model of MI.Methods Forty-five male Wistar rats were randomized into three groups: MI or control group (n=15), MI plus cell transplantation (n=15), and sham group (n=15). Acute myocardial infarction (AMI) was established by ligating the left anterior descending artery, thereafter, hUCBC were implanted into the marginal area of infarcted myocardium. In MI/control group, DMEM was injected instead of hUCBC following the same protocol. Left ventricular function assessment was carried out by echocardiography and invasive hemodynamic measurements one month post MI. All rats were sacrificed for histological and immunochemical examinations.Results The transplanted hUCBC survived and engaged in the process of myocardial repair in the host heart.Echocardiography demonstrated that left ventricular function improved significantly in the rats that underwent cell transplantation. Hemodynamic studies found a significantly decreased left ventricular end-diastolic pressure (LVEDP) [(21.08±8.10) mmHg vs (30.82±9.59) mmHg, P<0.05], increase in +dp/dtmax [(4.29± 1.27)mmHg/ms vs (3.24±0.75) mmHg/ms, P<0.05), and increase in -dp/dtmax [(3.71 ±0.79) mmHg/ms vs (3.00±0.49) mmHg/ms, P<0.05] among MI group with hUCBC transplantation when compared with MI/control group.Masson's trichrome staining revealed that the collagen density in the left ventricle was significantly lower in rats of transplantation group than that in the MI control groups [(6.33±2.69)% vs (11.10±3.75)%, P< 0.01]. Based on immunostaining of α-actin, the numbers of microvessels were significantly (P<0.01) increased at the boundary of

  11. The ABCG5/8 cholesterol transporter and myocardial infarction versus gallstone disease.

    Science.gov (United States)

    Stender, Stefan; Frikke-Schmidt, Ruth; Nordestgaard, Børge G; Tybjaerg-Hansen, Anne

    2014-05-27

    The study sought to test the hypothesis that genetic variation in ABCG5/8, the transporter responsible for intestinal and hepatobiliary cholesterol efflux, may simultaneously influence plasma and biliary cholesterol levels, and hence risk of myocardial infarction (MI) and gallstone disease in opposite directions. High plasma levels of low-density lipoprotein (LDL) cholesterol are a causal risk factor for MI, whereas high levels of biliary cholesterol promote gallstone formation. A total of 60,239 subjects from Copenhagen were included, including 5,647 with MI and 3,174 with symptomatic gallstone disease. Subjects were genotyped for 6 common, nonsynonymous and functional variants in ABCG5/8, and a combined weighted genotype score was calculated. Combined, weighted genotype scores were associated with stepwise decreases in LDL cholesterol of up to 5.9% (0.20 mmol/l) for individuals with a score ≥8.0 (prevalence = 11%) versus gallstone disease as a function of age and increasing genotype score were decreased and increased (log-rank ps for trend: 6 × 10E-4 and 9 × 10E-45), respectively. The multifactorially adjusted odds ratios were 0.83 (95% confidence interval: 0.73 to 0.94) for MI and 2.85 (95% confidence interval: 2.39 to 3.39) for symptomatic gallstone disease for individuals with a genotype score ≥8.0 versus gallstone disease. These results suggest that MI and gallstones, 2 seemingly unrelated diseases, are intrinsically linked via the function of the ABCG5/8 cholesterol transporter. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  12. [Risk factors for cardiovascular diseases in the descendants of patients after early myocardial infarction].

    Science.gov (United States)

    Mateřánková, Markéta; Karnosová, Petra; Mlíková Seidlerová, Jitka; Filipovský, Jan; Mayer, Otto

    2017-01-01

    The cardiovascular diseases (CVDs) developing as the result of atherosclerosis are among the most frequent causes of morbidity and mortality within the Czech Republic and elsewhere. Genetic predisposition for cardiovascular diseases is amplified in the presence of routine risk factors which can be influenced. Our aim was to establish whether the level of the risk factors for ICHS already differs in the population of healthy descendants of the patients after early myocardial infarction, as opposed to the control group of examined individuals. We approached adult children (n = 127; age 28.7 ± 6.5 years) of the patients with early manifestation of ICHS, who were examined within the study EUROASPIRE IV. The examination of both the descendants and the control group (n = 199; age 28.9 ± 5.3 years) focused on identifying the risk factors for ICHS. Descendants presented arterial hypertension more often (18.9 vs 8.0 %, p = 0.003) and there were more smokers among them compared to the control group (37 vs 24.1 %, p = 0.01). The levels of triglycerides (1.13 vs 0.99 mmol/l, p = 0.05) and LDL-cholesterol (2.7 vs 2.45 mmol/l, p = 0.01) were higher in the descendant group, HDL-cholesterol was similar in both groups (1.6 vs 1.67 mmol/l, p = 0.17). Increased fasting glycemia occurred more frequent in the descendant group (5.5 vs 1.5 %, p = 0.05). None of the examined participants met the criteria for the diagnosis of diabetes mellitus. Aortic stiffness was higher in the descendant group as opposed to the control group (6.2 vs 5.8 m/s, p = 0.001). The total calculated cardiovascular risk based on the SCORE system was also higher in the descendant group as compared to the control group - the current risk related to the age of 40 years: 0.35 (0.19-0.64) vs 0.20 (0.13-0.47), p triglycerides and impaired fasting glycemia more frequently. Unfavourable genetic predisposition along with unfitting lifestyle contributes to a higher likelihood of accumulation of risk factors, and therefore

  13. Extremely high ferritin level after an acute myocardial infarction in an end stage renal disease patient.

    Science.gov (United States)

    Sandhu, Gagangeet; Mankal, Pavan; Gupta, Isha; Tagani, Adrian; Ranade, Aditi; Jones, James; Bansal, Anip

    2014-07-01

    We present here a case of an asymptomatic end-stage renal disease (ESRD) patient, who had an unexplained persistent mild leukocytosis in the setting of an extremely high ferritin level (8,997 ng/ml; reference range: 12 - 300 ng/ml) 3 weeks after she suffered from a myocardial infarction (MI). Infection as the cause of these laboratory abnormalities was ruled out. A week later, the patient was noted to have asymptomatic hypotension (100/60 mmHg; her baseline blood pressure was 120/70 mmHg) during a maintenance hemodialysis session. An echocardiography revealed an interval development of moderate pericardial effusion when compared to her previous echocardiography 4 weeks before. In the setting of a recent MI with other laboratory markers suggesting an ongoing inflammatory process, a tentative diagnosis of Dressler's syndrome was made. A pericardial tap yielded exudative (bloody) fluid, thus, confirming our suspicion. Dressler's syndrome results from an inflammation of the pericardium as a consequence of an underlying autoimmune process few weeks to months after a myocardial infarction or post-cardiac surgery. Although it typically presents with pleuritic chest pain, fever, leukocytosis, and a friction rub; our case illustrates that the initial presentation may be asymptomatic in ESRD patients. For the same reason, it is likely an under-recognized entity in such patients. An unexplained elevated ferritin in an ESRD patient with recent history of MI should prompt an investigation for Dressler's syndrome. In those with associated significant pericardial effusion, daily HD should be initiated and anticoagulation should be avoided. Unlike other ESRD associated pericarditis, steroids and NSAIDs should be avoided in Dressler's syndrome as they may hamper cardiac remodeling in the immediate post-MI period. Colchicine may offer some benefit in patients with associated chest pain. For those failing medical management or manifesting overt signs of tamponade, surgical drainage

  14. The relationship between cerebral infarction on MR and angiographic findings in moyamoya disease: significance of the posterior circulation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Ja; Song, Soon Young [College of Medicine, Kwangdong Univ., Koyang (Korea, Republic of); Yu, Won Jong; Jung, So Lyung; Chung, Bong Gak; Kag, Si Won [College of Medicine, The Catholic Univ. of Korea, Seoul (Korea, Republic of); Kim, Man Deuk [College of Medicine, Pochon CHA Univ., Pochon (Korea, Republic of)

    2002-06-01

    To investigate the relationship between changes in the posterior and anterior circulation, as seen at angiography, and the frequency and extent of cerebral infarction revealed by MR imaging in moyamoya disease. This study involved 34 patients (22 females and 12 males, aged 2-52 years) in whom cerebral angiography revealed the presence of moyamoya disease (bilateral; unilateral= 24:10; total hemispheres=58) and who also underwent brain MR imaging. To evaluate the angiographic findings, we applied each angiographic staging system to the anterior and posterior circulation. Leptomeningeal collateral circulation from the cortical branches of the posterior cerebral artery (PCA) was also assigned one of four grades. At MR imaging, areas of cerebral cortical or subcortical infarction in the hemisphere were divided into six zones. White matter and basal ganglionic infarction, ventricular dilatation, cortical atrophy, and hemorrhagic lesions were also evaluated. To demonstrate the statistical significance of the relationship between the angiographic and the MR findings, both the Mantel-Haenszel chi-square test for trend and the chi-square test were used. The degree of steno-occlusive PCA change correlated significantly with the internal carotid artery (ICA) stage (p<0.0001). As PCA stages advanced, the degree of leptomeningeal collaterals from the PCA decreased significantly (P<0.0001), but ICA stages were not significant (p>0.05). The prevalence of infarction showed significant correlation with the degree of steno-occlusive change in both the ICA and PCA. The degree of cerebral ischemia in moyamoya patients increased proportionally with the severity of PCA stenosis rather than with that of steno-occlusive lesins of the anterior circulation. Infarctions tended to be distributed in the anterior part of the hemisphere at PCA state I or II, while in more advanced PCA lesions, they were also found posteriorly, especially in the territories of the posterior middle cerebral artery

  15. Soluble CD163 does not predict first-time myocardial infarction in patients infected with human immunodeficiency virus

    DEFF Research Database (Denmark)

    Knudsen, Andreas; Møller, Holger Jon; Katzenstein, Terese Lea;

    2013-01-01

    BACKGROUND: Soluble CD163 (sCD163) has been associated with arterial inflammation and non-calcified plaques in human immunodeficiency virus (HIV)-infected individuals and has therefore been suggested as a predictive biomarker of myocardial infarction (MI). METHODS: We conducted a nested case...

  16. Cultured human embryonic neocortical cells survive and grow in infarcted cavities of adult rat brains and interconnect with host brain

    Institute of Scientific and Technical Information of China (English)

    ZENG Jin-sheng; YU Jian; CUI Chun-mei; ZHAO Zhan; HONG Hua; SHENG Wen-li; TAO Yu-qian; LI Ling; HUANG Ru-xun

    2005-01-01

    Background There are no reports on exnografting cultured human fetal neocortical cells in this infracted cavities of adult rat brains. This study was undertaken to observe whether cultured human cortical neurons and astrocytes can survive and grow in the infarcted cavities of adult rat brains and whether they interconnect with host brains.Methods The right middle cerebral artery was ligated distal to the striatal branches in 16 adult stroke-prone renovascular hypertensive rats. One week later, cultured cells from human embryonic cerebral cortexes were stereotaxically transferred to the infarcted cavity of 11 rats. The other 5 rats receiving sham transplants served as controls. For immunosuppression, all transplanted rats received intraperitoneal injection of cyclosporine A daily starting on the day of grafting. Immunohistochemistry for glial fibrillary acidic protein (GFAP), synaptophysin, neurofilament, and microtubule associated protein-2 (MAP-2) was performed on brain sections perfused in situ 8 weeks after transplantation.Results Grafts in the infarcted cavities of 6 of 10 surviving rats consisted of bands of neurons with an immature appearance, bundles of fibers, and GFAP-immunopositive astrocytes, which were unevenly distributed. The grafts were rich in synaptophysin, neurofilament, and MAP2-positive neurons with long processes. The graft/host border was diffuse with dendrites apparently bridging over to the host brain, into which neurofilament immunopositive fibers protruded. Conclusion Cultured human fetal brain cells can survive and grow in the infarcted cavities of immunodepressed rats and integrate with the host brain.

  17. Paradoxical embolism in acute myocardial infarction in a patient with congenital heart disease

    Directory of Open Access Journals (Sweden)

    Abdelrahman Jamiel

    2012-01-01

    Full Text Available We present a case of a young male with severe pulmonary stenosis, hypoplastic right ventricle, and atrial septal defect. Acute embolic myocardial infarction, followed by cardiac arrest, occurred during hospitalization after Glenn operation. The therapeutic challenges are discussed. Insufficient anticoagulation therapy during the postoperative period was a possible contributing factor leading to embolic myocardial infarction.

  18. Orbital wall infarction mimicking periorbital cellulitis in a patient with sickle cell disease

    Energy Technology Data Exchange (ETDEWEB)

    Ozkavukcu, Esra; Fitoz, Suat; Erden, Ilhan [Ankara University School of Medicine, Department of Radiology, Ankara (Turkey); Yagmurlu, Banu [Kirikkale University School of Medicine, Department of Radiology, Kirikkale (Turkey); Ciftci, Ergin [Ankara University School of Medicine, Department of Paediatric Infectious Diseases, Ankara (Turkey); Ertem, Mehmet [Ankara University School of Medicine, Department of Paediatric Haematology, Ankara (Turkey)

    2007-04-15

    Orbital wall infarction and subperiosteal haematomas are unusual manifestations of sickling disorders. Here we report an 11-year-old girl with sickle cell anaemia having multiple skull infarctions including the orbital bony structures associated with subperiosteal haematomas. The diagnosis was made by MRI, which showed bone marrow changes and associated haemorrhagic collections. The patient was successfully managed without surgical intervention. (orig.)

  19. ENDOTHELIAL DYSFUNCTION IN STABLE ANGINA AND MYOCARDIAL INFARCTION COMBINED WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

    Directory of Open Access Journals (Sweden)

    M. A. Popova

    2015-01-01

    Full Text Available The research objective is to determine the state of endothelium-dependent and endothelium-independent vasodilatation in patients with coronary heart disease (CHD associated with chronic obstructive pulmonary disease (COPD.Material and methods. In the cross-sectional study included 122 patients with CHD associated with COPD: 68 people of them are patients with stable angina without acute coronary events in history and 54 patients with acute ST segment elevation myocardial infarction (STEMI. Comparison group comprised 53 patients with stable angina and 51 patients after STEMI without concomitant COPD. Patients were included if they met the following inclusion criteria: male, age <60 years, verified forms of CHD (stable angina, STEMI, documented with COPD without exacerbation and forced expiratory volume in 1 second > 30% in the groups with CHD and COPD. Arterial endothelial function was tested with high-resolution ultrasonography: brachial artery diameter was measured at rest, after flow increase (which causes endothelium-dependent dilatation, and after administration of sublingual nitroglycerin (an endothelium-independent dilator.Results. We found that endothelial dysfunction in patients with acute and chronic forms of CHD in combination with COPD are more pronounced than in isolated CHD.Conclusion. Expressed depression functional vascular reserve in patients with CHD associated with COPD, should be taken into account when conducting individualized therapy of these patients.

  20. Viral diseases and human evolution

    OpenAIRE

    2000-01-01

    The interaction of man with viral agents was possibly a key factor shaping human evolution, culture and civilization from its outset. Evidence of the effect of disease, since the early stages of human speciation, through pre-historical times to the present suggest that the types of viruses associated with man changed in time. As human populations progressed technologically, they grew in numbers and density. As a consequence different viruses found suitable conditions to thrive and establish l...

  1. Effect of gene modified mesenchymal stem cells overexpression human receptor activity modified protein 1 on inflammation and cardiac repair in a rabbit model of myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    赵然尊

    2012-01-01

    Objective To investigate the effect of mesenchymal stem cells(MSCs) overexpressing human receptor activity modified protein 1(hRAMP1) by adenovirus vector on infarction related inflammation and cardiac repair in a rabbit model of myocardial infarction(MI)

  2. Effects of human umbilical cord mesenchymal stem cells therapy on CD61,CD62P and CD54 in elderly patients with old myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    李侠

    2013-01-01

    Objective To study the effects of human umbilical cord mesenchymal stem cells (hUCM-SCs) therapy on peripheral blood CD61,CD62P and CD54 in elderly patients with old myocardial infarction.Methods From July2010 to August 2012,30 elderly patients with old myocardial infarction were randomly selected.Patients were

  3. Viral diseases and human evolution

    Directory of Open Access Journals (Sweden)

    Leal Élcio de Souza

    2000-01-01

    Full Text Available The interaction of man with viral agents was possibly a key factor shaping human evolution, culture and civilization from its outset. Evidence of the effect of disease, since the early stages of human speciation, through pre-historical times to the present suggest that the types of viruses associated with man changed in time. As human populations progressed technologically, they grew in numbers and density. As a consequence different viruses found suitable conditions to thrive and establish long-lasting associations with man. Although not all viral agents cause disease and some may in fact be considered beneficial, the present situation of overpopulation, poverty and ecological inbalance may have devastating effets on human progress. Recently emerged diseases causing massive pandemics (eg., HIV-1 and HCV, dengue, etc. are becoming formidable challenges, which may have a direct impact on the fate of our species.

  4. Optimal time for human umbilical cord blood cell transplantation in rats with myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    XING Yun-li; SHEN Lu-hua; LI Hong-wei; ZHANG Yu-chen; ZHAO Lin; ZHAO Shu-mei; XU Qing

    2009-01-01

    Background Cell therapy for cardiac regeneration is still under investigation. To date there have been a limited number of studies describing the optimal time for cell injection. The present study aimed to examine the optimal time for human umbilical cord blood cells (HUCBCs) transplantation after myocardial infarction (MI).Methods The animals underwent MI by ligation of the left anterior descending coronary artery and received an intravenous injection of equal volumes of HUCBCs or phosphate buffered saline at days 1,5,10 and 30 after MI. HUCBCs were detected by immunostaining against human human leucocyte antigen (HLA). Cardiac function, histological analysis and measurement of vascular endothelial growth factor (VEGF) were performed 4 weeks after cell transplantation. Results HUCBCs transplantation could improve cardiac function in rats that received transplantation at 5 and 10 days after MI. The best benefit was achieved in rats that received cells at 10-day after MI. Survival of engrafted HUCBCs, angiogenesis and VEGF expression were more obvious in the 10-day transplantation group than in the other transplantation groups. No evidence of cardiomyocyte regeneration was detected in any transplanted rats. Conclusions HUCBCs transplantation could improve cardiac function in rats that received HUCBCs at days 5 and 10 after MI with the optimal time for transplantation being 10 days post MI. Angiogenesis, but not cardiomyocyte regeneration, played a key role in the cardiac function improvement.

  5. The role of matrix metalloproteinase-2 promoter polymorphisms in coronary artery disease and myocardial infarction.

    Science.gov (United States)

    Alp, Ebru; Menevse, Sevda; Tulmac, Murat; Yilmaz, Akin; Yalcin, Ridvan; Cengel, Atiye

    2011-04-01

    The matrix metalloproteinase (MMP) family are key enzymes involved in the breakdown of the extracellular matrix in normal physiological processes, including tissue remodeling, and disease processes, such as arthritis and metastasis. The promoter polymorphism in the MMP2 gene may be responsible for multiple diseases related to extracellular matrix degradation. Therefore, we aimed to investigate the relationship between genotypes or haplotypes of -1575 G/A, -1306 C/T, -790 T/G, and -735 C/T promoter polymorphisms and coronary artery disease (CAD) with or without myocardial infarction (MI) history. This study included 298 patients with angiographically confirmed CAD and 299 age matched controls. Genomic DNA was isolated from whole blood and genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism method. No significant associations were found between -1575 G/A, -1306 C/T, and -790 T/G polymorphisms and CAD with or without MI history. However, the frequency of the -735 TT genotype was significantly lower in the controls than in the patients with MI alone when compared with the CC genotype (p=0.021). Only the distribution of the ACGC haplotype in CAD patients exhibited a significant difference than that in controls (p<0.05). The distribution of other haplotypes did not differ between CAD patients and controls. The present investigation is the first report to detect an association between MMP2 promoter polymorphisms and CAD with or without MI history in the Turkish population. Further case-control studies in CAD development might be contributed to clarify the role of these polymorphisms.

  6. Obesity and premature coronary artery disease with myocardial infarction in Puerto Rican young adults.

    Science.gov (United States)

    Marcial, José M; Altieri, Pablo I

    2015-01-01

    A cross-sectional study examined adults aged 21 to 35 years who underwent left cardiac catheterization in the Cardiovascular Center for Puerto Rico and the Caribbean during 2008-2012 due to myocardial infarction. Demographic characteristics, clinical risk factors, and the extent of CAD were documented. Chi-square statistic or Fisher's exact test was used to compare the distribution of demographic, clinical, and lifestyle characteristics across CAD extent. Polytomous logistic regression models were fitted to estimate the prevalence odds ratios (POR) with 95% confidence intervals (Cl) for non-obstructive and obstructive coronary disease (OCD) compared with normal coronary anatomy. Statistical analyses were performed using Stata 11.0. Sixty-three (n = 63) adults were evaluated (81% were men). The mean age was 31 ± 4 years. The most frequent clinical risk factors were history of tobacco use, hyper tension, and dyslipidemia. Obesity was present in 45.9% of subjects and OCD was present in 52.38% of subjects. Obesity and family history of CAD were significantly associated with OCD when adjusted by age. Obese patients had 5.94 times the possibility of having OCD than normal weight patients. Obesity was the most important treatable predictor of premature obstructive CAD in our young adult population.

  7. Identification of women's coronary heart disease and risk factors prior to first myocardial infarction.

    Science.gov (United States)

    Yawn, Barbara P; Wollan, Peter C; Jacobsen, Steven J; Fryer, George E; Roger, Veronique L

    2004-12-01

    To understand when women's coronary heart disease (CHD) and CHD risk factors are recognized prior to first myocardial infarction (MI). Medical record review of the 10 years prior to incident MI among women with a confirmed incident MI between January 1, 1996, and December 31, 2001, to determine the timing of CHD diagnosis as well as assessment and treatment for risk factors. One hundred fifty women had incident MIs during the study period. They made 8732 ambulatory visits and had 457 hospitalizations during the period of review (mean 9.1 years, range 6.2-10 years). Average age at incident MI was 74.7 years (SD 12.6, range 38.9-99.8 years). A CHD diagnosis prior to first MI was present in 52% (n = 78) of the women but was less common in those <70 years (p = 0.001). All but 3 women had one or more modifiable risk factors identified prior to their first MI. Treatment of recognized risk factors varied from 81% (antihypertension medications) to only 28% (drug therapy for abnormal lipid levels). Having a diagnosis of CHD was associated with an increased likelihood of having identified risk factors and receiving drug treatment for identified risk factors. Women with undiagnosed CHD (48%) and those with unrecognized or untreated risk factors for CHD, especially younger women, represent missed opportunities for prevention of cardiac events.

  8. Alzheimer's disease and brain infarcts in the elderly. Agreement with neuropathology.

    Science.gov (United States)

    Zekry, Dina; Duyckaerts, Charles; Belmin, Joël; Geoffre, Caroline; Moulias, Robert; Hauw, Jean-Jacques

    2002-11-01

    Clarifying the etiology of dementia is one of the most difficult diagnostic challenges, especially in the elderly. We examined the accuracy of clinical criteria to distinguish Alzheimer's disease (AD) and dementia associated with infarcts of the brain, either isolated (vascular dementia) or associated with degenerative lesions (mixed dementia). We carried out a prospective clinico-neuropathological study in a selected series of hospitalized patients. We evaluated the clinical aspects of 33 patients aged over 75 years by use of the criteria and scores of DSMIII, NINCDS-ADRDA, Loeb and Gandolfo, ADDTC and NINDS-AIREN and the Hachinski Ischemic Score. The neuropathological diagnosis was considered to be the gold standard. When comparing clinical criteria and neuropathology, the agreement was moderate for Hachinski's score (0.50) and Loeb's score (0.43) and substantial for the ADDTC (0.63) and the NINDS-AIREN (0.67). When mixed dementias were excluded, the agreement between all clinical criteria and scores and the pathological diagnosis rose to 0.88. Hachinski's score was the most sensitive (0.89) and the NINDS-AIREN the most specific (0.86) for the diagnosis of vascular dementia. In conclusion, all sets of clinical criteria distinguished pure AD from vascular dementia with a high accuracy whereas mixed dementia was clinically under-recognized. The NINDS-AIREN criteria were the most discriminating for the accurate identification of patients with mixed dementia.

  9. Effect of long-term low dose of aspirin on severity of disease following onset of acute cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    Jun Xu; Lili Cao; Xiaomei Deng; Enji Han

    2006-01-01

    BACKGROUND: Aspirin can decrease the incidence risk of high-risk crowdgroup of cerebral infarction, but there are still controversy if it might decrease the degree of disease in degree of patients with acute cerebral infarction.OBJECTIVE: To observe the effect of lower dose of aspirin during taking for a long time on disease degree of disease following onset of acute cerebral infarction.DESIGN: Grouping according to the admission time and 1:1 paired observation.SETTING: Department of Neurology, Qilu Hospital of Shandong University.PARTICIPANTS: The participants in present study were 321 patients with acute cerebral infarction who received treatments in the Department of Neurology, Qilu Hospital of Shandong University from January 1999 to June 2000. There were 190 male and 131 female ,with mean (65±11 )years of age. Inclusive criteria: ① A focal neurological disturbance occurred suddenly and had lasted for more than 24 hours, patients were admitted within 3 days after onset of disease; ② A computed tomography of the brain was performed and excluded hemorrhage in all patients; ③ The patients were proved internal carotid occlusions by clinical features and image findings; ④ The functions of limbs were normal (before the first stroke) or almost normal (before the second stroke). Exclusive criteria: ①The patients who had have cardiogenic cerebral embolism; ②The patients who had taken warfarin orally and other platelet agglutination drugs.METHODS: ①All the patients were divided into 2 groups according to whether they had taken aspirin before: aspirin-treated group (n=110) and blank control group (n=211). There were 70 male and 40 female in aspirin-treated group, with average(65±10) years of age.All patients had taken 50-100 mg/d aspirin for 6 months to 10 years before onset. There were 120 male and 91 female in blank control group, with average (65±13)years of age. Patients received a clinical scoring within 3 days and similar therapeutic measures (such

  10. Linking Microbiota to Human Diseases

    DEFF Research Database (Denmark)

    Wu, Hao; Tremaroli, Valentina; Bäckhed, F

    2015-01-01

    diabetes (T2D), and irritable bowel syndrome, and some animal experiments have suggested causality. However, few studies have validated causality in humans and the underlying mechanisms remain largely to be elucidated. We discuss how systems biology approaches combined with new experimental technologies......The human gut microbiota encompasses a densely populated ecosystem that provides essential functions for host development, immune maturation, and metabolism. Alterations to the gut microbiota have been observed in numerous diseases, including human metabolic diseases such as obesity, type 2...... may disentangle some of the mechanistic details in the complex interactions of diet, microbiota, and host metabolism and may provide testable hypotheses for advancing our current understanding of human-microbiota interaction....

  11. Chromatin remodeling and human disease.

    Science.gov (United States)

    Huang, Cheng; Sloan, Emily A; Boerkoel, Cornelius F

    2003-06-01

    In the past few years, there has been a nascent convergence of scientific understanding of inherited human diseases with epigenetics. Identified epigenetic processes involved in human disease include covalent DNA modifications, covalent histone modifications, and histone relocation. Each of these processes influences chromatin structure and thereby regulates gene expression and DNA methylation, replication, recombination, and repair. The importance of these processes for nearly all aspects of normal growth and development is illustrated by the array of multi-system disorders and neoplasias caused by their dysregulation.

  12. Association between family risk of stroke and myocardial infarction with prevalent risk factors and coexisting diseases.

    Science.gov (United States)

    Kennedy, Richard E; Howard, George; Go, Rodney C; Rothwell, Peter M; Tiwari, Hemant K; Feng, Rui; McClure, Leslie A; Prineas, Ronald J; Banerjee, Amitava; Arnett, Donna K

    2012-04-01

    Familial transmission of stroke and myocardial infarction (MI) is partially mediated by transmission of cerebrovascular and cardiovascular risk factors. We examined relationships between family risk of stroke and MI with risk factors for these phenotypes. A cross-sectional association between the stratified log-rank family score for stroke and MI with prevalent risk factors was assessed in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. Individuals in the fourth quartile of stratified log-rank family scores for stroke were more likely to have prevalent risk factors including hypertension (OR, 1.43; 95% CI, 1.30-1.58), left ventricular hypertrophy (OR, 1.42; 95% CI, 1.16-1.42), diabetes (OR, 1.26; 95% CI, 1.12-1.43), and atrial fibrillation (OR, 1.23; 95% CI, 1.03-1.45) compared with individuals in the first quartile. Likewise, individuals in the fourth quartile of stratified log-rank family scores for MI were more likely to have prevalent risk factors including hypertension (OR, 1.57; 95% CI, 1.27-1.94) and diabetes (OR, 1.29; 95% CI, 1.12-1.43) than the first quartile. In contrast to stroke, the family risk score for MI was associated with dyslipidemia (OR, 1.38; 95% CI, 1.23-1.55) and overweight/obesity (OR, 1.22; 95% CI, 1.10-1.37). Family risk of stroke and MI is strongly associated with the majority of risk factors associated with each disease. Family history and genetic studies separating nonspecific contributions of intermediate phenotypes from specific contributions to the disease phenotype may lead to a more thorough understanding of transmission for these complex disorders.

  13. Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3—PRIMULTI)

    DEFF Research Database (Denmark)

    Engstrøm, Thomas; Kelbæk, Henning; Helqvist, Steffen

    2015-01-01

    BACKGROUND: Patients with acute ST-segment elevation myocardial infarction (STEMI) and multivessel coronary disease have a worse prognosis compared with individuals with single-vessel disease. We aimed to study the clinical outcome of patients with STEMI treated with fractional flow reserve (FFR...... in the infarct-related artery were included. After successful percutaneous coronary intervention (PCI) of the infarct-related artery, patients were randomly allocated (in a 1:1 ratio) either no further invasive treatment or complete FFR-guided revascularisation before discharge. Randomisation was done...... of the infarct-related artery only and in 40 (13%) patients who had complete revascularisation (hazard ratio 0∙56, 95% CI 0∙38–0∙83; p=0∙004). INTERPRETATION: In patients with STEMI and multivessel disease, complete revascularisation guided by FFR measurements significantly reduces the risk of future events...

  14. Cerebral hemodynamics and metabolism in patients with moyamoya disease not demonstrating either cerebral infarct or hemorrhage on MRI

    Energy Technology Data Exchange (ETDEWEB)

    Kuwabara, Yasuo; Ichiya, Yuichi; Sasaki, Masayuki; Akashi, Yuko; Yoshida, Tsuyoshi; Fukumura, Toshimitsu; Masuda, Kouji; Matsushima, Toshio; Fukui, Masashi [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1995-12-01

    We evaluated the cerebral hemodynamics and metabolism in moyamoya patients who did not demonstrate either cerebral infarct or hemorrhage on MRI. The subjects consisted of 5 patients with moyamoya disease (4 females and one male, aged from 15 to 40 ears). The CBF, OEF and CMRO{sub 2} of the moyamoya patients did not differ from those of the normal control subjects. The CBV did increase significantly in the cerebral cortices and striatum, but not in the cerebellum. The TT was also significantly prolonged in the frontal and parietal regions. The cerebrovascular CO{sub 2} response was markedly impaired in the frontal, temporal and parietal cortices. However, it was relatively preserved in the occipital cortex, thalamus and cerebellum. Thus, the cerebral hemodynamic reserve capacity decreased even in the moyamoya patients not demonstrating either cerebral infarct or hemorrhage on MRI, and it should be considered in the management of these patients. (author).

  15. Enhanced Electrical Integration of Engineered Human Myocardium via Intramyocardial versus Epicardial Delivery in Infarcted Rat Hearts.

    Directory of Open Access Journals (Sweden)

    Kaytlyn A Gerbin

    Full Text Available Cardiac tissue engineering is a promising approach to provide large-scale tissues for transplantation to regenerate the heart after ischemic injury, however, integration with the host myocardium will be required to achieve electromechanical benefits. To test the ability of engineered heart tissues to electrically integrate with the host, 10 million human embryonic stem cell (hESC-derived cardiomyocytes were used to form either scaffold-free tissue patches implanted on the epicardium or micro-tissue particles (~1000 cells/particle delivered by intramyocardial injection into the left ventricular wall of the ischemia/reperfusion injured athymic rat heart. Results were compared to intramyocardial injection of 10 million dispersed hESC-cardiomyocytes. Graft size was not significantly different between treatment groups and correlated inversely with infarct size. After implantation on the epicardial surface, hESC-cardiac tissue patches were electromechanically active, but they beat slowly and were not electrically coupled to the host at 4 weeks based on ex vivo fluorescent imaging of their graft-autonomous GCaMP3 calcium reporter. Histologically, scar tissue physically separated the patch graft and host myocardium. In contrast, following intramyocardial injection of micro-tissue particles and suspended cardiomyocytes, 100% of the grafts detected by fluorescent GCaMP3 imaging were electrically coupled to the host heart at spontaneous rate and could follow host pacing up to a maximum of 300-390 beats per minute (5-6.5 Hz. Gap junctions between intramyocardial graft and host tissue were identified histologically. The extensive coupling and rapid response rate of the human myocardial grafts after intramyocardial delivery suggest electrophysiological adaptation of hESC-derived cardiomyocytes to the rat heart's pacemaking activity. These data support the use of the rat model for studying electromechanical integration of human cardiomyocytes, and they

  16. Translation of Methdology used in Human Myocardial Imaging to a Sheep Model of Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Elizabeth A Bailey

    2013-10-01

    Full Text Available Introduction: Pre-clinical investigation of stem cells for repairing damaged myocardium predominantly used rodents, however large animals have cardiac circulation closely resembling the human heart. The aim of this study was to evaluate whether SPECT/CT myocardial perfusion imaging (MPI could be used for assessing sheep myocardium following an acute myocardial infarction (MI and response to intervention. Method: 18 sheep enrolled in a pilot study to evaluate [99mTc]-sestamibi MPI at baseline, post-MI and after therapy. Modifications to the standard MPI protocols were developed. All data was reconstructed with OSEM using CT-derived attenuation and scatter correction. Standard analyses were performed and inter-observer agreement were measured using Kappa (. Power determined the sample sizes needed to show statistically significant changes due to intervention. Results: Ten sheep completed the full protocol. Data processed were performed using pre-existing hardware and software used in human MPI scanning. No improvement in perfusion was seen in the control group, however improvements of 15% - 35% were seen after intra-myocardial stem cell administration. Inter-observer agreement was excellent (К=0.89. Using a target power of 0.9, 28 sheep were required to detect a 10-12% change in perfusion. Conclusions: Study demonstrates the suitability of large animal models for imaging with standard MPI protocols and it’s feasibility with a manageable number of animals. These protocols could be translated into humans to study the efficacy of stem cell therapy in heart regeneration and repair.

  17. Translation of Methdology used in Human Myocardial Imaging to a Sheep Model of Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Elizabeth Bailey

    2013-10-01

    Full Text Available Background: Pre-clinical investigation of stem cells for repairing damaged myocardium predominantly used rodents, however large animals have cardiac circulation closely resembling the human heart. The aim of this study was to evaluate whether SPECT/CT myocardial perfusion imaging (MPI could be used for assessing sheep myocardium following an acute myocardial infarction (MI and response to intervention. Method: 18 sheep enrolled in a pilot study to evaluate [99mTc]-sestamibi MPI at baseline, post-MI and after therapy. Modifications to the standard MPI protocols were developed. All data was reconstructed with OSEM using CT-derived attenuation and scatter correction. Standard analyses were performed and inter-observer agreement were measured using Kappa (. Power determined the sample sizes needed to show statistically significant changes due to intervention. Results: Ten sheep completed the full protocol. Data processed were performed using pre-existing hardware and software used in human MPI scanning. No improvement in perfusion was seen in the control group, however improvements of 15% - 35% were seen after intra-myocardial stem cell administration. Inter-observer agreement was excellent (К=0.89. Using a target power of 0.9, 28 sheep were required to detect a 10-12% change in perfusion. Conclusions: Study demonstrates the suitability of large animal models for imaging with standard MPI protocols and it’s feasibility with a manageable number of animals. These protocols could be translated into humans to study the efficacy of stem cell therapy in heart regeneration and repair.

  18. Genotype frequency of gelatinase B C-1562 T polymorphism in coronary heart disease and myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Hong JIANG; Dieter Niederacher; Ming DU; Roger Marx; Thomas Scheffold; Rolf Michael Klein

    2004-01-01

    Background One of the characteristics of atherosclerosis is a change in the content of extracellular matrix in the arterial wall. Gelatinase B, a member of the family of matrix metalloproteinase, can regulate extracellular matrix metabolismand play a role in the pathogenesis of atherosclerosis, coronary heart disease (CHD) and myocardial infarction (MI). Gelatinase B is polymorphic due to a C to T change at the position -1562 bp in the promoter region.Its relationship with gene product concentration in serum and its role in mediating the risk of CHD and MI in Germans is still unknown. Methods We enrolled 102 controls and 322 patients with angiographically documented CHD,including a sub-group of 173 patients with acute or chronic MI and 80 patients with acute coronary syndrome (ACS).All patients and controls were Germans and genotyped by polymerase chain reaction and digestion with SphI. Results We found that several classical risk factors for CHD and MI, including hypercholesterolemia and cigarette smoking,were significantly increased in CHD and MI patients compared with controls. Serum levels of gelatinase B and tissue inhibitor of metalloproteinase-1 were increased in the peripheral blood of patients with acute coronary syndrome. No significant differences in genotype or allelic frequencies between CHD, MI and control subjects of either men or women were found. Our search for a possible association of the polymorphisms with CHD and MI by logistic regression analysis was also negative. The serum concentrations of gelatinase B showed no differences between genotypes. Conclusions Our data showed that gelatinase B might provide an index of plaque activity in ACS, but gelatinase B protein was not affected by genotypes. Also, the T variant of gelatinase B was not associated with CHD or MI in Germans. (J Geriatr Cardiol 2004;1(2):114-118.)

  19. Risk factors and ankle brachial indexes in cerebral infarction combined with peripheral arterial disease

    Institute of Scientific and Technical Information of China (English)

    Huihua Liu; Jun Wang

    2006-01-01

    BACKGROUND: Ankle brachial index(ABI)is widely involved in researches and clinical application of peripheral vascular injury of patients with diabetes (DM);however ,the application in cerebral infarction(CI)is rare.OBJECTIVE: To investigate the possible risk factor of cerebral infarction plus peripheral arterial disease(PAD),compare metabolic characteristics of patients who having CI plus PAD or only having CI,and understand the significance of ABI on screening and diagnosing CI plus PAD of lower limb.DESIGN: Contrast observation based on CI patients.SETTING: Deparment of Neurology,Nanxishan Hospital of Guangxi Zhang Autonomous Region.PARTICIPANTS:A total of 124 CI patients were selected from Department of Neurology.Nanxishan Hospital of Guangxi Zhuang Autonomous Region from July 2005 to April 2006,including 72 males and 52 females aged from 45 to 88 years.All patients met the diagnostic criteria of cerebrovascular disease established by National Academic Conference of Cerebrovascular Diseases in 1995 and determined as cerebral infarction with MRI or CT examination.All patients provided informed consent.There were 46 cases(37.2%)with CI plus PAD and 78 cases(62.8%)only with CI.METHODS: Blood pressure of bilateral ankles and upper extremities was measured at plain clinostatism with DINAMAP blood pressure monitor(GE Company).The ratio between average systolic pressure of lateral ankle and average systolic pressure of both upper extremities was regarded as ABI.The normal ABI was equal to or more than 0.9.If ABI<0.9 occurred at one side,patients were diagnosed as PAD.On the second morning after hospitalization,blood was collected to measure fasting blood glucose(FBG),2-hour postprandial blood glucose(PBG2h),glycosylated hemoglobin(HbAlc),triglycerides(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C).Among them,blood glucose.lipid and other biochemical markers were measured with enzyme chemistry assay

  20. No evidence that genetically reduced 25-hydroxyvitamin D is associated with increased risk of ischaemic heart disease or myocardial infarction

    DEFF Research Database (Denmark)

    Brøndum-Jacobsen, Peter; Benn, Marianne; Afzal, Shoaib

    2015-01-01

    that genetically reduced plasma 25(OH)D is associated with increased risk of ischaemic heart disease and myocardial infarction. METHODS: We used a Mendelian randomization design in the Copenhagen City Heart Study, the Copenhagen General Population Study, and the Copenhagen Ischaemic Heart Disease Study. Two 25(OH......)D reducing genetic variants in the DCHR7 gene (rs7944926 and rs11234027) and two in the CYP2R1 gene (rs10741657 and rs12794714) were genotyped in 92 416 participants of Danish descent, of whom 14 455 developed ischaemic heart disease (ICD-8:410-414; ICD-10:I20-I25) and 7061 myocardial infarction (ICD-8...... (CI): 1.42-2.32] for ischaemic heart disease. Each allele increase in a combined allele score was associated with a 1.9-nmol/l decrease in p-25(OH)D (P = 7 × 10(-55); R(2) = 0.9%). The genetic variants were, however, not associated with increased risk of ischaemic heart disease. In instrumental...

  1. CD8+ T-Cells Count in Acute Myocardial Infarction in HIV Disease in a Predominantly Male Cohort

    Directory of Open Access Journals (Sweden)

    Oluwatosin A. Badejo

    2015-01-01

    Full Text Available Human Immunodeficiency Virus- (HIV- infected persons have a higher risk for acute myocardial infarction (AMI than HIV-uninfected persons. Earlier studies suggest that HIV viral load, CD4+ T-cell count, and antiretroviral therapy are associated with cardiovascular disease (CVD risk. Whether CD8+ T-cell count is associated with CVD risk is not clear. We investigated the association between CD8+ T-cell count and incident AMI in a cohort of 73,398 people (of which 97.3% were men enrolled in the U.S. Veterans Aging Cohort Study-Virtual Cohort (VACS-VC. Compared to uninfected people, HIV-infected people with high baseline CD8+ T-cell counts (>1065 cells/mm3 had increased AMI risk (adjusted HR=1.82, P<0.001, 95% CI: 1.46 to 2.28. There was evidence that the effect of CD8+ T-cell tertiles on AMI risk differed by CD4+ T-cell level: compared to uninfected people, HIV-infected people with CD4+ T-cell counts ≥200 cells/mm3 had increased AMI risk with high CD8+ T-cell count, while those with CD4+ T-cell counts <200 cells/mm3 had increased AMI risk with low CD8+ T-cell count. CD8+ T-cell counts may add additional AMI risk stratification information beyond that provided by CD4+ T-cell counts alone.

  2. Chronic obstructive pulmonary disease is an independent predictor of death but not atherosclerotic events in patients with myocardial infarction: analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT)

    DEFF Research Database (Denmark)

    Hawkins, Nathaniel M; Huang, Zhen; Pieper, Karen S

    2009-01-01

    AIMS: Chronic obstructive pulmonary disease is an independent predictor of mortality in patients with myocardial infarction (MI). However, the impact on mode of death and risk of atherosclerotic events is unknown. METHODS AND RESULTS: We assessed the risk of death and major cardiovascular (CV) ev...

  3. Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3—PRIMULTI)

    DEFF Research Database (Denmark)

    Engstrøm, Thomas; Kelbæk, Henning; Helqvist, Steffen

    2015-01-01

    )-guided complete revascularisation versus treatment of the infarct-related artery only. METHODS: We undertook an open-label, randomised controlled trial at two university hospitals in Denmark. Patients presenting with STEMI who had one or more clinically significant coronary stenosis in addition to the lesion......BACKGROUND: Patients with acute ST-segment elevation myocardial infarction (STEMI) and multivessel coronary disease have a worse prognosis compared with individuals with single-vessel disease. We aimed to study the clinical outcome of patients with STEMI treated with fractional flow reserve (FFR...... in the infarct-related artery were included. After successful percutaneous coronary intervention (PCI) of the infarct-related artery, patients were randomly allocated (in a 1:1 ratio) either no further invasive treatment or complete FFR-guided revascularisation before discharge. Randomisation was done...

  4. Proteins aggregation and human diseases

    Science.gov (United States)

    Hu, Chin-Kun

    2015-04-01

    Many human diseases and the death of most supercentenarians are related to protein aggregation. Neurodegenerative diseases include Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), frontotemporallobar degeneration, etc. Such diseases are due to progressive loss of structure or function of neurons caused by protein aggregation. For example, AD is considered to be related to aggregation of Aβ40 (peptide with 40 amino acids) and Aβ42 (peptide with 42 amino acids) and HD is considered to be related to aggregation of polyQ (polyglutamine) peptides. In this paper, we briefly review our recent discovery of key factors for protein aggregation. We used a lattice model to study the aggregation rates of proteins and found that the probability for a protein sequence to appear in the conformation of the aggregated state can be used to determine the temperature at which proteins can aggregate most quickly. We used molecular dynamics and simple models of polymer chains to study relaxation and aggregation of proteins under various conditions and found that when the bending-angle dependent and torsion-angle dependent interactions are zero or very small, then protein chains tend to aggregate at lower temperatures. All atom models were used to identify a key peptide chain for the aggregation of insulin chains and to find that two polyQ chains prefer anti-parallel conformation. It is pointed out that in many cases, protein aggregation does not result from protein mis-folding. A potential drug from Chinese medicine was found for Alzheimer's disease.

  5. Chagas disease and human migration

    Directory of Open Access Journals (Sweden)

    Felipe Guhl

    2000-08-01

    Full Text Available Human Chagas disease is a purely accidental occurrence. As humans came into contact with the natural foci of infection might then have become infected as a single addition to the already extensive host range of Trypanosoma cruzi that includes other primates. Thus began a process of adaptation and domiciliation to human habitations through which the vectors had direct access to abundant food as well as protection from climatic changes and predators. Our work deals with the extraction and specific amplification by polymerase chain reaction of T. cruzi DNA obtained from mummified human tissues and the positive diagnosis of Chagas disease in a series of 4,000-year-old Pre-Hispanic human mummies from the northern coast of Chile. The area has been inhabited at least for 7,000 years, first by hunters, fishers and gatherers, and then gradually by more permanent settlements. The studied specimens belonged to the Chinchorro culture, a people inhabiting the area now occupied by the modern city of Arica. These were essentially fishers with a complex religious ideology, which accounts for the preservation of their dead in the way of mummified bodies, further enhanced by the extremely dry conditions of the desert. Chinchorro mummies are, perhaps, the oldest preserved bodies known to date.

  6. Influence of multivessel disease with or without additional revascularization on mortality in patients with ST-segment elevation myocardial infarction

    DEFF Research Database (Denmark)

    Jensen, Lisette Okkels; Terkelsen, Christian Juhl; Horváth-Puhó, Erzsébet

    2015-01-01

    BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI), timely reperfusion with primary percutaneous coronary intervention (PCI) is the preferred treatment. In primary PCI patients with multivessel disease, it is unclear whether culprit vessel PCI only is the preferred...... treatment. We compared mortality among (1) STEMI patients with single-vessel disease and those with multivessel disease and (2) multivessel disease patients with and without additional revascularization of nonculprit lesions within 2 months after the index PCI. METHODS: From January 2002 to June 2009, all...... patients presenting with STEMI and treated with primary PCI were identified from the Western Denmark Heart Registry, which covers a population of 3.0 million. The hazard ratio (HR) for death was estimated using a Cox regression model, controlling for potential confounding. RESULTS: The study cohort...

  7. CT of Coronary Heart Disease : Part 1, CT of Myocardial Infarction, Ischemia, and Viability

    NARCIS (Netherlands)

    Vliegenthart, Rozemarijn; Henzler, Thomas; Moscariello, Antonio; Ruzsics, Balazs; Bastarrika, Gorka; Oudkerk, Matthijs; Schoepf, U. Joseph

    OBJECTIVE. This article reviews the CT-based approaches aimed at the assessment of myocardial infarction, ischemia, and viability described in the recent literature. CONCLUSION. Rapid advances in CT technology not only have improved visualization of coronary arteries but also increasingly enable

  8. CT of Coronary Heart Disease : Part 1, CT of Myocardial Infarction, Ischemia, and Viability

    NARCIS (Netherlands)

    Vliegenthart, Rozemarijn; Henzler, Thomas; Moscariello, Antonio; Ruzsics, Balazs; Bastarrika, Gorka; Oudkerk, Matthijs; Schoepf, U. Joseph

    2012-01-01

    OBJECTIVE. This article reviews the CT-based approaches aimed at the assessment of myocardial infarction, ischemia, and viability described in the recent literature. CONCLUSION. Rapid advances in CT technology not only have improved visualization of coronary arteries but also increasingly enable non

  9. [Alzheimer's disease and human memory].

    Science.gov (United States)

    Eustache, F; Giffard, B; Rauchs, G; Chételat, G; Piolino, P; Desgranges, B

    2006-10-01

    Memory disorders observed in Alzheimer's disease gave rise, from the eighties, to a detailed analysis into the framework of cognitive neuropsychology which aimed at describing the deficits of very specific processes. Beyond their clinical interest, these studies contributed to the modelisation of human memory thanks to the characterization of different memory systems and their relationships. The first part of this paper gives an overview of the memory deficits in Alzheimer's disease and insists on particular cognitive phenomena. Hence, several examples are developed in the domains of semantic memory (such as hyperpriming and hypopriming effects) and autobiographical memory. Recent results highlight the existence of severe autobiographical amnesia observed in all neurodegenerative diseases, though with contrasting profiles: Ribot's gradient in Alzheimer's disease (showing that remote memories are better preserved than recent ones), reverse gradient in semantic dementia and no clear gradient in the frontal variant of frontotemporal dementia. The second part of this article presents advances in cognitive neuroscience searching to disclose the cerebral substrates of these cognitive deficits in Alzheimer's disease. The studies using functional imaging techniques are the most informative regarding this problematic. While showing the dysfunctions of an extended network, they emphasize the selectivity of cerebral damages that are at the root of very specific cognitive dysfunctions, coming close in that way to the conceptions of cognitive neuropsychology. These neuroimaging studies unravel the existence of compensatory mechanisms, which until recently were clearly missing in the literature on neurodegenerative diseases. These different researches lead to a wide conception of human memory, not just limited to simple instrumental processes (encoding, storage, retrieval), but necessarily covering models of identity and continuity of the subject, which interact in a dynamic way

  10. Transfer RNA and human disease

    Directory of Open Access Journals (Sweden)

    Jamie A Abbott

    2014-06-01

    Full Text Available Pathological mutations in tRNA genes and tRNA processing enzymes are numerous and result in very complicated clinical phenotypes. Mitochondrial tRNA (mt-tRNA genes are hotspots for pathological mutations and over 200 mt-tRNA mutations have been linked to various disease states. Often these mutations prevent tRNA aminoacylation. Disrupting this primary function affects protein synthesis and the expression, folding, and function of oxidative phosphorylation enzymes. Mitochondrial tRNA mutations manifest in a wide panoply of diseases related to cellular energetics, including COX deficiency (cytochrome C oxidase, mitochondrial myopathy, MERRF (Myoclonic Epilepsy with Ragged Red Fibers, and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. Diseases caused by mt-tRNA mutations can also affect very specific tissue types, as in the case of neurosensory non-syndromic hearing loss and pigmentary retinopathy, diabetes mellitus, and hypertrophic cardiomyopathy. Importantly, mitochondrial heteroplasmy plays a role in disease severity and age of onset as well. Not surprisingly, mutations in enzymes that modify cytoplasmic and mitochondrial tRNAs are also linked to a diverse range of clinical phenotypes. In addition to compromised aminoacylation of the tRNAs, mutated modifying enzymes can also impact tRNA expression and abundance, tRNA modifications, tRNA folding, and even tRNA maturation (e.g., splicing. Some of these pathological mutations in tRNAs and processing enzymes are likely to affect non-canonical tRNA functions, and contribute to the diseases without significantly impacting on translation. This chapter will review recent literature on the relation of mitochondrial and cytoplasmic tRNA, and enzymes that process tRNAs, to human disease. We explore the mechanisms involved in the clinical presentation of these various diseases with an emphasis on neurological disease.

  11. Culprit only or multivessel percutaneous coronary interventions in patients with ST-segment elevation myocardial infarction and multivessel disease

    DEFF Research Database (Denmark)

    Jensen, Lisette Okkels; Thayssen, Per; Farkas, Dóra Körmendiné

    2012-01-01

    Aims: In patients with ST-segment elevation myocardial infarction (STEMI), timely reperfusion with primary percutaneous coronary intervention (PPCI) is the preferred treatment. However, it remains unclear whether the optimal strategy is complete revascularisation or culprit vessel PPCI only......% confidence interval (CI): 1.07-2.18), 0.60 (95% CI: 0.28-1.26), and 0.28 (95% CI: 0.14-0.54), respectively, compared to patients with single vessel disease. Conclusions: Acute multivessel PCI in patients with STEMI was associated with increased mortality....

  12. Myocardial infarction and ischemic heart disease in overweight and obesity with and without metabolic syndrome.

    Science.gov (United States)

    Thomsen, Mette; Nordestgaard, Børge G

    2014-01-01

    Overweight and obesity likely cause myocardial infarction (MI) and ischemic heart disease (IHD); however, whether coexisting metabolic syndrome is a necessary condition is unknown. To test the hypothesis that overweight and obesity with and without metabolic syndrome are associated with increased risk of MI and IHD. We examined 71,527 individuals from the Copenhagen General Population Study and categorized them according to body mass index (BMI) as normal weight, overweight, or obese and according to absence or presence of metabolic syndrome. Hazard ratios for incident MI and IHD according to combinations of BMI category and absence or presence of metabolic syndrome. During a median of 3.6 years' follow-up, we recorded 634 incident MI and 1781 incident IHD events. For MI, multivariable adjusted hazard ratios vs normal weight individuals without metabolic syndrome were 1.26 (95% CI, 1.00-1.61) in overweight and 1.88 (95% CI, 1.34-2.63) in obese individuals without metabolic syndrome and 1.39 (95% CI, 0.96-2.02) in normal weight, 1.70 (95% CI, 1.35-2.15) in overweight, and 2.33 (95% CI, 1.81-3.00) in obese individuals with metabolic syndrome. For IHD, results were similar but attenuated. Normal weight vs overweight vs obesity and presence vs absence of metabolic syndrome did not interact on risk of MI or IHD (P = .90 and P = .44). Among individuals both with and without metabolic syndrome there were increasing cumulative incidences of MI and IHD from normal weight through overweight to obese individuals (log-rank trend P = .006 to P metabolic syndrome was 1.54 (95% CI, 1.32-1.81) across all BMI categories, addition of metabolic syndrome to a multivariable model including BMI and other clinical characteristics improved the Harell C-statistic only slightly for risk of MI (comparison P = .03) but not for IHD (P = .41). These findings suggest that overweight and obesity are risk factors for MI and IHD regardless of the presence or absence of metabolic syndrome and that

  13. Correlation of diseased region and area with neglect and other neuropsychological dysfunctions in patients with cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    Jianping Niu; Hongyu Zhang; Bo Liu; Yiwen Zhang; Yehua Song; Lihong Chen

    2006-01-01

    BACKGROUND: Previous studies reported that frontal-temporal-parietal-occipital pathological changes and diseased range in the right cerbral hemisphere were correlated with neglect.But studies on the correlation of neglect with diseased region and area in patients who suffer from initial attack of single focus of cerebral infarction(CI) in left and right cerebral hemispheres are few.OBJECTIVE: To observe the status of neglect in patients who suffer from single focus of CI in cerebral hemisphere and analyze the correlation of neglect with diseased region and area of CI.DESIGN: Case analysis SETTING: Treatment Center for Cardiocerebrovascular Disease,Second Hospital of Xiamen city;Department of Neurology,First Hospital Affiliated to Baotou Medical College.PARTICIPANTS: All the CI patients hospitalized in the Department of Neurology.First Hospital Affiliated to Baotou Medical College from June 1998 to May 2001 were retrieved.Inclusive criteria:①Patients who suffered from initial attack of CI.which was confirmed by skull CT or MRI within 24 hours after onset and presented single focus in cerebral hemisphere. ②be conscious and could cooperate in the examination. ③did not receive formal education, but could do accounts and some simple writing and reading. ④Patients with homonymous hemianopia were excluded through the examination of perimeter.⑤Informed consents were obtained from all the patients.Among 67 patients who met the inclusive criteria.33 suffered from CI in the left cerebral hemisphere and 34 in the right cerebral hemisphere.METHODS:①Patients received neglect supplement examination and Chinese aphasia examination within 2.5 to 3 months after the attack of CI.The diagnostic criteria of neglect in the tests of line cancellation. 1ine bisection and copying the figures were as follows:In the line cancellation test based on the method of Albert.patients who could not cancel one or more lines were regarded as abnormal.In the line bisection test based on the

  14. Utility of unenhanced fat-suppressed T1-weighted MRI in children with sickle cell disease -- can it differentiate bone infarcts from acute osteomyelitis?

    Science.gov (United States)

    Delgado, Jorge; Bedoya, Maria A; Green, Abby M; Jaramillo, Diego; Ho-Fung, Victor

    2015-12-01

    Children with sickle cell disease (SCD) are at risk of bone infarcts and acute osteomyelitis. The clinical differentiation between a bone infarct and acute osteomyelitis is a diagnostic challenge. Unenhanced T1-W fat-saturated MR images have been proposed as a potential tool to differentiate bone infarcts from osteomyelitis. To evaluate the reliability of unenhanced T1-W fat-saturated MRI for differentiation between bone infarcts and acute osteomyelitis in children with SCD. We retrospectively reviewed the records of 31 children (20 boys, 11 girls; mean age 10.6 years, range 1.1-17.9 years) with SCD and acute bone pain who underwent MR imaging including unenhanced T1-W fat-saturated images from 2005 to 2010. Complete clinical charts were reviewed by a pediatric hematologist with training in infectious diseases to determine a clinical standard to define the presence or absence of osteomyelitis. A pediatric radiologist reviewed all MR imaging and was blinded to clinical information. Based on the signal intensity in T1-W fat-saturated images, the children were further classified as positive for osteomyelitis (low bone marrow signal intensity) or positive for bone infarct (high bone marrow signal intensity). Based on the clinical standard, 5 children were classified as positive for osteomyelitis and 26 children as positive for bone infarct (negative for osteomyelitis). The bone marrow signal intensity on T1-W fat-saturated imaging was not significant for the differentiation between bone infarct and osteomyelitis (P = 0.56). None of the additional evaluated imaging parameters on unenhanced MRI proved reliable in differentiating these diagnoses. The bone marrow signal intensity on unenhanced T1-W fat-saturated MR images is not a reliable criterion to differentiate bone infarcts from osteomyelitis in children.

  15. Utility of unenhanced fat-suppressed T1-weighted MRI in children with sickle cell disease - can it differentiate bone infarcts from acute osteomyelitis?

    Energy Technology Data Exchange (ETDEWEB)

    Delgado, Jorge; Bedoya, Maria A. [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Green, Abby M. [The Children' s Hospital of Philadelphia, Division of Oncology, Philadelphia, PA (United States); Jaramillo, Diego; Ho-Fung, Victor [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA (United States)

    2015-12-15

    Children with sickle cell disease (SCD) are at risk of bone infarcts and acute osteomyelitis. The clinical differentiation between a bone infarct and acute osteomyelitis is a diagnostic challenge. Unenhanced T1-W fat-saturated MR images have been proposed as a potential tool to differentiate bone infarcts from osteomyelitis. To evaluate the reliability of unenhanced T1-W fat-saturated MRI for differentiation between bone infarcts and acute osteomyelitis in children with SCD. We retrospectively reviewed the records of 31 children (20 boys, 11 girls; mean age 10.6 years, range 1.1-17.9 years) with SCD and acute bone pain who underwent MR imaging including unenhanced T1-W fat-saturated images from 2005 to 2010. Complete clinical charts were reviewed by a pediatric hematologist with training in infectious diseases to determine a clinical standard to define the presence or absence of osteomyelitis. A pediatric radiologist reviewed all MR imaging and was blinded to clinical information. Based on the signal intensity in T1-W fat-saturated images, the children were further classified as positive for osteomyelitis (low bone marrow signal intensity) or positive for bone infarct (high bone marrow signal intensity). Based on the clinical standard, 5 children were classified as positive for osteomyelitis and 26 children as positive for bone infarct (negative for osteomyelitis). The bone marrow signal intensity on T1-W fat-saturated imaging was not significant for the differentiation between bone infarct and osteomyelitis (P = 0.56). None of the additional evaluated imaging parameters on unenhanced MRI proved reliable in differentiating these diagnoses. The bone marrow signal intensity on unenhanced T1-W fat-saturated MR images is not a reliable criterion to differentiate bone infarcts from osteomyelitis in children. (orig.)

  16. Human cord blood progenitors with high aldehyde dehydrogenase activity improve vascular density in a model of acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Creer Michael H

    2010-03-01

    Full Text Available Abstract Human stem cells from adult sources have been shown to contribute to the regeneration of muscle, liver, heart, and vasculature. The mechanisms by which this is accomplished are, however, still not well understood. We tested the engraftment and regenerative potential of human umbilical cord blood-derived ALDHhiLin-, and ALDHloLin- cells following transplantation to NOD/SCID or NOD/SCID β2m null mice with experimentally induced acute myocardial infarction. We used combined nanoparticle labeling and whole organ fluorescent imaging to detect human cells in multiple organs 48 hours post transplantation. Engraftment and regenerative effects of cell treatment were assessed four weeks post transplantation. We found that ALDHhiLin- stem cells specifically located to the site of injury 48 hours post transplantation and engrafted the infarcted heart at higher frequencies than ALDHloLin- committed progenitor cells four weeks post transplantation. We found no donor derived cardiomyocytes and few endothelial cells of donor origin. Cell treatment was not associated with any detectable functional improvement at the four week endpoint. There was, however, a significant increase in vascular density in the central infarct zone of ALDHhiLin- cell-treated mice, as compared to PBS and ALDHloLin- cell-treated mice. Conclusions Our data indicate that adult human stem cells do not become a significant part of the regenerating tissue, but rapidly home to and persist only temporarily at the site of hypoxic injury to exert trophic effects on tissue repair thereby enhancing vascular recovery.

  17. Mental stress and human cardiovascular disease.

    Science.gov (United States)

    Esler, Murray

    2017-03-01

    The London physician and neuroanatomist Thomas Willis in the 17th century correctly attributed the source of emotions to the brain, not the heart as believed in antiquity. Contemporary research documents the phenomenon of "triggered" heart disease, when the autonomic nervous system control of the heart by the brain goes awry, producing heart disease of sudden onset, precipitated by acute emotional upheaval. This can take the form of, variously, cardiac arrhythmias, myocardial infarction, Takotsubo cardiomyopathy and sudden death. Chronic psychological distress also can have adverse cardiovascular consequences, in the causal linkage of depressive illness to heart disease, and in the probable causation of atherosclerosis and hypertension by chronic mental stress. In patients with essential hypertension, stress biomarkers are present. The sympathetic nervous system is the usual mediator between these acute and chronic psychological substrates and cardiovascular disease.

  18. Human Microbiota and Ophthalmic Disease.

    Science.gov (United States)

    Lu, Louise J; Liu, Ji

    2016-09-01

    The human ocular surface, consisting of the cornea and conjunctiva, is colonized by an expansive, diverse microbial community. Molecular-based methods, such as 16S rRNA sequencing, has allowed for more comprehensive and precise identification of the species composition of the ocular surface microbiota compared to traditional culture-based methods. Evidence suggests that the normal microbiota plays a protective immunological role in preventing the proliferation of pathogenic species and thus, alterations in the homeostatic microbiome may be linked to ophthalmic pathologies. Further investigation of the ocular surface microbiome, as well as the microbiome of other areas of the body such as the oral mucosa and gut, and their role in the pathophysiology of diseases is a significant, emerging field of research, and may someday enable the development of novel probiotic approaches for the treatment and prevention of ophthalmic diseases.

  19. Human Cytomegalovirus and Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Anne Halenius

    2014-01-01

    Full Text Available Human cytomegalovirus (HCMV represents a prototypic pathogenic member of the β-subgroup of the herpesvirus family. A range of HCMV features like its lytic replication in multiple tissues, the lifelong persistence through periods of latency and intermitting reactivation, the extraordinary large proteome, and extensive manipulation of adaptive and innate immunity make HCMV a high profile candidate for involvement in autoimmune disorders. We surveyed the available literature for reports on HCMV association with onset or exacerbation of autoimmune disease. A causative linkage between HCMV and systemic lupus erythematosus (SLE, systemic sclerosis (SSc, diabetes mellitus type 1, and rheumatoid arthritis (RA is suggested by the literature. However, a clear association of HCMV seroprevalence and disease could not be established, leaving the question open whether HCMV could play a coresponsible role for onset of disease. For convincing conclusions population-based prospective studies must be performed in the future. Specific immunopathogenic mechanisms by which HCMV could contribute to the course of autoimmune disease have been suggested, for example, molecular mimicry by UL94 in SSc and UL83/pp65 in SLE patients, as well as aggravation of joint inflammation by induction and expansion of CD4+/CD28− T-cells in RA patients. Further studies are needed to validate these findings and to lay the grounds for targeted therapeutic intervention.

  20. Aluminium and human breast diseases.

    Science.gov (United States)

    Darbre, P D; Pugazhendhi, D; Mannello, F

    2011-11-01

    The human breast is exposed to aluminium from many sources including diet and personal care products, but dermal application of aluminium-based antiperspirant salts provides a local long-term source of exposure. Recent measurements have shown that aluminium is present in both tissue and fat of the human breast but at levels which vary both between breasts and between tissue samples from the same breast. We have recently found increased levels of aluminium in noninvasively collected nipple aspirate fluids taken from breast cancer patients (mean 268 ± 28 μg/l) compared with control healthy subjects (mean 131 ± 10 μg/l) providing evidence of raised aluminium levels in the breast microenvironment when cancer is present. The measurement of higher levels of aluminium in type I human breast cyst fluids (median 150 μg/l) compared with human serum (median 6 μg/l) or human milk (median 25 μg/l) warrants further investigation into any possible role of aluminium in development of this benign breast disease. Emerging evidence for aluminium in several breast structures now requires biomarkers of aluminium action in order to ascertain whether the presence of aluminium has any biological impact. To this end, we report raised levels of proteins that modulate iron homeostasis (ferritin, transferrin) in parallel with raised aluminium in nipple aspirate fluids in vivo, and we report overexpression of mRNA for several S100 calcium binding proteins following long-term exposure of MCF-7 human breast cancer cells in vitro to aluminium chlorhydrate.

  1. Coronary angiography and pathogenesis of coronary artery disease in young male survivors of myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Szamosi, A.; Hamsten, A.; Walldius, G.; Faire, U. de

    Coronary angiography was performed 3 to 6 months after myocardial infarction in 107 males below the age of 45 (mean age 39.7+-3.9, range 23-44 years). The coronary angiograms were allocated to various groups according to the presence or absence of obvious atheromatous changes. Metabolic evaluation included determination of cholesterol and triglyceride concentrations in the major serum lipoproteins. Marked elevation of low density lipoprotein (LDL) cholesterol concentration was found in patients with angiographic evidence of atheromatosis, in contrast to patients with normal coronary angiograms or with single occlusion and no other abnormalities. Thus, there was a correlation between angiographic appearance of the coronary arteries and disturbances of LDL metabolism. It is proposed that coronary angiography may distinguish between atheromatous and nonatheromatous pathogenesis of myocardial infarction at young age.

  2. Magnetic resonance imaging of human cerebral infarction: Enhancement with Gd-DTPA

    Energy Technology Data Exchange (ETDEWEB)

    Imakita, S.; Nishimura, T.; Naito, H.; Yamada, N.; Yamamoto, K.; Takamiya, M.; Yamada, Y.; Sakashita, Y.; Minamikawa, J.; Kikuchi, H.

    1987-09-01

    Five patients (1 female and 4 males) with cerebral infarction of 4 h to 27 months duration were studied 9 times with magnetic resonance (MR) using Gd-DTPA. Spinecho (SE) MR images (MRI) were obtained before and after the administration of Gd-DTPA, and correlative CT scans were performed on the same day. In 2 cases, 4 h and 27 months after the ictus, there was no enhancement with Gd-DTPA. There was faint enhancement in 2 cases with cerebral infarction of about 24 h duration and obvious enhancement in all cases in the subacute stage. Compared with enhanced CT, MR using Gd-DTPA demonstrated more obvious enhancement of infarcted areas. MR enhancement using Gd-DTPA showed a gradual increase and the accumulated Gd-DTPA in infarcted areas slowly diffused to the periphery. MR enhancement with Gd-DTPA is similar to that of enhanced CT, but may be more sensitive in the detection of blood brain barrier breakdown.

  3. Human Cardiac Mesenchymal Stromal Cells with CD105+CD34- Phenotype Enhance the Function of Post-Infarction Heart in Mice.

    Directory of Open Access Journals (Sweden)

    Justyna Czapla

    Full Text Available The aim of the present study was to isolate mesenchymal stromal cells (MSC with CD105+CD34- phenotype from human hearts, and to investigate their therapeutic potential in a mouse model of hindlimb ischemia and myocardial infarction (MI. The study aimed also to investigate the feasibility of xenogeneic MSCs implantation.MSC isolated from human hearts were multipotent cells. Separation of MSC with CD105+CD34- phenotype limited the heterogeneity of the originally isolated cell population. MSC secreted a number of anti-inflammatory and proangiogenic cytokines (mainly IL-6, IL-8, and GRO. Human MSC were transplanted into C57Bl/6NCrl mice. Using the mouse model of hindlimb ischemia it was shown that human MSC treated mice demonstrated a higher capillary density 14 days after injury. It was also presented that MSC administrated into the ischemic muscle facilitated fast wound healing (functional recovery by ischemic limb. MSC transplanted into an infarcted myocardium reduced the post-infarction scar, fibrosis, and increased the number of blood vessels both in the border area, and within the post-infarction scar. The improvement of left ventricular ejection fraction was also observed.In two murine models (hindlimb ischemia and MI we did not observe the xenotransplant rejection. Indeed, we have shown that human cardiac mesenchymal stromal cells with CD105+CD34- phenotype exhibit therapeutic potential. It seems that M2 macrophages are essential for healing and repair of the post-infarcted heart.

  4. Human Cardiac Mesenchymal Stromal Cells with CD105+CD34- Phenotype Enhance the Function of Post-Infarction Heart in Mice

    Science.gov (United States)

    Wiśniewska, Ewa; Jarosz-Biej, Magdalena; Smolarczyk, Ryszard; Cichoń, Tomasz; Głowala-Kosińska, Magdalena; Śliwka, Joanna; Garbacz, Marcin; Szczypior, Mateusz; Jaźwiec, Tomasz; Langrzyk, Agnieszka; Zembala, Michał; Szala, Stanisław

    2016-01-01

    Aims The aim of the present study was to isolate mesenchymal stromal cells (MSC) with CD105+CD34- phenotype from human hearts, and to investigate their therapeutic potential in a mouse model of hindlimb ischemia and myocardial infarction (MI). The study aimed also to investigate the feasibility of xenogeneic MSCs implantation. Methods and Results MSC isolated from human hearts were multipotent cells. Separation of MSC with CD105+CD34- phenotype limited the heterogeneity of the originally isolated cell population. MSC secreted a number of anti-inflammatory and proangiogenic cytokines (mainly IL-6, IL-8, and GRO). Human MSC were transplanted into C57Bl/6NCrl mice. Using the mouse model of hindlimb ischemia it was shown that human MSC treated mice demonstrated a higher capillary density 14 days after injury. It was also presented that MSC administrated into the ischemic muscle facilitated fast wound healing (functional recovery by ischemic limb). MSC transplanted into an infarcted myocardium reduced the post-infarction scar, fibrosis, and increased the number of blood vessels both in the border area, and within the post-infarction scar. The improvement of left ventricular ejection fraction was also observed. Conclusion In two murine models (hindlimb ischemia and MI) we did not observe the xenotransplant rejection. Indeed, we have shown that human cardiac mesenchymal stromal cells with CD105+CD34- phenotype exhibit therapeutic potential. It seems that M2 macrophages are essential for healing and repair of the post-infarcted heart. PMID:27415778

  5. Computed tomography of splenic infarcts

    Energy Technology Data Exchange (ETDEWEB)

    Triller, J.; Bona, E.; Barbier, P.

    1985-04-01

    Splenic infarcts are represented by wedge-shaped, oval or linear areas. Haemorrhagic infarcts are characterised by being hyperdense. Disseminated infarction occurs predominantly in myeloproliferative diseases. During the early stages, the infarct appears as an ill-defined hypodense defect, with non-homogeneous contrast enhancement. During the acute and sub-acute stage, the density of the infarct is low and there is no contrast enhancement. During the chronic stage, its density increases and there is slight contrast enhancement. Complications following splenic infarcts, such as abscesses, bleeding and rupture can be demonstrated by CT with great accuracy. Problems in differential diagnosis may occur if there are atypical manifestations of the infarct, with respect to abscess or leukaemic infiltrations.

  6. Medication regimen complexity and readmissions after hospitalization for heart failure, acute myocardial infarction, pneumonia, and chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Nada Abou-Karam

    2016-02-01

    Full Text Available Objectives: Readmission rate is increasingly being viewed as a key indicator of health system performance. Medication regimen complexity index scores may be predictive of readmissions; however, few studies have examined this potential association. The primary objective of this study was to determine whether medication regimen complexity index is associated with all-cause 30-day readmission after admission for heart failure, acute myocardial infarction, pneumonia, or chronic obstructive pulmonary disease. Methods: This study was an institutional review board–approved, multi-center, case–control study. Patients admitted with a primary diagnosis of heart failure, acute myocardial infarction, pneumonia, or chronic obstructive pulmonary disease were randomly selected for inclusion. Patients were excluded if they discharged against medical advice or expired during their index visit. Block randomization was utilized for equal representation of index diagnosis and site. Discharge medication regimen complexity index scores were compared between subjects with readmission versus those without. Medication regimen complexity index score was then used as a predictor in logistic regression modeling for readmission. Results: Seven hundred and fifty-six patients were randomly selected for inclusion, and 101 (13.4% readmitted within 30 days. The readmission group had higher medication regimen complexity index scores than the no-readmission group (p < 0.01. However, after controlling for demographics, disease state, length of stay, site, and medication count, medication regimen complexity index was no longer a significant predictor of readmission (odds ratio 0.99, 95% confidence interval 0.97–1.01 or revisit (odds ratio 0.99, 95% confidence interval 0.98–1.02. Conclusion: There is little evidence to support the use of medication regimen complexity index in readmission prediction when other measures are available. Medication regimen complexity index

  7. MicroRNAs, Innate Immunity and Ventricular Rupture in Human Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Nina Zidar

    2011-01-01

    Full Text Available MicroRNAs are non-coding RNAs, functionioning as post-transcriptional regulators of gene expression. Some microRNAs have been demonstrated to play a role in regulation of innate immunity. After myocardial infarction (MI, innate immunity is activated leading to an acute inflammatory reaction. There is evidence that an intense inflammatory reaction might contribute to the development of ventricular rupture (VR after MI.

  8. Acute bone crises in sickle cell disease: the T1 fat-saturated sequence in differentiation of acute bone infarcts from acute osteomyelitis

    Energy Technology Data Exchange (ETDEWEB)

    Jain, R. [Department of Radiology, College of Medicine, Sultan Qaboos University, Muscat (Oman)], E-mail: rajeevjn@yahoo.com; Sawhney, S. [Department of Radiology, College of Medicine, Sultan Qaboos University, Muscat (Oman); Rizvi, S.G. [Department of Community Medicine and Public Health, College of Medicine, Sultan Qaboos University, Muscat (Oman)

    2008-01-15

    Aim: To prove the hypothesis that acute bone infarcts in sickle cell disease are caused by sequestration of red blood cells (RBCs) in bone marrow, and to evaluate the unenhanced T1 fat-saturated (fs) sequence in the differentiation of acute bone infarction from acute osteomyelitis in patients with sickle-cell disease. Materials and methods: Two studies were undertaken: an experimental study using in-vitro packed red blood cells and normal volunteers, and a retrospective clinical study of 86 magnetic resonance imaging (MRI) studies. For the experimental study containers of packed RBCs were placed between the knees of four healthy volunteers with a saline bag under the containers as an additional control, and were scanned with the pre-contrast T1-fs sequence. Signal intensity (SI) ratios were obtained for packed RBCs:skeletal muscle and packed RBCs:saline. For the clinical study, the SIs of normal bone marrow, packed RBCs, bone and/or soft-tissue lesions, and normal skeletal muscle of 74 patients (86 MRI studies) were measured using unenhanced, T1 fat-saturated MRI. The ratios of the above SIs to normal skeletal muscle were calculated and subjected to statistical analysis. Results: Fifty-one of 86 MRI studies were included in the final analysis. The ratios of SIs for normal bone marrow, packed red cells, bone infarction, acute osteomyelitis, and soft-tissue lesions associated with bone infarct, compared with normal skeletal muscle were (mean {+-} SD) 0.9 {+-} 0.2, 2.1 {+-} 0.7, 1.7 {+-} 0.5, 1.0 {+-} 0.3, and 2.2 {+-} 0.7, respectively. The difference in the ratio of SIs of bone infarcts and osteomyelitis was significant (p = 0.003). The final diagnoses were bone infarction (n = 50), acute osteomyelitis (n = 1), and co-existent bone infarction and osteomyelitis (n = 2). Seven patients who had suspected osteomyelitis underwent image-guided aspiration. Conclusion: Acute bone infarcts in sickle cell disease are caused by sequestration of red blood cells in the bone

  9. Clinical impact of simultaneous complete revascularization vs. culprit only primary angioplasty in patients with st-elevation myocardial infarction and multivessel disease: a meta-analysis

    NARCIS (Netherlands)

    Navarese, E.P.; Servi, S. de; Buffon, A.; Suryapranata, H.; Luca, G. de

    2011-01-01

    Primary Percutaneous Intervention (PCI) is the treatment of choice for acute ST-elevation myocardial infarction (STEMI). Nearly half of STEMI patients have multivessel (MV) disease that has been associated with worse survival. However, current guidelines recommend to treat only the culprit artery (C

  10. Clinical efficacy of intra-aortic balloon pumping in treating patients with acute myocardial infarction with left main coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    赵昕

    2012-01-01

    Objective To evaluate the efficacy and safety of intra-aortic balloon pump(IABP) counter pulsation in the treatment of ST-segment elevation myocardial infarction(STEMI) with concurrent left main coronary artery(LM-CA) disease. Methods A retrospective analysis was performed

  11. Therapeutic effects of human multilineage-differentiating stress enduring (MUSE cell transplantation into infarct brain of mice.

    Directory of Open Access Journals (Sweden)

    Tomohiro Yamauchi

    Full Text Available Bone marrow stromal cells (BMSCs are heterogeneous and their therapeutic effect is pleiotropic. Multilineage-differentiating stress enduring (Muse cells are recently identified to comprise several percentages of BMSCs, being able to differentiate into triploblastic lineages including neuronal cells and act as tissue repair cells. This study was aimed to clarify how Muse and non-Muse cells in BMSCs contribute to functional recovery after ischemic stroke.Human BMSCs were separated into stage specific embryonic antigen-3-positive Muse cells and -negative non-Muse cells. Immunodeficient mice were subjected to permanent middle cerebral artery occlusion and received transplantation of vehicle, Muse, non-Muse or BMSCs (2.5×104 cells into the ipsilateral striatum 7 days later.Motor function recovery in BMSC and non-Muse groups became apparent at 21 days after transplantation, but reached the plateau thereafter. In Muse group, functional recovery was not observed for up to 28 days post-transplantation, but became apparent at 35 days post-transplantation. On immunohistochemistry, only Muse cells were integrated into peri-infarct cortex and differentiate into Tuj-1- and NeuN-expressing cells, while negligible number of BMSCs and non-Muse cells remained in the peri-infarct area at 42 days post-transplantation.These findings strongly suggest that Muse cells and non-Muse cells may contribute differently to tissue regeneration and functional recovery. Muse cells may be more responsible for replacement of the lost neurons through their integration into the peri-infarct cortex and spontaneous differentiation into neuronal marker-positive cells. Non-Muse cells do not remain in the host brain and may exhibit trophic effects rather than cell replacement.

  12. Correlation of echocardiographic epicardial fat thickness with severity of coronary artery disease in patients with acute myocardial infarction.

    Science.gov (United States)

    Wang, Tao; Liu, Qiang; Liu, Cuixia; Sun, Ling; Li, Daixu; Liu, Aihua; Jia, Ruyi

    2014-11-01

    The aim of this study was to test the hypotheses that epicardial adipose tissue (EAT) can be a marker of severe coronary artery disease in patients with acute myocardial infarction. Overall, 373 cases who underwent coronary angiography were classified into 2 groups by SYNTAX score: low-score and high-score group. EAT was measured by transthoracic echocardiography. Obtained data were compared using Pearson correlation analyses and univariate and multiple logistic regression analysis. The results showed that EAT in the high-score group was significantly greater than in the normal group (5.6 ± 1.1 vs. 4.1 ± 1.0 mm, P correlation with SYNTAX score (r = 0.61, P score (≥ 33) [AUC: 0.86, 95% confidence interval (CI): 0.822-0.898, P score.

  13. Genetically Modified Pig Models for Human Diseases

    Institute of Scientific and Technical Information of China (English)

    Nana Fan; Liangxue Lai

    2013-01-01

    Genetically modified animal models are important for understanding the pathogenesis of human disease and developing therapeutic strategies.Although genetically modified mice have been widely used to model human diseases,some of these mouse models do not replicate important disease symptoms or pathology.Pigs are more similar to humans than mice in anatomy,physiology,and genome.Thus,pigs are considered to be better animal models to mimic some human diseases.This review describes genetically modified pigs that have been used to model various diseases including neurological,cardiovascular,and diabetic disorders.We also discuss the development in gene modification technology that can facilitate the generation of transgenic pig models for human diseases.

  14. Infarct related artery only versus complete revascularization in ST-segment elevation myocardial infarction and multi vessel disease: a meta-analysis

    Science.gov (United States)

    Devarapally, Santhosh R.; Arora, Sameer

    2017-01-01

    Background The 2015 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) focused update on primary percutaneous coronary intervention (PCI) for patients with ST-segment elevation myocardial infarction (STEMI) only gives a class II b (weak) indication for non-infarct artery intervention at the time of primary PCI. Recent randomized controlled trials, however, suggest strong evidence supporting complete revascularization. Methods A systematic search was conducted in PUBMED, MEDLINE, EMBASE and Cochrane central register for randomized controlled trials comparing complete versus infarct artery (IRA) only revascularization in patients with STEMI. A meta-analysis was performed using the data extracted from each study. Summary risk ratios (RR) and 95% confidence intervals (CI) were calculated for five outcomes. Results Six trials fulfilled the inclusion criteria yielding 1,792 patients. Follow up ranged from 6 months to 2.5 years. The incidence of major adverse cardiac events (MACE) was significantly lower in the complete revascularization group compared to the IRA only revascularization (13.8% vs. 25.1%, RR =0.51; 95% CI: 0.41–0.64, P<0.00001). It was attributed to significantly lower repeat revascularization rate in the complete revascularization group (8.2% vs. 18.9%, RR =0.41; 95% CI: 0.31–0.54, P<0.00001). This meta-analysis also showed a significant reduction in cardiovascular mortality (2.0% vs. 4.6%, RR =0.42; 95% CI: 0.24–0.74; P=0.003), non-fatal myocardial infarction (4.37% vs. 5.76%, RR =0.64; 95% CI: 0.34–1.20; P=0.16) and all-cause mortality rates [(4.6% vs. 6%), RR =0.75; 95% CI: 0.49–1.14, P=0.17] in the complete revascularization group, compared to the IRA revascularization group. Conclusions In patients who present with STEMI, complete revascularization is associated with lower rates of MACE and cardiovascular deaths as compared to revascularization of the IRA alone. Even though the outcomes of all-cause mortality and

  15. Preliminary observations of increased diffusional kurtosis in human brain following recent cerebral infarction.

    Science.gov (United States)

    Jensen, Jens H; Falangola, Maria F; Hu, Caixia; Tabesh, Ali; Rapalino, Otto; Lo, Calvin; Helpern, Joseph A

    2011-06-01

    By application of the MRI method of diffusional kurtosis imaging, a substantially increased diffusional kurtosis was observed within the cerebral ischemic lesions of three stroke subjects, 13-26 h following the onset of symptoms. This increase is interpreted as probably reflecting a higher degree of diffusional heterogeneity in the lesions when compared with normal-appearing contralateral tissue. In addition, for two of the subjects with white matter infarcts, the increase had a strong fiber tract orientational dependence. It is proposed that this effect is consistent with a large drop in the intra-axonal diffusivity, possibly related to either axonal varicosities or alterations associated with the endoplasmic reticulum.

  16. Uncovering disease-disease relationships through the incomplete human interactome

    Science.gov (United States)

    Menche, Jörg; Sharma, Amitabh; Kitsak, Maksim; Ghiassian, Susan; Vidal, Marc; Loscalzo, Joseph; Barabási, Albert-László

    2015-01-01

    According to the disease module hypothesis the cellular components associated with a disease segregate in the same neighborhood of the human interactome, the map of biologically relevant molecular interactions. Yet, given the incompleteness of the interactome and the limited knowledge of disease-associated genes, it is not obvious if the available data has sufficient coverage to map out modules associated with each disease. Here we derive mathematical conditions for the identifiability of disease modules and show that the network-based location of each disease module determines its pathobiological relationship to other diseases. For example, diseases with overlapping network modules show significant co-expression patterns, symptom similarity, and comorbidity, while diseases residing in separated network neighborhoods are clinically distinct. These tools represent an interactome-based platform to predict molecular commonalities between clinically related diseases, even if they do not share disease genes. PMID:25700523

  17. Dobutamine stress thallium-201 single-photon emission tomography versus echocardiography for evaluation of the extent and location of coronary artery disease late after myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Elhendy, A.; Bax, J.J.; Domburg, R.T. van; Cornel, J.H.; Roelandt, J.R.T.C. [Thoraxcenter, Univ. Hospital Rotterdam-Dijkzigt, Rotterdam (Netherlands); Valkema, R.; Reijs, A.E.M.; Krenning, E.P. [Dept. of Nuclear Medicine, University Hospital Rotterdam-Dijkzigt, Rotterdam (Netherlands)

    1999-05-01

    Dobutamine stress echocardiography and thallium-201 myocardial perfusion scintigraphy are clinically useful methods for the evaluation of coronary artery disease (CAD). However, the relative merits of these imaging modalities in the evaluation of the extent of CAD after myocardial infarction have not been well studied. The aim of this study was to compare the accuracy of dobutamine stress echocardiography and simultaneous {sup 201}Tl single-photon emission tomography (SPET) imaging for the diagnosis and localization of CAD late after acute myocardial infarction. Dobutamine (up to 40 {mu}g kg{sup -1} min{sup -1})-atropine (up to 1 mg) stress echocardiography in conjunction with stress-reinjection {sup 201}Tl SPET was performed for the evaluation of myocardial ischaemia in 90 patients with previous myocardial infarction who underwent coronary angiography. Significant CAD was predicted on bases of myocardial ischemia (new or worsening wall motion abnormalities on echocardiography and reversible perfusion defects on {sup 201}Tl SPET). Significant CAD ({>=} 50% luminal diameter stenosis) was detected in 73 (81%) patients. The sensitivity, specificity and accuracy of echocardiography in detecting remote ischaemia for the diagnosis of remote CAD (present in 53 patients) were, respectively, 79% (CI 70%-88%), 85% (CI 77%-93%) and 81% (CI 73%-90%), while the corresponding figures for {sup 201}Tl SPET were 75% (CI 66%-85%), 78% (CI 69%-87%) and 76% (CI 67%-86%) respectively (P = NS vs echocardiography). The sensitivity, specificity and accuracy of echocardiography in detecting peri-infarction ischaemia for the diagnosis of infarct-related artery stenosis (present in 70 patients) were, rspectively, 77% (CI 68%-86%), 85% (CI 78%-92%) and 79% (CI 70%-87%) while the corresponding figures for {sup 201}Tl SPET were 73% (CI 64%-82%), 85% (CI 78%-92%) and 76% (CI 67%-84%) respectively (P = NS vs echocardiography). The agreement between the two methods for the diagnosis of peri-infarction

  18. Multiorgan with renal infarction following treatment of cerebral infarction.

    Science.gov (United States)

    Kim, Ji Hee; Kang, Chung; Moon, Hyo Jeong; Joo, Min Cheol

    2013-08-01

    Acute renal infarction is a rare disease and it is often difficult to make a clinical diagnosis due to the non-specific clinical presentations and lack of the physicians' awarenesses. We experienced a case of a 72-year-old man who was diagnosed as multiorgan with renal infarction during the bridge therapy of cerebral infarction with atrial fibrillation. Computed tomogram (CT) with intravenous contrast of the abdomen and pelvis revealed left renal infarction with renal artery occlusion, multifocal splenic infarction, and ischemic colitis on rectum and sigmoid colon. The patient was treated with low molecular weight heparin for 10 days, his symptoms were improved and laboratory findings were normalized. Follow-up CT was performed on the 43th day, there were persisted left renal infarction with atrophic change shown and the splenic perfusion was improved.

  19. Behavior in a stressful situation, personality factors, and disease severity in patients with acute myocardial infarction: baseline findings from the prospective cohort study SECAMI (The Secondary Prevention and Compliance following Acute Myocardial Infarction-study

    Directory of Open Access Journals (Sweden)

    Tydén Patrik

    2011-07-01

    Full Text Available Abstract Background Psychosocial stress has been identified as a risk factor in association with cardiovascular disease but less attention has been paid to heterogeneity in vulnerability to stress. The serial Color Word Test (CWT measures adaptation to a stressful situation and it can be used to identify individuals that are vulnerable to stress. Prospective studies have shown that individuals with a maladaptive behavior in this test are exposed to an increased risk of future cardiovascular events. The aim of the present study was to investigate whether maladaptive behavior in the serial CWT alone or in combination with any specific personality dimension was associated with severity of myocardial infarction (MI. Methods MI-patients (n = 147 completed the test and filled in a personality questionnaire in close proximity to the acute event. The results were analyzed in association with four indicators of severity: maximum levels above median of the cardiac biomarkers troponin I and creatine kinase-MB (CKMB, Q-wave infarctions, and a left ventricular ejection fraction (LVEF ≤ 50%. Results Maladaptive behavior in the serial CWT together with low scores on extraversion were associated with maximum levels above median of cardiac troponin I (OR 2.97, CI 1.08-8.20, p = 0.04 and CKMB (OR 3.33, CI 1.12-9.93, p = 0.03. No associations were found between the combination maladaptive behavior and low scores on extraversion and Q-wave infarctions or a decreased LVEF. Conclusions Maladaptive behavior in combination with low scores on extraversion is associated with higher cardiac biomarker levels following an MI. The serial CWT and personality questionnaires could be used to identify individuals vulnerable to the hazardous effects of stress and thereby are exposed to an increased risk of a more severe infarction.

  20. Does biodiversity protect humans against infectious disease?

    Science.gov (United States)

    Wood, Chelsea L; Lafferty, Kevin D; DeLeo, Giulio; Young, Hillary S; Hudson, Peter J; Kuris, Armand M

    2014-04-01

    Control of human infectious disease has been promoted as a valuable ecosystem service arising from the conservation of biodiversity. There are two commonly discussed mechanisms by which biodiversity loss could increase rates of infectious disease in a landscape. First, loss of competitors or predators could facilitate an increase in the abundance of competent reservoir hosts. Second, biodiversity loss could disproportionately affect non-competent, or less competent reservoir hosts, which would otherwise interfere with pathogen transmission to human populations by, for example, wasting the bites of infected vectors. A negative association between biodiversity and disease risk, sometimes called the "dilution effect hypothesis," has been supported for a few disease agents, suggests an exciting win-win outcome for the environment and society, and has become a pervasive topic in the disease ecology literature. Case studies have been assembled to argue that the dilution effect is general across disease agents. Less touted are examples in which elevated biodiversity does not affect or increases infectious disease risk for pathogens of public health concern. In order to assess the likely generality of the dilution effect, we review the association between biodiversity and public health across a broad variety of human disease agents. Overall, we hypothesize that conditions for the dilution effect are unlikely to be met for most important diseases of humans. Biodiversity probably has little net effect on most human infectious diseases but, when it does have an effect, observation and basic logic suggest that biodiversity will be more likely to increase than to decrease infectious disease risk.

  1. Parasitic diseases in humans transmitted by vectors.

    Science.gov (United States)

    Cholewiński, Marcin; Derda, Monika; Hadaś, Edward

    2015-01-01

    Despite the considerable progress of medicine, parasitic diseases still pose a great threat to human health and life. Among parasitic diseases, those transmitted by vectors, mainly arthropods, play a particular role. These diseases occur most frequently in the poorest countries and affect a vast part of the human population. They include malaria, babesiosis, trypanosomiasis, leishmaniasis and filariasis. This study presents those vector-transmitted diseases that are responsible for the greatest incidence and mortality of people on a global scale. Attention is focused primarily on diseases transmitted by mosquitoes, flies, Hemiptera and ticks.

  2. Cardiac αVβ3 integrin expression following acute myocardial infarction in humans.

    Science.gov (United States)

    Jenkins, William S A; Vesey, Alex T; Stirrat, Colin; Connell, Martin; Lucatelli, Christophe; Neale, Anoushka; Moles, Catriona; Vickers, Anna; Fletcher, Alison; Pawade, Tania; Wilson, Ian; Rudd, James H F; van Beek, Edwin J R; Mirsadraee, Saeed; Dweck, Marc R; Newby, David E

    2017-04-01

    Maladaptive repair contributes towards the development of heart failure following myocardial infarction (MI). The αvβ3 integrin receptor is a key mediator and determinant of cardiac repair. We aimed to establish whether αvβ3 integrin expression determines myocardial recovery following MI. (18)F-Fluciclatide (a novel αvβ3-selective radiotracer) positron emission tomography (PET) and CT imaging and gadolinium-enhanced MRI (CMR) were performed in 21 patients 2 weeks after ST-segment elevation MI (anterior, n=16; lateral, n=4; inferior, n=1). CMR was repeated 9 months after MI. 7 stable patients with chronic total occlusion (CTO) of a major coronary vessel and nine healthy volunteers underwent a single PET/CT and CMR. (18)F-Fluciclatide uptake was increased at sites of acute infarction compared with remote myocardium (tissue-to-background ratio (TBRmean) 1.34±0.22 vs 0.85±0.17; pinfarction in patients with CTO, with activity similar to the myocardium of healthy volunteers (TBRmean 0.71±0.06 vs 0.70±0.03, p=0.83). (18)F-Fluciclatide uptake occurred at sites of regional wall hypokinesia (wall motion index≥1 vs 0; TBRmean 0.93±0.31 vs 0.80±0.26 respectively, pinfarction. Importantly, although there was no correlation with infarct size (r=0.03, p=0.90) or inflammation (C reactive protein, r=-0.20, p=0.38), (18)F-fluciclatide uptake was increased in segments displaying functional recovery (TBRmean 0.95±0.33 vs 0.81±0.27, p=0.002) and associated with increase in probability of regional recovery. (18)F-Fluciclatide uptake is increased at sites of recent MI acting as a biomarker of cardiac repair and predicting regions of recovery. NCT01813045; Post-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  3. Depression after myocardial infarction.

    Science.gov (United States)

    Ziegelstein, R C

    2001-01-01

    Depression is an independent risk factor for increased postmyocardial infarction morbidity and mortality, even after controlling for the extent of coronary artery disease, infarct size, and the severity of left ventricular dysfunction. This risk factor takes on added significance when one considers that almost half of patients recovering from a myocardial infarction have major or minor depression and that major depression alone occurs in about one in five of these individuals. Despite the well-documented risk of depression, questions remain about the mechanism of the relationship between mood disturbance and adverse outcome. The link may be explained by an association with lower levels of social support, poor adherence to recommended medical therapy and lifestyle changes intended to reduce the risk of subsequent cardiac events, disturbances in autonomic tone, enhanced platelet activation and aggregation, and systemic immune activation. Unfortunately, questions about the pathophysiologic mechanism of depression in this setting are paralleled by uncertainties about the optimal treatment of depression for patients recovering from a myocardial infarction and by a lack of knowledge about whether treating depression lowers the associated increased mortality risk. Ongoing research studies will help to determine the benefits of psychosocial interventions and of antidepressant therapy for patients soon after myocardial infarction. Although the identification of depression as a risk factor may by itself be a reason to incorporate a comprehensive psychological evaluation into the routine care of patients with myocardial infarction, this practice should certainly become standard if studies show that treating depression reduces the increased mortality risk of these patients.

  4. Differential proteome profile in ischemic heart disease: Prognostic value in chronic angina versus myocardial infarction. A proof of concept.

    Science.gov (United States)

    Scebba, Francesca; Papale, Massimo; Rocchiccioli, Silvia; Ucciferri, Nadia; Bigazzi, Federico; Sampietro, Tiziana; Carpeggiani, Clara; L'Abbate, Antonio; Coceani, Flavio; Angeloni, Debora

    2017-08-01

    The initial clinical manifestation of ischemic heart disease (IHD) i.e. unheralded myocardial infarction (MI) versus chronic angina pectoris (AP) is statistically associated with adverse or mild disease progression respectively in the long-term follow-up. Here, we subjected AP and MI patients to blood proteomic analysis by Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS) in order to investigate putative new prognostic biomarkers of IHD manifestation. We found several differentially expressed peaks but four of them (4176, 4475, 14,158m/z and 8922m/z for AP and MI, respectively) were most reliable. Two of them were identified; 14,158m/z peak was the double-charged form of Apolipoprotein A-I and its vasoprotective action accords with prominence in AP. The 4176m/z peak was related to FAM83C protein, while neither the 4475m/z peak nor the MI-linked 8922m/z peak could be identified. We conclude that SELDI-TOF-MS analysis may yield a panel of molecular signals able to retrospectively classify patients according to their clinical and molecular features, exploitable for predicting the natural course of IHD. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Comparison of risk and age at diagnosis of myocardial infarction, end-stage renal disease, and non-AIDS-defining cancer in HIV-infected versus uninfected adults.

    Science.gov (United States)

    Althoff, Keri N; McGinnis, Kathleen A; Wyatt, Christina M; Freiberg, Matthew S; Gilbert, Cynthia; Oursler, Krisann K; Rimland, David; Rodriguez-Barradas, Maria C; Dubrow, Robert; Park, Lesley S; Skanderson, Melissa; Shiels, Meredith S; Gange, Stephen J; Gebo, Kelly A; Justice, Amy C

    2015-02-15

    Although it has been shown that human immunodeficiency virus (HIV)-infected adults are at greater risk for aging-associated events, it remains unclear as to whether these events happen at similar, or younger ages, in HIV-infected compared with uninfected adults. The objective of this study was to compare the median age at, and risk of, incident diagnosis of 3 age-associated diseases in HIV-infected and demographically similar uninfected adults. The study was nested in the clinical prospective Veterans Aging Cohort Study of HIV-infected and demographically matched uninfected veterans, from 1 April 2003 to 31 December 2010. The outcomes were validated diagnoses of myocardial infarction (MI), end-stage renal disease (ESRD), and non-AIDS-defining cancer (NADC). Differences in mean age at, and risk of, diagnosis by HIV status were estimated using multivariate linear regression models and Cox proportional hazards models, respectively. A total of 98 687 (31% HIV-infected and 69% uninfected) adults contributed >450 000 person-years and 689 MI, 1135 ESRD, and 4179 NADC incident diagnoses. Mean age at MI (adjusted mean difference, -0.11; 95% confidence interval [CI], -.59 to .37 years) and NADC (adjusted mean difference, -0.10 [95% CI, -.30 to .10] years) did not differ by HIV status. HIV-infected adults were diagnosed with ESRD at an average age of 5.5 months younger than uninfected adults (adjusted mean difference, -0.46 [95% CI, -.86 to -.07] years). HIV-infected adults had a greater risk of all 3 outcomes compared with uninfected adults after accounting for important confounders. HIV-infected adults had a higher risk of these age-associated events, but they occurred at similar ages than those without HIV. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Stem cell differentiation and human liver disease

    Institute of Scientific and Technical Information of China (English)

    Wen-Li Zhou; Claire N Medine; Liang Zhu; David C Hay

    2012-01-01

    Human stem cells are scalable cell populations capable of cellular differentiation.This makes them a very attractive in vitro cellular resource and in theory provides unlimited amounts of primary cells.Such an approach has the potential to improve our understanding of human biology and treating disease.In the future it may be possible to deploy novel stem cell-based approaches to treat human liver diseases.In recent years,efficient hepatic differentiation from human stem cells has been achieved by several research groups including our own.In this review we provide an overview of the field and discuss the future potential and limitations of stem cell technology.

  7. Polyvascular Disease and Long-term Cardiovascular Outcomes in Older Patients with Non–ST-segment Elevation Myocardial Infarction

    Science.gov (United States)

    Subherwal, Sumeet; Bhatt, Deepak L.; Li, Shuang; Tracy Y., Wang; Thomas, Laine; Alexander, Karen P.; Patel, Manesh R.; Ohman, E. Magnus; Gibler, W. Brian; Peterson, Eric D.; Roe, Matthew T.

    2013-01-01

    Background The impact of polyvascular disease (peripheral arterial disease [PAD] and/or cerebrovascular disease [CVD]) on long-term cardiovascular outcomes among older patients with acute myocardial infarction (MI) has not been well studied. Methods Non–ST-elevation MI (NSTEMI) patients aged ≥65 years from the CRUSADE registry who survived to hospital discharge were linked to longitudinal data from the Centers for Medicare and Medicaid Services (n=34,205). All patients were presumed to have coronary artery disease (CAD) and were classified into 4 groups: 10.7% had prior CVD (CAD+CVD group); 11.5% had prior PAD (CAD+PAD); 3.1% had prior PAD and CVD (CAD+PAD+CVD); and 74.7% had no polyvascular disease (CAD alone). Cox proportional hazard modeling was used to examine the hazard of long-term mortality and the composite of death, readmission for MI, or readmission for stroke (median follow-up 35 months, IQR 17–49) among the 4 groups. Results Compared with the CAD-alone group, patients with polyvascular disease had a greater comorbidity burden, were less likely to undergo revascularization, and less often received recommended discharge interventions. Three-year mortality rates increased with a greater number of arterial beds involved: 33% for CAD alone, 49% for CAD+PAD, 52% for CAD+CVD, and 59% for CAD+PAD+CVD. Relative to the CAD-alone group, patients with all 3 arterial beds involved had the highest risk of long-term mortality (adjusted HR [95% CI]: 1.49 [1.38–1.61], with a lower risk for those with CAD+CVD, 1.38 [1.31–1.44], and those with CAD+PAD, 1.29 [1.23–1.35]). Similarly, the adjusted risk of long-term composite ischemic events was highest among the CAD+PAD+CVD group. Conclusions Older NSTEMI patients with polyvascular disease have substantially higher long-term risk, such that the 3-year mortality rate is >50%. Future studies targeting greater adherance to secondary prevention strategies and novel therapies are needed to help reduce long

  8. Reduced penetrance in human inherited disease

    African Journals Online (AJOL)

    Rabah M. Shawky

    2014-01-31

    Jan 31, 2014 ... tant role in cellular senescence, tumorigenesis and in several diseases ... A correlation between epigenetic DNA modifications and human life span ... Most studies demonstrated that aging is associated with a relaxation in ...

  9. Missed Kawasaki disease in childhood presenting as myocardial infarction in adults

    OpenAIRE

    Bhagwat, Ajit; Mukhedkar, Sachin; Ekbote, Shriganesh; Gordon, John B.

    2015-01-01

    Kawasaki disease (KD) is an acute, self-limited vasculitis that occurs in young children and was first described by Japanese pediatrician Tomisaku Kawasaki in 1967. Although originally thought to be a rare condition, KD has become the most common cause of acquired heart disease in the pediatric population in developed countries. The majority of patients with KD appear to have a benign prognosis, but a subset of patients with coronary artery aneurysms are at risk for ischemic events and requir...

  10. Mitochondrial DAMPs induce endotoxin tolerance in human monocytes: an observation in patients with myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Irene Fernández-Ruiz

    Full Text Available Monocyte exposure to mitochondrial Danger Associated Molecular Patterns (DAMPs, including mitochondrial DNA (mtDNA, induces a transient state in which these cells are refractory to further endotoxin stimulation. In this context, IRAK-M up-regulation and impaired p65 activity were observed. This phenomenon, termed endotoxin tolerance (ET, is characterized by decreased production of cytokines in response to the pro-inflammatory stimulus. We also show that monocytes isolated from patients with myocardial infarction (MI exhibited high levels of circulating mtDNA, which correlated with ET status. Moreover, a significant incidence of infection was observed in those patients with a strong tolerant phenotype. The present data extend our current understanding of the implications of endotoxin tolerance. Furthermore, our data suggest that the levels of mitochondrial antigens in plasma, such as plasma mtDNA, should be useful as a marker of increased risk of susceptibility to nosocomial infections in MI and in other pathologies involving tissue damage.

  11. Protein Misfolding and Human Disease

    DEFF Research Database (Denmark)

    Gregersen, Niels; Bross, Peter Gerd; Vang, Søren

    2006-01-01

    phenylketonuria, Parkinson's disease, α-1-antitrypsin deficiency, familial neurohypophyseal diabetes insipidus, and short-chain acyl-CoA dehydrogenase deficiency. Despite the differences, an emerging paradigm suggests that the cellular effects of protein misfolding provide a common framework that may contribute......Protein misfolding is a common event in living cells. In young and healthy cells, the misfolded protein load is disposed of by protein quality control (PQC) systems. In aging cells and in cells from certain individuals with genetic diseases, the load may overwhelm the PQC capacity, resulting...... in accumulation of misfolded proteins. Dependent on the properties of the protein and the efficiency of the PQC systems, the accumulated protein may be degraded or assembled into toxic oligomers and aggregates. To illustrate this concept, we discuss a number of very different protein misfolding diseases including...

  12. Impact of chronic obstructive pulmonary disease on patient with acute myocardial infarction undergoing primary percutaneous coronary intervention

    Directory of Open Access Journals (Sweden)

    Pei-Hsun Sung

    2013-12-01

    Full Text Available Background: This study reported the incidence and prognostic outcome of chronic obstructive lung disease (COPD patients with acute ST-segment elevation myocardial infarction (STEMI undergoing primary percutaneous coronary intervention (PCI. Methods: Between January 2002 and May 2011, totally 1554 consecutive patients who experienced STEMI undergoing primary PCI were enrolled into the study. Results: Of the 1554 patients, 124 (9.7% with diagnosis of COPD and 1430 (90.3% without COPD were categorized into group 1 and group 2. Although no difference in in-hospital mortality was noted between the two groups (p = 0.726. However, the hospitalization duration was notably longer (p = 0.003, the incidences of recurrent MI and re-hospitalization for congestive heart failure were significantly higher in group 1 than in group 2 (all p < 0.02. Although Kaplan-Meier analysis demonstrated that the incidence of freedom from one-year major adverse clinical outcome (MACO (defined as recurrent MI, re-admission for congestive heart failure was significantly lower in group 1 than group 2 (p = 0.012, multivariate Cox regression analysis showed COPD was not an independent predictor of MACO-free time after adjusting traditional risk factors. Conclusion: COPD was not an independent predictor of short-term and medium-term MACO in patients with STEMI undergoing primary PCI.

  13. Vascularization and restoration of heart function in rat myocardial infarction using transplantation of human cbMSC/HUVEC core-shell bodies.

    Science.gov (United States)

    Lee, Wen-Yu; Wei, Hao-Ji; Wang, Jiun-Jie; Lin, Kun-Ju; Lin, Wei-Wen; Chen, Ding-Yuan; Huang, Chieh-Cheng; Lee, Ting-Yin; Ma, Hsiang-Yang; Hwang, Shiaw-Min; Chang, Yen; Sung, Hsing-Wen

    2012-03-01

    Cell transplantation is a promising strategy for therapeutic treatment of ischemic heart diseases. In this study, cord blood mesenchymal stem cells (cbMSCs) and human umbilical vein endothelial cells (HUVECs) in the form of core-shell bodies (cbMSC/HUVEC bodies) were prepared to promote vascularization and restore heart functions in an experimentally-created myocardial infarction (MI) rat model. Saline, cbMSC bodies and HUVEC bodies were used as controls. In vitro results indicated that cbMSC/HUVEC bodies possessed the capability of heterotypic assembly of cbMSCs and HUVECs into robust and durable tubular networks on Matrigel. The up-regulated gene expressions of VEGF and IGF-1 reflected the robust expansion of tubular networks; in addition, the augmented levels of SMA and SM22 suggested smooth muscle differentiation of cbMSCs, possibly helping to improve the durability of networks. Moreover, according to the in vivo echocardiographic, magnetic resonance and computed-tomographic results, transplantation of cbMSC/HUVEC bodies benefited post-MI dysfunction. Furthermore, the vascularization analyses demonstrated the robust vasculogenic potential of cbMSC/HUVEC bodies in vivo, thus contributing to the greater viable myocardium and the less scar region, and ultimately restoring the cardiac function. The concept of core-shell bodies composed of perivascular cells and endothelial cells may serve as an attractive cell delivery vehicle for vasculogenesis, thus improving the cardiac function significantly.

  14. Headache and migraine in children with sickle cell disease are associated with lower hemoglobin and higher pain event rates but not silent cerebral infarction.

    Science.gov (United States)

    Dowling, Michael M; Noetzel, Michael J; Rodeghier, Mark J; Quinn, Charles T; Hirtz, Deborah G; Ichord, Rebecca N; Kwiatkowski, Janet L; Roach, E Steven; Kirkham, Fenella J; Casella, James F; DeBaun, Michael R

    2014-05-01

    To identify risk factors for headache and migraine in children with sickle cell disease and test the hypothesis that either or both are independently associated with silent cerebral infarcts. In this cross-sectional study, we evaluated the health history, laboratory values, and brain magnetic resonance imaging findings of participants with sickle cell disease (hemoglobinSS or hemoglobinSβ°-thalassemia) with no history of overt stroke or seizures. Participants characterized headache severity and quality. Migraine was defined by International Headache Society criteria modified for increased sensitivity in children. Neuroradiology and neurology committees adjudicated the presence of silent cerebral infarction by review of magnetic resonance imaging and standardized examination by pediatric neurologists. The cohort included 872 children (51.1% males), ranging in age from 5 to 15 years (mean age, 9.1 years). Of these children, 317 (36.4%) reported recurrent headaches, and 132 (15.1%) reported migraines. In multivariable logistic regression analyses, both were associated with lower steady-state hemoglobin (P = .01 for headaches; P headaches; P headaches or migraines. Only 1.9% (6 of 317) of children with recurrent headaches received medication for headache prophylaxis. Recurrent headaches and migraines are common and undertreated in children with sickle cell disease. Low hemoglobin levels and high pain rates are associated with recurrent headaches and migraines; whereas, silent cerebral infarction is not. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD): a scoring system for moyamoya severity based on multimodal hemodynamic imaging.

    Science.gov (United States)

    Ladner, Travis R; Donahue, Manus J; Arteaga, Daniel F; Faraco, Carlos C; Roach, Brent A; Davis, L Taylor; Jordan, Lori C; Froehler, Michael T; Strother, Megan K

    2017-02-01

    OBJECTIVE Quantification of the severity of vasculopathy and its impact on parenchymal hemodynamics is a necessary prerequisite for informing management decisions and evaluating intervention response in patients with moyamoya. The authors performed digital subtraction angiography and noninvasive structural and hemodynamic MRI, and they outline a new classification system for patients with moyamoya that they have named Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD). METHODS Healthy control volunteers (n = 11; age 46 ± 12 years [mean ± SD]) and patients (n = 25; 42 ± 13.5 years) with angiographically confirmed moyamoya provided informed consent and underwent structural (T1-weighted, T2-weighted, FLAIR, MR angiography) and hemodynamic (T2*- and cerebral blood flow-weighted) 3-T MRI. Cerebrovascular reactivity (CVR) in the internal carotid artery territory was assessed using susceptibility-weighted MRI during a hypercapnic stimulus. Only hemispheres without prior revascularization were assessed. Each hemisphere was considered symptomatic if localizing signs were present on neurological examination and/or there was a history of transient ischemic attack with symptoms referable to that hemisphere. The PIRAMD factor weighting versus symptomatology was optimized using binary logistic regression and receiver operating characteristic curve analysis with bootstrapping. The PIRAMD finding was scored from 0 to 10. For each hemisphere, 1 point was assigned for prior infarct, 3 points for reduced CVR, 3 points for a modified Suzuki Score ≥ Grade II, and 3 points for flow impairment in ≥ 2 of 7 predefined vascular territories. Hemispheres were divided into 3 severity grades based on total PIRAMD score, as follows: Grade 1, 0-5 points; Grade 2, 6-9 points; and Grade 3, 10 points. RESULTS In 28 of 46 (60.9%) hemispheres the findings met clinical symptomatic criteria. With decreased CVR, the odds ratio of having a symptomatic hemisphere was 13 (95% CI

  16. Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium.

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    Abbas Dehghan

    Full Text Available Data are limited on genome-wide association studies (GWAS for incident coronary heart disease (CHD. Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting.We performed a two-stage GWAS analysis of incident myocardial infarction (MI and CHD in a total of 64,297 individuals (including 3898 MI cases, 5465 CHD cases. SNPs that passed an arbitrary threshold of 5×10-6 in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with total mortality in individuals who experienced MI during follow-up.In Stage I 15 loci passed the threshold of 5×10-6; 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value<8.8×10-3 and three exceeded the genome-wide significance threshold when Stage I and Stage II results were combined (top SNP rs6941513: p = 6.2×10-9. Despite excellent power, the 9p21 locus SNP (rs1333049 was only modestly associated with MI (HR = 1.09, p-value = 0.02 and marginally with CHD (HR = 1.06, p-value = 0.08. Among an inception cohort of those who experienced MI during follow-up, the risk allele of rs1333049 was associated with a decreased risk of subsequent mortality (HR = 0.90, p-value = 3.2×10-3.QKI represents a novel locus that may serve as a predictor of incident CHD in prospective studies. The association of the 9p21 locus both with increased risk of first myocardial infarction and longer survival after MI highlights the importance of study design in investigating genetic determinants of complex disorders.

  17. Physiochemical basis of human degenerative disease

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    Zeliger Harold I.

    2015-03-01

    Full Text Available The onset of human degenerative diseases in humans, including type 2 diabetes, cardiovascular disease, neurological disorders, neurodevelopmental disease and neurodegenerative disease has been shown to be related to exposures to persistent organic pollutants, including polychlorinated biphenyls, chlorinated pesticides, polybrominated diphenyl ethers and others, as well as to polynuclear aromatic hydrocarbons, phthalates, bisphenol-A and other aromatic lipophilic species. The onset of these diseases has also been related to exposures to transition metal ions. A physiochemical mechanism for the onset of degenerative environmental disease dependent upon exposure to a combination of lipophilic aromatic hydrocarbons and transition metal ions is proposed here. The findings reported here also, for the first time, explain why aromatic hydrocarbons exhibit greater toxicity than aliphatic hydrocarbons of equal carbon numbers.

  18. Human Echinococcosis: A Neglected Disease

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    António Menezes da Silva

    2010-01-01

    Full Text Available Echinococcosis is among the most neglected parasitic diseases. Development of new drugs and other treatment modalities receives very little attention, if any. In most developed countries, Cystic Echinococcosis (CE is an imported disease of very low incidence and prevalence and is found almost exclusively in migrants from endemic regions. In endemic regions, predominantly settings with limited resources, patient numbers are high. Whole communities do not have access to appropriate treatment. The choice of treatment modalities is limited because of poor infrastructure and shortage of equipment and drugs. In this context, CE meets the criteria for a neglected disease. Furthermore, the terminology related to the designations around the parasite, its evolution and some therapeutic procedures is not uniform and sometimes inappropriate terms and wrong designations are used based on incorrect concepts. Although all of us know the different aspects of the disease it is pertinent to remember some important points and, above all, to clarify some aspects concerning the hydatid cyst's nomenclature in order to understand better the therapeutic options in the liver locations, particularly the different surgical approaches.

  19. Molecular Pathology of Human Prion Diseases

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    2009-03-01

    Full Text Available Prion diseases are fatal neurodegenerative conditions in humans and animals. In this review, we summarize the molecular background of phenotypic variability, relation of prion protein (PrP to other proteins associated with neurodegenerative diseases, and pathogenesis of neuronal vulnerability. PrP exists in different forms that may be present in both diseased and non-diseased brain, however, abundant disease-associated PrP together with tissue pathology characterizes prion diseases and associates with transmissibility. Prion diseases have different etiological background with distinct pathogenesis and phenotype. Mutations of the prion protein gene are associated with genetic forms. The codon 129 polymorphism in combination with the Western blot pattern of PrP after proteinase K digestion serves as a basis for molecular subtyping of sporadic Creutzfeldt-Jakob disease. Tissue damage may result from several parallel, interacting or subsequent pathways that involve cellular systems associated with synapses, protein processing, oxidative stress, autophagy, and apoptosis.

  20. Migrainous infarction

    DEFF Research Database (Denmark)

    Laurell, K; Artto, V; Bendtsen, L

    2011-01-01

    Migrainous infarction (MI), i.e. an ischemic stroke developing during an attack of migraine with aura is rare and the knowledge of its clinical characteristics is limited. Previous case series using the International Classification of Headache Disorders (ICHD) included......Migrainous infarction (MI), i.e. an ischemic stroke developing during an attack of migraine with aura is rare and the knowledge of its clinical characteristics is limited. Previous case series using the International Classification of Headache Disorders (ICHD) included...

  1. [Primary human demodicosis. A disease sui generis].

    Science.gov (United States)

    Hsu, C-K; Zink, A; Wei, K-J; Dzika, E; Plewig, G; Chen, W

    2015-03-01

    Human Demodex mites (Demodex folliculorum and Demodex brevis) are unique in that they are an obligate human ectoparasite that can inhabit the pilosebaceous unit lifelong without causing obvious host immune response in most cases. The mode of symbiosis between humans and human Demodex mites is unclear, while the pathogenicity of human Demodex mites in many inflammatory skin diseases is now better understood. Primary human demodicosis is a skin disease sui generis not associated with local or systemic immunosuppression. Diagnosis is often underestimated and differentiation from folliculitis, papulopustular rosacea and perioral dermatitis is not always straightforward. Dependent on the morphology and degree of inflammation, the clinical manifestations can be classified into spinulate, papulopustular, nodulocystic, crustic and fulminant demodicosis. Therapy success can be achieved only with acaricides/arachidicides. The effective doses, optimal regimen and antimicrobial resistance remain to be determined.

  2. Global biogeography of human infectious diseases.

    Science.gov (United States)

    Murray, Kris A; Preston, Nicholas; Allen, Toph; Zambrana-Torrelio, Carlos; Hosseini, Parviez R; Daszak, Peter

    2015-10-13

    The distributions of most infectious agents causing disease in humans are poorly resolved or unknown. However, poorly known and unknown agents contribute to the global burden of disease and will underlie many future disease risks. Existing patterns of infectious disease co-occurrence could thus play a critical role in resolving or anticipating current and future disease threats. We analyzed the global occurrence patterns of 187 human infectious diseases across 225 countries and seven epidemiological classes (human-specific, zoonotic, vector-borne, non-vector-borne, bacterial, viral, and parasitic) to show that human infectious diseases exhibit distinct spatial grouping patterns at a global scale. We demonstrate, using outbreaks of Ebola virus as a test case, that this spatial structuring provides an untapped source of prior information that could be used to tighten the focus of a range of health-related research and management activities at early stages or in data-poor settings, including disease surveillance, outbreak responses, or optimizing pathogen discovery. In examining the correlates of these spatial patterns, among a range of geographic, epidemiological, environmental, and social factors, mammalian biodiversity was the strongest predictor of infectious disease co-occurrence overall and for six of the seven disease classes examined, giving rise to a striking congruence between global pathogeographic and "Wallacean" zoogeographic patterns. This clear biogeographic signal suggests that infectious disease assemblages remain fundamentally constrained in their distributions by ecological barriers to dispersal or establishment, despite the homogenizing forces of globalization. Pathogeography thus provides an overarching context in which other factors promoting infectious disease emergence and spread are set.

  3. Relative Roles of CD90 and c‐Kit to the Regenerative Efficacy of Cardiosphere‐Derived Cells in Humans and in a Mouse Model of Myocardial Infarction

    Science.gov (United States)

    Cheng, Ke; Ibrahim, Ahmed; Hensley, M. Taylor; Shen, Deliang; Sun, Baiming; Middleton, Ryan; Liu, Weixin; Smith, Rachel R.; Marbán, Eduardo

    2014-01-01

    Background The regenerative potential of cardiosphere‐derived cells (CDCs) for ischemic heart disease has been demonstrated in mice, rats, pigs, and a recently completed clinical trial (CADUCEUS). CDCs are CD105+ stromal cells of intrinsic cardiac origin, but the antigenic characteristics of the active fraction remain to be defined. CDCs contain a small minority of c‐kit+ cells, which have been argued to be cardiac progenitors, and a variable fraction of CD90+ cells whose bioactivity is unclear. Methods We performed a retrospective analysis of data from the CADUCEUS trial and a prospective mouse study to elucidate the roles of c‐kit+ and CD90+ cells in human CDCs. Here, we show, surprisingly, that c‐kit expression has no relationship to CDCs' therapeutic efficacy in humans, and depletion of c‐kit+ cells does not undermine the structural and functional benefits of CDCs in a mouse model of myocardial infarction (MI). In contrast, CD90 expression negatively correlates with the therapeutic benefit of CDCs in humans (ie, higher CD90 expression associated with lower efficacy). Depletion of CD90+ cells augments the functional potency of CDCs in murine MI. CD90− CDCs secrete lower levels of inflammatory cytokines and can differentiate into cardiomyocytes in vitro and in vivo. Conclusion The majority population of CDCs (CD105+/CD90−/c‐kit−) constitutes the active fraction, both in terms of therapeutic efficacy and in the ability to undergo cardiomyogenic differentiation. The c‐kit+ fraction is neither necessary for, nor contributory to, the regenerative efficacy of CDCs. PMID:25300435

  4. Multimodality imaging of pulmonary infarction

    Energy Technology Data Exchange (ETDEWEB)

    Bray, T.J.P., E-mail: timothyjpbray@gmail.com [Department of Radiology, Papworth Hospital NHS Foundation Trust, Ermine Street, Papworth Everard, Cambridge CB23 3RE (United Kingdom); Mortensen, K.H., E-mail: mortensen@doctors.org.uk [Department of Radiology, Papworth Hospital NHS Foundation Trust, Ermine Street, Papworth Everard, Cambridge CB23 3RE (United Kingdom); University Department of Radiology, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Box 318, Cambridge CB2 0QQ (United Kingdom); Gopalan, D., E-mail: deepa.gopalan@btopenworld.com [Department of Radiology, Papworth Hospital NHS Foundation Trust, Ermine Street, Papworth Everard, Cambridge CB23 3RE (United Kingdom)

    2014-12-15

    Highlights: • A plethora of pulmonary and systemic disorders, often associated with grave outcomes, may cause pulmonary infarction. • A stereotypical infarct is a peripheral wedge shaped pleurally based opacity but imaging findings can be highly variable. • Multimodality imaging is key to diagnosing the presence, aetiology and complications of pulmonary infarction. • Multimodality imaging of pulmonary infarction together with any ancillary features often guide to early targeted treatment. • CT remains the principal imaging modality with MRI increasingly used alongside nuclear medicine studies and ultrasound. - Abstract: The impact of absent pulmonary arterial and venous flow on the pulmonary parenchyma depends on a host of factors. These include location of the occlusive insult, the speed at which the occlusion develops and the ability of the normal dual arterial supply to compensate through increased bronchial arterial flow. Pulmonary infarction occurs when oxygenation is cut off secondary to sudden occlusion with lack of recruitment of the dual supply arterial system. Thromboembolic disease is the commonest cause of such an insult but a whole range of disease processes intrinsic and extrinsic to the pulmonary arterial and venous lumen may also result in infarcts. Recognition of the presence of infarction can be challenging as imaging manifestations often differ from the classically described wedge shaped defect and a number of weighty causes need consideration. This review highlights aetiologies and imaging appearances of pulmonary infarction, utilising cases to illustrate the essential role of a multimodality imaging approach in order to arrive at the appropriate diagnosis.

  5. Acute Paraplegia with Cognitive Alterations After Bilateral Infarcts in Cerebral Small Vessel Disease

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    Francisco Javier Ros Forteza

    2017-08-01

    Full Text Available Cerebral small vessel disease (SVD affects the small arteries, arterioles, venules and capillaries in the brain and can be identified clinically and/or radiologically. We describe the case of a 71-year-old man with sporadic cerebral SVD who presented with acute paraplegia with urinary incontinence and recent cognitive impairment that developed after the occurrence of ischaemic lesions.

  6. Cystatin C: A prognostic marker after myocardial infarction in patients without chronic kidney disease

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    Leila Abid

    2016-07-01

    Conclusion: High cystatin C levels are associated with the severity of coronary artery disease in patients presenting an acute coronary syndrome and a normal renal function. Cystatin C is also associated to unfavourable cardiovascular outcomes during follow-up and appears as a strong predictor for risk of cardiovascular events and death.

  7. Free radical scavenger, edaravone, reduces the lesion size of lacunar infarction in human brain ischemic stroke

    Science.gov (United States)

    2011-01-01

    Background Although free radicals have been reported to play a role in the expansion of ischemic brain lesions, the effect of free radical scavengers is still under debate. In this study, the temporal profile of ischemic stroke lesion sizes was assessed for more than one year to evaluate the effect of edaravone which might reduce ischemic damage. Methods We sequentially enrolled acute ischemic stroke patients, who admitted between April 2003 and March 2004, into the edaravone(-) group (n = 83) and, who admitted between April 2004 and March 2005, into the edaravone(+) group (n = 93). Because, edaravone has been used as the standard treatment after April 2004 in our hospital. To assess the temporal profile of the stroke lesion size, the ratio of the area [T2-weighted magnetic resonance images (T2WI)/iffusion-weighted magnetic resonance images (DWI)] were calculated. Observations on T2WI were continued beyond one year, and observational times were classified into subacute (1-2 months after the onset), early chronic (3-6 month), late chronic (7-12 months) and old (≥13 months) stages. Neurological deficits were assessed by the National Institutes of Health Stroke Scale upon admission and at discharge and by the modified Rankin Scale at 1 year following stroke onset. Results Stroke lesion size was significantly attenuated in the edaravone(+) group compared with the edaravone(-) group in the period of early and late chronic observational stages. However, this reduction in lesion size was significant within a year and only for the small-vessel occlusion stroke patients treated with edaravone. Moreover, patients with small-vessel occlusion strokes that were treated with edaravone showed significant neurological improvement during their hospital stay, although there were no significant differences in outcome one year after the stroke. Conclusion Edaravone treatment reduced the volume of the infarct and improved neurological deficits during the subacute period, especially

  8. Cis-regulatory mutations in human disease.

    Science.gov (United States)

    Epstein, Douglas J

    2009-07-01

    Cis-acting regulatory sequences are required for the proper temporal and spatial control of gene expression. Variation in gene expression is highly heritable and a significant determinant of human disease susceptibility. The diversity of human genetic diseases attributed, in whole or in part, to mutations in non-coding regulatory sequences is on the rise. Improvements in genome-wide methods of associating genetic variation with human disease and predicting DNA with cis-regulatory potential are two of the major reasons for these recent advances. This review will highlight select examples from the literature that have successfully integrated genetic and genomic approaches to uncover the molecular basis by which cis-regulatory mutations alter gene expression and contribute to human disease. The fine mapping of disease-causing variants has led to the discovery of novel cis-acting regulatory elements that, in some instances, are located as far away as 1.5 Mb from the target gene. In other cases, the prior knowledge of the regulatory landscape surrounding the gene of interest aided in the selection of enhancers for mutation screening. The success of these studies should provide a framework for following up on the large number of genome-wide association studies that have identified common variants in non-coding regions of the genome that associate with increased risk of human diseases including, diabetes, autism, Crohn's, colorectal cancer, and asthma, to name a few.

  9. Paroxysmal atrial fibrillation during acute myocardial infarction associated with subclinical hyperthyroidism, severe three vessels coronary artery disease and elevation of prostate-specific antigen after TURP.

    Science.gov (United States)

    Patanè, Salvatore; Marte, Filippo

    2010-01-21

    Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. Paroxysmal atrial fibrillation is a frequent complication of acute myocardial infarction. It has been reported that subclinical hyperthyroidism is not associated with CHD or mortality from cardiovascular causes but it is sufficient to induce an increase in atrial fibrillation rate and increased factor X activity in patients with subclinical hyperthyroidism represents a potential hypercoagulable state. It has also been reported that serum prostate-specific antigen (PSA) decreases drastically in patients who undergo transurethral resection of the prostate(TURP). We present a case of paroxysmal atrial fibrillation during acute myocardial infarction associated with subclinical hyperthyroidism, severe three vessels coronary artery disease and elevation of PSA after TURP in a 78-year-old Italian man.

  10. The complement system in human cardiometabolic disease.

    Science.gov (United States)

    Hertle, E; Stehouwer, C D A; van Greevenbroek, M M J

    2014-10-01

    The complement system has been implicated in obesity, fatty liver, diabetes and cardiovascular disease (CVD). Complement factors are produced in adipose tissue and appear to be involved in adipose tissue metabolism and local inflammation. Thereby complement links adipose tissue inflammation to systemic metabolic derangements, such as low-grade inflammation, insulin resistance and dyslipidaemia. Furthermore, complement has been implicated in pathophysiological mechanisms of diet- and alcohol induced liver damage, hyperglycaemia, endothelial dysfunction, atherosclerosis and fibrinolysis. In this review, we summarize current evidence on the role of the complement system in several processes of human cardiometabolic disease. C3 is the central component in complement activation, and has most widely been studied in humans. C3 concentrations are associated with insulin resistance, liver dysfunction, risk of the metabolic syndrome, type 2 diabetes and CVD. C3 can be activated by the classical, the lectin and the alternative pathway of complement activation; and downstream activation of C3 activates the terminal pathway. Complement may also be activated via extrinsic proteases of the coagulation, fibrinolysis and the kinin systems. Studies on the different complement activation pathways in human cardiometabolic disease are limited, but available evidence suggests that they may have distinct roles in processes underlying cardiometabolic disease. The lectin pathway appeared beneficial in some studies on type 2 diabetes and CVD, while factors of the classical and the alternative pathway were related to unfavourable cardiometabolic traits. The terminal complement pathway was also implicated in insulin resistance and liver disease, and appears to have a prominent role in acute and advanced CVD. The available human data suggest a complex and potentially causal role for the complement system in human cardiometabolic disease. Further, preferably longitudinal studies are needed to

  11. [Management of heart diseases in pregnancy: rheumatic and congenital heart disease, myocardial infarction and post partum cardiomyopathy].

    Science.gov (United States)

    Westhoff-Bleck, M; Hilfiker-Kleiner, D; Günter, H H; Schieffer, E; Drexler, H

    2008-07-01

    Heart disease is present in 0.5-1% of all pregnancies. It is the leading non-obstetric cause of maternal mortality accounting for about 10-15% of all maternal death. Over the last decades the underlying cardiac disease has changed. Also new therapeutic options have been developed. In western industrial countries the incidence of acquired rheumatic heart disease has declined. In contrast, as a result of neonatal corrective or palliative surgery, congenital heart disease has become an increasing and challenging problem. Maternal older age and the increase in women's smoking habits amplify the likelihood of coronary artery disease. Multiple therapeutic options including percutaneous interventions are available and novel therapeutic concepts are emerging i.e. for peripartum cardiomyopathy. Management of pregnancy, labor and delivery requires accurate diagnosis of the underlying cardiac disorder. Hemodynamic changes physiologically occurring during pregnancy have a different impact depending on the type and severity of cardiac anomalies. Management of these patients requires teamwork of obstetricians, neonatologists, cardiologists, anesthetists and sometimes cardiac surgeons.

  12. Proteomic Analysis of the Peri-Infarct Area after Human Umbilical Cord Mesenchymal Stem Cell Transplantation in Experimental Stroke

    Science.gov (United States)

    He, Dongsheng; Zhang, Zhuo; Lao, Jiamin; Meng, Hailan; Han, Lijuan; Chen, Fan; Ye, Dan; Zhang, He; Xu, Yun

    2016-01-01

    Among various therapeutic approaches for stroke, treatment with human umbilical cord mesenchymal stem cells (hUC-MSCs) has acquired some promising results. However, the underlying mechanisms remain unclear. We analyzed the protein expression spectrum of the cortical peri-infarction region after ischemic stroke followed by treatment with hUC-MSCs, and found 16 proteins expressed differentially between groups treated with or without hUC-MSCs. These proteins were further determined by Gene Ontology term analysis and network with CD200-CD200R1, CCL21-CXCR3 and transcription factors. Three of them: Abca13, Grb2 and Ptgds were verified by qPCR and ELISA. We found the protein level of Abca13 and the mRNA level of Grb2 consistent with results from the proteomic analysis. Finally, the function of these proteins was described and the potential proteins that deserve to be further studied was also highlighted. Our data may provide possible underlying mechanisms for the treatment of stroke using hUC-MSCs. PMID:27699085

  13. A myocardial infarction-associated SNP at 6p24 interferes with MEF2 binding and associates with PHACTR1 expression levels in human coronary arteries

    Science.gov (United States)

    Won, Hong-Hee; Lo, Ken Sin; Do, Ron; Henderson, Christopher A.; Lavoie-St-Amour, Claire; Langlois, Simon; Rivas, Daniel; Lehoux, Stephanie; Kathiresan, Sekar; Tardif, Jean-Claude; Musunuru, Kiran; Lettre, Guillaume

    2015-01-01

    Objective Coronary artery disease (CAD), including myocardial infarction (MI), is the main cause of death in the world. Genome-wide association studies (GWAS) have identified dozens of single nucleotide polymorphisms (SNPs) associated with CAD/MI. One of the most robust CAD/MI genetic associations is with intronic SNPs in the gene PHACTR1 on chromosome 6p24. How these PHACTR1 SNPs influence CAD/MI risk, and whether PHACTR1 itself is the causal gene at the locus, is currently unknown. Approach and results Using genetic fine-mapping and DNA re-sequencing experiments, we prioritized an intronic SNP (rs9349379) in PHACTR1 as causal variant.We showed that this variant is an expression quantitative trait locus (eQTL) for PHACTR1 expression in human coronary arteries. Experiments in endothelial cell extracts confirmed that alleles at rs9349379 are differentially bound by the transcription factors MEF2. We engineered a deletion of this MEF2 binding site using CRISPR/Cas9 genome-editing methodology. Heterozygous endothelial cells carrying this deletion express 35% less PHACTR1. Finally, we found no evidence that PHACTR1 expression levels are induced when stimulating human endothelial cells with VEGF, TNFα or shear stress. Conclusions Our results establish a link between intronic SNPs in PHACTR1, MEF2 binding and transcriptional functions at the locus, PHACTR1 expression levels in coronary arteries and CAD/MI risk. Because PHACTR1 SNPs are not associated with the traditional risk factors for CAD/MI (e.g. blood lipids or pressure, diabetes), our results suggest that PHACTR1 may influence CAD/MI risk through as yet unknown mechanisms in the vascular endothelium. PMID:25838425

  14. Renal infarction secondary to ketamine abuse.

    Science.gov (United States)

    Chen, Chin-Li; Chen, Jin-Li; Cha, Tai-Lung; Wu, Sheng-Tang; Tang, Shou-Hung; Tsao, Chih-Wei; Meng, En

    2013-07-01

    Renal infarction is an uncommon condition that resulted from inadequate perfusion of the kidney and is easily missed diagnosed due to its nonspecific clinical presentations. Major risk factors for renal infarction are atrial fibrillation, previous embolism, and ischemic and valvular heart disease. Progressive decrease in renal function or even death can occur if renal infarction is not diagnosed accurately and promptly. Ketamine abuse may cause variable urinary tract injury. However, renal infarction caused by ketamine abuse has never been reported. To our knowledge, this is the first documented case of renal infarction following nasal insufflation of ketamine.

  15. Assessing the Associations Between Awareness of Myocardial Infarction Symptoms, Socioeconomic Factors, and Cardiovascular Disease Risk Factors Through Regression Models.

    Science.gov (United States)

    Tran, Phoebe; Mittleman, Murray A

    2016-11-18

    There are few studies that consider the association between awareness of symptoms of acute myocardial infarction (MI), socioeconomic factors (household income, sex, race/ethnicity, and educational attainment), and cardiovascular (CVD) risk factors. It is important to understand these associations because there is evidence that suggests that disparities in the awareness of MI symptoms lead to disparities in delays in receiving treatment and outcomes of patients with MI. The study was to determine if there are disparities in the awareness of different MI symptoms among different groups with respect to self-reported race, ethnicity, education, age, and income (i.e., various SES factors) in the presence/absence of modifiable cardiovascular disease risk factors. We utilized the 2003-2009 Behavioral Risk Factor Surveillance Survey, a nationally representative telephone-based survey, to evaluate the relationships between five common symptoms of MI, socioeconomic factors, and four major modifiable CVD risk factors. We found that being college-educated, a higher household income, making $75,000 a year or more, being female, being non-Hispanic White, having hypertension, and exercising regularly were generally associated with a higher probability of being aware of the MI symptoms evaluated in this study. Additionally, awareness that jaw/back/neck pain and feeling weak/light-headed/faint are symptoms of MI were found to be consistently lower compared to that of other MI symptoms, ranging from 50 to 75%, across all SES factors and CVD risk factors. The findings from this study can serve as a useful guide to facilitating targeted educational efforts aimed at improving awareness of MI symptoms that may ultimately reduce disparities in the outcomes of patients at risk for MI.

  16. Engineering large animal models of human disease.

    Science.gov (United States)

    Whitelaw, C Bruce A; Sheets, Timothy P; Lillico, Simon G; Telugu, Bhanu P

    2016-01-01

    The recent development of gene editing tools and methodology for use in livestock enables the production of new animal disease models. These tools facilitate site-specific mutation of the genome, allowing animals carrying known human disease mutations to be produced. In this review, we describe the various gene editing tools and how they can be used for a range of large animal models of diseases. This genomic technology is in its infancy but the expectation is that through the use of gene editing tools we will see a dramatic increase in animal model resources available for both the study of human disease and the translation of this knowledge into the clinic. Comparative pathology will be central to the productive use of these animal models and the successful translation of new therapeutic strategies.

  17. Association of genetic polymorphisms in ADH and ALDH2 with risk of coronary artery disease and myocardial infarction: a meta-analysis.

    Science.gov (United States)

    Han, Hongguang; Wang, Huishan; Yin, Zongtao; Jiang, Hui; Fang, Minhua; Han, Jingsong

    2013-09-10

    Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the major enzymes responsible for alcohol metabolism in humans. Emerging evidences have shown that functional polymorphisms in ADH and ALDH genes might play a critical role in increasing coronary artery disease (CAD) and myocardial infarction (MI) risks; however, individually published studies showed inconclusive results. The aim of this meta-analysis is to evaluate the associations between the genetic polymorphisms of ADH and ALDH genes with susceptibility to CAD and MI. A literature search was conducted on PubMed, Embase, Web of Science and Chinese BioMedical databases from inception through December 1st, 2012. Crude relative risks (RRs) with 95% confidence intervals (CIs) were calculated. Twelve case-control studies were included with a total of 9616 subjects, including 2053 CAD patients, 1436 MI patients, and 6127 healthy controls. Meta-analysis showed that mutant genotypes (GA+AA) of the rs671 polymorphism in the ALDH2 gene were associated with increased risk of both CAD and MI (CAD: RR=1.20, 95%CI: 1.03-1.40, P=0.021; MI: RR=1.32, 95%CI: 1.11-1.57, P=0.002). However, there were no significant associations of ADH genetic polymorphisms to CAD and MI risks (CAD: RR=0.92, 95%CI: 0.73-1.15, P=0.445; MI: RR=0.93, 95%CI: 0.84-1.03, P=0.148). In conclusion, this meta-analysis provides strong evidence that ALDH2 rs671 polymorphism may be associated with increased risks of CAD and MI. However, further studies are still needed to accurately determine whether ADH genetic polymorphisms are associated with susceptibility to CAD and MI.

  18. Effect of recombinant human brain natriuretic peptide-assisted interventional treatment on prognosis of acute myocardial infarction patients complicated with cardiogenic shock

    Institute of Scientific and Technical Information of China (English)

    Xi-Zhou Chen

    2016-01-01

    Objective:To analyze the effect of recombinant human brain natriuretic peptide-assisted interventional treatment on prognosis of acute myocardial infarction patients complicated with cardiogenic shock.Methods: A total of 112 cases of inpatients treated in Cardiology Department of our hospital from March 2013 to March 2015 were selected, all of whom had acute myocardial infarction within 12 hours of onset and received direct PCI treatment. They were divided into observation group and control group according to random number table, each group with 56 cases, control group received conventional interventional treatment and observation group received recombinant human brain natriuretic peptide-assisted interventional treatment. Then differences of regional myocardial deformability, myocardial enzyme spectrum indicators, brain natriuretic peptide and inflammatory factors, blood sugar and stress hormones as well as myocardial infarction prognosis-associated indexes, etc, between two groups after treatment were compared.Results:After treatment, LVEF, SRs, SRe and Sra levels of observation group were higher than those of control group, WMSI level was lower than that of control group; serum myocardial enzyme spectrum indicators CK, CK-MB, AST and LDH values were lower than those of control group; serum BNP, CRP, TNF-α and IL-6 levels were lower than those of control group; serum cortisol, growth hormone and glucagon levels were lower than those of control group, insulin level was higher than that of control group; FT3 and IGF-1 levels were higher than those of control group, sPLA2 and Hcy levels were lower than those of control group.Conclusion: Recombinant human brain natriuretic peptide-assisted interventional treatment for acute myocardial infarction patients complicated with cardiogenic shock can reduce myocardial function injury, protect normal myocardial function and optimize patients' long-term prognosis; it has active clinical significance.

  19. The effect of tobacco control measures during a period of rising cardiovascular disease risk in India: a mathematical model of myocardial infarction and stroke.

    Directory of Open Access Journals (Sweden)

    Sanjay Basu

    Full Text Available BACKGROUND: We simulated tobacco control and pharmacological strategies for preventing cardiovascular deaths in India, the country that is expected to experience more cardiovascular deaths than any other over the next decade. METHODS AND FINDINGS: A microsimulation model was developed to quantify the differential effects of various tobacco control measures and pharmacological therapies on myocardial infarction and stroke deaths stratified by age, gender, and urban/rural status for 2013 to 2022. The model incorporated population-representative data from India on multiple risk factors that affect myocardial infarction and stroke mortality, including hypertension, hyperlipidemia, diabetes, coronary heart disease, and cerebrovascular disease. We also included data from India on cigarette smoking, bidi smoking, chewing tobacco, and secondhand smoke. According to the model's results, smoke-free legislation and tobacco taxation would likely be the most effective strategy among a menu of tobacco control strategies (including, as well, brief cessation advice by health care providers, mass media campaigns, and an advertising ban for reducing myocardial infarction and stroke deaths over the next decade, while cessation advice would be expected to be the least effective strategy at the population level. In combination, these tobacco control interventions could avert 25% of myocardial infarctions and strokes (95% CI: 17%-34% if the effects of the interventions are additive. These effects are substantially larger than would be achieved through aspirin, antihypertensive, and statin therapy under most scenarios, because of limited treatment access and adherence; nevertheless, the impacts of tobacco control policies and pharmacological interventions appear to be markedly synergistic, averting up to one-third of deaths from myocardial infarction and stroke among 20- to 79-y-olds over the next 10 y. Pharmacological therapies could also be considerably more potent

  20. Underutilization of aspirin in people living with human immunodeficiency virus at increased risk for acute myocardial infarction: Systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Stella Pak

    2017-01-01

    Full Text Available Context: With the increased availability of potent combination antiretroviral therapies, the life expectancy of people living with human immunodeficiency virus (PLHIV has greatly increased. This rapid improvement in lifespan has served as a catalyst for a paradigm shift in human immunodeficiency virus (HIV care. The focus of HIV care models has transitioned from the sole treatment of acute opportunistic infections to comprehensive management of chronic diseases, such as cardiovascular disease (CVD. Multiple studies have demonstrated that PLHIV are 50% more likely to develop acute myocardial infarction (AMI, compared to the general population. Cardiovascular risk prevention is becoming an essential component of the overarching HIV treatment plan. Aims: This meta-analysis aims to compare the rate of aspirin use for AMI prevention in indicated patients between PLHIV and general population. Methods: PubMed, EMBASE, Web of Science, Cochrane Library, CINAHL, and MEDLINE databases were used to identify observational cohort trials. Studies were assessed by two reviewers for inclusion criteria. Two separate random-effects meta-analyses' models were performed using the DerSimonian and Laird method. Heterogeneity was assessed using the I2 value. Meta-regression with study level variables was used to explore potential sources of heterogeneity. The funnel-plot-based trim-and-fill method was applied to detect and adjust for potential publication bias. Statistical tests were two-sided and P< 0.05 was considered statistically significant. Results: A total of 13 studies were included for analysis. In these trials, 30.4% of PLHIV with increased risk for coronary heart disease (CHD used aspirin for AMI prevention, compared to 36.9% of patients at risk of CHD in the general population. Conclusions: The results of this meta-analysis provide evidence that aspirin is underutilized in both PLHIV and the general population across broad geographical zones. Aspirin use

  1. Culprit vessel only versus“one-week”staged percutaneous coronary intervention for multivessel disease in patients presenting with ST-segment elevation myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Li-Xiang MA; Zhen-Hua LU; Le WANG; Xin DU; Chang-Sheng MA

    2015-01-01

    Objective To explore the impact of a“one-week”staged multivessel percutaneous coronary intervention (PCI) versus culprit-only PCI on deaths and major adverse cardiac events (MACE). Methods We retrospectively analyzed 447 patients with multivessel disease who experienced a ST-segment elevation myocardial infarction (STEMI) within 12 h before undergoing PCI between July 26, 2008 and Septem-ber 25, 2011. After completion of PCI in the infarct artery, 201 patients still in the hospital agreed to undergo PCI in non-infarct arteries with more than 70%stenosis for a“one-week”staged multivessel PCI. A total of 246 patients only received intervention for the culprit vessel. Follow-up ended on September 9, 2014. This study examined the differences in deaths from any cause (i.e., cardiac and noncardiac) and MACE between the two treatment groups. Results Compared to a culprit-only PCI treatment approach, the“one-week”staged multivessel PCI was strongly associated with greater benefits for 55-month all cause death [41 (16.7%) vs.13 (6.5%), P=0.004] and MACE [82 (33.3%) vs. 40 (19.9%), P=0.002] rates. In addition, there were significant differences in the number of myocardial infarctions [43 (17.5%) vs. 20 (10.0%), P=0.023], coronary-artery bypass grafting [CABG;20 (8.1%) vs. 6 (3.0%), P=0.021], and PCI [31 (12.6%) vs. 12 (6.0%), P=0.018]. Patients undergoing culprit-only PCI compared to“one-week”PCI had the same number of stent thrombosis events [7 (2.8%) vs. 3 (1.5%), P=0.522]. Conclusions Compared to a culprit-only PCI treatment approach,“one-week”staged multi-vessel PCI was a safe and effective selection for STEMI and multi-vessel PCI.

  2. Micro RNAs: Important Regulators in Acute Myocardial Infarction in Humans%微小RNA:人类急性心肌梗死的重要调控因子

    Institute of Scientific and Technical Information of China (English)

    娄宇

    2012-01-01

    Micro RNA (miRNA) are short about 19 -22 nucleotides long noncoding RNA. They were isolated from plasmas from well-characterized patients with varying degrees of cardiac damage; acute myocardial infarction. More and more research show miRNA are novel biomarkers for cardiovascular diseases. Disease of the myocardial infarction i?the most common cardiovascular defect and causes of adult morbidity and mortality. An early diagnosis may ensure immediate initiation of reperfusion therapy to potentially reduce the death rate. To compare the plasma of miRNA between healthy people and patients with acute myocardial infarction, it can be found that the plasma level of miRNA in patients with acute myocardial infarction are raised significantly.%微小RNA (miRNAs)是短的大约19-22个核苷酸长的非编码RNA,它具有调节多种细胞的作用.研究发现miRNA存在于人类血液中,血液中的miRNA可能成为诊断疾病的新的生物学标志物.急性心肌梗死是世界上发病率及死亡率极高的疾病,早期正确的诊断可以确保立即开始再灌注治疗,从而减少死亡率.对照急性心肌梗死患者和健康志愿者血浆中miRNA水平,可发现miRNA在心肌梗死患者中组明显升高.

  3. Modeling human muscle disease in zebrafish

    OpenAIRE

    Guyon, Jeffrey R.; Steffen, Leta S; Howell, Melanie H.; Pusack, Timothy J; Lawrence, Chris; Kunkel, Louis M

    2007-01-01

    Modeling human muscle disease in zebrafish correspondence: Corresponding author. Children's Hospital Boston, Enders Bldg, Rm 570, 300 Longwood Ave Boston, MA 02115. Tel.: +1 617 355 7576. (Kunkel, Louis M.) (Kunkel, Louis M.) Program in Genomics and Howard Hughes Medical Institute at Children's Hospital Boston - Boston--> , MA 02115--> - UNITED STATES (Guyon, Jeffrey R.) Program in Genomics a...

  4. Donepezil, anti-Alzheimer's disease drug, prevents cardiac rupture during acute phase of myocardial infarction in mice.

    Directory of Open Access Journals (Sweden)

    Mikihiko Arikawa

    Full Text Available BACKGROUND: We have previously demonstrated that the chronic intervention in the cholinergic system by donepezil, an acetylcholinesterase inhibitor, plays a beneficial role in suppressing long-term cardiac remodeling after myocardial infarction (MI. In comparison with such a chronic effect, however, the acute effect of donepezil during an acute phase of MI remains unclear. Noticing recent findings of a cholinergic mechanism for anti-inflammatory actions, we tested the hypothesis that donepezil attenuates an acute inflammatory tissue injury following MI. METHODS AND RESULTS: In isolated and activated macrophages, donepezil significantly reduced intra- and extracellular matrix metalloproteinase-9 (MMP-9. In mice with MI, despite the comparable values of heart rate and blood pressure, the donepezil-treated group showed a significantly lower incidence of cardiac rupture than the untreated group during the acute phase of MI. Immunohistochemistry revealed that MMP-9 was localized at the infarct area where a large number of inflammatory cells including macrophages infiltrated, and the expression and the enzymatic activity of MMP-9 at the left ventricular infarct area was significantly reduced in the donepezil-treated group. CONCLUSION: The present study suggests that donepezil inhibits the MMP-9-related acute inflammatory tissue injury in the infarcted myocardium, thereby reduces the risk of left ventricular free wall rupture during the acute phase of MI.

  5. [Human prion diseases in the Czech Republic].

    Science.gov (United States)

    Rohan, Z; Rusina, R; Marešová, M; Matěj, R

    2015-09-01

    Human prion diseases are a group of very rare diseases with a unique pathogenesis and, due to an inauspicious prognosis and unavailability of therapy, with fatal consequences. The etiopathogenetic background is the presence of pathologically misfolded prion protein, highly resistant to denaturation, the aggregation and presence of which in the brain tissue causes irreversible neuronal damage. The most frequent prion disease in humans is Creutzfeldt-Jakob disease (CJD) which occurs in sporadic, hereditary/familial, or acquired/infectious/iatrogenic forms. A new form of CJD, variant CJD, is considered to be linked to dietary exposure to beef products from cattle infected with bovine spongiform encephalopathy (BSE) and to infection via blood transfusion. The clinical picture of these diseases is characterized by a rapidly progressing dementia, cerebellar and extrapyramidal symptoms, and rather specific MRI, EEG, and CSF findings. Clinically, the diagnosis is described as possible or probable prion disease and needs to be confirmed by neuropathological or immunological investigation of the brain tissue. Epidemiological data from the Czech Republic spanning the last decade are presented.

  6. Patients With and Without Diabetes Without Significant Angiographic Coronary Artery Disease Have the Same Risk of Myocardial Infarction in a Real-World Population Receiving Appropriate Prophylactic Treatment

    DEFF Research Database (Denmark)

    Olesen, Kevin K W; Madsen, Morten; Egholm, Gro

    2017-01-01

    OBJECTIVE: The risk of myocardial infarction (MI) in patients with diabetes is greater than for patients without diabetes. Consequently, prophylactic treatment is recommended for patients with diabetes and risk factors for ischemic heart disease. We aimed to estimate the risk of adverse cardiac...... without CAD were more often treated with statins (75.3% vs. 46.0%) and aspirin (65.7% vs. 52.7%) than patients without diabetes and CAD. CONCLUSIONS: In a real-world population, patients with diabetes with high rates of statin and aspirin treatment had the same risk of cardiovascular events as patients...

  7. Significance of calcific valvular heart disease in /sup 99m/Tc pyrophosphate myocardial infarction scanning: radiographic, scintigraphic, and pathological correlation

    Energy Technology Data Exchange (ETDEWEB)

    Jengo, J.A.; Mena, I.; Joe, S.H.; Criley, J.M.

    1977-08-01

    Technetium-99m pyrophosphate (PP/sub i/) is currently considered the best scanning agent for the diagnosis of acute myocardial infarction. False-positive scans have been reported in association with unstable angina, alcoholic cardiomyopathy, and ventricular aneurysms. In this study, 86 percent of patients (12/14) with either calcific aortic or mitral valvular heart disease had positive PP/sub i/ cardiac scintiscans and the location of the PP/sub i/ uptake was limited to the calcific valve in all (9/9) of the patients who underwent valve replacement surgery. Six patients with valvular disease without radiologic evidence of calcium had negative PP/sub i/ heart images. Three of these patients had surgical valve replacement, and in none was there increased uptake in the resected valve. Seventy-five percent of the patients with calcified aortic valves had localization of the PP/sub i/ activity to the area of the aortic valve, whereas 50 percent of the patients with calcified mitral valves showed a diffuse pattern of uptake on the cardiac image. In vitro demonstration of increased radioactivity in surgically removed cardiac valves warrants the conclusion that Tc-99m PP/sub i/ is taken up by calcified heart valves. We conclude that while PP/sub i/ heart scanning is a sensitive indicator of acute myocardial infarction, false-positive scans can occur in the presence of calcific valvular disease, due to localization of PP/sub i/ in the calcified portion of the valve.

  8. Human lagochilascariasis-A rare helminthic disease.

    Directory of Open Access Journals (Sweden)

    Dulcinea Maria Barbosa Campos

    2017-06-01

    Full Text Available Lagochilascariasis is a parasitic disease caused by a helminth of the order Ascaroidea, genus Lagochilascaris that comprises 6 species, among which only Lagochilascaris minor Leiper, 1909, is implicated in the human form of the disease. It is remarkable that the majority of cases of human lagochilascariasis in the Americas have been reported in Brazil. The natural definitive hosts of this parasite seem to be wild felines and canines. Lagochilascariasis is mostly a chronic human disease that can persist for several years, in which the parasite burrows into the subcutaneous tissues of the neck, paranasal sinuses, and mastoid. L. minor exhibits remarkable ability to migrate through the tissues of its hosts, destroying even bone tissue. Fatal cases have been described in which the parasite was found in the lungs or central nervous system. Treatment is often palliative, with recurrence of lesions. This paper summarizes the main features of the disease and its etiologic agent, including prevalence, life cycle, clinical course, and treatment.

  9. Heartworm disease in animals and humans.

    Science.gov (United States)

    McCall, John W; Genchi, Claudio; Kramer, Laura H; Guerrero, Jorge; Venco, Luigi

    2008-01-01

    Heartworm disease due to Dirofilaria immitis continues to cause severe disease and even death in dogs and other animals in many parts of the world, even though safe, highly effective and convenient preventatives have been available for the past two decades. Moreover, the parasite and vector mosquitoes continue to spread into areas where they have not been reported previously. Heartworm societies have been established in the USA and Japan and the First European Dirofilaria Days (FEDD) Conference was held in Zagreb, Croatia, in February of 2007. These organizations promote awareness, encourage research and provide updated guidelines for the diagnosis, treatment and prevention of heartworm disease. The chapter begins with a review of the biology and life cycle of the parasite. It continues with the prevalence and distribution of the disease in domestic and wild animals, with emphasis on more recent data on the spreading of the disease and the use of molecular biology techniques in vector studies. The section on pathogenesis and immunology also includes a discussion of the current knowledge of the potential role of the Wolbachia endosymbiont in inflammatory and immune responses to D. immitis infection, diagnostic use of specific immune responses to the bacteria, immunomodulatory activity and antibiotic treatment of infected animals. Canine, feline and ferret heartworm disease are updated with regard to the clinical presentation, diagnosis, prevention, therapy and management of the disease, with special emphasis on the recently described Heartworm Associated Respiratory Disease (HARD) Syndrome in cats. The section devoted to heartworm infection in humans also includes notes on other epizootic filariae, particularly D. repens in humans in Europe. The chapter concludes with a discussion on emerging strategies in heartworm treatment and control, highlighting the potential role of tetracycline antibiotics in adulticidal therapy.

  10. Comparison of human adipose-derived stem cells and bone marrow-derived stem cells in a myocardial infarction model

    DEFF Research Database (Denmark)

    Rasmussen, Jeppe; Frøbert, Ole; Holst-Hansen, Claus

    2014-01-01

    Background: Treatment of myocardial infarction with bone marrow-derived mesenchymal stem cells and recently also adipose-derived stem cells has shown promising results. In contrast to clinical trials and their use of autologous bone marrow-derived cells from the ischemic patient, the animal...... myocardial infarction models are often using young donors and young, often immune-compromised, recipient animals. Our objective was to compare bone marrow-derived mesenchymal stem cells with adipose-derived stem cells from an elderly ischemic patient in the treatment of myocardial infarction, using a fully...... grown non-immunecompromised rat model. Methods: Mesenchymal stem cells were isolated from adipose tissue and bone marrow and compared with respect to surface markers and proliferative capability. To compare the regenerative potential of the two stem cell populations, male Sprague-Dawley rats were...

  11. Unsolved issues related to human mitochondrial diseases.

    Science.gov (United States)

    Lombès, Anne; Auré, Karine; Bellanné-Chantelot, Christine; Gilleron, Mylène; Jardel, Claude

    2014-05-01

    Human mitochondrial diseases, defined as the diseases due to a mitochondrial oxidative phosphorylation defect, represent a large group of very diverse diseases with respect to phenotype and genetic causes. They present with many unsolved issues, the comprehensive analysis of which is beyond the scope of this review. We here essentially focus on the mechanisms underlying the diversity of targeted tissues, which is an important component of the large panel of these diseases phenotypic expression. The reproducibility of genotype/phenotype expression, the presence of modifying factors, and the potential causes for the restricted pattern of tissular expression are reviewed. Special emphasis is made on heteroplasmy, a specific feature of mitochondrial diseases, defined as the coexistence within the cell of mutant and wild type mitochondrial DNA molecules. Its existence permits unequal segregation during mitoses of the mitochondrial DNA populations and consequently heterogeneous tissue distribution of the mutation load. The observed tissue distributions of recurrent human mitochondrial DNA deleterious mutations are diverse but reproducible for a given mutation demonstrating that the segregation is not a random process. Its extent and mechanisms remain essentially unknown despite recent advances obtained in animal models.

  12. The role of formins in human disease.

    Science.gov (United States)

    DeWard, Aaron D; Eisenmann, Kathryn M; Matheson, Stephen F; Alberts, Arthur S

    2010-02-01

    Formins are a conserved family of proteins that play key roles in cytoskeletal remodeling. They nucleate and processively elongate non-branched actin filaments and also modulate microtubule dynamics. Despite their significant contributions to cell biology and development, few studies have directly implicated formins in disease pathogenesis. This review highlights the roles of formins in cell division, migration, immunity, and microvesicle formation in the context of human disease. In addition, we discuss the importance of controlling formin activity and protein expression to maintain cell homeostasis.

  13. Human papillomavirus-associated diseases and cancers

    Institute of Scientific and Technical Information of China (English)

    Lan Yang; Jianbo Zhu Co-first author; Xiaoyue Song; Yan Qi; Xiaobin Cui; Feng Li 

    2015-01-01

    Human papilomaviruses (HPVs) have been detected in cervical cancer cels and skin papiloma cels, which have a variety of types, including low-risk and high-risk types. HPV genome replication requires the host cel’s DNA synthesis machinery, and HPVs encode proteins that maintain diferentiated epithelial cels in a replication-competent state. HPV types are tissue-specific and generaly produce diferent types of le-sions, either benign or malignant. This review examines diferent HPV types and their associated diseases and presents therapeutic options for the treatment of HPV-positive diseases.

  14. [Human hantavirus diseases - still neglected zoonoses?].

    Science.gov (United States)

    Vrbovská, V; Chalupa, P; Straková, P; Hubálek, Z; Rudolf, I

    2015-10-01

    Hantavirus disease is the most common rodent-borne viral infection in the Czech Republic, with a mean annual incidence of 0.02 cases per 100 000 population and specific antibodies detected in 1% of the human population. Four hantaviruses (Puumala, Dobrava-Belgrade, Tula, and Seewis) circulate in this country, of which Puumala virus (responsible for a mild form of hemorrhagic fever with renal syndrome called nephropathia epidemica) and Dobrava-Belgrade virus (causing haemorrhagic fever with renal syndrome) have been proven to cause human disease. The aim of this study is to provide a comprehensive review of the hantaviruses occurring in the Czech Republic, based on the literature published during the past three decades, including their geographical distribution and clinical symptoms. The recent detection of Tula virus in an immunocompromised person as well as reports of Seoul virus infections in Europe highlight the possible emergence of neglected hantavirus infections in the foreseeable future.

  15. Molecular biology of human muscle disease

    Energy Technology Data Exchange (ETDEWEB)

    Dunne, P.W.; Epstein, H.F. (Baylor Coll. of Medicine, Houston, TX (United States))

    1991-01-01

    The molecular revolution that is transforming the entire biomedical field has had far-reaching impact in its application to inherited human muscle disease. The gene for Duchenne muscular dystrophy was one of the first cloned without knowledge of the defective protein product. This success was based upon the availability of key chromosomal aberrations that provided molecular landmarks for the disease locus. Subsequent discoveries regarding the mode of expression for this gene, the structure and localization of its protein product dystrophin, and molecular diagnosis of affected and carrier individuals constitute a paradigm for investigation of human genetics. Finding the gene for myotonic muscular dystrophy is requiring the brute force approach of cloning several million bases of DNA, identifying expressed sequences, and characterizing candidate genes. The gene that causes hypertrophic cardiomyopathy has been found serendipitously to be one of the genetic markers on chromosome 14, the {beta} myosin heavy chain.

  16. N-epsilon-(carboxymethyl)lysine depositions in intramyocardial blood vessels in human and rat acute myocardial infarction - A predictor or reflection of infarction?

    NARCIS (Netherlands)

    A. Baidoshvili; P.A.J. Krijnen; K. Kupreishvili; C. Ciurana; W. Bleeker; R. Nijmeijer; C.A. Visser; F.C. Visser; C.J.L.M. Meijer; W. Stooker; L. Eijsman; V.W.M. van Hinsbergh; C.E. Hack; H.W.M. Niessen; C.G. Schalkwijk

    2006-01-01

    Objective - Advanced glycation end products ( AGEs), such as N-epsilon-( carboxymethyl) lysine ( CML), are implicated in vascular disease. We previously reported increased CML accumulation in small intramyocardial blood vessels in diabetes patients. Diabetes patients have an increased risk for acute

  17. Spontaneous gastric ulcer perforation and acute spleen infarction caused by invasive gastric and splenic mucormycosis.

    Science.gov (United States)

    Enani, Mushira Abdulaziz; Alharthi, Bandar N; Dewanjee, Nancy; Bhat, Nadeem A; Fagih, Mosa

    2014-07-01

    Mucormycosis is a rare life-threatening fungal infection mostly affecting immunocompromised hosts. The main categories of human disease with the Mucorales are sinusitis/rhinocerebral, pulmonary, cutaneous/subcutaneous, gastrointestinal and disseminated disease. Other disease states occur with a much lower frequency and include cystitis, vaginitis; external otitis and allergic disease. We report a diabetic patient with comorbidities, who developed gastric perforation clinically indistinguishable from perforated peptic ulcer due to invasive gastric mucormycosis complicated by spleen infarction.

  18. Spontaneous gastric ulcer perforation and acute spleen infarction caused by invasive gastric and splenic mucormycosis

    Directory of Open Access Journals (Sweden)

    Mushira Abdulaziz Enani

    2014-01-01

    Full Text Available Mucormycosis is a rare life-threatening fungal infection mostly affecting immunocompromised hosts. The main categories of human disease with the Mucorales are sinusitis/rhinocerebral, pulmonary, cutaneous/subcutaneous, gastrointestinal and disseminated disease. Other disease states occur with a much lower frequency and include cystitis, vaginitis; external otitis and allergic disease. We report a diabetic patient with comorbidities, who developed gastric perforation clinically indistinguishable from perforated peptic ulcer due to invasive gastric mucormycosis complicated by spleen infarction.

  19. The role of chemerin in human disease

    Directory of Open Access Journals (Sweden)

    Magdalena Stojek

    2017-02-01

    Full Text Available Adipose tissue is not merely a storage depot of triacylglycerols but also a major endocrine organ. Its cells, including adipocytes, synthesize and secrete a range of biologically active molecules termed adipokines. Adipokines that display the properties of cytokines are often called adipocytokines. In recent years there has been increasing interest in a new adipokine called chemerin. Chemerin is a protein synthesized mostly by the adipose tissue and the liver as inactive pre-pro-chemerin. After the intracellular hydrolytic cutting off of the 20-amino-acid N-terminal polypeptide, it is secreted into the bloodstream as inactive pro-chemerin. Biologically active chemerin is then derived from pro-chemerin after cleavage of the C-terminal fragment by serum proteases involved in inflammation, coagulation and fibrinolysis. Proteolytic cleavage leads to formation of several chemerin-derived peptides, both biologically active (often with opposing functions and inactive.Within the last decade, there has been a growing number of publications regarding the role of chemerin in human disease. It seems to be implicated in the inflammatory response, metabolic syndrome, cardiovascular disease and alimentary tract disorders. The article presents the most recent information on the role of chemerin in human disease, and specifically alimentary tract disorders. The available evidence suggests that chemerin is an important link between adipose tissue mass, metabolic processes, the immune system and inflammation, and therefore plays a major role in human pathophysiology.

  20. Genes of periodontopathogens expressed during human disease.

    Science.gov (United States)

    Song, Yo-Han; Kozarov, Emil V; Walters, Sheila M; Cao, Sam Linsen; Handfield, Martin; Hillman, Jeffrey D; Progulske-Fox, Ann

    2002-12-01

    Since many bacterial genes are environmentally regulated, the screening for virulence-associated factors using classical genetic and molecular biology approaches can be biased under laboratory growth conditions of a given pathogen, because the required conditions for expression of many virulence factors may not occur during in vitro growth. Thus, technologies have been developed during the past several years to identify genes that are expressed during disease using animal models of human disease. However, animal models are not always truly representative of human disease, and with many pathogens, there is no appropriate animal model. A new technology, in vivo-induced antigen technology (IVIAT) was thus engineered and tested in our laboratory to screen for genes of pathogenic organisms induced specifically in humans, without the use of animal or artificial models of infection. This technology uses pooled sera from patients to probe for genes expressed exclusively in vivo (or ivi, in vivo-induced genes). IVIAT was originally designed for the study of Actinobacillus actinomycetemcomitans pathogenesis, but we have now extended it to other oral pathogens including Porphyromonas gingivalis. One hundred seventy-one thousand (171,000) clones from P. gingivalis strain W83 were screened and 144 were confirmed positive. Over 300,000 A. actinomycetemcomitans clones were probed, and 116 were confirmed positive using a quantitative blot assay. MAT has proven useful in identifying previously unknown in vivo-induced genes that are likely involved in virulence and are thus excellent candidates for use in diagnostic : and therapeutic strategies, including vaccine design.

  1. Ultra-Sensitive C-Reactive Protein (US-CRP) in Patients With Periodontal Disease and Risk of Acute Myocardial Infarction

    Science.gov (United States)

    Uriza, Catalina Latorre; Arregoces, Francina Escobar; Porras, Juliana Velosa; Camargo, Maria Beatriz Ferro; Morales, Alvaro Ruiz

    2011-01-01

    Background The purpose of this study was to determine if the US-CRP values associated with periodontal disease are risk markers for Acute Myocardial Infarction (AMI) and to determine if the US-CRP levels associated with recent AMI are higher in patients with Periodontal disease. Methods In order to meet the goal of the study, a case control study design was conducted. The analysis sample consisted of 401 adults (30 - 75 years old), living in Bogota D.C., Colombia, from the Hospital Universitario San Ignacio, the Faculty of Dentistry at the Pontificia Universidad Javeriana, and the Fundacion Cardio Infantil. Patients with current infections, antibiotic use in the last 3 months, periodontal treatment at least six months before the baseline of this study, mouth ulcerations caused by any type of prosthesis, candidiasis, stomatitis, or less than 7 teeth in mouth were excluded. Periodontal examination for the case group and the control group was conducted by three previously calibrated examiners. Periodontal disease was diagnosed by the presence of bleeding on probing and attachment loss. The Chronic Periodontitis diagnosis was confirmed with these clinical signs, according to the 1999 Armitage classification. The assessment of the US-CRP was performed using the IMMULITE method containing one monoclonal and one polyclonal anti-CRP antibody. This method provides a measurement range of 0.1 - 500 mg/L. Statistical analysis of variables was performed with OR and confidence intervals. A multivariate analysis was performed to determine the association between the US-CRP increase, periodontal disease and acute myocardial infarction, adjusting for smoking and other confounding factors identified in the analysis. Results The study population was constituted by 401 patients, 56.1% (225) males, with a mean age of 52.6. When groups were compared it was observed that, in those patients with AMI and chronic severe or moderate periodontitis, 24.2% had HDL-C values lower than 40 mg

  2. Mitochondria: impaired mitochondrial translation in human disease.

    Science.gov (United States)

    Boczonadi, Veronika; Horvath, Rita

    2014-03-01

    Defects of the mitochondrial protein synthesis cause a subgroup of mitochondrial diseases, which are usually associated with decreased activities of multiple respiratory chain (RC) enzymes. The clinical presentations of these disorders are often disabling, progressive or fatal, affecting the brain, liver, skeletal muscle, heart and other organs. Currently there are no effective cures for these disorders and treatment is at best symptomatic. The diagnosis in patients with multiple respiratory chain complex defects is particularly difficult because of the massive number of nuclear genes potentially involved in intra-mitochondrial protein synthesis. Many of these genes are not yet linked to human disease. Whole exome sequencing rapidly changed the diagnosis of these patients by identifying the primary defect in DNA, and preventing the need for invasive and complex biochemical testing. Better understanding of the mitochondrial protein synthesis apparatus will help us to explore disease mechanisms and will provide clues for developing novel therapies.

  3. Genetic engineering of mesenchymal stem cells and its application in human disease therapy.

    Science.gov (United States)

    Hodgkinson, Conrad P; Gomez, José A; Mirotsou, Maria; Dzau, Victor J

    2010-11-01

    The use of stem cells for tissue regeneration and repair is advancing both at the bench and bedside. Stem cells isolated from bone marrow are currently being tested for their therapeutic potential in a variety of clinical conditions including cardiovascular injury, kidney failure, cancer, and neurological and bone disorders. Despite the advantages, stem cell therapy is still limited by low survival, engraftment, and homing to damage area as well as inefficiencies in differentiating into fully functional tissues. Genetic engineering of mesenchymal stem cells is being explored as a means to circumvent some of these problems. This review presents the current understanding of the use of genetically engineered mesenchymal stem cells in human disease therapy with emphasis on genetic modifications aimed to improve survival, homing, angiogenesis, and heart function after myocardial infarction. Advancements in other disease areas are also discussed.

  4. Ser um miR-126 and miR-146a levels in patients with acute cerebral infarction and their relationship with sever ity of the disease

    Directory of Open Access Journals (Sweden)

    Xiao-Yan Zhu

    2016-09-01

    Full Text Available Objective: To analyze the serum levels of miR-126, miR-146a and its relationship with infarction area, severity of disease and inflammatory reaction degree in patients with acute cerebral infarction (ACI. Methods: A total of 75 cases with ACI treated in our hospital from April 2014 to October 2015 and 80 healthy cases were respectively selected as ACI group and control group for retrospective study. Patients' clinical data were collected, and the serum levels of miR-126, miR-146a, tumor necrosis factor-a (TNF-a, interleukin-1b (IL-1b and IL-6 were detected. Results: Serum contents of miR-126 (0.286 ± 0.078 vs. 1.000 ± 0.169 and miR-146a (0.337 ± 0.084 vs. 1.000 ± 0.158 in patients of ACI group were significantly lower than those of control group. Contents of IL-1b [(68.4 ± 10.3 vs. (22.7 ± 5.8 ng/L], TNFa [(126.9 ± 22.4 vs. (49.6 ± 8.4 ng/L] and IL-6 [(89.3 ± 14.7 vs. (34.8 ± 5.9 ng/L] were obviously higher than those of control group. The bigger the infarction area was, the more severer the degree of nerve defect could be. The lower the serum levels of miR-126, miR-146a were, the higher the levels of TNF-a, IL-1b, IL-6 could be. Levels of miR-126 and miR-146a were negative correlation with levels of TNF-a, IL-1b and IL-6. Conclusions: An abnormal decrease in serum levels of miR-126 and miR-146a in patients with ACI was closely related to the severity of disease. Through regulating the generation of inflammatory factors TNF-a, IL-1b and IL-6, miR-126 and miR-146a may get involved in the changes of cerebral infarction condition.

  5. Humanized Mouse Model of Ebola Virus Disease Mimics the Immune Responses in Human Disease.

    Science.gov (United States)

    Bird, Brian H; Spengler, Jessica R; Chakrabarti, Ayan K; Khristova, Marina L; Sealy, Tara K; Coleman-McCray, JoAnn D; Martin, Brock E; Dodd, Kimberly A; Goldsmith, Cynthia S; Sanders, Jeanine; Zaki, Sherif R; Nichol, Stuart T; Spiropoulou, Christina F

    2016-03-01

    Animal models recapitulating human Ebola virus disease (EVD) are critical for insights into virus pathogenesis. Ebola virus (EBOV) isolates derived directly from human specimens do not, without adaptation, cause disease in immunocompetent adult rodents. Here, we describe EVD in mice engrafted with human immune cells (hu-BLT). hu-BLT mice developed EVD following wild-type EBOV infection. Infection with high-dose EBOV resulted in rapid, lethal EVD with high viral loads, alterations in key human antiviral immune cytokines and chemokines, and severe histopathologic findings similar to those shown in the limited human postmortem data available. A dose- and donor-dependent clinical course was observed in hu-BLT mice infected with lower doses of either Mayinga (1976) or Makona (2014) isolates derived from human EBOV cases. Engraftment of the human cellular immune system appeared to be essential for the observed virulence, as nonengrafted mice did not support productive EBOV replication or develop lethal disease. hu-BLT mice offer a unique model for investigating the human immune response in EVD and an alternative animal model for EVD pathogenesis studies and therapeutic screening.

  6. Human Genome Sequencing in Health and Disease

    Science.gov (United States)

    Gonzaga-Jauregui, Claudia; Lupski, James R.; Gibbs, Richard A.

    2013-01-01

    Following the “finished,” euchromatic, haploid human reference genome sequence, the rapid development of novel, faster, and cheaper sequencing technologies is making possible the era of personalized human genomics. Personal diploid human genome sequences have been generated, and each has contributed to our better understanding of variation in the human genome. We have consequently begun to appreciate the vastness of individual genetic variation from single nucleotide to structural variants. Translation of genome-scale variation into medically useful information is, however, in its infancy. This review summarizes the initial steps undertaken in clinical implementation of personal genome information, and describes the application of whole-genome and exome sequencing to identify the cause of genetic diseases and to suggest adjuvant therapies. Better analysis tools and a deeper understanding of the biology of our genome are necessary in order to decipher, interpret, and optimize clinical utility of what the variation in the human genome can teach us. Personal genome sequencing may eventually become an instrument of common medical practice, providing information that assists in the formulation of a differential diagnosis. We outline herein some of the remaining challenges. PMID:22248320

  7. Conditional Lineage Ablation to Model Human Diseases

    Science.gov (United States)

    Lee, Paul; Morley, Gregory; Huang, Qian; Fischer, Avi; Seiler, Stephanie; Horner, James W.; Factor, Stephen; Vaidya, Dhananjay; Jalife, Jose; Fishman, Glenn I.

    1998-09-01

    Cell loss contributes to the pathogenesis of many inherited and acquired human diseases. We have developed a system to conditionally ablate cells of any lineage and developmental stage in the mouse by regulated expression of the diphtheria toxin A (DTA) gene by using tetracycline-responsive promoters. As an example of this approach, we targeted expression of DTA to the hearts of adult mice to model structural abnormalities commonly observed in human cardiomyopathies. Induction of DTA expression resulted in cell loss, fibrosis, and chamber dilatation. As in many human cardiomyopathies, transgenic mice developed spontaneous arrhythmias in vivo, and programmed electrical stimulation of isolated-perfused transgenic hearts demonstrated a strikingly high incidence of spontaneous and inducible ventricular tachycardia. Affected mice showed marked perturbations of cardiac gap junction channel expression and localization, including a subset with disorganized epicardial activation patterns as revealed by optical action potential mapping. These studies provide important insights into mechanisms of arrhythmogenesis and suggest that conditional lineage ablation may have wide applicability for studies of disease pathogenesis.

  8. Striatocapsular infarction: MRI and MR angiography

    Energy Technology Data Exchange (ETDEWEB)

    Croisille, P. (Dept. of Neuroradiology, Hopital Neurologique et Neurochirurgical Pierre Wertheimer, Lyon (France)); Turjman, F. (Dept. of Neuroradiology, Hopital Neurologique et Neurochirurgical Pierre Wertheimer, Lyon (France)); Croisile, B. (Dept. of Neurology, Hopital Neurologique et Neurochirurgical Pierre Wertheimer, Lyon (France)); Tournut, P. (Dept. of Neuroradiology, Hopital Neurologique et Neurochirurgical Pierre Wertheimer, Lyon (France)); Laharotte, J.C. (Dept. of Neuroradiology, Hopital Neurologique et Neurochirurgical Pierre Wertheimer, Lyon (France)); Aimard, G. (Dept. of Neurology, Hopital Neurologique et Neurochirurgical Pierre Wertheimer, Lyon (France)); Trillet, M. (Dept. of Neurology, Hopital Neurologique et Neurochirurgical Pierre Wertheimer, Lyon (France)); Duquesnel, J. (Dept. of Neuroradiology, Hopital Neurologique et Neurochirurgical Pierre Wertheimer, Lyon (France)); Froment, J.C. (Dept. of Neuroradiology, Hopital Neurologique et Neurochirurgical Pierre

    1994-08-01

    We present a case of left striatocapsular infarction manifest clinically as a transient right hemiparesis. MRI showed a left striatocapsular infarct. Striatocapsular infarction, unlike lacunar infarction, is often associated with occlusive disease of the carotid artery. In order to screen the carotid vessels, cervical MR angiography (MRA) was performed during the same examination, demonstrating a left internal carotid artery occlusion, confirmed by contrast arteriography. MRA, a noninvasive modality, can be a useful adjunct to MRI, when diagnostic information concerning the cervical carotid artery is needed. (orig.)

  9. Is kidney function affecting the management of myocardial infarction? A retrospective cohort study in patients with normal kidney function, chronic kidney disease stage III–V, and ESRD

    Directory of Open Access Journals (Sweden)

    Saad M

    2016-01-01

    Full Text Available Marc Saad,1 Boutros Karam,1 Geovani Faddoul,2 Youssef El Douaihy,1 Harout Yacoub,1 Hassan Baydoun,3 Christine Boumitri,1 Iskandar Barakat,1 Chadi Saifan,4 Elie El-Charabaty,4 Suzanne El Sayegh4 1Department of Internal Medicine, Staten Island University Hospital, Staten Island, 2Department of Nephrology, Icahn School of Medicine, New York, NY, 3Department of Cardiology, Tulane University Medical Center, New Orleans, LA, 4Department of Nephrology, Staten Island University Hospital, Staten Island, NY, USA Abstract: Patients with chronic kidney disease (CKD are three times more likely to have myocardial infarction (MI and suffer from increased morbidity and higher mortality. Traditional and unique risk factors are prevalent and constitute challenges for the standard of care. However, CKD patients have been largely excluded from clinical trials and little evidence is available to guide evidence-based treatment of coronary artery disease in patients with CKD. Our objective was to assess whether a difference exists in the management of MI (ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction among patients with normal kidney function, CKD stage III–V, and end-stage renal disease (ESRD patients. We conducted a retrospective cohort study on patients admitted to Staten Island University Hospital for the diagnosis of MI between January 2005 and December 2012. Patients were assigned to one of three groups according to their kidney function: Data collected on the medical management and the use of statins, platelet inhibitors, beta-blockers, and angiotensin converting enzyme inhibitors/angiotensin receptor blockers were compared among the three cohorts, as well as medical interventions including: catheterization and coronary artery bypass graft (CABG when indicated. Chi-square test was used to compare the proportions between nominal variables. Binary logistic analysis was used in order to determine associations

  10. Alternate-day fasting and chronic disease prevention: a review of human and animal trials.

    Science.gov (United States)

    Varady, Krista A; Hellerstein, Marc K

    2007-07-01

    Calorie restriction (CR) and alternate-day fasting (ADF) represent 2 different forms of dietary restriction. Although the effects of CR on chronic disease prevention were reviewed previously, the effects of ADF on chronic disease risk have yet to be summarized. Accordingly, we review here animal and human evidence concerning ADF and the risk of certain chronic diseases, such as type 2 diabetes, cardiovascular disease, and cancer. We also compare the magnitude of risk reduction resulting from ADF with that resulting from CR. In terms of diabetes risk, animal studies of ADF find lower diabetes incidence and lower fasting glucose and insulin concentrations, effects that are comparable to those of CR. Human trials to date have reported greater insulin-mediated glucose uptake but no effect on fasting glucose or insulin concentrations. In terms of cardiovascular disease risk, animal ADF data show lower total cholesterol and triacylglycerol concentrations, a lower heart rate, improved cardiac response to myocardial infarction, and lower blood pressure. The limited human evidence suggests higher HDL-cholesterol concentrations and lower triacylglycerol concentrations but no effect on blood pressure. In terms of cancer risk, there is no human evidence to date, yet animal studies found decreases in lymphoma incidence, longer survival after tumor inoculation, and lower rates of proliferation of several cell types. The findings in animals suggest that ADF may effectively modulate several risk factors, thereby preventing chronic disease, and that ADF may modulate disease risk to an extent similar to that of CR. More research is required to establish definitively the consequences of ADF.

  11. Uniparental disomy and human disease: an overview.

    Science.gov (United States)

    Yamazawa, Kazuki; Ogata, Tsutomu; Ferguson-Smith, Anne C

    2010-08-15

    Uniparental disomy (UPD) refers to the situation in which both homologues of a chromosomal region/segment have originated from only one parent. This can involve the entire chromosome or only a small segment. As a consequence of UPD, or uniparental duplication/deficiency of part of a chromosome, there are two types of developmental risk: aberrant dosage of genes regulated by genomic imprinting and homozygosity of a recessive mutation. UPD models generated by reciprocal and Robertsonian translocation heterozygote intercrosses have been a powerful tool to investigate genomic imprinting in mice, whereas novel UPD patients such as those with cystic fibrosis and Prader-Willi syndrome, triggered the clarification of recessive diseases and genomic imprinting disorders in human. Newly developed genomic technologies as well as conventional microsatellite marker methods have been contributing to the functional and mechanistic investigation of UPD, leading to not only the acquisition of clinically valuable information, but also the further clarification of diverse genetic processes and disease pathogenesis.

  12. Mitochondrial Fusion Proteins and Human Diseases

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    Michela Ranieri

    2013-01-01

    Full Text Available Mitochondria are highly dynamic, complex organelles that continuously alter their shape, ranging between two opposite processes, fission and fusion, in response to several stimuli and the metabolic demands of the cell. Alterations in mitochondrial dynamics due to mutations in proteins involved in the fusion-fission machinery represent an important pathogenic mechanism of human diseases. The most relevant proteins involved in the mitochondrial fusion process are three GTPase dynamin-like proteins: mitofusin 1 (MFN1 and 2 (MFN2, located in the outer mitochondrial membrane, and optic atrophy protein 1 (OPA1, in the inner membrane. An expanding number of degenerative disorders are associated with mutations in the genes encoding MFN2 and OPA1, including Charcot-Marie-Tooth disease type 2A and autosomal dominant optic atrophy. While these disorders can still be considered rare, defective mitochondrial dynamics seem to play a significant role in the molecular and cellular pathogenesis of more common neurodegenerative diseases, for example, Alzheimer’s and Parkinson’s diseases. This review provides an overview of the basic molecular mechanisms involved in mitochondrial fusion and focuses on the alteration in mitochondrial DNA amount resulting from impairment of mitochondrial dynamics. We also review the literature describing the main disorders associated with the disruption of mitochondrial fusion.

  13. Human brain disease recreated in mice

    Energy Technology Data Exchange (ETDEWEB)

    Marx, J.

    1990-12-14

    In the early 1980s, neurologist Stanley Prusiner suggested that scrapie, an apparently infectious degenerative brain disease of sheep, could be transmitted by prions, infectious particles made just of protein - and containing no nucleic acids. But prion research has come a long way since then. In 1985, the cloning of the gene encoding the prion protein proved that it does in fact exist. And the gene turned out to be widely expressed in the brains of higher organisms, a result suggesting that the prion protein has a normal brain function that can somehow be subverted, leading to brain degeneration. Then studies done during the past 2 years suggested that specific mutations in the prion gene might cause two similar human brain diseases, Gerstmann-Straeussler-Scheinker syndrome (GSS) and Creutzfelt-Jakob disease. Now, Prusiner's group at the University of California, San Francisco, has used genetic engineering techniques to recreate GSS by transplanting the mutated prion gene into mice. Not only will the animal model help neurobiologists answer the many remaining questions about prions and how they work, but it may also shed some light on other neurodegenerative diseases as well.

  14. The Microbiota, Chemical Symbiosis, and Human Disease

    Science.gov (United States)

    Redinbo, Matthew R.

    2014-01-01

    Our understanding of mammalian-microbial mutualism has expanded by combing microbial sequencing with evolving molecular and cellular methods, and unique model systems. Here, the recent literature linking the microbiota to diseases of three of the key mammalian mucosal epithelial compartments – nasal, lung and gastrointestinal (GI) tract – is reviewed with a focus on new knowledge about the taxa, species, proteins and chemistry that promote health and impact progression toward disease. The information presented is further organized by specific diseases now associated with the microbiota:, Staphylococcus aureus infection and rhinosinusitis in the nasal-sinus mucosa; cystic fibrosis (CF), chronic obstructive pulmonary disorder (COPD), and asthma in the pulmonary tissues. For the vast and microbially dynamic GI compartment, several disorders are considered, including obesity, atherosclerosis, Crohn’s disease, ulcerative colitis, drug toxicity, and even autism. Our appreciation of the chemical symbiosis ongoing between human systems and the microbiota continues to grow, and suggest new opportunities for modulating this symbiosis using designed interventions. PMID:25305474

  15. Human prion diseases in the United States.

    Directory of Open Access Journals (Sweden)

    Robert C Holman

    Full Text Available BACKGROUND: Prion diseases are a family of rare, progressive, neurodegenerative disorders that affect humans and animals. The most common form of human prion disease, Creutzfeldt-Jakob disease (CJD, occurs worldwide. Variant CJD (vCJD, a recently emerged human prion disease, is a zoonotic foodborne disorder that occurs almost exclusively in countries with outbreaks of bovine spongiform encephalopathy. This study describes the occurrence and epidemiology of CJD and vCJD in the United States. METHODOLOGY/PRINCIPAL FINDINGS: Analysis of CJD and vCJD deaths using death certificates of US residents for 1979-2006, and those identified through other surveillance mechanisms during 1996-2008. Since CJD is invariably fatal and illness duration is usually less than one year, the CJD incidence is estimated as the death rate. During 1979 through 2006, an estimated 6,917 deaths with CJD as a cause of death were reported in the United States, an annual average of approximately 247 deaths (range 172-304 deaths. The average annual age-adjusted incidence for CJD was 0.97 per 1,000,000 persons. Most (61.8% of the CJD deaths occurred among persons >or=65 years of age for an average annual incidence of 4.8 per 1,000,000 persons in this population. Most deaths were among whites (94.6%; the age-adjusted incidence for whites was 2.7 times higher than that for blacks (1.04 and 0.40, respectively. Three patients who died since 2004 were reported with vCJD; epidemiologic evidence indicated that their infection was acquired outside of the United States. CONCLUSION/SIGNIFICANCE: Surveillance continues to show an annual CJD incidence rate of about 1 case per 1,000,000 persons and marked differences in CJD rates by age and race in the United States. Ongoing surveillance remains important for monitoring the stability of the CJD incidence rates, and detecting occurrences of vCJD and possibly other novel prion diseases in the United States.

  16. Human bone marrow-derived adult stem cells for post-myocardial infarction cardiac repair: current status and future directions.

    Science.gov (United States)

    Wei, H M; Wong, P; Hsu, L F; Shim, W

    2009-10-01

    Stem cell-based cell therapy has emerged as a potentially therapeutic option for patients with acute myocardial infarction (AMI) and heart failure. With the completion of a number of trials using bone marrow (BM)-derived adult stem cells, critical examination of the overall clinical benefits, limitations and potential side effects of this revolutionary treatment will pave the way for future clinical research. At present, clinical trials have been conducted almost exclusively using BM stem cells. The primary endpoints of these trials are mainly safety and feasibility, with secondary endpoints in the efficacy of post-myocardial infarction (MI) cardiac repair. Intervention with BM-derived cells was mainly carried out by endogenously-mobilised BM cells with granulocyte-colony stimulating factor, and more frequently, by intracoronary infusion or direct intramyocardial injection of autologous BM cells. While these studies have been proven safe and feasible without notable side effects, mixed outcomes in terms of clinical benefits have been reported. The major clinical benefits observed are improved cardiac contractile function and suppressed left ventricular negative remodelling, including reduced infarct size and improved cardiac perfusion of infarct zone. Moderate and transient clinical benefits have been mostly observed in studies with intracoronary infusion or direct intramyocardial injection of BM cells. These effects are widely considered to be indirect effects of implanted cells in association with paracrine factors, cell fusion, passive ventricular remodelling, or the responses of endogenous cardiac stem cells. In contrast, evidence of cardiac regeneration characterised by differentiation of implanted stem cells into cardiomyocytes and other cardiac cell lineages, is weak or lacking. To elucidate a clear risk-benefit of this exciting therapy, future studies on the mechanisms of cardiac cell therapy will need to focus on confirming the ideal cell types in relation

  17. Comparison of clinical outcomes between culprit vessel only and multivessel percutaneous coronary intervention for ST-segment elevation myocardial infarction patients with multivessel coronary diseases

    Institute of Scientific and Technical Information of China (English)

    Kwang Sun Ryu; Sang Yeub Lee; Jang Whan Bae; Kyung Kuk Hwang; Dong Woon Kim; Myeong Chan Cho; Young Keun Ahn; Myung Ho Jeong; Chong Jin Kim; Jong Seon Park; Young Jo Kim; Hyun Woo Park; Yang Soo Jang; Hyo Soo Kim; Ki Bae Seung; Soo Ho Park; Ho Sun Shon; Keun Ho Ryu; Dong Gyu Lee; Mohamed EA Bashir; Ju Hee Lee; Sang Min Kim

    2015-01-01

    Background The clinical significance of complete revascularization for ST segment elevation myocardial infarction (STEMI) pa-tients during admission is still debatable. Methods A total of 1406 STEMI patients from the Korean Myocardial Infarction Registry with multivessel diseases without cardiogenic shock who underwent primary percutaneous coronary intervention (PPCI) were analyzed. We used propensity score matching (PSM) to control differences of baseline characteristics between culprit only intervention (CP) and multivessel percutaneous coronary interventions (MP), and between double vessel disease (DVD) and triple vessel disease (TVD). The major adverse cardiac event (MACE) was analyzed for one year after discharge. Results TVD patients showed higher incidence of MACE (14.2%vs. 8.6%, P=0.01), any cause of revascularization (10.6%vs. 5.9%, P=0.01), and repeated PCI (9.5%vs. 5.7%, P=0.02), as compared to DVD patients during one year after discharge. MP reduced MACE effectively (7.3%vs. 13.8%, P=0.03), as compared to CP for one year, but all cause of death (1.6%vs. 3.2%, P=0.38), MI (0.4%vs. 0.8%, P=1.00), and any cause of revascularization (5.3%vs. 9.7%, P=0.09) were comparable in the two treatment groups. Conclusions STEMI patients with TVD showed higher rate of MACE, as compared to DVD. MP performed during PPCI or ad hoc during admission for STEMI patients without cardiogenic shock showed lower rate of MACE in this large scaled database. Therefore, MP could be considered as an effective treatment option for STEMI patients without cardiogenic shock.

  18. Cardiac remodeling and physical training post myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Michael; A; Garza; Emily; A; Wason; John; Q; Zhang

    2015-01-01

    After myocardial infarction(MI), the heart undergoes extensive myocardial remodeling through the accumulation of fibrous tissue in both the infarcted and noninfarcted myocardium, which distorts tissue structure, increases tissue stiffness, and accounts for ventricular dysfunction. There is growing clinical consensus that exercise training may beneficially alter the course of post-MI myocardial remodeling and improve cardiac function. This review summarizes the present state of knowledge regarding the effect of post-MI exercise training on infarcted hearts. Due to the degree of difficulty to study a viable human heart at both protein and molecular levels, most of the detailed studies have been performed by using animal models. Although there are some negative reports indicating that post-MI exercise may further cause deterioration of the wounded hearts, a growing body of research from both human and animal experiments demonstrates that post-MI exercise may beneficially alter the course of wound healing and improve cardiac function. Furthermore, the improved function is likely due to exercise training-induced mitigation of reninangiotensin-aldosterone system, improved balance between matrix metalloproteinase-1 and tissue inhibitor of matrix metalloproteinase-1, favorable myosin heavy chain isoform switch, diminished oxidative stress, enhanced antioxidant capacity, improved mitochondrial calcium handling, and boosted myocardial angiogenesis. Additionally, meta-analyses revealed that exercise-based cardiac rehabilitation has proven to be effective, and remains one of the least expensive therapies for both the prevention and treatment of cardiovascular disease, and prevents re-infarction.

  19. Idiopathic Renal Infarction Mimicking Appendicitis

    Science.gov (United States)

    Lisanti, Francesco; Scarano, Enrico

    2017-01-01

    Renal infarction is a rare cause of referral to the emergency department, with very low estimated incidence (0.004%–0.007%). Usually, it manifests in patients aged 60–70 with risk factors for thromboembolism, mostly related to heart disease, atrial fibrillation in particular. We report a case of idiopathic segmental renal infarction in a 38-year-old patient, presenting with acute abdominal pain with no previous known history or risk factors for thromboembolic diseases. Because of its aspecific clinical presentation, this condition can mimic more frequent pathologies including pyelonephritis, nephrolithiasis, or as in our case appendicitis. Here we highlight the extremely ambiguous presentation of renal infarct and the importance for clinicians to be aware of this condition, particularly in patients without clear risk factors, as it usually has a good prognosis after appropriate anticoagulant therapy. PMID:28203466

  20. Coincidence of cerebrovascular accident and silent myocardial infarction.

    Science.gov (United States)

    Badui, E; Estañol, B; Garcia-Rubi, D

    1982-11-01

    Although it is well known that a myocardial and a cerebral infarction may be coincident, the nature of this association is not clear. The problem is further complicated because the myocardial infarction may be silent. This is a report of 3 patients with cerebral infarct in whom a silent recent myocardial infarction was found. All patients with cerebrovascular disease should be screened for a possible myocardial lesion.

  1. Successful Thrombolytic Therapy for Bilateral Renal Infarction: A Case Report

    Directory of Open Access Journals (Sweden)

    Han-Ching Lin

    2006-08-01

    Full Text Available Acute renal infarction is a rarely reported disease in the medical literature. Angiography, renal scintigraphy, intravenous pyelography, sonography, and enhanced computed tomography may be useful in diagnosing acute renal infarction antemortem. Therapeutic guidelines for the treatment of renal infarction have not been established. We report a case of bilateral renal infarction in an elderly woman with atrial fibrillation, which was successfully treated by thrombolytic therapy.

  2. HIV and the spectrum of human disease.

    Science.gov (United States)

    Lucas, Sebastian; Nelson, Ann Marie

    2015-01-01

    Infection with the human immunodeficiency virus (HIV) causes systemic T cell destruction and reduced cell-mediated immunity that leads to a wide range of opportunistic infections and cancers. Second, it directly damages many tissues - gut, brain, lung - through mononuclear cell infection and activation. Third, through immune activation and effects on endothelia, it can cause more subtle systemic organ damage, such as chronic cardiovascular, hepatic, pulmonary and central nervous system disease. Antiretroviral treatment has enabled HIV-infected persons to live with chronic infection, although with some side-effects and mortality, including reactions due to the immune reconstitution inflammatory syndrome (IRIS). As cohorts of infected people get older, age-related diseases will combine with chronic HIV infection to produce disabilities whose scale is not yet understood. HIV is detectable in tissues by immunohistochemistry when infection loads are high, such as at first presentation. Pathologists should proactively consider HIV disease in routine diagnostic work, so as to identify more HIV-infected patients and enable their optimal management.

  3. Blood type biochemistry and human disease.

    Science.gov (United States)

    Ewald, D Rose; Sumner, Susan C J

    2016-11-01

    Associations between blood type and disease have been studied since the early 1900s when researchers determined that antibodies and antigens are inherited. In the 1950s, the chemical identification of the carbohydrate structure of surface antigens led to the understanding of biosynthetic pathways. The blood type is defined by oligosaccharide structures, which are specific to the antigens, thus, blood group antigens are secondary gene products, while the primary gene products are various glycosyltransferase enzymes that attach the sugar molecules to the oligosaccharide chain. Blood group antigens are found on red blood cells, platelets, leukocytes, plasma proteins, certain tissues, and various cell surface enzymes, and also exist in soluble form in body secretions such as breast milk, seminal fluid, saliva, sweat, gastric secretions, urine, and amniotic fluid. Recent advances in technology, biochemistry, and genetics have clarified the functional classifications of human blood group antigens, the structure of the A, B, H, and Lewis determinants and the enzymes that produce them, and the association of blood group antigens with disease risks. Further research to identify differences in the biochemical composition of blood group antigens, and the relationship to risks for disease, can be important for the identification of targets for the development of nutritional intervention strategies, or the identification of druggable targets. WIREs Syst Biol Med 2016, 8:517-535. doi: 10.1002/wsbm.1355 For further resources related to this article, please visit the WIREs website.

  4. HECT E3s and human disease

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    Staub Olivier

    2007-11-01

    Full Text Available Abstract In a simplified view, members of the HECT E3 family have a modular structure consisting of the C-terminal HECT domain, which is catalytically involved in the attachment of ubiquitin to substrate proteins, and N-terminal extensions of variable length and sequence that mediate the substrate specificity of the respective HECT E3. Although the physiologically relevant substrates of most HECT E3s have remained elusive, it is becoming increasingly clear that HECT E3s play an important role in sporadic and hereditary human diseases including cancer, cardiovascular (Liddle's syndrome and neurological (Angelman syndrome disorders, and/or in disease-relevant processes including bone homeostasis, immune response and retroviral budding. Thus, molecular approaches to target the activity of distinct HECT E3s, regulators thereof, and/or of HECT E3 substrates could prove valuable in the treatment of the respective diseases. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com.

  5. Diet, disease and pigment variation in humans.

    Science.gov (United States)

    Khan, R; Khan, B S Razib

    2010-10-01

    There are several hypotheses which explain the de-pigmentation of humans. The most prominent environmental explanation is that reduced endogenous vitamin D production due to diminished radiation at higher latitudes had a deleterious impact on fitness. This drove de-pigmentation as an adaptive response. A model of natural selection explains the high correlations found between low vitamin D levels and ill health, as vitamin D's role in immune response has clear evolutionary implications. But recent genomic techniques have highlighted the likelihood that extreme de-pigmentation in Eurasia is a feature of the last 10,000years, not the Upper Pleistocene, when modern humans first settled northern Eurasia. Additionally the data imply two independent selection events in eastern and western Eurasia. Therefore new parameters must be added to the model of natural selection so as to explain the relatively recent and parallel adaptive responses. I propose a model of gene-culture co-evolution whereby the spread of agriculture both reduced dietary vitamin D sources and led to more powerful selection on immune response because of the rise of infectious diseases with greater population densities. This model explains the persistence of relatively dark-skinned peoples at relatively high latitudes and the existence of relatively light-skinned populations at low latitudes. It also reinforces the importance of vitamin D as a micronutrient because of the evidence of extremely powerful fitness implications in the recent human past of pigmentation. Copyright 2010 Elsevier Ltd. All rights reserved.

  6. Reversible posterior leukoencephalopathy syndrome and silent cerebral infarcts are associated with severe acute chest syndrome in children with sickle cell disease.

    Science.gov (United States)

    Henderson, Jessica N; Noetzel, Michael J; McKinstry, Robert C; White, Desiree A; Armstrong, Melissa; DeBaun, Michael R

    2003-01-15

    Patients with severe acute chest syndrome (ACS) requiring endotracheal intubation and erythrocytopheresis are at increased risk for neurologic morbidity. This study examines patients with sickle cell disease who developed severe episodes of ACS, leading to endotracheal intubation, ventilatory support for respiratory failure, and erythrocytapheresis. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) studies, a neurologic examination by a pediatric neurologist, and cognitive testing were done in all patients. Five consecutive patients, aged 3 to 9 years, were identified with severe ACS. All patients developed neurologic complications resulting from ACS episodes, including seizures (n = 2), silent cerebral infarcts (n = 3), cerebral hemorrhage (n = 2), and reversible posterior leukoencephalopathy syndrome (n = 3). Children with severe ACS should have a magnetic resonance image of the brain, neurologic examination by a neurologist, and cognitive testing to detect the presence of neurologic morbidity.

  7. Acute non-atherosclerotic ST-segment elevation myocardial infarction in an adolescent with concurrent hemoglobin H-Constant Spring disease and polycythemia vera

    Directory of Open Access Journals (Sweden)

    Ekarat Rattarittamrong

    2015-09-01

    Full Text Available Thrombosis is a major complication of polycythemia vera (PV and also a well-known complication of thalassemia. We reported a case of non-atherosclerotic ST-segment elevation myocardial infarction (STEMI in a 17- year-old man with concurrent post-splenectomized hemoglobin H-Constant Spring disease and JAK2 V617F mutation-positive PV. The patient initially presented with extreme thrombocytosis (platelet counts greater than 1,000,000/μL and three months later developed an acute STEMI. Coronary artery angiography revealed an acute clot in the right coronary artery without atherosclerotic plaque. He was treated with plateletpheresis, hydroxyurea and antiplatelet agents. The platelet count decreased and his symptoms improved. This case represents the importance of early diagnosis, awareness of the increased risk for thrombotic complications, and early treatment of PV in patients who have underlying thalassemia with marked thrombocytosis.

  8. Evolutionary history of human disease genes reveals phenotypic connections and comorbidity among genetic diseases.

    Science.gov (United States)

    Park, Solip; Yang, Jae-Seong; Kim, Jinho; Shin, Young-Eun; Hwang, Jihye; Park, Juyong; Jang, Sung Key; Kim, Sanguk

    2012-01-01

    The extent to which evolutionary changes have impacted the phenotypic relationships among human diseases remains unclear. In this work, we report that phenotypically similar diseases are connected by the evolutionary constraints on human disease genes. Human disease groups can be classified into slowly or rapidly evolving classes, where the diseases in the slowly evolving class are enriched with morphological phenotypes and those in the rapidly evolving class are enriched with physiological phenotypes. Our findings establish a clear evolutionary connection between disease classes and disease phenotypes for the first time. Furthermore, the high comorbidity found between diseases connected by similar evolutionary constraints enables us to improve the predictability of the relative risk of human diseases. We find the evolutionary constraints on disease genes are a new layer of molecular connection in the network-based exploration of human diseases.

  9. United States stock market performance and acute myocardial infarction rates in 2008-2009 (from the Duke Databank for Cardiovascular Disease).

    Science.gov (United States)

    Fiuzat, Mona; Shaw, Linda K; Thomas, Laine; Felker, G Michael; O'Connor, Christopher M

    2010-12-01

    We sought to examine the relation between the United States economic decrease in 2008 and cardiovascular events as measured by local acute myocardial infarction (AMI) rates. Mental stress and traumatic events have been shown to be associated with increased risk of MI in patients with ischemic heart disease. This was an observational study of data from the Duke Databank for Cardiovascular Disease and includes patients undergoing angiography for evaluation of ischemic heart disease from January 2006 to July 2009. Patients with AMI occurring within 3 days before catheterization were used to calculate AMI rates. Stock market values were examined to determine the period of severe economic decrease, and time trends in AMI rates were examined over the same period. Time series models were used to assess the relation between United States stock market National Association of Securities Dealers Automated Quotation (NASDAQ) and rates of AMI. Of 11,590 patients included in the study cohort, 2,465 patients had an AMI during this period. Time series analysis showed a significant increase in AMI rates during a period of stock market decrease from October 2008 to April 2009 (p = 0.003), which remained statistically significant when adjusted for seasons (p = 0.02). In conclusion, unadjusted and adjusted analyses of patients in the Duke Databank for Cardiovascular Disease indicated a significant correlation between a period of stock market decrease and increased AMI rates in our local cohort.

  10. Isolation of Proteins which Interact with Phospholipase A2 (IIA from Human Serum after Myocardial Infarction. Flavonoids from Bidens tripartita Extract as Phospholipase A2 Inhibitors

    Directory of Open Access Journals (Sweden)

    Anna Król

    2017-03-01

    Full Text Available The aim of the work was to isolate proteins which interact with phospholipase A2 (PLA2 from human serum after myocardial infarction. During this study, the effect of flavonoid inhibitors from the extract of Bidens Tripartita was examined. First, the paper describes phytochemical characterisation of compounds found in the plant Bidens tripartita.  Plant material was harvested at different vegetation stages, and extracts of each were studied for presence of flavonoids by methods such as spectrophotometry and high-performance liquid chromatography (HPLC. Six different flavonoids were identified in extracts. The largest amount of phenolic compounds (mainly rutin and quercetin was found in the intensive growth vegetation stage, and antioxidant activity corresponds with this result. The conducted analysis shows the dependence of phytochemical composition on the vegetation stage when the plant was collected. These results support the use of bur marigold extracts in pharmaceutical or food industry as a potential source of natural inhibitors of PLA2. Biochemistry analysis using the pull-down method shows that 7 proteins which bind sPLA2 were found in healthy blood serum and after myocardial infarction. The biggest fraction was albumins. According to the variant of the sample, different proteins are bound to PLA2. The data of the pull-down analysis correspond with phytochemical analysis, i.e., they support the presence of natural inhibitors of PLA2 in Bidens tripartita extract.DOI: http://dx.doi.org/10.5755/j01.erem.72.4.16494

  11. Human KATP channelopathies: diseases of metabolic homeostasis

    Science.gov (United States)

    2009-01-01

    Assembly of an inward rectifier K+ channel pore (Kir6.1/Kir6.2) and an adenosine triphosphate (ATP)-binding regulatory subunit (SUR1/SUR2A/SUR2B) forms ATP-sensitive K+ (KATP) channel heteromultimers, widely distributed in metabolically active tissues throughout the body. KATP channels are metabolism-gated biosensors functioning as molecular rheostats that adjust membrane potential-dependent functions to match cellular energetic demands. Vital in the adaptive response to (patho)physiological stress, KATP channels serve a homeostatic role ranging from glucose regulation to cardioprotection. Accordingly, genetic variation in KATP channel subunits has been linked to the etiology of life-threatening human diseases. In particular, pathogenic mutations in KATP channels have been identified in insulin secretion disorders, namely, congenital hyperinsulinism and neonatal diabetes. Moreover, KATP channel defects underlie the triad of developmental delay, epilepsy, and neonatal diabetes (DEND syndrome). KATP channelopathies implicated in patients with mechanical and/or electrical heart disease include dilated cardiomyopathy (with ventricular arrhythmia; CMD1O) and adrenergic atrial fibrillation. A common Kir6.2 E23K polymorphism has been associated with late-onset diabetes and as a risk factor for maladaptive cardiac remodeling in the community-at-large and abnormal cardiopulmonary exercise stress performance in patients with heart failure. The overall mutation frequency within KATP channel genes and the spectrum of genotype–phenotype relationships remain to be established, while predicting consequences of a deficit in channel function is becoming increasingly feasible through systems biology approaches. Thus, advances in molecular medicine in the emerging field of human KATP channelopathies offer new opportunities for targeted individualized screening, early diagnosis, and tailored therapy. PMID:20033705

  12. Pregnancy-related myocardial infarction

    NARCIS (Netherlands)

    Lameijer, H.; Lont, M. C.; Buter, H.; van Boven, A. J.; Boonstra, P. W.; Pieper, P. G.

    Introduction The risk of acute myocardial infarction in young women is low, but increases during pregnancy due to the physiological changes in pregnancy, including hypercoagulability. Ischaemic heart disease during pregnancy is not only associated with increased maternal morbidity and mortality, but

  13. Major trends in human parasitic diseases in China.

    Science.gov (United States)

    Li, Ting; He, Shenyi; Zhao, Hong; Zhao, Guanghui; Zhu, Xing-Quan

    2010-05-01

    Tremendous progress has been made in the control and prevention of human parasitic diseases in mainland China in the past 30 years because of China's Reform and Opening to the Outside Policies initiated in 1978. However, parasitic diseases remain a major human health problem, with significant morbidity and mortality as well as adverse socioeconomic consequences. Although soil-transmitted parasitic diseases are in the process of being gradually controlled, food-borne parasitic diseases and emerging parasitic diseases are becoming the focus of new campaigns for control and prevention. This article reviews major trends in human parasitic diseases in mainland China, with perspectives for control.

  14. Wolbachia endosymbionts and human disease control.

    Science.gov (United States)

    Slatko, Barton E; Luck, Ashley N; Dobson, Stephen L; Foster, Jeremy M

    2014-07-01

    Most human filarial nematode parasites and arthropods are hosts for a bacterial endosymbiont, Wolbachia. In filaria, Wolbachia are required for normal development, fertility and survival, whereas in arthropods, they are largely parasitic and can influence development and reproduction, but are generally not required for host survival. Due to their obligate nature in filarial parasites, Wolbachia have been a target for drug discovery initiatives using several approaches including diversity and focused library screening and genomic sequence analysis. In vitro and in vivo anti-Wolbachia antibiotic treatments have been shown to have adulticidal activity, a long sought goal of filarial parasite drug discovery. In mosquitoes, it has been shown that the presence of Wolbachia can inhibit the transmission of certain viruses, such as Dengue, Chikungunya, Yellow Fever, West Nile, as well as the infectivity of the malaria-causing protozoan, Plasmodium and filarial nematodes. Furthermore, Wolbachia can cause a form of conditional sterility that can be used to suppress populations of mosquitoes and additional medically important insects. Thus Wolbachia, a pandemic endosymbiont offers great potential for elimination of a wide-variety of devastating human diseases.

  15. MicroRNAs in Human Diseases: From Autoimmune Diseases to Skin, Psychiatric and Neurodegenerative Diseases.

    Science.gov (United States)

    Ha, Tai-You

    2011-10-01

    MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their target messenger RNAs (mRNAs). Recent studies have clearly demonstrated that miRNAs play critical roles in several biologic processes, including cell cycle, differentiation, cell development, cell growth, and apoptosis and that miRNAs are highly expressed in regulatory T (Treg) cells and a wide range of miRNAs are involved in the regulation of immunity and in the prevention of autoimmunity. It has been increasingly reported that miRNAs are associated with various human diseases like autoimmune disease, skin disease, neurological disease and psychiatric disease. Recently, the identification of mi- RNAs in skin has added a new dimension in the regulatory network and attracted significant interest in this novel layer of gene regulation. Although miRNA research in the field of dermatology is still relatively new, miRNAs have been the subject of much dermatological interest in skin morphogenesis and in regulating angiogenesis. In addition, miRNAs are moving rapidly onto center stage as key regulators of neuronal development and function in addition to important contributions to neurodegenerative disorder. Moreover, there is now compelling evidence that dysregulation of miRNA networks is implicated in the development and onset of human neruodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, Down syndrome, depression and schizophrenia. In this review, I briefly summarize the current studies about the roles of miRNAs in various autoimmune diseases, skin diseases, psychoneurological disorders and mental stress.

  16. [Myocardial infarction caused by exertion].

    Science.gov (United States)

    Bernard, F; Weber, S

    1997-01-01

    Myocardial infarction is the main cause of sudden death during physical exercise, particularly in subjects over 40 and may even occur in high-performance young athletes. Sports and physical activity have a beneficial effect in preventing cardiovascular diseases, but certain rules of prudence must be followed to avoid the risk of a severe coronary event. Myocardial infarction always occurs in particularly susceptible subjects with several risk factors, predominantly smoking, hypercholesterolemia, family history of atherosclerosis. Dietary factors, either before, during or after the exercise, are always found. Distribution of coronary lesions differs with age. Before 40 years, the coronary network is normal in 40% of the cases. The infarction is partially explained by platelet hyperaggregahility and coronary spasms at exercise or in the post-exercise period.

  17. Renal infarction complicating fibromuscular dysplasia.

    Science.gov (United States)

    Gavalas, M; Meisner, R; Labropoulos, N; Gasparis, A; Tassiopoulos, A

    2014-01-01

    Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory vascular disease that most commonly affects the renal and extracranial carotid arteries. We present 3 cases of renal infarction complicating renal artery FMD in 42-, 43-, and 46-year-old females and provide a comprehensive review of the literature on this topic. In our patients, oral anticoagulation therapy was used to treat all cases of infarction, and percutaneous angioplasty was used nonemergently in one case to treat refractory hypertension. All patients remained stable at 1-year follow-up. This is consistent with outcomes in previously published reports where conservative medical management was comparable to surgical and interventional therapies. Demographic differences may also exist in patients with renal infarction and FMD. A higher prevalence of males and a younger age at presentation have been found in these patients when compared to the general population with FMD.

  18. Effect of the Diagnosis of Inflammatory Bowel Disease on Risk-Adjusted Mortality in Hospitalized Patients with Acute Myocardial Infarction, Congestive Heart Failure and Pneumonia

    Science.gov (United States)

    Ehrenpreis, Eli D.; Zhou, Ying; Alexoff, Aimee; Melitas, Constantine

    2016-01-01

    Introduction Measurement of mortality in patients with acute myocardial infarction (AMI), congestive heart failure (CHF) and pneumonia (PN) is a high priority since these are common reasons for hospitalization. However, mortality in patients with inflammatory bowel disease (IBD) that are hospitalized for these common medical conditions is unknown. Methods A retrospective review of the 2005–2011 National Inpatient Sample (NIS), (approximately a 20% sample of discharges from community hospitals) was performed. A dataset for all patients with ICD-9-CM codes for primary diagnosis of acute myocardial infarction, pneumonia or congestive heart failure with a co-diagnosis of IBD, Crohn’s disease (CD) or ulcerative colitis (UC). 1:3 propensity score matching between patients with co-diagnosed disease vs. controls was performed. Continuous variables were compared between IBD and controls. Categorical variables were reported as frequency (percentage) and analyzed by Chi-square tests or Fisher’s exact test for co-diagnosed disease vs. control comparisons. Propensity scores were computed through multivariable logistic regression accounting for demographic and hospital factors. In-hospital mortality between the groups was compared. Results Patients with IBD, CD and UC had improved survival after AMI compared to controls. 94/2280 (4.1%) of patients with IBD and AMI died, compared to 251/5460 (5.5%) of controls, p = 0.01. This represents a 25% improved survival in IBD patients that were hospitalized with AMI. There was a 34% improved survival in patients with CD and AMI. There was a trend toward worsening survival in patients with IBD and CHF. Patients with CD and PN had improved survival compared to controls. 87/3362 (2.59%) patients with CD and PN died, compared to 428/10076 (4.25%) of controls, p < .0001. This represents a 39% improved survival in patients with CD that are hospitalized for PN. Conclusion IBD confers a survival benefit for patients hospitalized with AMI. A

  19. Heart Disease: A Price Humans Pay for Fertility?

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_166826.html Heart Disease: A Price Humans Pay for Fertility? Study finds ... 22, 2017 (HealthDay News) -- Certain genes linked to heart disease may also improve your chances of having children, ...

  20. Technetium-99m antimyosin antibody (3-48) myocardial imaging: human biodistribution, safety and clinical results in detection of acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Taillefer, R. [Dept. of Nuclear Medicine, Hotel-Dieu de Montreal, Univ. Montreal (Canada); Boucher, L. [Dept. of Nuclear Medicine, Hotel-Dieu de Montreal, Univ. Montreal (Canada); Lambert, R. [Dept. of Nuclear Medicine, Hotel-Dieu de Montreal, Univ. Montreal (Canada); Gregoire, J. [Dept. of Nuclear Medicine, Hotel-Dieu de Montreal, Univ. Montreal (Canada); Phaneuf, D.C. [Dept. of Nuclear Medicine, Hotel-Dieu de Montreal, Univ. Montreal (Canada); Sikorsa, H. [Rougier Bio-Tech Ltd., Montreal (Canada)

    1995-05-01

    The purpose of this study was to determine the human biodistribution, the safety profile and the sensitivity of {sup 99m}Tc-AM (3-48) imaging in the detection of both Q-wave and non-Q-wave myocardial infarction (MI). Biodistribution and safety parameters were mainly determined in 12 normal healthy volunteers while 40 patients with proven MI (22 Q-wave, 18 non-Q-wave) were injected with {sup 99m}Tc-AM (20-25 mCi) between 5 h and 7 days after the onset of acute chest pain. Three standard planar views were performed at 6 h and at 24 h post injection. Both sets of images were completed in 33 patients while two patients were imaged only at 6 h, three patients only at 18 h and one at 18 and 24 h. One patient was not imaged. Vital signs and ECG were recorded and blood samples for haematology, biochemistry and human antimurine antibodies (HAMA) and urinalysis were obtained in all volunteers and patients. No serious adverse reactions or side-effects attributable to {sup 99m}-Tc-AM have been reported. No volunteers or patients developed allergic reactions or significant increases in HAMA titres. Reading of {sup 99m}Tc-AM imaging was performed by two blinded experienced observers. The sensitivity of {sup 99m}Tc-AM in the detection of MI was 100% for Q-wave and 83.3% for non-Q-wave infarctions. The overall sensitivity was 92.3%. The three false-negative case were inferoposterior MI. A certain degree of uptake focalization was seen in 26 out of 35 at 6 h. At 24 h, two patients did not show {sup 99m}Tc-AM uptake while 22 showed intense focal uptake, seven moderate uptake and 3 slight uptake. (orig./MG)

  1. Reg gene family and human diseases

    Institute of Scientific and Technical Information of China (English)

    Yu-Wei Zhang; Liu-Song Ding; Mao-De Lai

    2003-01-01

    Regenerating gene (Reg or REG) family, within the superfamily of C-type lectin, is mainly involved in the liver,pancreatic, gastric and intestinal cell proliferation or differentiation. Considerable attention has focused on Reg family and its structurally related molecules. Over the last 15 years, 17 members of the Reg family have been cloned and sequenced. They have been considered as members of a conserved protein family sharing structural and some functional properties being involved in injury, inflammation,diabetes and carcinogenesis. We previously identified Reg Ⅳ as a strong candidate for a gene that was highly expressed in colorectal adenoma when compared to normal mucosa based on suppression subtractive hybridization (SSH),reverse Northern blot, semi-quantitative reverse transcriptase PCR (RT-PCR)and Northern blot. In situ hybridization results further support that overexpression of Reg Ⅳ may be an early event in colorectal carcinogenesis. We suggest that detection of Reg Ⅳ overexpression might be useful in the early diagnosis of carcinomatous transformation of adenoma.This review summarizes the roles of Reg family in diseases in the literature as well as our recent results of Reg Ⅳ in colorectal cancer. The biological properties of Reg family and its possible roles in human diseases are discussed. We particularly focus on the roles of Reg family as sensitive reactants of tissue injury, prognostic indicators of tumor survival and early biomarkers of carcinogenesis. In addition to our current understanding of Reg gene functions, we postulate that there might be relationships between Reg family and microsatellite instability, apoptosis and cancer with a poor prognosis. Investigation of the correlation between tumor Reg expression and survival rate, and analysis of the Reg gene status in human maliganancies, are required to elucidate the biologic consequences of Reg gene expression, the implications for Reg gene regulation of cell growth, tumorigenesis

  2. Myocardial infarction in young adults

    OpenAIRE

    Egred, M; Viswanathan, G; Davis, G.

    2005-01-01

    Although myocardial infarction (MI) mainly occurs in patients older than 45, young men or women can suffer MI. Fortunately, its incidence is not common in patients younger than 45 years. However, the disease carries a significant morbidity, psychological effects, and financial constraints for the person and the family when it occurs at a young age. The causes of MI among patients aged less than 45 can be divided into four groups: (1) atheromatous coronary artery disease; (2) non-atheromatous ...

  3. Intensity of human prion disease surveillance predicts observed disease incidence

    NARCIS (Netherlands)

    G.M. Klug (Genevieve); H. Wand (Handan); M. Simpson (Marion); A. Boyd (Alison); M. Law (Matthew); C. Masters (Colin); R. Mateǰ (Radoslav); R. Howley (Rachel); M. Farrell (Michael); M. Breithaupt; I. Zerr (Inga); C.M. van Duijn (Cock); C.A. Ibrahim-Verbaas (Carla); J. Mackenzie; R.G. Will (Robert); J-P. Brandel (Jean-Philippe); A. Alperovitch (Annick); H. Budka (Herbert); G.G. Kovacs (Gabor); G.H. Jansen (Gerard); M. Coulthard (Michael); S.J. Collins (Steven)

    2013-01-01

    textabstractBackground: Prospective national screening and surveillance programmes serve a range of public health functions. Objectively determining their adequacy and impact on disease may be problematic for rare disorders. We undertook to assess whether objective measures of disease surveillance

  4. Acute multiple infarction involving the anterior circulation.

    Science.gov (United States)

    Bogousslavsky, J; Bernasconi, A; Kumral, E

    1996-01-01

    To evaluate the frequency and clinical, topographic, and etiologic patterns of acute multiple infarction involving the anterior circulation. Data analysis from a prospective acute stroke registry in a community-based primary care center. Among 751 patients with first ischemic stroke in the anterior circulation over a 4-year period, 40 patients (5%) had acute multiple infarcts involving the anterior circulation. On computed tomography and magnetic resonance imaging with gadolinium enhancement, there were four topographic patterns of infarction: (1) superficial infarcts (11 patients [28%]); (2) superficial and deep infarcts (12 patients [30%]); (3) deep infarcts (three patients [8%]); and (4) infarcts involving the anterior and the posterior circulation (14 patients [35%]). Both cerebral hemispheres were involved in one fourth of the cases. A specific clinical picture was found in up to 20% of the patients. This included global aphasia with left hemianopia, hemisensory loss or hemiparesis (in right-handed patients), transcortical mixed aphasia with hemianopia, and acute pure cognitive impairment ("dementia"). Large-artery disease was found in 13 patients (33%); a cardiac source of embolism was found in 11 patients (28%); and both were found in three patients (8%). Bilateral infarcts were related to cardioembolism (four patients) and bilateral large-artery disease (three patients). One month after stroke, one fourth of the patients were independent, one third had some disability, and 40% were either dead or completely dependent. Acute multiple infarcts involving the anterior circulation may be bilateral more frequently than is currently thought, and they are often associated with posterior circulation infarcts. They mainly involve the pial hemispheral territories, commonly being caused by cardioembolism or bilateral carotid atheroma. They may be associated with a specific neurologic-neuropsychological dysfunction pattern in up to one fifth of the patients, allowing

  5. Original article The Me and My Disease Scale: measuring state hope and determining its impact on coping in patients with type 2 diabetes mellitus and myocardial infarction

    Directory of Open Access Journals (Sweden)

    Zuzanna Kwissa-Gajewska

    2015-05-01

    Full Text Available Background The aim of this study was to examine the psychometric properties, factor structure, measurement invariance, internal consistency reliability and construct validity of the Me and My Disease Scale – a tool for state hope measurement for adults suffering from chronic medical conditions. Participants and procedure Two clinical groups, patients with type 2 diabetes (DM (n = 278 just before and 1 month after introducing insulin treatment, and cardiac patients (n = 232 five days and one month after their first uncomplicated myocardial infarction (MI, participated in the study. Cognitive appraisal, emotions and depression (MI group were measured to establish the construct validity of the scale. Results A single-factor model which consisted of 4 items was established. The structure was characterized by good measurement model fit and satisfactory indicators of reliability for the MI subgroup. A less satisfactory model fit was obtained for the DM subgroup – this may point to the impact of specific medical conditions on the scale. Furthermore, the findings indicated metric invariance for the scale. The moderate correlations between hope and cognitive appraisal, emotion and depression confirm the construct validity of the scale. Conclusions The Me and My Disease Scale is characterized by satisfactory psychometric parameters and can be used in scientific research to measure hope as a dimension of cognition and to compare the relationships between hope and other variables in medical patients. However, caution should be taken during analysis when comparing means between clinical groups.

  6. Analysis of MMP-7 and TIMP-2 gene polymorphisms in coronary artery disease and myocardial infarction: A Turkish case-control study.

    Science.gov (United States)

    Alp, Ebru; Yilmaz, Akin; Tulmac, Murat; Ugras Dikmen, Asiye; Cengel, Atiye; Yalcin, Ridvan; Menevse, Emine Sevda

    2017-02-01

    Matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP) have a significant role in tissue remodeling related to cardiac function. In earlier studies, MMP-7 A-181G (rs11568818), C-153T (rs11568819), C-115T (rs17886546), and TIMP-2 G-418C (rs8179090) polymorphisms have been studied in various diseases. However, association between coronary artery disease (CAD) and these polymorphisms has been poorly studied. The goal of this study is to investigate the association of CAD and myocardial infarction (MI) with MMP-7 or TIMP-2 polymorphisms. This study included 122 CAD patients and 132 control individuals. DNA was extracted from whole blood. Polymerase chain reaction-restriction fragment length polymorphism and automated direct sequencing method were used for genotyping of these polymorphisms. No significant differences were found between MMP-7 A-181G, C-115T, and TIMP-2 G-418C polymorphism and CAD or MI in a Turkish population. Despite the fact that the genotypes of MMP-7 C-153T polymorphism had no significant differences among MI and control groups, allele frequencies of C-153T polymorphism were significantly different between the two groups. Our study is the first report to clarify the appreciable relationship between MMP-7 C-153T polymorphism and MI development in CAD patients. However, these findings also need to be confirmed in other populations so we can improve our knowledge about the genetic factors affecting the development of CAD. Copyright © 2017. Published by Elsevier Taiwan.

  7. Analysis of MMP-7 and TIMP-2 gene polymorphisms in coronary artery disease and myocardial infarction: A Turkish case-control study

    Directory of Open Access Journals (Sweden)

    Ebru Alp

    2017-02-01

    Full Text Available Matrix metalloproteinase (MMP and tissue inhibitors of metalloproteinase (TIMP have a significant role in tissue remodeling related to cardiac function. In earlier studies, MMP-7 A-181G (rs11568818, C-153T (rs11568819, C-115T (rs17886546, and TIMP-2 G-418C (rs8179090 polymorphisms have been studied in various diseases. However, association between coronary artery disease (CAD and these polymorphisms has been poorly studied. The goal of this study is to investigate the association of CAD and myocardial infarction (MI with MMP-7 or TIMP-2 polymorphisms. This study included 122 CAD patients and 132 control individuals. DNA was extracted from whole blood. Polymerase chain reaction-restriction fragment length polymorphism and automated direct sequencing method were used for genotyping of these polymorphisms. No significant differences were found between MMP-7 A-181G, C-115T, and TIMP-2 G-418C polymorphism and CAD or MI in a Turkish population. Despite the fact that the genotypes of MMP-7 C-153T polymorphism had no significant differences among MI and control groups, allele frequencies of C-153T polymorphism were significantly different between the two groups. Our study is the first report to clarify the appreciable relationship between MMP-7 C-153T polymorphism and MI development in CAD patients. However, these findings also need to be confirmed in other populations so we can improve our knowledge about the genetic factors affecting the development of CAD.

  8. Intestinal ischemia and infarction

    Science.gov (United States)

    ... medlineplus.gov/ency/article/001151.htm Small intestinal ischemia and infarction To use the sharing features on this page, please enable JavaScript. Intestinal ischemia and infarction occurs when there is a narrowing ...

  9. Risk of ischaemic heart disease and acute myocardial infarction in a Spanish population: observational prospective study in a primary-care setting

    Directory of Open Access Journals (Sweden)

    Cucalón José M

    2006-02-01

    Full Text Available Abstract Background Ischaemic heart disease is a global priority of health-care policy, because of its social repercussions and its impact on the health-care system. Yet there is little information on coronary morbidity in Spain and on the effect of the principal risk factors on risk of coronary heart disease. The objective of this study is to describe the epidemiology of coronary disease (incidence, mortality and its association with cardiovascular risk factors using the information gathered by primary care practitioners on cardiovascular health of their population. Methods A prospective study was designed. Eight primary-care centres participated, each contributing to the constitution of the cohort with the entire population covered by the centre. A total of 6124 men and women aged over 25 years and free of cardiovascular disease agreed to participate and were thus enrolled and followed-up, with all fatal and non-fatal coronary disease episodes being registered during a 5-year period. Repeated measurements were collected on smoking, blood pressure, weight and height, serum total cholesterol, high-density and low-density lipoproteins and fasting glucose. Rates were calculated for acute myocardial infarction and ischaemic heart disease. Associations between cardiovascular risk factors and coronary disease-free survival were evaluated using Kaplan-Meier and Cox regression analyses. Results Mean age at recruitment was 51.6 ± 15, with 24% of patients being over 65. At baseline, 74% of patients were overweight, serum cholesterol over 240 was present in 35% of patients, arterial hypertension in 37%, and basal glucose over 126 in 11%. Thirty-four percent of men and 13% of women were current smokers. During follow-up, 155 first episodes of coronary disease were detected, which yielded age-adjusted rates of 362 and 191 per 100,000 person-years in men and women respectively. Disease-free survival was associated with all risk factors in univariate

  10. Classification of myocardial infarction

    DEFF Research Database (Denmark)

    Saaby, Lotte; Poulsen, Tina Svenstrup; Hosbond, Susanne Elisabeth

    2013-01-01

    The classification of myocardial infarction into 5 types was introduced in 2007 as an important component of the universal definition. In contrast to the plaque rupture-related type 1 myocardial infarction, type 2 myocardial infarction is considered to be caused by an imbalance between demand...... and supply of oxygen in the myocardium. However, no specific criteria for type 2 myocardial infarction have been established....

  11. Cardiovascular Disease Burden: Evolving Knowledge of Risk Factors in Myocardial Infarction and Stroke through Population-Based Research and Perspectives in Global Prevention

    Directory of Open Access Journals (Sweden)

    GUSTAVO B.F. OLIVEIRA

    2015-08-01

    Full Text Available Current knowledge and research perspectives on the top ranking causes of mortality worldwide, i.e., ischemic heart disease and cerebrovascular diseases have developed rapidly. In fact, until recently, it was considered that only half of the myocardial infarctions were due to traditional risk factors such as hypertension, hypercholesterolemia, smoking and diabetes. In addition, most of the available evidence of incidence, risk factors, and clinical outcomes, if not all of it, was derived from studies conducted in developed countries, which included lower proportion of female individuals and with low ethnic diversity. Recent reports by the WHO have provided striking public health information, i.e., the global burden of cardiovascular mortality for the next decades is expected to predominantly occur among developing countries. Therefore, multi-ethnic population-based research including prospective cohorts and, when appropriate, case-control studies, is warranted. These studies should be specifically designed to ascertain key public health measures such as geographic variations in noncommunicable diseases, diagnosis of traditional and potential newly discovered risk factors, causes of death and disability, and gaps for improvement in healthcare prevention (both primary and secondary and specific treatments. As an example, a multinational, multiethnic population-based cohort study is the Prospective Urban and Rural Epidemiology (PURE study, which is the largest global initiative of 150,000 adults aged 35-70 yrs, looking at environmental, societal and biological influences on obesity and chronic health conditions such as ischemic heart disease, stroke and cancer among urban and rural communities in low-, middle-, and high-income countries, with national, community, household and individual-level data. Implementation of population-based strategies is crucial to optimizing limited health system resources while improving care and cardiovascular morbidity

  12. The dynamics of mortality in follow-up time after an acute myocardial infarction, lower extremity arterial disease and ischemic stroke

    Directory of Open Access Journals (Sweden)

    Grobbee Diederick E

    2010-11-01

    Full Text Available Abstract Background Most studies providing data on survival in patients with atherosclerosis only address a single disease site: heart, brain or legs. Therefore, our objective was to determine risk of death after first hospital admission for atherosclerotic disease located at different sites. Methods A nationwide cohort of patients hospitalized for the first time for acute myocardial infarction (AMI, peripheral arterial disease of the lower extremities (PAD or ischemic stroke was identified through linkage of national registers. The mortality rate in AMI patients was compared to mortality rate in ischemic stroke and PAD patients by estimating relative risks (with 95%CI. Cox's proportional hazard models were used to estimate sex differences in risk of death. Results Case fatality was high for ischemic stroke patients (men:21.0%, women:23.8% and AMI patients (men:12.7%, women:20.9% though low for PAD patients (men:2.4%, women:3.5%. The five-year risk of death was similar for male AMI compared to PAD patients (men: RR1.04; 95%CI 0.98-1.11. The risk of death for ischemic stroke patients remained the highest though the differences with AMI and PAD patients attenuated. Conclusions The dynamics of mortality over follow-up time clearly differ between atherosclerotic diseases, located at different vascular beds. The risk of death increases considerably over follow-up time for PAD patients, and 5 years after first hospital admission the differences in risks of death between AMI- and PAD patients and between AMI- and ischemic stroke patients have largely attenuated. Clinicians should be aware of these dynamics of mortality over follow-up time to provide optimal secondary prevention treatment.

  13. Association of splenic and renal infarctions in acute abdominal emergencies

    Energy Technology Data Exchange (ETDEWEB)

    Romano, Stefania E-mail: stefromano@libero.it; Scaglione, Mariano; Gatta, Gianluca; Lombardo, Patrizia; Stavolo, Ciro; Romano, Luigia; Grassi, Roberto

    2004-04-01

    Introduction: Splenic and renal infarctions are usually related to vascular disease or haematologic abnormalities. Their association is infrequent and rarely observed in trauma. In this study, we analyze our data to look at the occurrence of renal and splenic infarctions based on CT findings in a period of 4 years. Materials and Methods: We retrospectively reviewed the imaging findings of 84 patients admitted to our Department of Diagnostic Imaging from June 1998 to December 2002, who underwent emergency abdominal spiral CT examination and in whom there was evidence of splenic and/or renal infarction. Results: We found 40 cases of splenic infarction and 54 cases of renal infarction, associated in 10 patients. In 26 patients, there was also evidence of intestinal infarction. A traumatic origin was found in 19 cases; non-traumatic causes were found in 65 patients. Association between renal and splenic infarction in the same patient was related to trauma in two cases. Conclusions: Although renal and splenic infarctions are a common manifestation of cardiac thromboembolism, other systemic pathologies, infections or trauma may lead to this occurrence. Renal infarction may be clinically and/or surgically managed with success in most cases. There are potential complications in splenic infarction, such as development of pseudocysts, abscesses, hemorrhage, subcapsular haematoma or splenic rupture; splenectomy in these cases may be necessary. Some patients with splenic and/or renal infarction may be clinically asymptomatic. The high accuracy of CT examination is needed to allow a correct evaluation of infarcted organs.

  14. [Effects of overexpression of human tissue inhibitor of metalloproteinase-1 on the inflammatory response in rats with myocardial infarction and related mechanisms].

    Science.gov (United States)

    Zhao, L L; Song, Y Q; Zhang, Y; Shi, Y; Ren, M; Liu, S; Mao, Y M

    2017-06-24

    Objective: To observe the effects of recombinant adenovirus with human tissue inhibitor of metalloproteinase-1(Ad-hTIMP-1) on the inflammatory response in rats with myocardial infarction (MI) and explore the related mechanisms. Methods: The male Wistar rats were randomly divided into sham-operated group, saline group, Ad-Track group and Ad-hTIMP-1 group according to the random number table (n=8 each group). MI was induced by ligation of the left anterior descending coronary artery and MI rats were injected with saline, Ad-Track and Ad-hTIMP-1, respectively. Sham-operated rats received similar surgical procedure without ligation of the left anterior descending coronary artery. After 4 weeks, the cardiac function was measured by echocardiography, then rats were sacrificed and hearts were removed for morphological and biological analysis. The morphology of myocardial tissue in each group was detected by HE staining and Masson staining. The mRNA expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and C-reactive protein(CRP) were detected by real-time PCR. Immune histochemical staining was performed to observe the protein expression levels of IL-6 and CRP. Results: (1) Left ventricular end systolic dimension derived from echocardiography was increased in saline group ((5.10±0.72) mm) and Ad-Track group ((4.88±0.64) mm) compared to sham-operated group ((4.25±0.46) mm), which was reduced in Ad-hTIMP-1 group ((4.13±0.35) mm, all Prats with myocardial infarction via inhibiting the inflammatory response and downregulating the expression of TNF-α, IL-6 and CRP.

  15. Recent efforts to model human diseases in vivo in Drosophila.

    Science.gov (United States)

    Pfleger, Cathie M; Reiter, Lawrence T

    2008-01-01

    Upon completion of sequencing the Drosophila genome, it was estimated that 61% of human disease-associated genes had sequence homologs in flies, and in some diseases such as cancer, the number was as high as 68%. We now know that as many as 75% of the genes associated with genetic disease have counterparts in Drosophila. Using better tools for mutation detection, association studies and whole genome analysis the number of human genes associated with genetic disease is steadily increasing. These detection efforts are outpacing the ability to assign function and understand the underlying cause of the disease at the molecular level. Drosophila models can therefore advance human disease research in a number of ways by: establishing the normal role of these gene products during development, elucidating the mechanism underlying disease pathology, and even identifying candidate therapeutic agents for the treatment of human disease. At the 49(th) Annual Drosophila Research Conference in San Diego this year, a number of labs presented their exciting findings on Drosophila models of human disease in both platform presentations and poster sessions. Here we can only briefly review some of these developments, and we apologize that we do not have the time or space to review all of the findings presented which use Drosophila to understand human disease etiology.

  16. Human pluripotent stem cells: applications and challenges in neurological diseases

    Directory of Open Access Journals (Sweden)

    Youssef eHIBAOUI

    2012-07-01

    Full Text Available The ability to generate human pluripotent stem cells (hPSCs holds great promise for the understanding and the treatment of human neurological diseases in modern medicine. The hPSCs are considered for their in vitro use as research tools to provide relevant cellular model for human diseases, drug discovery and toxicity assays and for their in vivo use in regenerative medicine applications. In this review, we highlight recent progress, promises and challenges of hPSC applications in human neurological disease modelling and therapies.

  17. Modeling human disease using organotypic cultures

    DEFF Research Database (Denmark)

    Schweiger, Pawel J; Jensen, Kim B

    2016-01-01

    Reliable disease models are needed in order to improve quality of healthcare. This includes gaining better understanding of disease mechanisms, developing new therapeutic interventions and personalizing treatment. Up-to-date, the majority of our knowledge about disease states comes from in vivo...

  18. In vivo differentiation of human amniotic epithelial cells into cardiomyocyte-like cells and cell transplantation effect on myocardial infarction in rats: comparison with cord blood and adipose tissue-derived mesenchymal stem cells.

    Science.gov (United States)

    Fang, Cheng-Hu; Jin, Jiyong; Joe, Jun-Ho; Song, Yi-Sun; So, Byung-Im; Lim, Sang Moo; Cheon, Gi Jeong; Woo, Sang-Keun; Ra, Jeong-Chan; Lee, Young-Yiul; Kim, Kyung-Soo

    2012-01-01

    Human amniotic epithelial cells (h-AECs), which have various merits as a cell source for cell therapy, are known to differentiate into cardiomyocytes in vitro. However, the ability of h-AECs to differentiate into cardiomyocytes in vivo and their cell transplantation effects on myocardial infarction are still unknown. In this study, we assessed whether h-AECs could differentiate into cardiomyocytes in vivo and whether h-AECs transplantation can decrease infarct size and improve cardiac function, in comparison to transplantation of cord blood-derived mesenchymal stem cells (MSCs) or adipose tissue-derived MSCs. For our study, we injected h-AECs, cord blood-derived MSCs, adipose tissue-derived MSCs, and saline into areas of myocardial infarction in athymic nude rats. After 4 weeks, 3% of the surviving h-AECs expressed myosin heavy chain, a marker specific to the myocardium. Compared with the saline group, all cell-implanted groups showed a higher ejection fraction, lower infarct area by positron emission tomography and histology, and more abundant myocardial gene and protein expression in the infarct area. We showed that h-AECs can differentiate into cardiomyocyte-like cells, decrease infarct size, and improve cardiac function in vivo. The beneficial effects of h-AECs were comparable to those of cord blood and adipose tissue-derived MSCs. These results support the need for further studies of h-AECs as a cell source for myocardial regeneration due to their plentiful availability, low immunity, and lack of ethical issues related to their use.

  19. Segmental Renal Infarction due to Blunt Trauma.

    Science.gov (United States)

    Alevizopoulos, Aristeidis; Hamilton, Lauren; Stratu, Natalia; Rix, Gerald

    2016-05-01

    Segmental renal infarction is a rare situation which has been reported so far in the form of case reports. It's caused usually by cardiac conditions, such as atrial fibrillation, and systemic diseases (e.g. systemic lupus erythematous). We are presenting a case of a 31 year old healthy male, who sustained a left segmental renal infarction, following a motorbike accident. We report his presentation, management and outcome. We also review the literature in search of the optimal diagnostic and treatment pathway. To our knowledge, this is the first report of segmental renal infarction due to blunt trauma.

  20. Myocardial infarction-induced N-terminal fragment of cardiac myosin-binding protein C (cMyBP-C) impairs myofilament function in human myocardium.

    Science.gov (United States)

    Witayavanitkul, Namthip; Ait Mou, Younss; Kuster, Diederik W D; Khairallah, Ramzi J; Sarkey, Jason; Govindan, Suresh; Chen, Xin; Ge, Ying; Rajan, Sudarsan; Wieczorek, David F; Irving, Thomas; Westfall, Margaret V; de Tombe, Pieter P; Sadayappan, Sakthivel

    2014-03-28

    Myocardial infarction (MI) is associated with depressed cardiac contractile function and progression to heart failure. Cardiac myosin-binding protein C, a cardiac-specific myofilament protein, is proteolyzed post-MI in humans, which results in an N-terminal fragment, C0-C1f. The presence of C0-C1f in cultured cardiomyocytes results in decreased Ca(2+) transients and cell shortening, abnormalities sufficient for the induction of heart failure in a mouse model. However, the underlying mechanisms remain unclear. Here, we investigate the association between C0-C1f and altered contractility in human cardiac myofilaments in vitro. To accomplish this, we generated recombinant human C0-C1f (hC0C1f) and incorporated it into permeabilized human left ventricular myocardium. Mechanical properties were studied at short (2 μm) and long (2.3 μm) sarcomere length (SL). Our data demonstrate that the presence of hC0C1f in the sarcomere had the greatest effect at short, but not long, SL, decreasing maximal force and myofilament Ca(2+) sensitivity. Moreover, hC0C1f led to increased cooperative activation, cross-bridge cycling kinetics, and tension cost, with greater effects at short SL. We further established that the effects of hC0C1f occur through direct interaction with actin and α-tropomyosin. Our data demonstrate that the presence of hC0C1f in the sarcomere is sufficient to induce depressed myofilament function and Ca(2+) sensitivity in otherwise healthy human donor myocardium. Decreased cardiac function post-MI may result, in part, from the ability of hC0C1f to bind actin and α-tropomyosin, suggesting that cleaved C0-C1f could act as a poison polypeptide and disrupt the interaction of native cardiac myosin-binding protein C with the thin filament.

  1. Culprit vessel only versus multivessel percutaneous coronary intervention in patients presenting with ST-segment elevation myocardial infarction and multivessel disease.

    Directory of Open Access Journals (Sweden)

    Dongfeng Zhang

    Full Text Available BACKGROUND: The best strategy for ST-segment elevation myocardial infarction (STEMI patients with multivessel disease (MVD, who underwent primary percutaneous coronary intervention (PCI in the acute phase, is not well established. OBJECTIVES: Our goal was to conduct a meta-analysis comparing culprit vessel only percutaneous coronary intervention (culprit PCI with multivessel percutaneous coronary intervention (MV-PCI for treatment of patients with STEMI and MVD. METHODS: Pubmed, Elsevier, Embase, and China National Knowledge Infrastructure (CNKI databases were systematically searched for randomized and nonrandomized studies comparing culprit PCI and MV-PCI strategies during the index procedure. A meta-analysis was performed using Review Manager 5.1 (Cochrane Center, Denmark. RESULTS: Four randomized and fourteen nonrandomized studies involving 39,390 patients were included. MV-PCI strategy is associated with an increased short-term mortality (OR: 0.50, 95% CI: 0.32 to 0.77, p = 0.002, long-term mortality (OR: 0.52, 95% CI: 0.36 to 0.74, p<0.001, and risk of renal dysfunction (OR: 0.77, 95% CI: 0.61 to 0.97, p = 0.03 compared with culprit PCI strategy, while it reduced the incidence of revascularization (OR: 2.65, 95% CI: 1.80 to 3.90, p<0.001. CONCLUSIONS: This meta-analysis supports current guidelines which indicate that the non-culprit vessel should not be treated during the index procedure.

  2. Omega-3 Status and the Relationship between Plasma Asymmetric Dimethylarginine and Risk of Myocardial Infarction in Patients with Suspected Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Heidi Borgeraas

    2012-01-01

    Full Text Available Background. Asymmetric dimethylarginine (ADMA is an endogenous inhibitor of nitric oxide synthase. A previous rat study revealed an ADMA lowering effect following treatment with omega-3 polyunsaturated fatty acids (n-3 PUFAs. We sought to examine if an association between plasma ADMA and risk of acute myocardial infarction (AMI was modified by serum n-3 PUFA status. Methods. The cohort included 1364 patients who underwent coronary angiography for suspected coronary artery disease in 2000-2001. Fatal and nonfatal AMI events were registered until December 31, 2006. Risk associations with AMI were estimated across ADMA quartiles (linear trend and the upper decile. Results. No association between concentration of any n-3 PUFA and ADMA was observed. Only ADMA levels in upper decile were significantly associated with AMI with a multivariate adjusted hazard ratio (HR (95% confidence interval versus the rest of the population of 2.11 (1.34, 3.32. The association was strengthened among patients with below median levels of α-linolenic acid (ALA (HR 3.12 (1.64, 5.93, but was only influenced by longer chain n-3 PUFA after additional adjustments for HbA1c, estimated glomerular filtration rate, and hypercholesterolemia. Conclusions. The association of ADMA with risk of AMI is influenced by serum n-3 PUFA and particularly ALA.

  3. The optimal strategy of percutaneous coronary intervention for ST-elevation myocardial infarction patients with multivessel disease: an updated meta-analysis of 9 randomized controlled trials.

    Science.gov (United States)

    Fan, Zhong G; Gao, Xiao F; Li, Xiao B; Mao, Wen X; Chen, Li W; Tian, Nai L

    2017-04-01

    The optimal strategy of percutaneous coronary intervention (PCI) for patients with ST-elevation myocardial infarction (STEMI) and multivessel disease (MVD) still remains controversial. This study sought to explore the optimal PCI strategy for those patients. Medline, EMBASE and the Cochrane Controlled Trials Registry were searched for relevant studies. We analyzed the comparison of major adverse cardiac events (MACEs) as the primary end point between the preventive PCI strategy and the culprit only PCI strategy (CV-PCI). The further analysis of two subgroups described as the complete multivessel PCI strategy during primary procedure (CMV-PCI) and the staged PCI strategy (S-PCI) was also performed. Nine randomized trials were identified. The risk of MACEs was reduced significantly regarding to preventive PCI strategy (OR=0.41, 95% CI: 0.31-0.53, Pstrategy. There were lower risks of long-term mortality, reinfarction and repeat revascularization in the preventive PCI group compared to the CV-PCI group (OR=0.41, 95% CI: 0.27-0.62, Pstrategy reduced the incidence of long-term mortality versus CMV-PCI strategy. The preventive PCI is associated with the lower risk of MACEs in STEMI patients with MVD compared to the CV-PCI strategy, and the S-PCI strategy seems to be an optimal choice for these patients rather than the CMV-PCI.

  4. Multinational corporations and infectious disease: Embracing human rights management techniques.

    Science.gov (United States)

    Salcito, Kendyl; Singer, Burton H; Weiss, Mitchell G; Winkler, Mirko S; Krieger, Gary R; Wielga, Mark; Utzinger, Jürg

    2014-01-01

    Global health institutions have called for governments, international organisations and health practitioners to employ a human rights-based approach to infectious diseases. The motivation for a human rights approach is clear: poverty and inequality create conditions for infectious diseases to thrive, and the diseases, in turn, interact with social-ecological systems to promulgate poverty, inequity and indignity. Governments and intergovernmental organisations should be concerned with the control and elimination of these diseases, as widespread infections delay economic growth and contribute to higher healthcare costs and slower processes for realising universal human rights. These social determinants and economic outcomes associated with infectious diseases should interest multinational companies, partly because they have bearing on corporate productivity and, increasingly, because new global norms impose on companies a responsibility to respect human rights, including the right to health. We reviewed historical and recent developments at the interface of infectious diseases, human rights and multinational corporations. Our investigation was supplemented with field-level insights at corporate capital projects that were developed in areas of high endemicity of infectious diseases, which embraced rights-based disease control strategies. Experience and literature provide a longstanding business case and an emerging social responsibility case for corporations to apply a human rights approach to health programmes at global operations. Indeed, in an increasingly globalised and interconnected world, multinational corporations have an interest, and an important role to play, in advancing rights-based control strategies for infectious diseases. There are new opportunities for governments and international health agencies to enlist corporate business actors in disease control and elimination strategies. Guidance offered by the United Nations in 2011 that is widely embraced

  5. Experimental cell transplantation therapy in rat myocardial infarction model including nude rat preparation.

    Science.gov (United States)

    Dai, Wangde; Kloner, Robert A

    2010-01-01

    As a novel potential therapeutic strategy for cardiac disease, cell transplantation therapy has been extensively investigated in experimental studies and clinical trials. Although encouraging results have been demonstrated, a number of critical questions still remain to be answered. For example, what kind of stem cell and how many cells should be used; what is the best time for cell transplantation after acute myocardial infarction; which delivery approach is better, intravenous injection or direct intramyocardial injection? Transplantation of cells derived from human tissues into experimental animals may elicit an immune rejection. Immunodeficient nude rats provide a useful myocardial infarction model for cell transplantation therapy studies. We introduce our detailed methods of direct intramyocardial injection of immature heart cells and stem cells into the myocardial infarction region of rats and nude rats. Careful maintenance under aseptic conditions and proper surgical technique are essential to improve the survival of immunodeficient rats after surgery.

  6. Acute Myocardial Infarction and Pulmonary Diseases Result in Two Different Degradation Profiles of Elastin as Quantified by Two Novel ELISAs

    DEFF Research Database (Denmark)

    Skjøt-Arkil, Helene; Clausen, Rikke E; Rasmussen, Lars M

    2013-01-01

    BACKGROUND: Elastin is a signature protein of the arteries and lungs, thus it was hypothesized that elastin is subject to enzymatic degradation during cardiovascular and pulmonary diseases. The aim was to investigate if different fragments of the same protein entail different information associated......: ELM and ELM-2 neoepitopes were both localized in diseased carotid arteries and fibrotic lungs. In the cardiovascular cohort, ELM-2 levels were 66% higher in serum from AMI patients compared to patients with no AMI (p... to two different diseases and if these fragments have the potential of being diagnostic biomarkers. METHODS: Monoclonal antibodies were raised against an identified fragment (the ELM-2 neoepitope) generated at the amino acid position '552 in elastin by matrix metalloproteinase (MMP) -9/-12. A newly...

  7. Intramyocardial transplantation and tracking of human mesenchymal stem cells in a novel intra-uterine pre-immune fetal sheep myocardial infarction model: a proof of concept study.

    Science.gov (United States)

    Emmert, Maximilian Y; Weber, Benedikt; Wolint, Petra; Frauenfelder, Thomas; Zeisberger, Steffen M; Behr, Luc; Sammut, Sebastien; Scherman, Jacques; Brokopp, Chad E; Schwartländer, Ruth; Vogel, Viola; Vogt, Peter; Grünenfelder, Jürg; Alkadhi, Hatem; Falk, Volkmar; Boss, Andreas; Hoerstrup, Simon P

    2013-01-01

    Although stem-cell therapies have been suggested for cardiac-regeneration after myocardial-infarction (MI), key-questions regarding the in-vivo cell-fate remain unknown. While most available animal-models require immunosuppressive-therapy when applying human cells, the fetal-sheep being pre-immune until day 75 of gestation has been proposed for the in-vivo tracking of human cells after intra-peritoneal transplantation. We introduce a novel intra-uterine myocardial-infarction model to track human mesenchymal stem cells after direct intra-myocardial transplantation into the pre-immune fetal-sheep. Thirteen fetal-sheep (gestation age: 70-75 days) were included. Ten animals either received an intra-uterine induction of MI only (n = 4) or MI+intra-myocardial injection (IMI;n = 6) using micron-sized, iron-oxide (MPIO) labeled human mesenchymal stem cells either derived from the adipose-tissue (ATMSCs;n = 3) or the bone-marrow (BMMSCs;n = 3). Three animals received an intra-peritoneal injection (IPI;n = 3; ATMSCs;n = 2/BMMSCs;n = 1). All procedures were performed successfully and follow-up was 7-9 days. To assess human cell-fate, multimodal cell-tracking was performed via MRI and/or Micro-CT, Flow-Cytometry, PCR and immunohistochemistry. After IMI, MRI displayed an estimated amount of 1×10(5)-5×10(5) human cells within ventricular-wall corresponding to the injection-sites which was further confirmed on Micro-CT. PCR and IHC verified intra-myocardial presence via detection of human-specific β-2-microglobulin, MHC-1, ALU-Sequence and anti-FITC targeting the fluorochrome-labeled part of the MPIOs. The cells appeared viable, integrated and were found in clusters or in the interstitial-spaces. Flow-Cytometry confirmed intra-myocardial presence, and showed further distribution within the spleen, lungs, kidneys and brain. Following IPI, MRI indicated the cells within the intra-peritoneal-cavity involving the liver and kidneys. Flow

  8. Intramyocardial transplantation and tracking of human mesenchymal stem cells in a novel intra-uterine pre-immune fetal sheep myocardial infarction model: a proof of concept study.

    Directory of Open Access Journals (Sweden)

    Maximilian Y Emmert

    Full Text Available Although stem-cell therapies have been suggested for cardiac-regeneration after myocardial-infarction (MI, key-questions regarding the in-vivo cell-fate remain unknown. While most available animal-models require immunosuppressive-therapy when applying human cells, the fetal-sheep being pre-immune until day 75 of gestation has been proposed for the in-vivo tracking of human cells after intra-peritoneal transplantation. We introduce a novel intra-uterine myocardial-infarction model to track human mesenchymal stem cells after direct intra-myocardial transplantation into the pre-immune fetal-sheep. Thirteen fetal-sheep (gestation age: 70-75 days were included. Ten animals either received an intra-uterine induction of MI only (n = 4 or MI+intra-myocardial injection (IMI;n = 6 using micron-sized, iron-oxide (MPIO labeled human mesenchymal stem cells either derived from the adipose-tissue (ATMSCs;n = 3 or the bone-marrow (BMMSCs;n = 3. Three animals received an intra-peritoneal injection (IPI;n = 3; ATMSCs;n = 2/BMMSCs;n = 1. All procedures were performed successfully and follow-up was 7-9 days. To assess human cell-fate, multimodal cell-tracking was performed via MRI and/or Micro-CT, Flow-Cytometry, PCR and immunohistochemistry. After IMI, MRI displayed an estimated amount of 1×10(5-5×10(5 human cells within ventricular-wall corresponding to the injection-sites which was further confirmed on Micro-CT. PCR and IHC verified intra-myocardial presence via detection of human-specific β-2-microglobulin, MHC-1, ALU-Sequence and anti-FITC targeting the fluorochrome-labeled part of the MPIOs. The cells appeared viable, integrated and were found in clusters or in the interstitial-spaces. Flow-Cytometry confirmed intra-myocardial presence, and showed further distribution within the spleen, lungs, kidneys and brain. Following IPI, MRI indicated the cells within the intra-peritoneal-cavity involving the liver and kidneys. Flow

  9. Extracellular RNAs: development as biomarkers of human disease

    Directory of Open Access Journals (Sweden)

    Joseph F. Quinn

    2015-08-01

    Full Text Available Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described. These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid. The disorders studied include hepatic and gastric cancer, cardiovascular disease, chronic kidney disease, neurodegenerative disease, brain tumours, intracranial haemorrhage, multiple sclerosis and placental disorders. Progress to date and the plans for future studies are outlined.

  10. Protein kinase CK2 in human diseases

    DEFF Research Database (Denmark)

    Guerra, Barbara; Issinger, Olaf-Georg

    2008-01-01

    in various disease processes including cancer has been gained in recent years, and the present review may help to further elucidate its aberrant role in many disease states. Its peculiar structural features [3-9] may be advantageous in designing tailor-made compounds with the possibility to specifically...

  11. The genus Malassezia and human disease

    Directory of Open Access Journals (Sweden)

    Inamadar A

    2003-07-01

    Full Text Available Sabouraud's Pityrosporum is now recognized as Malassezia. With taxonomic revision of the genus, newer species have been included. The role of this member of the normal human skin flora in different cutaneous and systemic disorders is becoming clearer. The immunological responses it induces in the human body are conflicting and their relevance to clinical features is yet to be explored.

  12. Myocardial infarction and subsequent pregnancy

    Directory of Open Access Journals (Sweden)

    Tedoldi Citânia Lúcia

    2000-01-01

    Full Text Available We report the case of a 40-year-old woman with 2 previous myocardial infarctions, revascularization surgery, and an ongoing pregnancy complicated with preeclampsia and fetal hypoxia. Her follow-up performed by a multidisciplinary team made possible the birth through cesarean section of a premature infant of the female sex with a very low birth weight, but without severe respiratory distress of the hyaline membrane disease type. Three months after the delivery, mother and daughter were healthy.

  13. Statistical insights into major human muscular diseases.

    Science.gov (United States)

    Gupta, Shakti; Kim, Sung-Min; Wang, Yu; Dinasarapu, Ashok Reddy; Subramaniam, Shankar

    2014-07-15

    Muscular diseases lead to muscle fiber degeneration, impairment of mobility, and in some cases premature death. Many of these muscular diseases are largely idiopathic. The goal of this study was to identify biomarkers based on their functional role and possible mechanisms of pathogenesis, specific to individual muscular disease. We analyzed the muscle transcriptome from five major muscular diseases: acute quadriplegic myopathy (AQM), amyotrophic lateral sclerosis (ALS), mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), dermatomyositis (DM) and polymyositis (PM) using pairwise statistical comparison to identify uniquely regulated genes in each muscular disease. The genome-wide information encoded in the transcriptome provided biomarkers and functional insights into dysregulation in each muscular disease. The analysis showed that the dysregulation of genes in forward membrane pathway, responsible for transmitting action potential from neural excitation, is unique to AQM, while the dysregulation of myofibril genes, determinant of the mechanical properties of muscle, is unique to ALS, dysregulation of ER protein processing, responsible for correct protein folding, is unique to DM, and upregulation of immune response genes is unique to PM. We have identified biomarkers specific to each muscular disease which can be used for diagnostic purposes.

  14. Metatranscriptomics of the human oral microbiome during health and disease.

    Science.gov (United States)

    Jorth, Peter; Turner, Keith H; Gumus, Pinar; Nizam, Nejat; Buduneli, Nurcan; Whiteley, Marvin

    2014-04-01

    The human microbiome plays important roles in health, but when disrupted, these same indigenous microbes can cause disease. The composition of the microbiome changes during the transition from health to disease; however, these changes are often not conserved among patients. Since microbiome-associated diseases like periodontitis cause similar patient symptoms despite interpatient variability in microbial community composition, we hypothesized that human-associated microbial communities undergo conserved changes in metabolism during disease. Here, we used patient-matched healthy and diseased samples to compare gene expression of 160,000 genes in healthy and diseased periodontal communities. We show that health- and disease-associated communities exhibit defined differences in metabolism that are conserved between patients. In contrast, the metabolic gene expression of individual species was highly variable between patients. These results demonstrate that despite high interpatient variability in microbial composition, disease-associated communities display conserved metabolic profiles that are generally accomplished by a patient-specific cohort of microbes. IMPORTANCE The human microbiome project has shown that shifts in our microbiota are associated with many diseases, including obesity, Crohn's disease, diabetes, and periodontitis. While changes in microbial populations are apparent during these diseases, the species associated with each disease can vary from patient to patient. Taking into account this interpatient variability, we hypothesized that specific microbiota-associated diseases would be marked by conserved microbial community behaviors. Here, we use gene expression analyses of patient-matched healthy and diseased human periodontal plaque to show that microbial communities have highly conserved metabolic gene expression profiles, whereas individual species within the community do not. Furthermore, disease-associated communities exhibit conserved changes

  15. Enlarged perivascular spaces and lacunar infarction Cerebral magnetic resonance evaluation

    Institute of Scientific and Technical Information of China (English)

    Weihong Yan; Jing Fang; Cuijuan Zhou

    2008-01-01

    BACKGROUND:Previous studies have demonstrated that enlarged perivascular spaces(EPVS)arg a result of microvaseular disease.To date,there age few reports about the relationship between EPVS and lacunar infarction.OBJECTIVE:To investigate whether EPVS is associated with lacunar infarction on the basis of cerebral magnetic resonance(MR)examination,clinical symptoms and signs,and past medical history of patients.DESIGN,TIME AND SETTING:Case contrast analysis was performed at the Department of Neurology,Shanghai Ninth People's Hospital from January 2007 to January 2008.PARTICIPANTS:Sixty-eight patients with lacunar infarction were admired to the Department of Neurology of Shanghai Ninth People's Hospital,including 37 cases with first-ever infarction,and 31 with infarction recurrence.In addition,53 healthy people were selected as controls.METHODS:All participants underwent past medical history investigation,nervous system examination.and cranial MR.The subjects were assessed using the JMW rating scale to identify the EPVS grade.MAIN OUTCOME MEASURES:EPVS scores of patients and controls;risk factors for cerebral vascular disease in patients with first-ever or recurrence of lacunar infarction.RESULTS:The EPVS grade from lacunar infarction patients was significantly higher than of the control group(P<0.05).The EPVS grade in patients with recurring lacunar infarction was significantly higher than in patients with first-ever infarction(P<0.05).In addition,hypertension incidence in patients with recurring lacunar infarction was significantly higher than in patients wim first-ever infarction (P<0.05).CONCLUSION:Results indicate that EPVS is related to the incidence of lacunar infarction.Earlier screening of EPVS.and the evaluation of EPVS severity,is of great importance to control the risk factors for cerebral vascular disease and to prevent lacunar infarction.

  16. Human Milk and Allergic Diseases: An Unsolved Puzzle

    Science.gov (United States)

    Peroni, Diego G.; Boix-Amorós, Alba; Hsu, Peter S.; Van’t Land, Belinda; Skevaki, Chrysanthi; Collado, Maria Carmen; Garssen, Johan; Geddes, Donna T.; Nanan, Ralph; Slupsky, Carolyn; Wegienka, Ganesa; Kozyrskyj, Anita L.; Warner, John O.

    2017-01-01

    There is conflicting evidence on the protective role of breastfeeding in relation to the development of allergic sensitisation and allergic disease. Studies vary in methodology and definition of outcomes, which lead to considerable heterogeneity. Human milk composition varies both within and between individuals, which may partially explain conflicting data. It is known that human milk composition is very complex and contains variable levels of immune active molecules, oligosaccharides, metabolites, vitamins and other nutrients and microbial content. Existing evidence suggests that modulation of human breast milk composition has potential for preventing allergic diseases in early life. In this review, we discuss associations between breastfeeding/human milk composition and allergy development. PMID:28817095

  17. Disease Human - MDC_CLRDMortality2006

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — Polygon feature class based on Zip Code boundaries showing the rate of deaths per 100,000 residents due to Chronic Lower Respiratory Disease (CLRD) in Miami-Dade...

  18. "Miniguts" from plucked human hair meet Crohn's disease.

    Science.gov (United States)

    Hohwieler, M; Renz, S; Liebau, S; Lin, Q; Lechel, A; Klaus, J; Perkhofer, L; Zenke, M; Seufferlein, T; Illing, A; Müller, M; Kleger, A

    2016-08-01

    Human pluripotent stem cells represent a powerful tool to study human embryonic development and disease but also open up novel strategies for cell replacement therapies. Their capacity to give rise to every cell type of the human body, meanwhile, enables researchers to generate high yields of mesodermal, ectodermal, but also endodermal-derived tissues such as hepatic, pancreatic, or intestinal cells. Another progress in the field came with the advent of 3-dimensional culture conditions, so-called organoids, which facilitate maturation of stem cells and in turn more faithfully recapitulate human tissue architecture. While several studies reported the derivation of organoid cultures from adult intestinal tissue, the derivation of intestinal organoids derived from plucked human hair of Crohn's disease patients has not been reported. The current research project reports such successful generation and characterization of induced pluripotent stem cells (iPSCs) derived from hair sheet keratinocyte cultures of a patient with Crohn's disease. Stepwise differentiation along the intestinal lineage showed no differences in intermediate stages such as definitive endoderm formation. We also directed the patterned primitive gut tube toward intestinal organoids resembling the cellular architecture of human "miniguts". As expected from current pathophysiological knowledge on Crohn's disease, there were no obvious morphological differences in the "miniguts" derived from healthy control and diseased patient-induced pluripotent stem cells. Taken together, our platform will enable for detailed and complementary phenotyping of the pathophysiology of Crohn's disease in a novel disease-in-a-dish format.

  19. Genomic responses in mouse models poorly mimic human inflammatory diseases.

    Science.gov (United States)

    Seok, Junhee; Warren, H Shaw; Cuenca, Alex G; Mindrinos, Michael N; Baker, Henry V; Xu, Weihong; Richards, Daniel R; McDonald-Smith, Grace P; Gao, Hong; Hennessy, Laura; Finnerty, Celeste C; López, Cecilia M; Honari, Shari; Moore, Ernest E; Minei, Joseph P; Cuschieri, Joseph; Bankey, Paul E; Johnson, Jeffrey L; Sperry, Jason; Nathens, Avery B; Billiar, Timothy R; West, Michael A; Jeschke, Marc G; Klein, Matthew B; Gamelli, Richard L; Gibran, Nicole S; Brownstein, Bernard H; Miller-Graziano, Carol; Calvano, Steve E; Mason, Philip H; Cobb, J Perren; Rahme, Laurence G; Lowry, Stephen F; Maier, Ronald V; Moldawer, Lyle L; Herndon, David N; Davis, Ronald W; Xiao, Wenzhong; Tompkins, Ronald G

    2013-02-26

    A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R(2) between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.

  20. Genomic responses in mouse models poorly mimic human inflammatory diseases

    Science.gov (United States)

    Seok, Junhee; Warren, H. Shaw; Cuenca, Alex G.; Mindrinos, Michael N.; Baker, Henry V.; Xu, Weihong; Richards, Daniel R.; McDonald-Smith, Grace P.; Gao, Hong; Hennessy, Laura; Finnerty, Celeste C.; López, Cecilia M.; Honari, Shari; Moore, Ernest E.; Minei, Joseph P.; Cuschieri, Joseph; Bankey, Paul E.; Johnson, Jeffrey L.; Sperry, Jason; Nathens, Avery B.; Billiar, Timothy R.; West, Michael A.; Jeschke, Marc G.; Klein, Matthew B.; Gamelli, Richard L.; Gibran, Nicole S.; Brownstein, Bernard H.; Miller-Graziano, Carol; Calvano, Steve E.; Mason, Philip H.; Cobb, J. Perren; Rahme, Laurence G.; Lowry, Stephen F.; Maier, Ronald V.; Moldawer, Lyle L.; Herndon, David N.; Davis, Ronald W.; Xiao, Wenzhong; Tompkins, Ronald G.; Abouhamze, Amer; Balis, Ulysses G. J.; Camp, David G.; De, Asit K.; Harbrecht, Brian G.; Hayden, Douglas L.; Kaushal, Amit; O’Keefe, Grant E.; Kotz, Kenneth T.; Qian, Weijun; Schoenfeld, David A.; Shapiro, Michael B.; Silver, Geoffrey M.; Smith, Richard D.; Storey, John D.; Tibshirani, Robert; Toner, Mehmet; Wilhelmy, Julie; Wispelwey, Bram; Wong, Wing H

    2013-01-01

    A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R2 between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases. PMID:23401516

  1. Human papillomavirus infection and disease in men: Impact of HIV ...

    African Journals Online (AJOL)

    Human papillomavirus infection and disease in men: Impact of HIV. ... Journal Home > Vol 14, No 4 (2013) > ... HIV infection increases HPV prevalence, incidence and persistence and is strongly associated with the development of anogenital ...

  2. Altered gene expression pattern in peripheral blood mononuclear cells in patients with acute myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Marek Kiliszek

    Full Text Available BACKGROUND: Despite a substantial progress in diagnosis and therapy, acute myocardial infarction (MI is a major cause of mortality in the general population. A novel insight into the pathophysiology of myocardial infarction obtained by studying gene expression should help to discover novel biomarkers of MI and to suggest novel strategies of therapy. The aim of our study was to establish gene expression patterns in leukocytes from acute myocardial infarction patients. METHODS AND RESULTS: Twenty-eight patients with ST-segment elevation myocardial infarction (STEMI were included. The blood was collected on the 1(st day of myocardial infarction, after 4-6 days, and after 6 months. Control group comprised 14 patients with stable coronary artery disease, without history of myocardial infarction. Gene expression analysis was performed with Affymetrix Human Gene 1.0 ST microarrays and GCS3000 TG system. Lists of genes showing altered expression levels (fold change >1.5, p<0.05 were submitted to Ingenuity Pathway Analysis. Gene lists from each group were examined for canonical pathways and molecular and cellular functions. Comparing acute phase of MI with the same patients after 6 months (stable phase and with control group we found 24 genes with changed expression. In canonical analysis three pathways were highlighted: signaling of PPAR (peroxisome proliferator-activated receptor, IL-10 and IL-6 (interleukin 10 and 6. CONCLUSIONS: In the acute phase of STEMI, dozens of genes from several pathways linked with lipid/glucose metabolism, platelet function and atherosclerotic plaque stability show altered expression. Up-regulation of SOCS3 and FAM20 genes in the first days of myocardial infarction is observed in the vast majority of patients.

  3. [Segmental testicular infarction in sickle cell anemia].

    Science.gov (United States)

    Mueller, F E

    2014-05-01

    Vascular occlusions are the clinical indicators of sickle cell disease and in urology they can lead to papillary necrosis, renal infarction or priapism. Segmental testicular infarction in patients with sickle cell disease is a rare event and only a few cases have been reported. We present a 25-year-old man with right testicular pain increasing over 3 days and sickle cell disease. Ultrasound of the right scrotum presented an inhomogeneous, mainly hypoechegenic mass with a hyperechogenic margin and no sign of blood flow. A partial orchiectomy was performed with total enucleation of the lesion, which was histologically diagnosed as benign hemorrhagic necrotic testicular tissue.

  4. Human copy number variation and complex genetic disease.

    Science.gov (United States)

    Girirajan, Santhosh; Campbell, Catarina D; Eichler, Evan E

    2011-01-01

    Copy number variants (CNVs) play an important role in human disease and population diversity. Advancements in technology have allowed for the analysis of CNVs in thousands of individuals with disease in addition to thousands of controls. These studies have identified rare CNVs associated with neuropsychiatric diseases such as autism, schizophrenia, and intellectual disability. In addition, copy number polymorphisms (CNPs) are present at higher frequencies in the population, show high diversity in copy number, sequence, and structure, and have been associated with multiple phenotypes, primarily related to immune or environmental response. However, the landscape of copy number variation still remains largely unexplored, especially for smaller CNVs and those embedded within complex regions of the human genome. An integrated approach including characterization of single nucleotide variants and CNVs in a large number of individuals with disease and normal genomes holds the promise of thoroughly elucidating the genetic basis of human disease and diversity.

  5. The human microbiome in rheumatic autoimmune diseases: A comprehensive review.

    Science.gov (United States)

    Coit, Patrick; Sawalha, Amr H

    2016-09-01

    The human microbiome consists of the total diversity of microbiota and their genes. High-throughput sequencing has allowed for inexpensive and rapid evaluation of taxonomic representation and functional capability of the microbiomes of human body sites. Autoimmune and inflammatory rheumatic diseases are characterized by dysbiosis of the microbiome. Microbiome dysbiosis can be influenced by host genetics and environmental factors. Dysbiosis is also associated with shifts in certain functional pathways. The goal of this article is to provide a current and comprehensive review of the unique characteristics of the microbiome of patients with autoimmune and inflammatory rheumatic diseases, measured using high-throughput sequencing. We also highlight the need for broader studies utilizing a longitudinal approach to better understand how the human microbiome contributes to disease susceptibility, and to characterize the role of the interaction between host genetics and microbial diversity in the pathogenesis of autoimmune diseases, disease manifestations, and progression.

  6. A collagen α2(I) mutation impairs healing after experimental myocardial infarction.

    Science.gov (United States)

    Hofmann, Ulrich; Bonz, Andreas; Frantz, Stefan; Hu, Kai; Waller, Christiane; Roemer, Katrin; Wolf, Jürgen; Gattenlöhner, Stefan; Bauersachs, Johann; Ertl, Georg

    2012-01-01

    Collagen breakdown and de novo synthesis are important processes during early wound healing after myocardial infarction (MI). We tested the hypothesis that collagen I, the main constituent of the extracellular matrix, affects wound healing after MI. The osteogenesis imperfecta mouse (OIM), lacking procollagen-α2(I) expression, represents a model of the type III form of the disease in humans. Homozygous (OIM/OIM), heterozygous (OIM/WT), and wild-type (WT/WT) mice were subjected to a permanent myocardial infarction protocol or sham surgery. Baseline functional and geometrical parameters determined by echocardiography did not differ between genotypes. After MI but not after sham surgery, OIM/OIM animals exhibited significantly increased mortality, due to early ventricular rupture between day 3 and 7. Echocardiography at day 1 demonstrated increased left ventricular dilation in OIM/OIM animals. Less collagen I mRNA within the infarct area was found in OIM/OIM animals. At 2 days after MI, MMP-9 expression in the infarct border zone was higher in OIM/OIM than in WT/WT animals. Increased granulocyte infiltration into the infarct border zone occurred in OIM/OIM animals. Neither granulocyte depletion nor MMP inhibition reduced mortality in OIM/OIM animals. In this murine model, deficiency of collagen I leads to a myocardial wound-healing defect. Both structural alterations within pre-existing collagen matrix and impaired collagen de novo expression contribute to a high rate of early myocardial rupture after MI.

  7. Ambulatory ST segment monitoring after myocardial infarction

    DEFF Research Database (Denmark)

    Mickley, H

    1994-01-01

    The prevalence of transient myocardial ischaemia after myocardial infarction seems to be lower than in other subgroups with coronary artery disease. In postinfarction patients, however, a greater proportion of ischaemic episodes are silent. At present there is substantial evidence that transient...... ischaemia provides prognostic information in different subsets of patients with previous myocardial infarction, but there is considerable disagreement about how this is expressed in terms of cardiac events. Small patient numbers, patient selection, and different timing of ambulatory monitoring are proposed...... be that it can be performed early after infarction at the time of maximum risk. Secondly, it can be performed in most patients after infarction, including those recognised as being at high risk who are unable to perform an exercise stress test....

  8. Discoidin Domain Receptors Role in Human Diseases

    Directory of Open Access Journals (Sweden)

    Iker BADIOLA

    2011-11-01

    Full Text Available Discoidin Domain Receptor 1 and Discodin Domain Receptor 2 are the two only members of the DDR family. The DDR family is a Tyrosine Kinase Receptor (TKR family with some peculiarities compared with other Tyrosine Kinase Receptors such as their natural ligand; which in this case is the fibrillar collagen; or the slow phosphorylation pattern. These peculiarities confer a special role to the receptors present in many diseases development processes as cancer, cirrhosis or lung fibrosis. In this review it is described the overview of the DDRs structure and their role in the different disease development and the possibility to consider them as therapeutic targets.

  9. Advances in chromatin remodeling and human disease.

    Science.gov (United States)

    Cho, Kyoung Sang; Elizondo, Leah I; Boerkoel, Cornelius F

    2004-06-01

    Epigenetic factors alter phenotype without changing genotype. A primary molecular mechanism underlying epigenetics is the alteration of chromatin structure by covalent DNA modifications, covalent histone modifications, and nucleosome reorganization. Remodeling of chromatin structure regulates DNA methylation, replication, recombination, and repair as well as gene expression. As these functions would predict, dysfunction of the proteins that remodel chromatin causes an array of multi-system disorders and neoplasias. Insights from these diseases suggest that during embryonic and fetal life, environmental distortions of chromatin remodeling encode a 'molecular memory' that predispose the individual to diseases in adulthood.

  10. Protein kinase CK2 in human diseases

    DEFF Research Database (Denmark)

    Guerra, Barbara; Issinger, Olaf-Georg

    2008-01-01

    in various disease processes including cancer has been gained in recent years, and the present review may help to further elucidate its aberrant role in many disease states. Its peculiar structural features [3-9] may be advantageous in designing tailor-made compounds with the possibility to specifically...... target this protein kinase [10]. Since not all the aspects of what has been published on CK2 can be covered in this review, we would like to recommend the following reviews; (i) for general information on CK2 [11-18] and (ii) with a focus on aberrant CK2 [19-22]....

  11. [Stem cell perspectives in myocardial infarctions].

    Science.gov (United States)

    Aceves, José Luis; Archundia, Abel; Díaz, Guillermo; Páez, Araceli; Masso, Felipe; Alvarado, Martha; López, Manuel; Aceves, Rocío; Ixcamparij, Carlos; Puente, Adriana; Vilchis, Rafael; Montaño, Luis Felipe

    2005-01-01

    Myocardial infarction is the leading cause of congestive heart failure and death in industrializated countries. The cellular cardiomyoplasty has emerged as an alternative treatment in the regeneration of infarted myocardial tissue. In animals' models, different cellular lines such as cardiomyocites, skeletal myoblasts, embryonic stem cells and adult mesenchymal stem cells have been used, resulting in an improvement in ventricular function and decrease in amount of infarcted tissue. The first three cells lines have disvantages as they are allogenics and are difficult to obtain. The adult mesenchymal stem cells are autologous and can be obtained throught the aspiration of bone marrow or from peripherical circulation, after stimulating with cytokines (G-CSF). The implantation in humans with recent and old myocardial infarction have shown improvements similar to those shown in animal models. These findings encourage the continued investigation in the mechanism of cellular differentiation and implantation methods in infarcted myocardial tissue.

  12. Polymorphisms of the Toll-like receptors and human disease.

    Science.gov (United States)

    Schwartz, David A; Cook, Donald N

    2005-11-15

    The Toll-like receptor (TLR) family regulates both innate and adaptive immune responses. Given its broad effect on immunity, the function of TLRs in various human diseases has been investigated largely by comparing the incidence of disease among persons with different polymorphisms in the genes that participate in TLR signaling. These studies demonstrate that TLR function affects several diseases, including sepsis, immunodeficiencies, atherosclerosis, and asthma. These findings have resulted in new opportunities to study the pathogenesis of disease, identify subpopulations at greater risk of disease, and, potentially, identify novel therapeutic approaches.

  13. Immunoregulatory networks in human Chagas disease

    Science.gov (United States)

    Dutra, Walderez O.; Menezes, Cristiane A.S.; Magalhães, Luisa M. D.; Gollob, Kenneth J.

    2014-01-01

    Summary Chagas disease, caused by the infection with Trypanosoma cruzi, is endemic in all Latin America. Due to the increase in population migration, Chagas disease has spread worldwide and is now considered a health issue not only in endemic countries. While most chronically infected individuals remain asymptomatic, approximately 30% of the patients develop a potentially deadly cardiomyopathy. The exact mechanisms that underlie the establishment and maintenance of the cardiac pathology are not clear. However, there is consistent evidence that immunoregulatory cytokines are critical for orchestrating the immune response and, thus, influence disease development or control. While the asymptomatic (indeterminate) form represents a state of balance between the host and the parasite, the establishment of the cardiac form represents the loss of this balance. Analysis of data obtained from several studies have led to the hypothesis that the indeterminate form is associated with an anti-inflammatory cytokine profile, represented by high expression of IL-10, while cardiac form is associated with a high production of IFN-gamma and TNF-alpha in relation to IL-10, leading to an inflammatory profile. Here, we discuss the immunoregulatory events that might influence disease outcome, as well as the mechanisms that influence the establishment of these complex immunoregulatory networks. PMID:24611805

  14. Cognitive impairment in human chronic Chagas' disease

    Directory of Open Access Journals (Sweden)

    C.A. Mangone

    1994-06-01

    Full Text Available We proposed to investigate subclinical cognitive impairment secondary to chronic Chagas' disease (CCD. No similar study was previously done. The neuropsychological performance of 45 chronic Chagasic patients and 26 matched controls (age, education place and years of residency in endemic area was compared using the Mini Mental State Exam (MMSE, Weschler Memory Scale (WMS and the Weschler Adult Intelligent Scale (WAIS. Non-parametric tests and Chi2 were used to compare group means and multivariate statistics in two way frequency tables for measures of independence and association of categorical variables with the disease. Results: Chagasic patients showed lower MMSE scores (p<004, poor orientation (p<.004, and attention (p<.007. Lower WMS MQ were associated with CCD (Chi2 5.9; p<.01; Fisher test p<.02. Lower WAIS IQ were associated with CCD (Chi2 6.3, p<.01; Fisher test p<.01 being the digit symbol (p<.03, picture completion (p<.03, picture arrangement (p<.01 and object assembly (p<.03 subtests the most affected. The impairment in non-verbal reasoning, speed of information processing, problem solving, learning and sequencing observed in chronic Chagas disease patients resembles the cognitive dysfunction associated with white matter disease.

  15. infarction in rats

    Directory of Open Access Journals (Sweden)

    Keyvan Yousefi

    2014-03-01

    Full Text Available Introduction: Nowadays, finding new therapeutic compounds from natural products for treatment and prevention of a variety of diseases including cardiovascular disorders is getting a great deal of attention. This approach would result in finding new drugs which are more effective and have fewer side effects than the conventional medicines. The present study was designed to investigate the anti-inflammatory effect of the methanolic extract of Marrubium vulgare, a popular traditional medicinal herb, on isoproterenol-induced myocardial infarction (MI in rat model. Methods: Male Wistar rats were assigned to 6 groups of control, sham, isoproterenol, and treatment with 10, 20, and 40 mg/kg/12h of the extract given orally concurrent with MI induction. A subcutaneous injection of isoproterenol (100 mg/kg/day for two consecutive days was used to induce MI. Then, histopathological changes and inflammatory markers were evaluated. Results: Isoproterenol injection increased inflammatory response, as shown by a significant increase in peripheral neutrophil count, myocardial myeloperoxidase (MPO activity and serum levels of creatinine kinase-MB (CK-MB and TNF-α (pM.vulgare extract serum CK-MB was subsided by 55.4%, 52.2% and 69%, respectively. Also treatment with the extract (40 mg/kg significantly reduced (p<0.001 MPO activity in MI group. The levels of TNF-α was also considerably declined in the serums of MI group (p<0.001. In addition, peripheral neutrophil count, was significantly lowered by all doses of the extract (p<0.001. Interstitial fibrosis significantly was attenuated in treated groups compared with control MI group.Conclusion:The results of study demonstrate that the M. vulgare extract has strong protective effects against isoproterenol-induced myocardial infarction and it seems possible that this protection is due to its anti-inflammatory effects.

  16. The DNA-damage response in human biology and disease

    DEFF Research Database (Denmark)

    Jackson, Stephen P; Bartek, Jiri

    2009-01-01

    , signal its presence and mediate its repair. Such responses, which have an impact on a wide range of cellular events, are biologically significant because they prevent diverse human diseases. Our improving understanding of DNA-damage responses is providing new avenues for disease management....

  17. Skin Diseases: Cross-section of human skin

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Skin Diseases Cross-section of human skin Past Issues / Fall 2008 Table of Contents For ... Logical Images, Inc. I n the areas of skin health and skin diseases, the NIH's National Institute ...

  18. Impact of chronic obstructive pulmonary disease on in-hospital morbidity and mortality in patients with ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention.

    Science.gov (United States)

    Șerban, Răzvan Constantin; Hadadi, Laszlo; Șuș, Ioana; Lakatos, Eva Katalin; Demjen, Zoltan; Scridon, Alina

    2017-09-15

    Patients with chronic obstructive pulmonary disease (COPD) presenting with ST-segment elevation myocardial infarction (STEMI) are less likely to beneficiate of primary percutaneous coronary intervention (pPCI), and have poorer prognosis. We aimed to evaluate the impact of COPD on the in-hospital outcomes of pPCI-treated STEMI patients. Data were collected from 418 STEMI patients treated by pPCI. Inotropics and diuretics usage, cardiogenic shock, asystole, kidney dysfunction, and left ventricular ejection fraction were used as markers of hemodynamic complications. Atrial and ventricular fibrillation, conduction disorders, and antiarrhythmics usage were used as markers of arrhythmic complications. In-hospital mortality was evaluated. The associations between these parameters and COPD were assessed. COPD was present in 7.42% of STEMI patients. COPD patients were older (p=0.02) and less likely to receive beta-blockers (OR 0.29; 95%CI 0.13-0.64; p<0.01). They had higher Killip class on admission (p<0.001), received more often inotropics (p<0.001) and diuretics (p<0.01), and presented more often atrial (p=0.01) and ventricular fibrillation (p=0.02). Unadjusted in-hospital mortality was higher in COPD patients (OR 4.18, 95%CI 1.55-11.30, p<0.01). After adjustment for potentially confounding factors except beta-blockers, COPD remained an independent predictor of in-hospital mortality (p=0.02). After further adjustment with beta-blocker therapy, no excess mortality was noted in COPD patients. Despite being treated by pPCI, COPD patients with STEMI are more likely to develop hemodynamic and arrhythmic complications, and have higher in-hospital mortality. This appears to be due to lower beta-blockers usage in COPD patients. Increasing beta-blockers usage in COPD patients with STEMI may improve survival. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  19. Intronic Polymorphisms in the CDKN2B-AS1 Gene Are Strongly Associated with the Risk of Myocardial Infarction and Coronary Artery Disease in the Saudi Population

    Directory of Open Access Journals (Sweden)

    Sayed AbdulAzeez

    2016-03-01

    Full Text Available Recent genome-wide association studies identified single nucleotide polymorphisms (SNPs on the chromosome 9p21.3 conferring the risk for CAD (coronary artery disease in individuals of Caucasian ancestry. We performed a genetic association study to investigate the effect of 12 candidate SNPs within 9p21.3 locus on the risk of CAD in the Saudi population of the Eastern Province of Saudi Arabia. A total of 250 Saudi CAD patients who had experienced an myocardial infarction (MI and 252 Saudi age-matched healthy controls were genotyped using TaqMan assay. Controls with evidenced lack of CAD provided 90% of statistical power at the type I error rate of 0.05. Five percent of the results were rechecked for quality control using Sanger sequencing, the results of which concurred with the TaqMan genotyping results. Association analysis of 12 SNPs indicated a significant difference in the genotype distribution for four SNPs between cases and controls (rs564398 p = 0.0315, χ2 = 4.6, odds ratio (OD = 1.5; rs4977574 p = 0.0336, χ2 = 4.5, OD = 1.4; rs2891168 p = 1.85 × 10 − 10, χ2 = 40.6, OD = 2.1 and rs1333042 p = 5.14 × 10 − 9, χ2 = 34.1, OD = 2.2. The study identified three protective haplotypes (TAAG p = 1.00 × 10 − 4; AGTA p = 0.022 and GGGCC p = 0.0175 and a risk haplotype (TGGA p = 2.86 × 10 − 10 for the development of CAD. This study is in line with others that indicated that the SNPs located in the intronic region of the CDKN2B-AS1 gene are associated with CAD.

  20. [Right ventricular dilatation in patients with coronary heart disease without myocardial infarction: According to the data of the Coronary Angiography Surgery Registry].

    Science.gov (United States)

    Kuznetsov, V A; Yaroslavskaya, E I; Pushkarev, G S; Krinochkin, D V; Bessonov, I S; Gorbatenko, E A

    2015-01-01

    To identify factors associated with right ventricular (RV) dilatation in patients with coronary heart disease (CHD) without prior myocardial infarction (Ml). Out of 16 839 patents from the Coronary Angiography Surgery Registry, the investigators selected patients with >75% stenosis in at least one coronary artery without acute or prior MI: 75 patients with echocardiographically detected RV dilatation and 1134 without RV dilatation. Among the patients with RV dilatation, there were more men (92% versus 80.2%; p=0.01 2). In this group, the mean body mass index (BMI) was higher (31.7±5.2 kg/m2 versus 30.1±4.7 kg/m2; p=0.01 9); there was more commonly higher NYHA functional class (FC) (III) chronic heart failure (CHF) (22.2% versus 12.5%; p=0.002), clinically relevant mitral regurgitation (29.4% versus 4.0%; all ps<0.001), and cardiac rhythm and conduction disturbances (45.5% versus 17.8%; p<0.001) in rarer severe FC (III-IV) exertional angina (30.3% versus 52.8%; p=0.007). The groups were different as evidenced by coronarography and major blood biochemical indicators. Decreased myocardial contractility (odds ratio (OR), 4.22; p=0.002), male sex (OR, 4.03;p=0.007), cardiac rhythm and conduction disturbances (OR, 2.98; p<0.001), clinically relevant mitral regurgitation (OR, 2.34; p=0.001); higher FC CHF (OR, 1.87; p=0.034), BMI (OR, 1.08; p=0.01 0), and lower FC exertional angina (OR, 0.42; p=0.001) demonstrated an independent relationship to RV dilatation, as evidenced by a multivariateanalysis. In the patients with CHD without MI, RV dilatation is independently related to male sex, left ventricular functional characteristics, and higher BMI.

  1. Clinical values of left ventricular mechanical dyssynchrony assessment by gated myocardial perfusion SPECT in patients with acute myocardial infarction and multivessel disease

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sang-Geon; Park, Ki Seong; Kim, Jahae; Kim, Jong Sang; Song, Ho-Chun [Chonnam National University Hospital, Department of Nuclear Medicine, Gwang-ju (Korea, Republic of); Jabin, Zeenat; Kang, Sae-Ryung; Kwon, Seong Young; Jeong, Geum-Cheol; Song, Minchul; Min, Jung-Joon; Bom, Hee-Seung [Chonnam National University Hwasun Hospital, Department of Nuclear Medicine, Hwasun-gun, Jeonnam (Korea, Republic of); Cho, Jae Yeong; Kim, Hyun Kuk [Chonnam National University Hospital, Department of Cardiology, Gwang-ju (Korea, Republic of)

    2017-02-15

    The aim of this study was to evaluate the prognostic value of additional evaluation of left ventricular mechanical dyssynchrony (LVMD) by gated myocardial perfusion single-photon emission computed tomography (GMPS) in patients with acute myocardial infarction (MI) and multivessel disease. One hundred and nine acute MI patients with >50 % stenosis in at least one non-culprit artery who underwent GMPS within 2 weeks were enrolled. All patients underwent successful revascularization of the culprit arteries. Those with previous MI, atrial fibrillation, or frequent ventricular premature complexes, cardiac devices, significant patient motion, or procedure-related events were excluded. Phase standard deviation (PSD) and phase histogram bandwidth (PBW) were measured for assessment of LVMD. Patients were followed up for a median of 26 months after index MI, for composite major adverse cardiac events (MACE), which consisted with all-cause death, unplanned hospitalization due to heart failure and severe ventricular arrhythmias (sustained ventricular tachycardia or ventricular fibrillation). Independent predictors of MACE were evaluated. MACE occurred in 22 patients (20 %). Stress PSD (53.3 ± 17.3 vs. 35.3 ± 18.9 ; p <0.001), stress PBW (147.6 ± 54.6 vs. 96.8 ± 59.2 ; p = 0.001) and resting PBW (126.8 ± 37.5 vs. 96.6 ± 48.9 ; p = 0.001) were significantly higher in patients with MACE compared to those without. Multivariate analysis revealed that stress PSD ≥45.5 and stress PBW ≥126.0 were predictive of MACE, as well as suboptimal non-culprit artery revascularization (SNR) and renin-angiotensin system (RAS) blockade medication. Higher stress PSD and stress PBW were associated with poorer prognosis both in patients with and without SNR, and those with RAS blockade medication, but not in those without RAS blockade medication. LVMD measured by GMPS showed added prognostic value in acute MI with multivessel disease. GMPS could serve as a comprehensive evaluation imaging

  2. Genetics and epigenetics of repeat derepression in human disease

    NARCIS (Netherlands)

    Thijssen, P.E.

    2016-01-01

    A large part of the human genome consists of repetitive DNA. In this thesis two human diseases have been studied in which deregulation of repetitive DNA is a central feature: facioscapulohumeral muscular dystrophy (FSHD) and immunodeficiency, centromere instability and facial anomalies (ICF) syndrom

  3. Evaluation of cat brain infarction model using microPET

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Jin; Lee, Dong Soo; Kim, Yun Hui; Hwang, Do Won; Kim, Jin Su; Chung, June Key; Lee, Myung Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of); Lim, Sang Moo [Korea Institite of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2004-12-01

    PET has some disadvantage in the imaging of small animal due to poor resolution. With the advent of microPET scanner, it is possible to image small animals. However, the image quality was not good enough as human image. Due to larger brain, cat brain imaging was superior to mouse or rat. In this study, we established the cat brain infarction model and evaluate it and its temporal change using microPET scanner. Two adult male cats were used. Anesthesia was done with xylazine and ketamine HCI. A burr hole was made at 1 cm right lateral to the bregma. Collagenase type IV 10 {mu}l was injected using 30 G needle for 5 minutes to establish the infarction model. {sup 18}F-FDG microPET (Concorde Microsystems Inc., Knoxville, TN) scans were performed 1, 11 and 32 days after the infarction. In addition, {sup 18}F-FDG PET scans were performed using human PET scanner (Gemini, Philips medical systems, CA, USA) 13 and 47 days after the infarction. Two cat brain infarction models were established. The glucose metabolism of an infarction lesion improved with time. An infarction lesion was also distinguishable in the human PET scan. We successfully established the cat brain infarction model and evaluated the infarcted lesion and its temporal change using {sup 18}F-FDG microPET scanner.

  4. DEGAS: de novo discovery of dysregulated pathways in human diseases.

    Directory of Open Access Journals (Sweden)

    Igor Ulitsky

    Full Text Available BACKGROUND: Molecular studies of the human disease transcriptome typically involve a search for genes whose expression is significantly dysregulated in sick individuals compared to healthy controls. Recent studies have found that only a small number of the genes in human disease-related pathways show consistent dysregulation in sick individuals. However, those studies found that some pathway genes are affected in most sick individuals, but genes can differ among individuals. While a pathway is usually defined as a set of genes known to share a specific function, pathway boundaries are frequently difficult to assign, and methods that rely on such definition cannot discover novel pathways. Protein interaction networks can potentially be used to overcome these problems. METHODOLOGY/PRINCIPAL FINDINGS: We present DEGAS (DysrEgulated Gene set Analysis via Subnetworks, a method for identifying connected gene subnetworks significantly enriched for genes that are dysregulated in specimens of a disease. We applied DEGAS to seven human diseases and obtained statistically significant results that appear to home in on compact pathways enriched with hallmarks of the diseases. In Parkinson's disease, we provide novel evidence for involvement of mRNA splicing, cell proliferation, and the 14-3-3 complex in the disease progression. DEGAS is available as part of the MATISSE software package (http://acgt.cs.tau.ac.il/matisse. CONCLUSIONS/SIGNIFICANCE: The subnetworks identified by DEGAS can provide a signature of the disease potentially useful for diagnosis, pinpoint possible pathways affected by the disease, and suggest targets for drug intervention.

  5. TU-G-204-06: Correlation Between Texture Analysis-Based Model Observer and Human Observer in Diagnosis of Ischemic Infarct in Non-Contrast Head CT of Adults

    Energy Technology Data Exchange (ETDEWEB)

    Li, B; Fujita, A; Buch, K; Sakai, O [Boston University Medical Center, Boston, MA (United States)

    2015-06-15

    Purpose: To investigate the correlation between texture analysis-based model observer and human observer in the task of diagnosis of ischemic infarct in non-contrast head CT of adults. Methods: Non-contrast head CTs of five patients (2 M, 3 F; 58–83 y) with ischemic infarcts were retro-reconstructed using FBP and Adaptive Statistical Iterative Reconstruction (ASIR) of various levels (10–100%). Six neuro -radiologists reviewed each image and scored image quality for diagnosing acute infarcts by a 9-point Likert scale in a blinded test. These scores were averaged across the observers to produce the average human observer responses. The chief neuro-radiologist placed multiple ROIs over the infarcts. These ROIs were entered into a texture analysis software package. Forty-two features per image, including 11 GLRL, 5 GLCM, 4 GLGM, 9 Laws, and 13 2-D features, were computed and averaged over the images per dataset. The Fisher-coefficient (ratio of between-class variance to in-class variance) was calculated for each feature to identify the most discriminating features from each matrix that separate the different confidence scores most efficiently. The 15 features with the highest Fisher -coefficient were entered into linear multivariate regression for iterative modeling. Results: Multivariate regression analysis resulted in the best prediction model of the confidence scores after three iterations (df=11, F=11.7, p-value<0.0001). The model predicted scores and human observers were highly correlated (R=0.88, R-sq=0.77). The root-mean-square and maximal residual were 0.21 and 0.44, respectively. The residual scatter plot appeared random, symmetric, and unbiased. Conclusion: For diagnosis of ischemic infarct in non-contrast head CT in adults, the predicted image quality scores from texture analysis-based model observer was highly correlated with that of human observers for various noise levels. Texture-based model observer can characterize image quality of low contrast

  6. Impacts of Gut Bacteria on Human Health and Diseases

    Directory of Open Access Journals (Sweden)

    Yu-Jie Zhang

    2015-04-01

    Full Text Available Gut bacteria are an important component of the microbiota ecosystem in the human gut, which is colonized by 1014 microbes, ten times more than the human cells. Gut bacteria play an important role in human health, such as supplying essential nutrients, synthesizing vitamin K, aiding in the digestion of cellulose, and promoting angiogenesis and enteric nerve function. However, they can also be potentially harmful due to the change of their composition when the gut ecosystem undergoes abnormal changes in the light of the use of antibiotics, illness, stress, aging, bad dietary habits, and lifestyle. Dysbiosis of the gut bacteria communities can cause many chronic diseases, such as inflammatory bowel disease, obesity, cancer, and autism. This review summarizes and discusses the roles and potential mechanisms of gut bacteria in human health and diseases.

  7. Connexin mutant embryonic stem cells and human diseases

    Institute of Scientific and Technical Information of China (English)

    Kiyomasa; Nishii; Yosaburo; Shibata; Yasushi; Kobayashi

    2014-01-01

    Intercellular communication via gap junctions allows cells within multicellular organisms to share small molecules. The effect of such interactions has been elucidated using mouse gene knockout strategies. Although several mutations in human gap junction-encoding connexin(Cx) have been described, Cx mutants in mice do not always recapitulate the human disease. Among the 20 mouse Cxs, Cx26, Cx43, and Cx45 play roles in early cardiac or placental development, and disruption of the genes results in lethality that hampers further analyses. Embryonic stem cells(ESCs) that lack Cx43 or Cx45 have made analysis feasible in both in vitro differentiated cell cultures and in vivo chimeric tissues. The success of mouse ESCs studies is leading to the use of induced pluripotent stem cells to learn more about the pathogenesis of human Cx diseases. This review summarizes the current status of mouse Cx disruption models and ESC differentiation studies, and discusses their implication for understanding human Cx diseases.

  8. Human Microbiome and its Association With Health and Diseases.

    Science.gov (United States)

    Althani, Asmaa A; Marei, Hany E; Hamdi, Wedad S; Nasrallah, Gheyath K; El Zowalaty, Mohamed E; Al Khodor, Souhaila; Al-Asmakh, Maha; Abdel-Aziz, Hassan; Cenciarelli, Carlo

    2016-08-01

    Human microbiota are distinct communities of microorganisms that resides at different body niches. Exploration of the human microbiome has become a reality due to the availability of powerful metagenomics and metatranscriptomic analysis technologies. Recent advances in sequencing and bioinformatics over the past decade help provide a deep insight into the nature of the host-microbial interactions and identification of potential deriver genes and pathways associated with human health, well-being, and predisposition to different diseases. In the present review, we outline recent studies devoted to elucidate the possible link between the microbiota and various type of diseases. The present review also highlights the potential utilization of microbiota as a potential therapeutic option to treat a wide array of human diseases. J. Cell. Physiol. 231: 1688-1694, 2016. © 2015 Wiley Periodicals, Inc.

  9. Connexin mutant embryonic stem cells and human diseases.

    Science.gov (United States)

    Nishii, Kiyomasa; Shibata, Yosaburo; Kobayashi, Yasushi

    2014-11-26

    Intercellular communication via gap junctions allows cells within multicellular organisms to share small molecules. The effect of such interactions has been elucidated using mouse gene knockout strategies. Although several mutations in human gap junction-encoding connexin (Cx) have been described, Cx mutants in mice do not always recapitulate the human disease. Among the 20 mouse Cxs, Cx26, Cx43, and Cx45 play roles in early cardiac or placental development, and disruption of the genes results in lethality that hampers further analyses. Embryonic stem cells (ESCs) that lack Cx43 or Cx45 have made analysis feasible in both in vitro differentiated cell cultures and in vivo chimeric tissues. The success of mouse ESCs studies is leading to the use of induced pluripotent stem cells to learn more about the pathogenesis of human Cx diseases. This review summarizes the current status of mouse Cx disruption models and ESC differentiation studies, and discusses their implication for understanding human Cx diseases.

  10. MicroRNA in human cancer and chronic inflammatory diseases.

    Science.gov (United States)

    Kanwar, Jagat R; Mahidhara, Ganesh; Kanwar, Rupinder K

    2010-06-01

    MicroRNAs (miRNAs) are the non-coding RNAs that act as post-translational regulators to their complimentary messenger RNAs (mRNA). Due to their specific gene silencing property, miRNAs have been implicated in a number of cellular and developmental processes. Also, it has been proposed that a particular set of miRNA spectrum is expressed only in a particular type of tissue. Many interesting findings related to the differential expression of miRNAs in various human diseases including several types of cancers, neurodegenerative diseases and metabolic diseases have been reported. Deregulation of miRNA expression in different types of human diseases and the roles various miRNAs play as tumour suppressors as well as oncogenes, suggest their contribution to cancer and/or in other disease development. These findings have possible implications in the development of diagnostics and/or therapeutics in human malignancies. In this review, we discuss various miRNAs that are differentially expressed in human chronic inflammatory diseases, neurodegenerative diseases, cancer and the further prospective development of miRNA based diagnostics and therapeutics.

  11. Natural selection on genes that underlie human disease susceptibility

    Science.gov (United States)

    Blekhman, Ran; Man, Orna; Herrmann, Leslie; Boyko, Adam R.; Indap, Amit; Kosiol, Carolin; Bustamante, Carlos D.; Teshima, Kosuke M.; Przeworski, Molly

    2008-01-01

    What evolutionary forces shape genes that contribute to the risk of human disease? Do similar selective pressures act on alleles that underlie simple vs. complex disorders? [1-3]. Answers to these questions will shed light on the origin of human disorders (e.g., [4]), and help to predict the population frequencies of alleles that contribute to disease risk, with important implications for the efficient design of mapping studies [5-7]. As a first step towards addressing them, we created a hand-curated version of the Mendelian Inheritance in Man database (OMIM). We then examined selective pressures on Mendelian disease genes, genes that contribute to complex disease risk and genes known to be essential in mouse, by analyzing patterns of human polymorphism and of divergence between human and rhesus macaque. We find that Mendelian disease genes appear to be under widespread purifying selection, especially when the disease mutations are dominant (rather than recessive). In contrast, the class of genes that influence complex disease risk shows little signs of evolutionary conservation, possibly because this category includes both targets of purifying and positive selection. PMID:18571414

  12. Integrated Genomic and Network-Based Analyses of Complex Diseases and Human Disease Network.

    Science.gov (United States)

    Al-Harazi, Olfat; Al Insaif, Sadiq; Al-Ajlan, Monirah A; Kaya, Namik; Dzimiri, Nduna; Colak, Dilek

    2016-06-20

    A disease phenotype generally reflects various pathobiological processes that interact in a complex network. The highly interconnected nature of the human protein interaction network (interactome) indicates that, at the molecular level, it is difficult to consider diseases as being independent of one another. Recently, genome-wide molecular measurements, data mining and bioinformatics approaches have provided the means to explore human diseases from a molecular basis. The exploration of diseases and a system of disease relationships based on the integration of genome-wide molecular data with the human interactome could offer a powerful perspective for understanding the molecular architecture of diseases. Recently, subnetwork markers have proven to be more robust and reliable than individual biomarker genes selected based on gene expression profiles alone, and achieve higher accuracy in disease classification. We have applied one of these methodologies to idiopathic dilated cardiomyopathy (IDCM) data that we have generated using a microarray and identified significant subnetworks associated with the disease. In this paper, we review the recent endeavours in this direction, and summarize the existing methodologies and computational tools for network-based analysis of complex diseases and molecular relationships among apparently different disorders and human disease network. We also discuss the future research trends and topics of this promising field.

  13. Therapeutic Effects of Human Multilineage-Differentiating Stress Enduring (MUSE) Cell Transplantation into Infarct Brain of Mice

    OpenAIRE

    Tomohiro Yamauchi; Yasumasa Kuroda; Takahiro Morita; Hideo Shichinohe; Kiyohiro Houkin; Mari Dezawa; Satoshi Kuroda

    2015-01-01

    Objective Bone marrow stromal cells (BMSCs) are heterogeneous and their therapeutic effect is pleiotropic. Multilineage-differentiating stress enduring (Muse) cells are recently identified to comprise several percentages of BMSCs, being able to differentiate into triploblastic lineages including neuronal cells and act as tissue repair cells. This study was aimed to clarify how Muse and non-Muse cells in BMSCs contribute to functional recovery after ischemic stroke. Methods Human BMSCs were se...

  14. Long Non-Coding RNAs and Complex Human Diseases

    Directory of Open Access Journals (Sweden)

    Changning Liu

    2013-09-01

    Full Text Available Long non-coding RNAs (lncRNAs are a heterogeneous class of RNAs that are generally defined as non-protein-coding transcripts longer than 200 nucleotides. Recently, an increasing number of studies have shown that lncRNAs can be involved in various critical biological processes, such as chromatin remodeling, gene transcription, and protein transport and trafficking. Moreover, lncRNAs are dysregulated in a number of complex human diseases, including coronary artery diseases, autoimmune diseases, neurological disorders, and various cancers, which indicates their important roles in these diseases. Here, we reviewed the current understanding of lncRNAs, including their definition and subclassification, regulatory functions, and potential roles in different types of complex human diseases.

  15. Are human endogenous retroviruses triggers of autoimmune diseases?

    DEFF Research Database (Denmark)

    Nexø, Bjørn A; Villesen, Palle; Nissen, Kari K

    2016-01-01

    Autoimmune diseases encompass a plethora of conditions in which the immune system attacks its own tissue, identifying them as foreign. Multiple factors are thought to contribute to the development of immune response to self, including differences in genotypes, hormonal milieu, and environmental...... manner. In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. We found that at least one human endogenous retroviral locus...... was associated with each of the three diseases. Although there was a significant overlap, most loci only occurred in one of the studied disease. Remarkably, within each disease, there was a statistical interaction (synergy) between two loci. Additional synergy between retroviral loci and human lymphocyte...

  16. DUF1220 domains, cognitive disease, and human brain evolution.

    Science.gov (United States)

    Dumas, L; Sikela, J M

    2009-01-01

    We have established that human genome sequences encoding a novel protein domain, DUF1220, show a dramatically elevated copy number in the human lineage (>200 copies in humans vs. 1 in mouse/rat) and may be important to human evolutionary adaptation. Copy-number variations (CNVs) in the 1q21.1 region, where most DUF1220 sequences map, have now been implicated in numerous diseases associated with cognitive dysfunction, including autism, autism spectrum disorder, mental retardation, schizophrenia, microcephaly, and macrocephaly. We report here that these disease-related 1q21.1 CNVs either encompass or are directly flanked by DUF1220 sequences and exhibit a dosage-related correlation with human brain size. Microcephaly-producing 1q21.1 CNVs are deletions, whereas macrocephaly-producing 1q21.1 CNVs are duplications. Similarly, 1q21.1 deletions and smaller brain size are linked with schizophrenia, whereas 1q21.1 duplications and larger brain size are associated with autism. Interestingly, these two diseases are thought to be phenotypic opposites. These data suggest a model which proposes that (1) DUF1220 domain copy number may be involved in influencing human brain size and (2) the evolutionary advantage of rapidly increasing DUF1220 copy number in the human lineage has resulted in favoring retention of the high genomic instability of the 1q21.1 region, which, in turn, has precipitated a spectrum of recurrent human brain and developmental disorders.

  17. The Leeuwenhoek Lecture 2001. Animal origins of human infectious disease.

    Science.gov (United States)

    Weiss, R A

    2001-06-29

    Since time immemorial animals have been a major source of human infectious disease. Certain infections like rabies are recognized as zoonoses caused in each case by direct animal-to-human transmission. Others like measles became independently sustained with the human population so that the causative virus has diverged from its animal progenitor. Recent examples of direct zoonoses are variant Creutzfeldt-Jakob disease arising from bovine spongiform encephalopathy, and the H5N1 avian influenza outbreak in Hong Kong. Epidemics of recent animal origin are the 1918-1919 influenza pandemic, and acquired immune deficiency syndrome caused by human immunodeficiency virus (HIV). Some retroviruses jump into and out of the chromosomal DNA of the host germline, so that they oscillate between being inherited Mendelian traits or infectious agents in different species. Will new procedures like animal-to-human transplants unleash further infections? Do microbes become more virulent upon cross-species transfer? Are animal microbes a threat as biological weapons? Will the vast reservoir of immunodeficient hosts due to the HIV pandemic provide conditions permissive for sporadic zoonoses to take off as human-to-human transmissible diseases? Do human infections now pose a threat to endangered primates? These questions are addressed in this lecture.

  18. The active metabolite of prasugrel, R-138727, improves cerebral blood flow and reduces cerebral infarction and neurologic deficits in a non-human primate model of acute ischaemic stroke.

    Science.gov (United States)

    Sugidachi, Atsuhiro; Mizuno, Makoto; Ohno, Kousaku; Jakubowski, Joseph A; Tomizawa, Atsuyuki

    2016-10-05

    Previously, we showed preventive effects of prasugrel, a P2Y12 antagonist, in a non-human primate model of thrombotic middle cerebral artery occlusion (MCAO); however, it remains unclear if P2Y12 inhibition after MCAO reduces cerebral injury and dysfunction. Here we investigated the effects of R-138727, the major active metabolite of prasugrel, on ex vivo platelet aggregation at 5min, 15min, 60min, and 24h after administration to non-human primates (n=3). A single intravenous dose of R-138727 (0.03-0.3mg/kg) resulted in significant and sustained dose-related effects on platelets for up to 24h. R-138727 was administered 1h after MCAO induction, and its effects on thrombosis, cerebral infarction, and neurological deficits were determined (n=8-10). R-138727 (0.3mg/kg) significantly increased total patency rate of the MCA (P=0.0211). Although there was no effect on the patency rate before R-138727 dosing (P=0.3975), it increased 1h after dosing (P=0.0114). R-138727 significantly reduced total ischaemic infarction volumes (P=0.0147), including those of basal ganglia (P=0.0028), white matter (P=0.0393), and haemorrhagic infarction (P=0.0235). Additionally, treatment with R-138727 reduced overall neurological deficits (P=0.0019), including the subcategories of consciousness (P=0.0042), sensory system (P=0.0045), motor system (P=0.0079) and musculoskeletal coordination (P=0.0082). These findings support the possible utility of P2Y12 inhibition during early-onset MCAO to limit the progression and degree of cerebral ischaemia and infarction and also associated neurological deficits.

  19. Interneurons in the human olfactory system in Alzheimer's disease.

    Science.gov (United States)

    Saiz-Sanchez, Daniel; Flores-Cuadrado, Alicia; Ubeda-Bañon, Isabel; de la Rosa-Prieto, Carlos; Martinez-Marcos, Alino

    2016-02-01

    The principal olfactory structures display Alzheimer's disease (AD) related pathology at early stages of the disease. Consequently, olfactory deficits are among the earliest symptoms. Reliable olfactory tests for accurate clinical diagnosis are rarely made. In addition, neuropathological analysis postmortem of olfactory structures is often not made. Therefore, the relationship between the clinical features and the underlying pathology is poorly defined. Traditionally, research into Alzheimer's disease has focused on the degeneration of cortical temporal projection neurons and cholinergic neurons. Recent evidence has demonstrated the neurodegeneration of interneuron populations in AD. This review provides an updated overview of the pathological involvement of interneuron populations in the human olfactory system in Alzheimer's disease.

  20. [Spinal cord infarction].

    Science.gov (United States)

    Naumann, N; Shariat, K; Ulmer, S; Stippich, C; Ahlhelm, F J

    2012-05-01

    Infarction of the spinal cord can cause a variety of symptoms and neurological deficits because of the complex vascular supply of the myelon. The most common leading symptom is distal paresis ranging from paraparesis to tetraplegia caused by arterial ischemia or infarction of the myelon. Venous infarction, however, cannot always be distinguished from arterial infarction based on the symptoms alone.Modern imaging techniques, such as computed tomography angiography (CTA) and magnetic resonance angiography (MRA) assist in preoperative planning of aortic operations to reliably identify not only the most important vascular structure supplying the spinal cord, the artery of Adamkiewicz, but also other pathologies such as tumors or infectious disorders. In contrast to CT, MRI can reliably depict infarction of the spinal cord.

  1. Part 1: The Human Gut Microbiome in Health and Disease

    OpenAIRE

    Bull, Matthew J.; Plummer, Nigel T.

    2014-01-01

    The bacterial cells harbored within the human gastrointestinal tract (GIT) outnumber the host’s cells by a factor of 10 and the genes encoded by the bacteria resident within the GIT outnumber their host’s genes by more than 100 times. These human digestive-tract associated microbes are referred to as the gut microbiome. The human gut microbiome and its role in both health and disease has been the subject of extensive research, establishing its involvement in human metabolism, nutrition, physi...

  2. FISH CONSUMPTION, METHYLMERCURY, AND HUMAN HEART DISEASE.

    Energy Technology Data Exchange (ETDEWEB)

    LIPFERT, F.W.; SULLIVAN, T.M.

    2005-09-21

    Environmental mercury continues to be of concern to public health advocates, both in the U.S. and abroad, and new research continues to be published. A recent analysis of potential health benefits of reduced mercury emissions has opened a new area of public health concern: adverse effects on the cardiovascular system, which could account for the bulk of the potential economic benefits. The authors were careful to include caveats about the uncertainties of such impacts, but they cited only a fraction of the applicable health effects literature. That literature includes studies of the potentially harmful ingredient (methylmercury, MeHg) in fish, as well as of a beneficial ingredient, omega-3 fatty acids or ''fish oils''. The U.S. Food and Drug Administration (FDA) recently certified that some of these fat compounds that are primarily found in fish ''may be beneficial in reducing coronary heart disease''. This paper briefly summarizes and categorizes the extensive literature on both adverse and beneficial links between fish consumption and cardiovascular health, which are typically based on studies of selected groups of individuals (cohorts). Such studies tend to comprise the ''gold standard'' of epidemiology, but cohorts tend to exhibit a great deal of variability, in part because of the limited numbers of individuals involved and in part because of interactions with other dietary and lifestyle considerations. Note that eating fish will involve exposure to both the beneficial effects of fatty acids and the potentially harmful effects of contaminants like Hg or PCBs, all of which depend on the type of fish but tend to be correlated within a population. As a group, the cohort studies show that eating fish tends to reduce mortality, especially due to heart disease, for consumption rates up to about twice weekly, above which the benefits tend to level off. A Finnish cohort study showed increased mortality risks

  3. Research priorities for Chagas disease, human African trypanosomiasis and leishmaniasis.

    Science.gov (United States)

    2012-01-01

    This report provides a review and analysis of the research landscape for three diseases - Chagas disease, human African trypanosomiasis and leishmaniasis - that disproportionately afflict poor and remote populations with limited access to health services. It represents the work of the disease reference group on Chagas Disease, Human African Trypanosomiasis and Leishmaniasis (DRG3) which was established to identify key research priorities through review of research evidence and input from stakeholders' consultations. The diseases, which are caused by related protozoan parasites, are described in terms of their epidemiology and diseases burden, clinical forms and pathogenesis, HIV coinfection, diagnosis, drugs and drug resistance, vaccines, vector control, and health-care interventions. Priority areas for research are identified based on criteria such as public health relevance, benefit and impact on poor populations and equity, and feasibility. The priorities are found in the areas of diagnostics, drugs, vector control, asymptomatic infection, economic analysis of treatment and vector control methods, and in some specific issues such as surveillance methods or transmission-blocking vaccines for particular diseases. This report will be useful to researchers, policy and decision-makers, funding bodies, implementation organizations, and civil society. This is one of ten disease and thematic reference group reports that have come out of the TDR Think Tank, all of which have contributed to the development of the Global Report for Research on Infectious Diseases of Poverty, available at: www.who.int/tdr/stewardship/global_report/en/index.html.

  4. Infectious prion diseases in humans: cannibalism, iatrogenicity and zoonoses.

    Science.gov (United States)

    Haïk, Stéphane; Brandel, Jean-Philippe

    2014-08-01

    In contrast with other neurodegenerative disorders associated to protein misfolding, human prion diseases include infectious forms (also called transmitted forms) such as kuru, iatrogenic Creutzfeldt-Jakob disease and variant Creutzfeldt-Jakob disease. The transmissible agent is thought to be solely composed of the abnormal isoform (PrP(Sc)) of the host-encoded prion protein that accumulated in the central nervous system of affected individuals. Compared to its normal counterpart, PrP(Sc) is β-sheet enriched and aggregated and its propagation is based on an autocatalytic conversion process. Increasing evidence supports the view that conformational variations of PrP(Sc) encoded the biological properties of the various prion strains that have been isolated by transmission studies in experimental models. Infectious forms of human prion diseases played a pivotal role in the emergence of the prion concept and in the characterization of the very unconventional properties of prions. They provide a unique model to understand how prion strains are selected and propagate in humans. Here, we review and discuss how genetic factors interplay with strain properties and route of transmission to influence disease susceptibility, incubation period and phenotypic expression in the light of the kuru epidemics due to ritual endocannibalism, the various series iatrogenic diseases secondary to extractive growth hormone treatment or dura mater graft and the epidemics of variant Creutzfeldt-Jakob disease linked to dietary exposure to the agent of bovine spongiform encephalopathy.

  5. Rapid initial reduction of hyperenhanced myocardium after reperfused first myocardial infarction suggests recovery of the peri-infarction zone: one-year follow-up by MRI.

    Science.gov (United States)

    Engblom, Henrik; Hedström, Erik; Heiberg, Einar; Wagner, Galen S; Pahlm, Olle; Arheden, Håkan

    2009-01-01

    The time course and magnitude of infarct involution, functional recovery, and normalization of infarct-related electrocardiographic (ECG) changes after acute myocardial infarction (MI) are not completely known in humans. We sought to explore these processes early after MI and during infarct-healing using cardiac MRI. Twenty-two patients with reperfused first-time MI were examined by MRI and ECG at 1, 7, 42, 182, and 365 days after infarction. Global left ventricular function and regional wall thickening were assessed by cine MRI, and injured myocardium was depicted by delayed contrast-enhanced MRI. Infarct size by ECG was estimated by QRS scoring. The reduction of hyperenhanced myocardium occurred predominantly during the first week after infarction (64% of the 1-year reduction). Furthermore, during the first week the amount of nonhyperenhanced myocardium increased significantly (Pinfarction. Also, the time course and magnitude for reduction of hyperenhanced myocardium were associated with normalization of infarct-related ECG changes.

  6. Use of aspirin and statins for the primary prevention of myocardial infarction and stroke in patients with human immunodeficiency virus infection.

    Science.gov (United States)

    Park, Tae Eun; Yusuff, Jameela; Sharma, Roopali

    2016-05-01

    This retrospective, cross-sectional study evaluated whether HIV-infected patients received aspirin and statins for the primary prevention of myocardial infarction and stroke. Among the 258 patients included, 50.4% (n = 130/258) of the patients had a high risk of myocardial infarction and 14% (n = 36/258) of stroke. Overall, 43.1% (n = 56/130) and 50% (n = 18/36) of the patients were prescribed aspirin for the primary prevention of myocardial infarction and stroke, respectively. Among the patients who required statin therapy, 42.5% (n = 34/80) and 37.1% (n = 13/35) of patients received it for the primary prevention of myocardial infarction and stroke, respectively. The patients who had hypertension (odds ratio 3.8, 95% confidence interval 1.5-10.9) and diabetes mellitus (odds ratio 5.6, 95% confidence interval 2.6-12.4) were more likely to receive aspirin. Interventions are needed to improve provider awareness of the use of aspirin and statins in the primary prevention of myocardial infarction and stroke in HIV-infected patients.

  7. Study on myocardial infarction in underground and surface workers of the Aachen coal field

    Energy Technology Data Exchange (ETDEWEB)

    Bruendel, K.H.; Kahabka, M.

    1981-11-01

    Risk-factors of 24 men with myocardial infarction and one with coronary heart disease were investigated. Low levels of HDL-cholesterol and nicotin seem to play the dominant role in the propagation of the infarct. Hypertension, diabetes mellitus and hyperuricaema were absent. Influences of work place and shift-work upon genesis of infarction remain unclear and need further investigation.

  8. Spectroscopy techniques for human disease diagnosis

    Science.gov (United States)

    Navas-Moreno, Maria

    2011-12-01

    Modern medicine would benefit from the pursuit of new, more specific and easier to implement diagnosis tools. In recent years, Raman scattering, surface-enhanced Raman scattering and fluorescence spectroscopy have proven to be successful diagnostic techniques for a wide range of diseases including atherosclerosis, kidney stones, bone diseases, diabetes, and a wide collection of neoplasms. Optical spectroscopy has several advantages over more traditional diagnostic methods (i.e., histopathology, quantitative PCR, etc.) such as faster data analysis, nonspecific sample preparation, nonspecific labels/reagents/antibodies usage requirements, and immediate on-site implementation. In the present work, label-free in vitro fluorescence and surface enhanced Raman scattering (SERS) spectroscopy have been used to differentiate between blood cells of patients affected with myeloproliferative neoplasms (MPN) and those of healthy subjects. The SERS technique has also been applied to hemoglobin variants as well as to serum obtained from patients affected with chronic heart failure who positively or negatively responded to the seasonal influenza vaccine. We found that spectral ratios of the background fluorescence intensity that accompanies the SERS spectra of granulocytes serve as excellent markers for the presence of MPNs. In addition, we also found expression dysregulation of two hypoxia induced factor regulated genes, which correlates with our results obtained by SERS spectroscopy assay in MPN patients and supports the presence of the Warburg effect in MPNs. We hypothesize that SERS measures metabolic change in granulocytes through two possible mechanisms: (i) Changes in dielectric properties of the environment surrounding the silver-cell interface; and (ii) changes in flavin adenine dinucleotide concentrations, which in turn changes the relative contribution of the autofluorescence to the emission spectrum. These hypotheses are supported by SERS measurement of 2-deoxy

  9. Early Stage Disease Diagnosis System Using Human Nail Image Processing

    Directory of Open Access Journals (Sweden)

    Trupti S. Indi

    2016-07-01

    Full Text Available Human’s hand nail is analyzed to identify many diseases at early stage of diagnosis. Study of person hand nail color helps in identification of particular disease in healthcare domain. The proposed system guides in such scenario to take decision in disease diagnosis. The input to the proposed system is person nail image. The system will process an image of nail and extract features of nail which is used for disease diagnosis. Human nail consist of various features, out of which proposed system uses nail color changes for disease diagnosis. Here, first training set data is prepared using Weka tool from nail images of patients of specific diseases. A feature extracted from input nail image is compared with the training data set to get result. In this experiment we found that using color feature of nail image average 65% results are correctly matched with training set data during three tests conducted.

  10. Modelling Neurodegenerative Diseases Using Human Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Hall, Vanessa J.

    2016-01-01

    Neurodegenerative diseases are being modelled in-vitro using human patient-specific, induced pluripotent stem cells and transgenic embryonic stem cells to determine more about disease mechanisms, as well as to discover new treatments for patients. Current research in modelling Alzheimer’s disease......, frontotemporal dementia and Parkinson’s disease using pluripotent stem cells is described, along with the advent of gene-editing, which has been the complimentary tool for the field. Current methods used to model these diseases are predominantly dependent on 2D cell culture methods. Outcomes reveal that only...... that includes studying more complex 3D cell cultures, as well as accelerating aging of the neurons, may help to yield stronger phenotypes in the cultured cells. Thus, the use and application of pluripotent stem cells for modelling disease have already shown to be a powerful approach for discovering more about...

  11. Rare human diseases: 9p deletion syndrome

    Directory of Open Access Journals (Sweden)

    Galagan V.O.

    2014-09-01

    Full Text Available Objective of the study was to review the anamnesis, pheno - and genotype in patients with rare chromosome disorders such as 9p deletion syndrome. Genetic methods of investigation (clinical and genealogical, cytogenetic, FISH- method, paraclinical and instrumental methods of examination were used. Karyotyping was performed by the G-method of differential staining of chromosomes. Only three cases of pathology were diagnosed in the Medical Genetics Center over the last 10 years. By anamnesis data nobody in the probands’ families had bad habits, was exposed to occupational hazards, took part in the elimination of the Chernobyl accident or lived in contaminated areas. Clinical signs of diseases have not been identified in probands’ parents. All probands had trigonocephaly, bilateral epicanthal folds, ocular hypertelorism, downslanting palpebral fissures, long philtrum, flat face and nasal bridge, low set ears with malformed auricles. Two patients of three ones had exophthalmos, contracture of the second and third fingers, abnormal external genitalia. In all three cases there was monosomy of chromosome 9 of critical segment p 24. Normal karyotypes were seen in all parents, so there were three cases of new mutations of 9p deletion syndrome. Retardation of physical, psycho-spech, mental development in proband with or without congenital anomalies requires medical genetic counseling in a specialized institution. Cases of reproductive loss in anamnesis require cytogenetic investigation of fetal membranes and amniotic fluid.

  12. Human Disease Diagnosis Using a Fuzzy Expert System

    CERN Document Server

    Hasan, Mir Anamul; Chowdhury, Ahsan Raja

    2010-01-01

    Human disease diagnosis is a complicated process and requires high level of expertise. Any attempt of developing a web-based expert system dealing with human disease diagnosis has to overcome various difficulties. This paper describes a project work aiming to develop a web-based fuzzy expert system for diagnosing human diseases. Now a days fuzzy systems are being used successfully in an increasing number of application areas; they use linguistic rules to describe systems. This research project focuses on the research and development of a web-based clinical tool designed to improve the quality of the exchange of health information between health care professionals and patients. Practitioners can also use this web-based tool to corroborate diagnosis. The proposed system is experimented on various scenarios in order to evaluate it's performance. In all the cases, proposed system exhibits satisfactory results.

  13. Human Disease Insight: An integrated knowledge-based platform for disease-gene-drug information.

    Science.gov (United States)

    Tasleem, Munazzah; Ishrat, Romana; Islam, Asimul; Ahmad, Faizan; Hassan, Md Imtaiyaz

    2016-01-01

    The scope of the Human Disease Insight (HDI) database is not limited to researchers or physicians as it also provides basic information to non-professionals and creates disease awareness, thereby reducing the chances of patient suffering due to ignorance. HDI is a knowledge-based resource providing information on human diseases to both scientists and the general public. Here, our mission is to provide a comprehensive human disease database containing most of the available useful information, with extensive cross-referencing. HDI is a knowledge management system that acts as a central hub to access information about human diseases and associated drugs and genes. In addition, HDI contains well-classified bioinformatics tools with helpful descriptions. These integrated bioinformatics tools enable researchers to annotate disease-specific genes and perform protein analysis, search for biomarkers and identify potential vaccine candidates. Eventually, these tools will facilitate the analysis of disease-associated data. The HDI provides two types of search capabilities and includes provisions for downloading, uploading and searching disease/gene/drug-related information. The logistical design of the HDI allows for regular updating. The database is designed to work best with Mozilla Firefox and Google Chrome and is freely accessible at http://humandiseaseinsight.com.

  14. Transient myocardial ischemia after myocardial infarction

    DEFF Research Database (Denmark)

    Mickley, H

    1995-01-01

    Ambulatory ST-segment monitoring is a relatively new device in the evaluation of myocardial ischemia. The method is unique in allowing us to continuously examine the patient over an extended period of time in a changing environmental milieu. In survivors of acute myocardial infarction...... the prevalence of ambulatory or transient myocardial ischemia is lower than in patients with chronic, stable coronary artery disease. A greater proportion of ischemic episodes, however, are silent than in other subgroups with ischemic heart disease. Early after the infarction, transient myocardial ischemia...... exhibits a circadian variation with a peak activity occurring in the late evening hours. Patients with non-Q wave infarction have more transient myocardial ischemia, whereas thrombolytic therapy seems to result in less residual ischemia. Exercise testing is more sensitive than ambulatory monitoring...

  15. Transient myocardial ischemia after myocardial infarction

    DEFF Research Database (Denmark)

    Mickley, H

    1995-01-01

    Ambulatory ST-segment monitoring is a relatively new device in the evaluation of myocardial ischemia. The method is unique in allowing us to continuously examine the patient over an extended period of time in a changing environmental milieu. In survivors of acute myocardial infarction...... the prevalence of ambulatory or transient myocardial ischemia is lower than in patients with chronic, stable coronary artery disease. A greater proportion of ischemic episodes, however, are silent than in other subgroups with ischemic heart disease. Early after the infarction, transient myocardial ischemia...... exhibits a circadian variation with a peak activity occurring in the late evening hours. Patients with non-Q wave infarction have more transient myocardial ischemia, whereas thrombolytic therapy seems to result in less residual ischemia. Exercise testing is more sensitive than ambulatory monitoring...

  16. Antisense Oligonucleotides: Translation from Mouse Models to Human Neurodegenerative Diseases.

    Science.gov (United States)

    Schoch, Kathleen M; Miller, Timothy M

    2017-06-21

    Multiple neurodegenerative diseases are characterized by single-protein dysfunction and aggregation. Treatment strategies for these diseases have often targeted downstream pathways to ameliorate consequences of protein dysfunction; however, targeting the source of that dysfunction, the affected protein itself, seems most judicious to achieve a highly effective therapeutic outcome. Antisense oligonucleotides (ASOs) are small sequences of DNA able to target RNA transcripts, resulting in reduced or modified protein expression. ASOs are ideal candidates for the treatment of neurodegenerative diseases, given numerous advancements made to their chemical modifications and delivery methods. Successes achieved in both animal models and human clinical trials have proven ASOs both safe and effective. With proper considerations in mind regarding the human applicability of ASOs, we anticipate ongoing in vivo research and clinical trial development of ASOs for the treatment of neurodegenerative diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Exploring human disease using the Rat Genome Database

    Directory of Open Access Journals (Sweden)

    Mary Shimoyama

    2016-10-01

    Full Text Available Rattus norvegicus, the laboratory rat, has been a crucial model for studies of the environmental and genetic factors associated with human diseases for over 150 years. It is the primary model organism for toxicology and pharmacology studies, and has features that make it the model of choice in many complex-disease studies. Since 1999, the Rat Genome Database (RGD; http://rgd.mcw.edu has been the premier resource for genomic, genetic, phenotype and strain data for the laboratory rat. The primary role of RGD is to curate rat data and validate orthologous relationships with human and mouse genes, and make these data available for incorporation into other major databases such as NCBI, Ensembl and UniProt. RGD also provides official nomenclature for rat genes, quantitative trait loci, strains and genetic markers, as well as unique identifiers. The RGD team adds enormous value to these basic data elements through functional and disease annotations, the analysis and visual presentation of pathways, and the integration of phenotype measurement data for strains used as disease models. Because much of the rat research community focuses on understanding human diseases, RGD provides a number of datasets and software tools that allow users to easily explore and make disease-related connections among these datasets. RGD also provides comprehensive human and mouse data for comparative purposes, illustrating the value of the rat in translational research. This article introduces RGD and its suite of tools and datasets to researchers – within and beyond the rat community – who are particularly interested in leveraging rat-based insights to understand human diseases.

  18. Exploring human disease using the Rat Genome Database

    Science.gov (United States)

    Laulederkind, Stanley J. F.; De Pons, Jeff; Nigam, Rajni; Smith, Jennifer R.; Tutaj, Marek; Petri, Victoria; Hayman, G. Thomas; Wang, Shur-Jen; Ghiasvand, Omid; Thota, Jyothi; Dwinell, Melinda R.

    2016-01-01

    ABSTRACT Rattus norvegicus, the laboratory rat, has been a crucial model for studies of the environmental and genetic factors associated with human diseases for over 150 years. It is the primary model organism for toxicology and pharmacology studies, and has features that make it the model of choice in many complex-disease studies. Since 1999, the Rat Genome Database (RGD; http://rgd.mcw.edu) has been the premier resource for genomic, genetic, phenotype and strain data for the laboratory rat. The primary role of RGD is to curate rat data and validate orthologous relationships with human and mouse genes, and make these data available for incorporation into other major databases such as NCBI, Ensembl and UniProt. RGD also provides official nomenclature for rat genes, quantitative trait loci, strains and genetic markers, as well as unique identifiers. The RGD team adds enormous value to these basic data elements through functional and disease annotations, the analysis and visual presentation of pathways, and the integration of phenotype measurement data for strains used as disease models. Because much of the rat research community focuses on understanding human diseases, RGD provides a number of datasets and software tools that allow users to easily explore and make disease-related connections among these datasets. RGD also provides comprehensive human and mouse data for comparative purposes, illustrating the value of the rat in translational research. This article introduces RGD and its suite of tools and datasets to researchers – within and beyond the rat community – who are particularly interested in leveraging rat-based insights to understand human diseases. PMID:27736745

  19. Linking Microbiota to Human Diseases: A Systems Biology Perspective.

    Science.gov (United States)

    Wu, Hao; Tremaroli, Valentina; Bäckhed, Fredrik

    2015-12-01

    The human gut microbiota encompasses a densely populated ecosystem that provides essential functions for host development, immune maturation, and metabolism. Alterations to the gut microbiota have been observed in numerous diseases, including human metabolic diseases such as obesity, type 2 diabetes (T2D), and irritable bowel syndrome, and some animal experiments have suggested causality. However, few studies have validated causality in humans and the underlying mechanisms remain largely to be elucidated. We discuss how systems biology approaches combined with new experimental technologies may disentangle some of the mechanistic details in the complex interactions of diet, microbiota, and host metabolism and may provide testable hypotheses for advancing our current understanding of human-microbiota interaction.

  20. DNA Aptamers in the Diagnosis and Treatment of Human Diseases

    Directory of Open Access Journals (Sweden)

    Qinchang Zhu

    2015-11-01

    Full Text Available Aptamers have a promising role in the field of life science and have been extensively researched for application as analytical tools, therapeutic agents and as vehicles for targeted drug delivery. Compared with RNA aptamers, DNA aptamers have inherent advantages in stability and facility of generation and synthesis. To better understand the specific potential of DNA aptamers, an overview of the progress in the generation and application of DNA aptamers in human disease diagnosis and therapy are presented in this review. Special attention is given to researches that are relatively close to practical application. DNA aptamers are expected to have great potential in the diagnosis and treatment of human diseases.

  1. Beyond membrane channelopathies: alternative mechanisms underlying complex human disease

    Institute of Scientific and Technical Information of China (English)

    Konstantinos Dean BOUDOULAS; Peter J MOHLER

    2011-01-01

    Over the past fifteen years, our understanding of the molecular mechanisms underlying human disease has flourished in large part due to the discovery of gene mutations linked with membrane ion channels and transporters. In fact, ion channel defects ("channelopathies" - the focus of this review series) have been associated with a spectrum of serious human disease phenotypes including cystic fibrosis, cardiac arrhythmia, diabetes, skeletal muscle defects, and neurological disorders. However, we now know that human disease, particularly excitable cell disease, may be caused by defects in non-ion channel polypeptides including in cellular components residing well beneath the plasma membrane. For example, over the past few years, a new class of potentially fatal cardiac arrhythmias has been linked with cytoplasmic proteins that include sub-membrane adapters such as ankyrin-B (ANK2),ankyrin-G (ANK3), and alpha-1 syntrophin, membrane coat proteins including caveolin-3 (CAV3), signaling platforms including yotiao (AKAPg), and cardiac enzymes (GPD1L). The focus of this review is to detail the exciting role of lamins, yet another class of gene products that have provided elegant new insight into human disease.

  2. Role of Epigenetics in Biology and Human Diseases

    OpenAIRE

    Moosavi, Azam; Ardekani, Ali Motevalizadeh

    2016-01-01

    For a long time, scientists have tried to describe disorders just by genetic or environmental factors. However, the role of epigenetics in human diseases has been considered from a half of century ago. In the last decade, this subject has attracted many interests, especially in complicated disorders such as behavior plasticity, memory, cancer, autoimmune disease, and addiction as well as neurodegenerative and psychological disorders. This review first explains the history and classification o...

  3. Linking adult hippocampal neurogenesis with human physiology and disease.

    Science.gov (United States)

    Bowers, Megan; Jessberger, Sebastian

    2016-07-01

    We here review the existing evidence linking adult hippocampal neurogenesis and human brain function in physiology and disease. Furthermore, we aim to point out where evidence is missing, highlight current promising avenues of investigation, and suggest future tools and approaches to foster the link between life-long neurogenesis and human brain function. Developmental Dynamics 245:702-709, 2016. © 2016 Wiley Periodicals, Inc.

  4. Therapy of Human Papillomavirus-Related Disease

    Science.gov (United States)

    Stern, Peter L.; van der Burg, Sjoerd H.; Hampson, Ian N.; Broker, Thomas; Fiander, Alison; Lacey, Charles J.; Kitchener, Henry C.; Einstein, Mark H.

    2014-01-01

    This chapter reviews the current treatment of chronic and neoplastic HPV-associated conditions and the development of novel therapeutic approaches. Surgical excision of HPV-associated lower genital tract neoplasia is very successful but largely depends on secondary prevention programmes for identification of disease. Only high-risk HPV-driven chronic, preneoplastic lesions and some very early cancers cannot be successfully treated by surgical procedures alone. Chemoradiation therapy of cervical cancer contributes to the 66–79% cervical cancer survival at 5 years. Outlook for those patients with persistent or recurrent cervical cancer following treatment is very poor. Topical agents such as imiquimod (immune response modifier), cidofovir (inhibition of viral replication; induction apoptosis) or photodynamic therapy (direct damage of tumour and augmentation of anti-tumour immunity) have all shown some useful efficacy (~50–60%) in treatment of high grade vulvar intraepithelial neoplasia. Provider administered treatments of genital warts include cryotherapy, trichloracetic acid, or surgical removal which has the highest primary clearance rate. Patient applied therapies include podophyllotoxin and imiquimod. Recurrence after “successful” treatment is 30–40%. Further improvements could derive from a rational combination of current therapy with new drugs targeting molecular pathways mediated by HPV in cancer. Small molecule inhibitors targeting the DNA binding activities of HPV E1/E2 or the anti-apoptotic consequences of E6/E7 oncogenes are in preclinical development. Proteasome and histone deacetylase inhibitors, which can enhance apoptosis in HPV positive tumour cells, are being tested in early clinical trials. Chronic high-risk HPV infection/neoplasia is characterised by systemic and/or local immune suppressive regulatory or escape factors. Recently two E6/E7 vaccines have shown some clinical efficacy in high grade VIN patients and this correlated with strong

  5. Comprehensive metabolomics identified lipid peroxidation as a prominent feature in human plasma of patients with coronary heart diseases

    Directory of Open Access Journals (Sweden)

    Jianhong Lu

    2017-08-01

    Full Text Available Coronary heart disease (CHD is a complex human disease associated with inflammation and oxidative stress. The underlying mechanisms and diagnostic biomarkers for the different types of CHD remain poorly defined. Metabolomics has been increasingly recognized as an enabling technique with the potential to identify key metabolomic features in an attempt to understand the pathophysiology and differentiate different stages of CHD. We performed comprehensive metabolomic analysis in human plasma from 28 human subjects with stable angina (SA, myocardial infarction (MI, and healthy control (HC. Subsequent analysis demonstrated a uniquely altered metabolic profile in these CHD: a total of 18, 37 and 36 differential metabolites were identified to distinguish SA from HC, MI from SA, and MI from HC groups respectively. Among these metabolites, glycerophospholipid (GPL metabolism emerged as the most significantly disturbed pathway. Next, we used a targeted metabolomic approach to systematically analyze GPL, oxidized phospholipid (oxPL, and downstream metabolites derived from polyunsaturated fatty acids (PUFAs, such as arachidonic acid and linoleic acid. Surprisingly, lipids associated with lipid peroxidation (LPO pathways including oxidized PL and isoprostanes, isomers of prostaglandins, were significantly elevated in plasma of MI patients comparing to HC and SA, consistent with the notion that oxidative stress-induced LPO is a prominent feature in CHD. Our studies using the state-of-the-art metabolomics help to understand the underlying biological mechanisms involved in the pathogenesis of CHD; LPO metabolites may serve as potential biomarkers to differentiation MI from SA and HC.

  6. Genome editing of human pluripotent stem cells to generate human cellular disease models

    Directory of Open Access Journals (Sweden)

    Kiran Musunuru

    2013-07-01

    Full Text Available Disease modeling with human pluripotent stem cells has come into the public spotlight with the awarding of the Nobel Prize in Physiology or Medicine for 2012 to Drs John Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent. This discovery has opened the door for the generation of pluripotent stem cells from individuals with disease and the differentiation of these cells into somatic cell types for the study of disease pathophysiology. The emergence of genome-editing technology over the past few years has made it feasible to generate and investigate human cellular disease models with even greater speed and efficiency. Here, recent technological advances in genome editing, and its utility in human biology and disease studies, are reviewed.

  7. Genome editing of human pluripotent stem cells to generate human cellular disease models.

    Science.gov (United States)

    Musunuru, Kiran

    2013-07-01

    Disease modeling with human pluripotent stem cells has come into the public spotlight with the awarding of the Nobel Prize in Physiology or Medicine for 2012 to Drs John Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent. This discovery has opened the door for the generation of pluripotent stem cells from individuals with disease and the differentiation of these cells into somatic cell types for the study of disease pathophysiology. The emergence of genome-editing technology over the past few years has made it feasible to generate and investigate human cellular disease models with even greater speed and efficiency. Here, recent technological advances in genome editing, and its utility in human biology and disease studies, are reviewed.

  8. Omental Infarction Mimicking Cholecystitis

    Directory of Open Access Journals (Sweden)

    David Smolilo

    2015-01-01

    Full Text Available Omental infarction can be difficult to diagnose preoperatively as imaging may be inconclusive and patients often present in a way that suggests a more common surgical pathology such as appendicitis. Here, a 40-year-old Caucasian man presented to casualty with shortness of breath and progressive right upper abdominal pain, accompanied with right shoulder and neck pain. Exploratory laparoscopy was eventually utilised to diagnose an atypical form of omental infarction that mimics cholecystitis. The vascular supply along the long axis of the segment was occluded initiating necrosis. In this case, the necrotic segment was adherent with the abdominal wall, a pathology not commonly reported in cases of omental infarction.

  9. Human prion diseases: surgical lessons learned from iatrogenic prion transmission.

    Science.gov (United States)

    Bonda, David J; Manjila, Sunil; Mehndiratta, Prachi; Khan, Fahd; Miller, Benjamin R; Onwuzulike, Kaine; Puoti, Gianfranco; Cohen, Mark L; Schonberger, Lawrence B; Cali, Ignazio

    2016-07-01

    The human prion diseases, or transmissible spongiform encephalopathies, have captivated our imaginations since their discovery in the Fore linguistic group in Papua New Guinea in the 1950s. The mysterious and poorly understood "infectious protein" has become somewhat of a household name in many regions across the globe. From bovine spongiform encephalopathy (BSE), commonly identified as mad cow disease, to endocannibalism, media outlets have capitalized on these devastatingly fatal neurological conditions. Interestingly, since their discovery, there have been more than 492 incidents of iatrogenic transmission of prion diseases, largely resulting from prion-contaminated growth hormone and dura mater grafts. Although fewer than 9 cases of probable iatrogenic neurosurgical cases of Creutzfeldt-Jakob disease (CJD) have been reported worldwide, the likelihood of some missed cases and the potential for prion transmission by neurosurgery create considerable concern. Laboratory studies indicate that standard decontamination and sterilization procedures may be insufficient to completely remove infectivity from prion-contaminated instruments. In this unfortunate event, the instruments may transmit the prion disease to others. Much caution therefore should be taken in the absence of strong evidence against the presence of a prion disease in a neurosurgical patient. While the Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have devised risk assessment and decontamination protocols for the prevention of iatrogenic transmission of the prion diseases, incidents of possible exposure to prions have unfortunately occurred in the United States. In this article, the authors outline the historical discoveries that led from kuru to the identification and isolation of the pathological prion proteins in addition to providing a brief description of human prion diseases and iatrogenic forms of CJD, a brief history of prion disease nosocomial transmission

  10. Three cases report of connective tissue disease complicated with knee joint bone infarction%结缔组织病合并膝关节骨梗死三例报道

    Institute of Scientific and Technical Information of China (English)

    郑桂敏; 王磊; 贾秀川; 张风肖; 高建霞

    2013-01-01

    Bone infarction is often found in patients with connective tissue disease due to long-term application of large amount of corticosteroids. For these patients, bone infarction more commonly occurs in hip joints rather than in knee joints. Aching joints and arthritis are routine presentations of connective tissue disease, which may easily result in the misdiagnosis of bone infarction in knee joints. Likewise, bone infarction may hinder the tracking of the development of connective tissue disease. The clinical manifestations, immunological characteristics and course of diagnosis and treatment of 3 cases of connective tissue disease complicated with bone infarction are retrospectively described in this paper. All are females, 2 of whom suffers from systemic lupus erythematosus, and the other Sjogren's syndrome. All of them are treated with corticosteroids and immunodepressants in a long term, exhibit Raynaud's phenomenon, and are complicated with multiple or single bone infarction. Management of anti-osteoporosis, blood circulation activation and bone metabolism promotion yields definite effect, and magnetic resonance imaging has a high value in diagnosis. A clinical comprehensive analysis on the basis of symptoms, laboratory results and imaging findings should be carried out to avoid the misdiagnosis.%结缔组织病患者因为长期大量应用激素,骨梗死并不少见,但多发生于髋关节,发生在膝关节较少见.由于结缔组织病常表现有关节疼或关节炎,发生在膝关节的骨梗死容易被误诊;同样,骨梗死的诊断也可能掩盖结缔组织病的病情活动.作者回顾性分析了3例结缔组织病合并膝关节骨梗死患者的临床表现、免疫学特征以及诊疗过程.患者均为年轻女性,其中2例为系统性红斑狼疮,1例为干燥综合征;均有长期应用激素和免疫抑制剂史,均有雷诺现象,骨梗死为多发或单发,抗骨质疏松和活血、改善骨代谢有一定的疗效,磁共振成

  11. Oral lesions associated with human immunodeficiency virus disease.

    Science.gov (United States)

    Patton, Lauren L

    2013-10-01

    Human immunodeficiency virus (HIV)-associated oral disease among people living with HIV infection includes oral candidiasis, oral hairy leukoplakia, Kaposi sarcoma, oral warts, herpes simplex virus ulcers, major aphthous ulcers or ulcers not otherwise specified, HIV salivary gland disease, and atypical gingival and periodontal diseases. Diagnosis of some oral lesions is based on clinical appearance and behavior, whereas others require biopsy, culture, or imaging for definitive diagnosis. Management strategies including pharmacologic and nonpharmacologic approaches are discussed in this article. Dentists also need to be cognizant of the potential oral side effects of HIV antiretroviral medications.

  12. Reverse engineering human neurodegenerative disease using pluripotent stem cell technology.

    Science.gov (United States)

    Liu, Ying; Deng, Wenbin

    2016-05-01

    With the technology of reprogramming somatic cells by introducing defined transcription factors that enables the generation of "induced pluripotent stem cells (iPSCs)" with pluripotency comparable to that of embryonic stem cells (ESCs), it has become possible to use this technology to produce various cells and tissues that have been difficult to obtain from living bodies. This advancement is bringing forth rapid progress in iPSC-based disease modeling, drug screening, and regenerative medicine. More and more studies have demonstrated that phenotypes of adult-onset neurodegenerative disorders could be rather faithfully recapitulated in iPSC-derived neural cell cultures. Moreover, despite the adult-onset nature of the diseases, pathogenic phenotypes and cellular abnormalities often exist in early developmental stages, providing new "windows of opportunity" for understanding mechanisms underlying neurodegenerative disorders and for discovering new medicines. The cell reprogramming technology enables a reverse engineering approach for modeling the cellular degenerative phenotypes of a wide range of human disorders. An excellent example is the study of the human neurodegenerative disease amyotrophic lateral sclerosis (ALS) using iPSCs. ALS is a progressive neurodegenerative disease characterized by the loss of upper and lower motor neurons (MNs), culminating in muscle wasting and death from respiratory failure. The iPSC approach provides innovative cell culture platforms to serve as ALS patient-derived model systems. Researchers have converted iPSCs derived from ALS patients into MNs and various types of glial cells, all of which are involved in ALS, to study the disease. The iPSC technology could be used to determine the role of specific genetic factors to track down what's wrong in the neurodegenerative disease process in the "disease-in-a-dish" model. Meanwhile, parallel experiments of targeting the same specific genes in human ESCs could also be performed to control

  13. Disease modeling and drug screening for neurological diseases using human induced pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    Xiao-hong XU; Zhong ZHONG

    2013-01-01

    With the general decline of pharmaceutical research productivity,there are concerns that many components of the drug discovery process need to be redesigned and optimized.For example,the human immortalized cell lines or animal primary cells commonly used in traditional drug screening may not faithfully recapitulate the pathological mechanisms of human diseases,leading to biases in assays,targets,or compounds that do not effectively address disease mechanisms.Recent advances in stem cell research,especially in the development of induced pluripotent stem cell (iPSC) technology,provide a new paradigm for drug screening by permitting the use of human cells with the same genetic makeup as the patients without the typical quantity constraints associated with patient primary cells.In this article,we will review the progress made to date on cellular disease models using human stem cells,with a focus on patient-specific iPSCs for neurological diseases.We will discuss the key challenges and the factors that associated with the success of using stem cell models for drug discovery through examples from monogenic diseases,diseases with various known genetic components,and complex diseases caused by a combination of genetic,environmental and other factors.

  14. Disease modeling and drug screening for neurological diseases using human induced pluripotent stem cells.

    Science.gov (United States)

    Xu, Xiao-hong; Zhong, Zhong

    2013-06-01

    With the general decline of pharmaceutical research productivity, there are concerns that many components of the drug discovery process need to be redesigned and optimized. For example, the human immortalized cell lines or animal primary cells commonly used in traditional drug screening may not faithfully recapitulate the pathological mechanisms of human diseases, leading to biases in assays, targets, or compounds that do not effectively address disease mechanisms. Recent advances in stem cell research, especially in the development of induced pluripotent stem cell (iPSC) technology, provide a new paradigm for drug screening by permitting the use of human cells with the same genetic makeup as the patients without the typical quantity constraints associated with patient primary cells. In this article, we will review the progress made to date on cellular disease models using human stem cells, with a focus on patient-specific iPSCs for neurological diseases. We will discuss the key challenges and the factors that associated with the success of using stem cell models for drug discovery through examples from monogenic diseases, diseases with various known genetic components, and complex diseases caused by a combination of genetic, environmental and other factors.

  15. Human gene therapy and imaging in neurological diseases

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, Andreas H.; Winkler, Alexandra [Max Planck-Institute for Neurological Research, Center of Molecular Medicine (CMMC) and Department of Neurology, Cologne (Germany); MPI for Neurological Research, Laboratory for Gene Therapy and Molecular Imaging, Cologne (Germany); Castro, Maria G.; Lowenstein, Pedro [University of California Los Angeles (United States). Department of Medicine

    2005-12-01

    Molecular imaging aims to assess non-invasively disease-specific biological and molecular processes in animal models and humans in vivo. Apart from precise anatomical localisation and quantification, the most intriguing advantage of such imaging is the opportunity it provides to investigate the time course (dynamics) of disease-specific molecular events in the intact organism. Further, molecular imaging can be used to address basic scientific questions, e.g. transcriptional regulation, signal transduction or protein/protein interaction, and will be essential in developing treatment strategies based on gene therapy. Most importantly, molecular imaging is a key technology in translational research, helping to develop experimental protocols which may later be applied to human patients. Over the past 20 years, imaging based on positron emission tomography (PET) and magnetic resonance imaging (MRI) has been employed for the assessment and ''phenotyping'' of various neurological diseases, including cerebral ischaemia, neurodegeneration and brain gliomas. While in the past neuro-anatomical studies had to be performed post mortem, molecular imaging has ushered in the era of in vivo functional neuro-anatomy by allowing neuroscience to image structure, function, metabolism and molecular processes of the central nervous system in vivo in both health and disease. Recently, PET and MRI have been successfully utilised together in the non-invasive assessment of gene transfer and gene therapy in humans. To assess the efficiency of gene transfer, the same markers are being used in animals and humans, and have been applied for phenotyping human disease. Here, we review the imaging hallmarks of focal and disseminated neurological diseases, such as cerebral ischaemia, neurodegeneration and glioblastoma multiforme, as well as the attempts to translate gene therapy's experimental knowledge into clinical applications and the way in which this process is being

  16. Modeling Human Graft-Versus-Host Disease in Immunocompromised Mice.

    Science.gov (United States)

    Norelli, Margherita; Camisa, Barbara; Bondanza, Attilio

    2016-01-01

    Hematopoietic stem cell transplantation (HSCT) from an allogeneic donor is an effective form of cancer immunotherapy, especially for acute leukemias. HSCT is however frequently complicated by the occurrence of graft-versus-host disease (GVHD). Immunocompromised mice infused with human T cells often develop a clinical syndrome resembling human GVHD (xenogeneic or X-GVHD). Herein, we describe a method for inducing X-GVHD in a highly reproducible manner. Given the human nature of immune effectors, this xenogeneic model can be routinely adopted for screening the efficacy of new treatments for GVHD.

  17. Mapping gene associations in human mitochondria using clinical disease phenotypes.

    Directory of Open Access Journals (Sweden)

    Curt Scharfe

    2009-04-01

    Full Text Available Nuclear genes encode most mitochondrial proteins, and their mutations cause diverse and debilitating clinical disorders. To date, 1,200 of these mitochondrial genes have been recorded, while no standardized catalog exists of the associated clinical phenotypes. Such a catalog would be useful to develop methods to analyze human phenotypic data, to determine genotype-phenotype relations among many genes and diseases, and to support the clinical diagnosis of mitochondrial disorders. Here we establish a clinical phenotype catalog of 174 mitochondrial disease genes and study associations of diseases and genes. Phenotypic features such as clinical signs and symptoms were manually annotated from full-text medical articles and classified based on the hierarchical MeSH ontology. This classification of phenotypic features of each gene allowed for the comparison of diseases between different genes. In turn, we were then able to measure the phenotypic associations of disease genes for which we calculated a quantitative value that is based on their shared phenotypic features. The results showed that genes sharing more similar phenotypes have a stronger tendency for functional interactions, proving the usefulness of phenotype similarity values in disease gene network analysis. We then constructed a functional network of mitochondrial genes and discovered a higher connectivity for non-disease than for disease genes, and a tendency of disease genes to interact with each other. Utilizing these differences, we propose 168 candidate genes that resemble the characteristic interaction patterns of mitochondrial disease genes. Through their network associations, the candidates are further prioritized for the study of specific disorders such as optic neuropathies and Parkinson disease. Most mitochondrial disease phenotypes involve several clinical categories including neurologic, metabolic, and gastrointestinal disorders, which might indicate the effects of gene defects

  18. The impact of winter cold weather on acute myocardial infarctions in Portugal.

    Science.gov (United States)

    Vasconcelos, João; Freire, Elisabete; Almendra, Ricardo; Silva, Giovani L; Santana, Paula

    2013-12-01

    Mortality due to cardiovascular diseases shows a seasonal trend that can be associated with cold weather. Portugal is the European country with the highest excess winter mortality, but nevertheless, the relationship between cold weather and health is yet to be assessed. The main aim of this study is to identify the contribution of cold weather to cardiovascular diseases within Portugal. Poisson regression analysis based on generalized additive models was applied to estimate the influence of a human-biometeorological index (PET) on daily hospitalizations for myocardial infarction. The main results revealed a negative effect of cold weather on acute myocardial infarctions in Portugal. For every degree fall in PET during winter, there was an increase of up to 2.2% (95% CI = 0.9%; 3.3%) in daily hospital admissions. This paper shows the need for public policies that will help minimize or, indeed, prevent exposure to cold.

  19. Molecular functions of human endogenous retroviruses in health and disease.

    Science.gov (United States)

    Suntsova, Maria; Garazha, Andrew; Ivanova, Alena; Kaminsky, Dmitry; Zhavoronkov, Alex; Buzdin, Anton

    2015-10-01

    Human endogenous retroviruses (HERVs) and related genetic elements form 504 distinct families and occupy ~8% of human genome. Recent success of high-throughput experimental technologies facilitated understanding functional impact of HERVs for molecular machinery of human cells. HERVs encode active retroviral proteins, which may exert important physiological functions in the body, but also may be involved in the progression of cancer and numerous human autoimmune, neurological and infectious diseases. The spectrum of related malignancies includes, but not limits to, multiple sclerosis, psoriasis, lupus, schizophrenia, multiple cancer types and HIV. In addition, HERVs regulate expression of the neighboring host genes and modify genomic regulatory landscape, e.g., by providing regulatory modules like transcription factor binding sites (TFBS). Indeed, recent bioinformatic profiling identified ~110,000 regulatory active HERV elements, which formed at least ~320,000 human TFBS. These and other peculiarities of HERVs might have played an important role in human evolution and speciation. In this paper, we focus on the current progress in understanding of normal and pathological molecular niches of HERVs, on their implications in human evolution, normal physiology and disease. We also review the available databases dealing with various aspects of HERV genetics.

  20. Molecular Genetic Approaches to Human Diseases Involving Mental Retardation.

    Science.gov (United States)

    Latt, Samuel A.; And Others

    1984-01-01

    Recombinant DNA techniques provide new approaches to the diagnosis and analysis of inherited human diseases associated with mental retardation, such as Lesch-Nyhan syndrome, phenylketonauria, the Fragile X syndrome, Down syndrome, and those associated with deletions or duplications of subchromosomal regions. (Author/CL)

  1. Recognizing filamentous basidiomycetes as agents of human disease: A review

    NARCIS (Netherlands)

    Chowdhary, A.; Kathuria, S.; Agarwal, K.; Meis, J.F.G.M.

    2014-01-01

    Filamentous basidiomycetes (BM) are common environmental fungi that have recently emerged as important human pathogens, inciting a wide array of clinical manifestations that include allergic and invasive diseases. We reviewed 218 reported global cases of BM fungi. The most common etiologic agent was

  2. Spinal Cord Infarction

    Science.gov (United States)

    ... arteries that supply it. It is caused by arteriosclerosis or a thickening or closing of the major ... infarction is caused by a specific form of arteriosclerosis called atheromatosis, in which a deposit or accumulation ...

  3. Lyme disease: a unique human model for an infectious etiology of rheumatic disease.

    Science.gov (United States)

    Malawista, S. E.; Steere, A. C.; Hardin, J. A.

    1984-01-01

    Lyme disease is a complex immune-mediated multi-system disorder that is infectious in origin and inflammatory or "rheumatic" in expression. Through its epidemiologic characteristics, large numbers of a seasonally synchronized patient population are readily available for prospective study. Lyme disease has a known clinical onset ("zero time"), marked by the characteristic expanding skin lesion, erythema chronicum migrans, and a clearly defined pre-articular phase. At least some manifestations of the disorder are responsive to antibiotics, and the causative agent--a spirochete--is now known. These advantages make Lyme disease unique as a human model for an infectious etiology of rheumatic disease. PMID:6516449

  4. PXR- and CAR-mediated herbal effect on human diseases.

    Science.gov (United States)

    Xu, Chenshu; Huang, Min; Bi, Huichang

    2016-09-01

    The pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are two members of the nuclear receptor superfamily that regulate a broad range of genes involved in drug metabolism and transport. A variety of naturally occurring compounds present in herbal medicines were identified as ligands of PXR and CAR. Recently, accumulative evidences have revealed the PXR- and CAR-mediated herbal effect against multiple human diseases, including inflammatory bowel disease (IBD), cholestatic liver disease, and jaundice. The current review summarized the recent progress in identifying the expanding libraries of herbal medicine as ligands for PXR and CAR. Moreover, the potential for herbal medicines as promising therapeutic agents which were mainly regulated through PXR/CAR signaling pathways was also discussed. The discovery of herbal medicines as modulators of PXR and CAR, and their PXR- and CAR-mediated effect on human diseases will provide a basis for rational drug design, and eventually be explored as a novel therapeutic approach against human diseases. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr. Wen Xie.

  5. Viral hepatitis E: A disease of humans and animals

    Directory of Open Access Journals (Sweden)

    Kureljušić Branislav

    2012-01-01

    Full Text Available The hepatitis E virus is ubiquitous in all parts of the world where pig production exists. The infection occurs in several animal species and its course is mostly asymptomatic. Viral strains isolated from pigs and humans are genetically similar, which indicates a potential zoonotic nature of the disease, and the possibility that pigs, and perhaps also other species of animals diseased with viral hepatitis E are a source of infection to humans. The pig hepatitis E virus, which is similar to the hepatitis E virus in humans, was isolated and described for the first time in the USA in 1997. The infection of pigs with hepatitis E virus occurs through faeco-oral transmission, by ingestion of feed and water contaminated with the virus, or through direct contact between infected and healthy animals. The pathogenesis of this infection in pigs differs from its pathogenesis in humans and it has not been sufficiently examined in all its aspects. Even though viral hepatitis E in pigs has been described as a subclinical disease, some authors describe changes in the concentration of certain biochemical parameters in blood serum of the infected pigs. Histologically, a mild to moderate lymphotic-plasma cellular infiltration is observed in livers of infected pigs, as well as focal areas of hepatocyte necrosis. Viral hepatitis E is an endemic disease of humans in Asia, Africa, and Latin America. In developed countries, hepatitis E sporadically occurs in humans, but it is becoming of increasing importance in particular in Japan, North America, and Europe, because the populations of these areas travel extensively to the endemic regions or as a result of the consumption of thermally untreated meat of wild boar and products made from thermally untreated meat. Pork products can be contaminated with hepatitis E virus. Further proof that indicates the zoonotic potential of this virus and places this diseases among the group of professional diseases of farmers and

  6. Early assessment and treatment of myocardial infarction

    NARCIS (Netherlands)

    Hoog, V.C. de

    2015-01-01

    Although the detection and treatment of acute myocardial infarction (MI) has dramatically improved the last decades, ischemic heart disease is still a leading cause of death worldwide. Whereas mortality has declined in industrialized countries, it continues to rise in other parts of the world. There

  7. Acute Thrombo-embolic Renal Infarction

    Directory of Open Access Journals (Sweden)

    Haijiang Zhou

    2016-07-01

    Full Text Available A 65-year-old woman was admitted for acute onset of right lower abdominal pain. She was taking anticoagulant medication regularly for rheumatic valvular disease and atrial fibrillation. Physical examination revealed no obvious abdominal or flank tenderness. Right thrombo-embolic renal infarction was diagnosed after performing computed tomography angiography (CTA.

  8. Acute Thrombo-embolic Renal Infarction.

    Science.gov (United States)

    Zhou, Haijiang; Yan, Yong; Li, Chunsheng; Guo, Shubin

    2016-07-01

    A 65-year-old woman was admitted for acute onset of right lower abdominal pain. She was taking anticoagulant medication regularly for rheumatic valvular disease and atrial fibrillation. Physical examination revealed no obvious abdominal or flank tenderness. Right thrombo-embolic renal infarction was diagnosed after performing computed tomography angiography (CTA).

  9. Unilateral adrenal hemorrhagic infarction in essential thrombocythemia.

    Science.gov (United States)

    Burnet, G; Lambert, M; Annet, L; Lefebvre, C

    2015-12-01

    Adrenal hemorrhage is a rare disease associated with various conditions. We report a case of a 68-year-old woman with abdominal and back pain. The diagnostic work-up showed a left adrenal gland infarction associated with essential thrombocythemia. Treatment consisted in painkillers and treating the underlying condition in order to prevent further thrombotic events.

  10. Human genetics of infectious diseases: a unified theory

    Science.gov (United States)

    Casanova, Jean-Laurent; Abel, Laurent

    2007-01-01

    Since the early 1950s, the dominant paradigm in the human genetics of infectious diseases postulates that rare monogenic immunodeficiencies confer vulnerability to multiple infectious diseases (one gene, multiple infections), whereas common infections are associated with the polygenic inheritance of multiple susceptibility genes (one infection, multiple genes). Recent studies, since 1996 in particular, have challenged this view. A newly recognised group of primary immunodeficiencies predisposing the individual to a principal or single type of infection is emerging. In parallel, several common infections have been shown to reflect the inheritance of one major susceptibility gene, at least in some populations. This novel causal relationship (one gene, one infection) blurs the distinction between patient-based Mendelian genetics and population-based complex genetics, and provides a unified conceptual frame for exploring the molecular genetic basis of infectious diseases in humans. PMID:17255931

  11. Leveraging human-centered design in chronic disease prevention.

    Science.gov (United States)

    Matheson, Gordon O; Pacione, Chris; Shultz, Rebecca K; Klügl, Martin

    2015-04-01

    Bridging the knowing-doing gap in the prevention of chronic disease requires deep appreciation and understanding of the complexities inherent in behavioral change. Strategies that have relied exclusively on the implementation of evidence-based data have not yielded the desired progress. The tools of human-centered design, used in conjunction with evidence-based data, hold much promise in providing an optimal approach for advancing disease prevention efforts. Directing the focus toward wide-scale education and application of human-centered design techniques among healthcare professionals will rapidly multiply their effective ability to bring the kind of substantial results in disease prevention that have eluded the healthcare industry for decades. This, in turn, would increase the likelihood of prevention by design.

  12. Impact of climate change on human infectious diseases: Empirical evidence and human adaptation.

    Science.gov (United States)

    Wu, Xiaoxu; Lu, Yongmei; Zhou, Sen; Chen, Lifan; Xu, Bing

    2016-01-01

    Climate change refers to long-term shifts in weather conditions and patterns of extreme weather events. It may lead to changes in health threat to human beings, multiplying existing health problems. This review examines the scientific evidences on the impact of climate change on human infectious diseases. It identifies research progress and gaps on how human society may respond to, adapt to, and prepare for the related changes. Based on a survey of related publications between 1990 and 2015, the terms used for literature selection reflect three aspects--the components of infectious diseases, climate variables, and selected infectious diseases. Humans' vulnerability to the potential health impacts by climate change is evident in literature. As an active agent, human beings may control the related health effects that may be effectively controlled through adopting proactive measures, including better understanding of the climate change patterns and of the compound disease-specific health effects, and effective allocation of technologies and resources to promote healthy lifestyles and public awareness. The following adaptation measures are recommended: 1) to go beyond empirical observations of the association between climate change and infectious diseases and develop more scientific explanations, 2) to improve the prediction of spatial-temporal process of climate change and the associated shifts in infectious diseases at various spatial and temporal scales, and 3) to establish locally effective early warning systems for the health effects of predicated climate change.

  13. Humane killing of animals for disease control purposes.

    Science.gov (United States)

    Thornber, P M; Rubira, R J; Styles, D K

    2014-04-01

    Killing for disease control purposes is an emotional issue for everyone concerned. Large-scale euthanasia or depopulation of animals may be necessary for the emergency control or eradication of animal diseases, to remove animals from a compromised situation (e.g. following flood, storm, fire, drought or a feed contamination event), to effect welfare depopulation when there is an oversupply due to a dysfunctional or closed marketing channel, or to depopulate and dispose of animals with minimal handling to decrease the risk of a zoonotic disease infecting humans. The World Organisation for Animal Health (OIE) developed international standards to provide advice on humane killing for various species and situations. Some fundamental issues are defined, such as competency of animal handling and implementation of humane killing techniques. Some of these methods have been used for many years, but novel approaches for the mass killing of particular species are being explored. Novel vaccines and new diagnostic techniques that differentiate between vaccinated and infected animals will save many animals from being killed as part of biosecurity response measures. Unfortunately, the destruction of affected livestock will still be required to control diseases whilst vaccination programmes are activated or where effective vaccines are not available. This paper reviews the principles of humane destruction and depopulation and explores available techniques with their associated advantages and disadvantages. It also identifies some current issues that merit consideration, such as legislative conflicts (emergency disease legislation versus animal welfare legislation, occupational health and safety), media issues, opinions on the future approaches to killing for disease control, and animal welfare.

  14. Transgenic rabbits as therapeutic protein bioreactors and human disease models.

    Science.gov (United States)

    Fan, Jianglin; Watanabe, Teruo

    2003-09-01

    Genetically modified laboratory animals provide a powerful approach for studying gene expression and regulation and allow one to directly examine structure-function and cause-and-effect relationships in pathophysiological processes. Today, transgenic mice are available as a research tool in almost every research institution. On the other hand, the development of a relatively large mammalian transgenic model, transgenic rabbits, has provided unprecedented opportunities for investigators to study the mechanisms of human diseases and has also provided an alternative way to produce therapeutic proteins to treat human diseases. Transgenic rabbits expressing human genes have been used as a model for cardiovascular disease, AIDS, and cancer research. The recombinant proteins can be produced from the milk of transgenic rabbits not only at lower cost but also on a relatively large scale. One of the most promising and attractive recombinant proteins derived from transgenic rabbit milk, human alpha-glucosidase, has been successfully used to treat the patients who are genetically deficient in this enzyme. Although the pronuclear microinjection is still the major and most popular method for the creation of transgenic rabbits, recent progress in gene targeting and animal cloning has opened new avenues that should make it possible to produce transgenic rabbits by somatic cell nuclear transfer in the future. Based on a computer-assisted search of the studies of transgenic rabbits published in the English literature here, we introduce to the reader the achievements made thus far with transgenic rabbits, with emphasis on the application of these rabbits as human disease models and live bioreactors for producing human therapeutic proteins and on the recent progress in cloned rabbits.

  15. Acute myopericarditis masquerading as acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Wen Tian; Zixin Zhang; Xiaojuan Bai; Dingyin Zeng; Guoxian Qi

    2008-01-01

    Patients with abrupt onset of chest pain, ischemic ECG abnormalities and elevated levels of cardiac markers could be given a diagnosis of acute myocardial infarction. However, some other diseases should be taken into consideration in this clinical setting when coronary arteries are proven to be normal. Here we report a case of acute myopericarditis with clinical presentation of myocardial infarction and normal coronary anatomy. The Herpes Simplex Virus Ⅱ was considered as the organism causing myopericarditis and the patient was recovered by the treatment with valacicloavir. A precise diagnosis is a prerequisite of successful treatment and favorable prognosis.

  16. Myocardial infarction in the young

    Directory of Open Access Journals (Sweden)

    Cengel A

    2009-01-01

    Full Text Available An increasing number of patients under 40 years of age are being hospitalized with the diagnosis of acute myocardial infarction. This is partly due to the increased prevalance of risk factors for atherosclerosis in the younger age group; especially increased incidence of impaired fasting glucose, high triglyceride, low high-density lipoprotein levels and increased waist to hip ratio. However, non-atherosclerotic coronary artery disease or hypercoagulability should also be investigated or at least suspected in the younger patients. The pathophysiology of different clinical conditions and disease states which cause acute coronary syndromes in the young patients are reviewed, and the diagnostic modalities and therapatic options for these conditions are briefly discussed by searching for "premature atherosclerosis", "hypercoagulable states", "risk factors for atherosclerosis in youth", "novel risk factors for atherosclerosis", "non-atherosclerotic coronary artery diseases" in PubMed.

  17. Anterograde and Retrograde Amnesia following Bitemporal Infarction

    Directory of Open Access Journals (Sweden)

    A. Schnider

    1994-01-01

    Full Text Available A patient suffered very severe anterograde and retrograde amnesia following infarction of both medial temporal lobes (hippocampus and adjacent cortex and the left inferior temporo-occipital area. The temporal stem and the amygdala were intact; these structures do not appear to be critical for new learning in humans. Extension of the left-sided infarct into the inferior temporo-occipital lobe, an area critically involved in visual processing, appears to be responsible for our patient's loss of remote memories.

  18. Hypersexuality following bilateral thalamic infarction: case report.

    Science.gov (United States)

    Mutarelli, Eduardo G; Omuro, Antonio M P; Adoni, Tarso

    2006-03-01

    Hypersexuality is a rare but well recognized condition following brain injury. It has been described secondarily to dysfunction in the hypothalamus, the temporal and frontal lobes. We report a 63 year-old man that developed neuropsychological disturbances with hypersexuality as a prominent feature, disinhibition and moderate memory loss, hypersomnia and irritability after a bilateral paramedian thalamic infarction. A SPECT showed frontal hypoperfusion. We believe that these findings are expression of frontal-subcortical circuits dysfunction, particularly the orbitofrontal circuit, secondary to dorso medial thalamic infarction which probably plays a role in the determination of human sexual behavior. This case favors a thalamic modulation of frontal function.

  19. MicroRNA miR-1 is up-regulated in remote myocardium in patients with myocardial infarction.

    Science.gov (United States)

    Bostjancic, E; Zidar, N; Stajner, D; Glavac, D

    2010-01-01

    MicroRNAs are small regulatory RNA molecules that mediate regulation of gene expression, thus affecting a variety of physiological, developmental and pathological conditions. They are believed to be new promising therapeutic targets. In recent studies two muscle-specific microRNAs were discovered to contribute to heart diseases and development: miR-1 and miR-133, but there is little data on their expression patterns in human myocardial infarction. We performed simultaneous expression analysis of miR-1, miR-133a, miR-133b in samples of infarcted tissue and remote myocardium from twenty- four patients with acute myocardial infarction. MicroRNA expression was analysed using quantitative real-time PCR and compared to the expression patterns in myocardium of eight healthy adults who died in accidents. We found ~3.8-fold miR-1 up-regulation in remote myocardium when compared to infarcted tissue or healthy adult hearts. As miR-1 has been shown in animal models and clinical studies to contribute to arrhythmogenesis by regulating pacemaker channel genes, our finding of miR-1 up-regulation in patients with myocardial infarction indicates that it might be responsible for the higher risk for arrhythmias in these patients. In addition, miR-133a/b down-regulation in infarcted tissue and remote myocardium was observed, indicating miR-133a/b involvement in the heart response to myocardial infarction. We conclude that miR-1 and miR-133 seem to be important regulators of heart adaptation after ischaemic stress.

  20. Human glia can both induce and rescue aspects of disease phenotype in Huntington disease

    DEFF Research Database (Denmark)

    Benraiss, Abdellatif; Wang, Su; Herrlinger, Stephanie

    2016-01-01

    (hGPCs), derived from either human embryonic stem cells or mHTT-transduced fetal hGPCs. Here we show that mHTT glia can impart disease phenotype to normal mice, since mice engrafted intrastriatally with mHTT hGPCs exhibit worse motor performance than controls, and striatal neurons in mHTT glial......The causal contribution of glial pathology to Huntington disease (HD) has not been heavily explored. To define the contribution of glia to HD, we established human HD glial chimeras by neonatally engrafting immunodeficient mice with mutant huntingtin (mHTT)-expressing human glial progenitor cells...... survival in R6/2 HD mice. These observations suggest a causal role for glia in HD, and further suggest a cell-based strategy for disease amelioration in this disorder....

  1. Molecular mechanisms of acrolein toxicity: relevance to human disease.

    Science.gov (United States)

    Moghe, Akshata; Ghare, Smita; Lamoreau, Bryan; Mohammad, Mohammad; Barve, Shirish; McClain, Craig; Joshi-Barve, Swati

    2015-02-01

    Acrolein, a highly reactive unsaturated aldehyde, is a ubiquitous environmental pollutant and its potential as a serious environmental health threat is beginning to be recognized. Humans are exposed to acrolein per oral (food and water), respiratory (cigarette smoke, automobile exhaust, and biocide use) and dermal routes, in addition to endogenous generation (metabolism and lipid peroxidation). Acrolein has been suggested to play a role in several disease states including spinal cord injury, multiple sclerosis, Alzheimer's disease, cardiovascular disease, diabetes mellitus, and neuro-, hepato-, and nephro-toxicity. On the cellular level, acrolein exposure has diverse toxic effects, including DNA and protein adduction, oxidative stress, mitochondrial disruption, membrane damage, endoplasmic reticulum stress, and immune dysfunction. This review addresses our current understanding of each pathogenic mechanism of acrolein toxicity, with emphasis on the known and anticipated contribution to clinical disease, and potential therapies.

  2. Exosomes and cardiac repair after myocardial infarction.

    Science.gov (United States)

    Sahoo, Susmita; Losordo, Douglas W

    2014-01-17

    Myocardial infarction is a leading cause of death among all cardiovascular diseases. The analysis of molecular mechanisms by which the ischemic myocardium initiates repair and remodeling indicates that secreted soluble factors are key players in communication to local and distant tissues, such as bone marrow. Recently, actively secreted membrane vesicles, including exosomes, are being recognized as new candidates with important roles in intercellular and tissue-level communication. In this review, we critically examine the emerging role of exosomes in local and distant microcommunication mechanisms after myocardial infarction. A comprehensive understanding of the role of exosomes in cardiac repair after myocardial infarction could bridge a major gap in knowledge of the repair mechanism after myocardial injury.

  3. Hepatic infarction following abdominal interventional procedures.

    Directory of Open Access Journals (Sweden)

    Fujiwara H

    2004-04-01

    Full Text Available To clarify the incidence, background, and progress of hepatic infarction following interventional procedures, cases of hepatic infarction following interventional procedures at our department during the last decade were identified by reviewing the clinical records of 1982 abdominal angiography and interventional procedures and records of abdominal CT. Nine episodes (0.5% in 8 patients were identified as hepatic infarction following an interventional procedure. Five episodes were preceded by embolization of the hepatic or celiac artery at emergency angiography for postoperative bleeding with hemorrhagic shock. Three episodes followed the elected interventional procedure for hepatocellular carcinoma, and the remaining episode occurred after 12 months of chemoinfusion through an indwelling catheter in the hepatic artery and portal vein. Hepatic arterial occlusion in all episodes and portal venous flow abnormality in 5 episodes were observed on angiography. Four patients whose liver function was initially impaired died of hepatic infarction, although the extent of the disease on CT did not appear to be related to the mortality. Multiple risk factors, including arterial insufficiency, were observed in each patient. The incidence of hepatic infarction following interventional procedures in this series was low but sometimes fatal, and occurred most frequently in emergency embolization in hemorrhagic shock.

  4. Postoperative omental infarction following colonic resection

    Energy Technology Data Exchange (ETDEWEB)

    Kerr, S.F., E-mail: skerr44@doctors.org.uk [Department of Radiology, Leeds General Infirmary, Leeds (United Kingdom); Hyland, R.; Rowbotham, E.; Chalmers, A.G. [Department of Radiology, Leeds General Infirmary, Leeds (United Kingdom)

    2012-02-15

    Aim: To illustrate the computed tomography (CT) appearances and natural history of postoperative omental infarction following colonic resection and to highlight the important clinical implications of this radiological diagnosis. Materials and methods: Over a 3 year period, 15 patients with a history of colonic resection were identified as having a CT diagnosis of postoperative omental infarction. Relevant clinical and pathological data were retrospectively collected from the institution's electronic patient records system and all relevant imaging was reviewed, including serial CT images in 10 patients. Results: A diagnosis of postoperative omental infarction was made in symptomatic and asymptomatic patients who had undergone open or laparoscopic colonic resection for benign or malignant disease. CT appearances ranged from diffuse omental stranding to discrete masses, which typically appeared within weeks of surgery and could persist for years. In four (36%) of the patients with colorectal cancer, the CT appearances raised concern for recurrent malignancy, but percutaneous biopsy and/or serial CT allowed a confident diagnosis of omental infarction to be made. Although most cases were self-limiting, three (20%) cases were complicated by secondary infection and required radiological or surgical intervention. Conclusion: Postoperative omental infarction is an under-recognized complication of colonic resection. It has the potential to mimic recurrent malignancy and may require radiological or surgical intervention for secondary infection.

  5. Mutations in inhibin and activin genes associated with human disease.

    Science.gov (United States)

    Shelling, Andrew N

    2012-08-15

    Inhibins and activins are members of the transforming growth factor (TGFβ) superfamily, that includes the TGFβs, inhibins and activins, bone morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs). The family members are expressed throughout the human body, and are involved in the regulation of a range of important functions. The precise regulation of the TGFβ pathways is critical, and mutations of individual molecules or even minor alterations of signalling will have a significant affect on function, that may lead to development of disease or predisposition to the development of disease. The inhibins and activins regulate aspects of the male and female reproductive system, therefore, it is not surprising that most of the diseases associated with abnormalities of the inhibin and activin genes are focused on reproductive disorders and reproductive cancers. In this review, I highlight the role of genetic variants in the development of conditions such as premature ovarian failure, pre-eclampsia, and various reproductive cancers. Given the recent advances in human genetic research, such as genome wide association studies and next generation sequencing, it is likely that inhibins and activins will be shown to play more important roles in a range of human genetic diseases in the future.

  6. Human anthrax as a re-emerging disease.

    Science.gov (United States)

    Doganay, Mehmet; Demiraslan, Hayati

    2015-01-01

    Anthrax is primarily a disease of herbivores and the etiological agent is B. anthracis which is a gram-positive, aerobic, spore-forming, and rod shaped bacterium. Bacillus anthracis spores are highly resistant to heat, pressure, ultraviolet and ionizing radiation, chemical agents and disinfectants. For these reasons, B. anthracis spores are an attractive choice as biological agents for the use of bioweapon and/or bioterrorism. Soil is the main reservoir for the infectious agent. The disease most commonly affects wild and domestic mammals. Human are secondarily infected by contact with infected animals and contaminated animal products or directly expose to B. anthracis spores. Anthrax occurs worldwide. This infection is still endemic or hyperendemic in both animals and humans in some part of areas of the world; particularly in Middle East, West Africa, Central Asia, some part of India, South America. However, some countries are claiming free of anthrax, and anthrax has become a re-emerging disease in western countries with the intentional outbreak. Currently, anthrax is classified according to its setting as (1) naturally occurring anthrax, (2) bioterrorism-related anthrax. Vast majority of human anthrax are occurring as naturally occurring anthrax in the world. It is also a threaten disease for western countries. The aim of this paper is to review the relevant patents, short historical perspective, microbiological and epidemiological features, clinical presentations and treatment.

  7. Proteomics in farm animals models of human diseases.

    Science.gov (United States)

    Ceciliani, Fabrizio; Restelli, Laura; Lecchi, Cristina

    2014-10-01

    The need to provide in vivo complex environments to understand human diseases strongly relies on the use of animal models, which traditionally include small rodents and rabbits. It is becoming increasingly evident that the few species utilised to date cannot be regarded as universal. There is a great need for new animal species that are naturally endowed with specific features relevant to human diseases. Farm animals, including pigs, cows, sheep and horses, represent a valid alternative to commonly utilised rodent models. There is an ample scope for the application of proteomic techniques in farm animals, and the establishment of several proteomic maps of plasma and tissue has clearly demonstrated that farm animals provide a disease environment that closely resembles that of human diseases. The present review offers a snapshot of how proteomic techniques have been applied to farm animals to improve their use as biomedical models. Focus will be on specific topics of biomedical research in which farm animal models have been characterised through the application of proteomic techniques.

  8. Noncommunicable diseases and human rights: a promising synergy.

    Science.gov (United States)

    Gruskin, Sofia; Ferguson, Laura; Tarantola, Daniel; Beaglehole, Robert

    2014-05-01

    Noncommunicable diseases (NCDs) have finally emerged onto the global health and development agenda. Despite the increasingly important role human rights play in other areas of global health, their contribution to NCD prevention and control remains nascent. The recently adopted Global Action Plan for the Prevention and Control of NCDs 2013-2020 is an important step forward, but the lack of concrete attention to human rights is a missed opportunity. With practical implications for policy development, priority setting, and strategic design, human rights offer a logical, robust set of norms and standards; define the legal obligations of governments; and provide accountability mechanisms that can be used to enhance current approaches to NCD prevention and control. Harnessing the power of human rights can strengthen action for NCDs at the local, national, and global levels.

  9. Chronic Inflammatory Periodontal Disease in Patients with Human Immunodeficiency Virus.

    Directory of Open Access Journals (Sweden)

    Vania López Rodríguez

    2009-07-01

    Full Text Available Background: The Chronic Inflammatory Periodontal Disease is related with multiple risk factors. Those patients with human immunodeficiency virus have higher risk of presenting this disease and it is usually more serious in these cases. Objective: To describe the prevalence of Chronic Inflammatory Periodontal Disease in patients with HIV. Methods: Descriptive, observational, cross-sectional study including patients with HIV in Sancti Spiritus province. The occurrence of the disease was determined after the Periodontics Cuban Standards, and oral hygiene was assessed through the simplified oral hygiene index. Other variables were measured, such as smoking habits, T CD4+ lymphocyte counting and virus load. The independent association of each risk factor with the disease was determined through a logistic regression model. Results: The 56, 5 % of the 154 patients presented Chronic Inflammatory Periodontal Disease; 60 (39.0% gingivitis and 27 (17,5% periodontitis. Gingivitis was associated with poor oral hygiene (OR: 3,71 and periodontitis with smoking habit (OR: 5,20. The severe forms of periodontitis occurred mainly in patients with lymphocyte counting lower than 500 cells/mm3 . Conclusions: The prevalence of Chronic Inflammatory Periodontal Disease in patients with HIV in Sancti Spiritus province is linked to known risk factors such as smoking habits and oral hygiene.

  10. Downregulation of sulfotransferase expression and activity in diseased human livers.

    Science.gov (United States)

    Yalcin, Emine B; More, Vijay; Neira, Karissa L; Lu, Zhenqiang James; Cherrington, Nathan J; Slitt, Angela L; King, Roberta S

    2013-09-01

    Sulfotransferase (SULT) function has been well studied in healthy human subjects by quantifying mRNA and protein expression and determining enzyme activity with probe substrates. However, it is not well known if sulfotransferase activity changes in metabolic and liver disease, such as diabetes, steatosis, or cirrhosis. Sulfotransferases have significant roles in the regulation of hormones and excretion of xenobiotics. In the present study of normal subjects with nonfatty livers and patients with steatosis, diabetic cirrhosis, and alcoholic cirrhosis, we sought to determine SULT1A1, SULT2A1, SULT1E1, and SULT1A3 activity and mRNA and protein expression in human liver tissue. In general, sulfotransferase activity decreased significantly with severity of liver disease from steatosis to cirrhosis. Specifically, SULT1A1 and SULT1A3 activities were lower in disease states relative to nonfatty tissues. Alcoholic cirrhotic tissues further contained lower SULT1A1 and 1A3 activities than those affected by either of the two other disease states. SULT2A1, on the other hand, was only reduced in alcoholic cirrhotic tissues. SULT1E1 was reduced both in diabetic cirrhosis and in alcoholic cirrhosis tissues, relative to nonfatty liver tissues. In conclusion, the reduced levels of sulfotransferase expression and activity in diseased versus nondiseased liver tissue may alter the metabolism and disposition of xenobiotics and affect homeostasis of endobiotic sulfotransferase substrates.

  11. Credit scores, cardiovascular disease risk, and human capital.

    Science.gov (United States)

    Israel, Salomon; Caspi, Avshalom; Belsky, Daniel W; Harrington, HonaLee; Hogan, Sean; Houts, Renate; Ramrakha, Sandhya; Sanders, Seth; Poulton, Richie; Moffitt, Terrie E

    2014-12-02

    Credit scores are the most widely used instruments to assess whether or not a person is a financial risk. Credit scoring has been so successful that it has expanded beyond lending and into our everyday lives, even to inform how insurers evaluate our health. The pervasive application of credit scoring has outpaced knowledge about why credit scores are such useful indicators of individual behavior. Here we test if the same factors that lead to poor credit scores also lead to poor health. Following the Dunedin (New Zealand) Longitudinal Study cohort of 1,037 study members, we examined the association between credit scores and cardiovascular disease risk and the underlying factors that account for this association. We find that credit scores are negatively correlated with cardiovascular disease risk. Variation in household income was not sufficient to account for this association. Rather, individual differences in human capital factors—educational attainment, cognitive ability, and self-control—predicted both credit scores and cardiovascular disease risk and accounted for ∼45% of the correlation between credit scores and cardiovascular disease risk. Tracing human capital factors back to their childhood antecedents revealed that the characteristic attitudes, behaviors, and competencies children develop in their first decade of life account for a significant portion (∼22%) of the link between credit scores and cardiovascular disease risk at midlife. We discuss the implications of these findings for policy debates about data privacy, financial literacy, and early childhood interventions.

  12. Credit scores, cardiovascular disease risk, and human capital

    Science.gov (United States)

    Israel, Salomon; Caspi, Avshalom; Belsky, Daniel W.; Harrington, HonaLee; Hogan, Sean; Houts, Renate; Ramrakha, Sandhya; Sanders, Seth; Poulton, Richie; Moffitt, Terrie E.

    2014-01-01

    Credit scores are the most widely used instruments to assess whether or not a person is a financial risk. Credit scoring has been so successful that it has expanded beyond lending and into our everyday lives, even to inform how insurers evaluate our health. The pervasive application of credit scoring has outpaced knowledge about why credit scores are such useful indicators of individual behavior. Here we test if the same factors that lead to poor credit scores also lead to poor health. Following the Dunedin (New Zealand) Longitudinal Study cohort of 1,037 study members, we examined the association between credit scores and cardiovascular disease risk and the underlying factors that account for this association. We find that credit scores are negatively correlated with cardiovascular disease risk. Variation in household income was not sufficient to account for this association. Rather, individual differences in human capital factors—educational attainment, cognitive ability, and self-control—predicted both credit scores and cardiovascular disease risk and accounted for ∼45% of the correlation between credit scores and cardiovascular disease risk. Tracing human capital factors back to their childhood antecedents revealed that the characteristic attitudes, behaviors, and competencies children develop in their first decade of life account for a significant portion (∼22%) of the link between credit scores and cardiovascular disease risk at midlife. We discuss the implications of these findings for policy debates about data privacy, financial literacy, and early childhood interventions. PMID:25404329

  13. Lipidomics of human brain aging and Alzheimer's disease pathology.

    Science.gov (United States)

    Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2015-01-01

    Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. © 2015 Elsevier Inc. All rights reserved.

  14. Plant Polyphenols as Dietary Antioxidants in Human Health and Disease

    Directory of Open Access Journals (Sweden)

    Kanti Bhooshan Pandey

    2009-01-01

    Full Text Available Polyphenols are secondary metabolites of plants and are generally involved in defense against ultraviolet radiation or aggression by pathogens. In the last decade, there has been much interest in the potential health benefits of dietary plant polyphenols as antioxidant. Epidemiological studies and associated meta-analyses strongly suggest that long term consumption of diets rich in plant polyphenols offer protection against development of cancers, cardiovascular diseases, diabetes, osteoporosis and neurodegenerative diseases. Here we present knowledge about the biological effects of plant polyphenols in the context of relevance to human health.

  15. Pulmonary disease in patients with human immunodeficiency virus infection

    DEFF Research Database (Denmark)

    Lundgren, J D; Orholm, Marianne; Lundgren, B

    1989-01-01

    Pulmonary disease is the most important cause of morbidity and mortality in patients infected with human immunodeficiency virus (HIV). All parts of the hospital system are expected to be involved in the diagnosis and treatment of HIV infected patients in the coming years. Many different processes...... cause pulmonary disease alone or in combination. Bilateral interstitial infiltrates are the most frequent chest x-ray abnormality and are most frequently caused by infection with Pneumocystis carinii. Cytomegalovirus, Mycobacterium tuberculosis, nonspecific interstitial pneumonitis and pulmonary Kaposi...

  16. Glycemic Control for Patients With Acute Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    Hai-peng XIAO; Juan CHEN

    2009-01-01

    @@ The risk of myocardial infarction increases in patients with diabetes mellitus. The incidence of myocardial in-farction is similar in patients with type 2 diabetes without history of myocardial infarction and in non-diabetic pa-tients with history of myocardial infarction. Diabetes mellitus was considered as a coronary disease equivalent by the National Cholesterol Education Program. Strict glycemic control can improve the long-term outcome of both type 1 and type 2 diabetes mellitus. Whatever with diabetic or non-diabetic, strict glycemic control with in-tensive insulin therapy can reduce the mortality of criti-cally ill patients in hospital. After myocardial infarction, there would be a worse outcome for patients with poor glycemic control, whatever in diabetic or non-diabetic patients with stress hyperglycemia.

  17. Human genetic variation and the gut microbiome in disease.

    Science.gov (United States)

    Hall, Andrew Brantley; Tolonen, Andrew C; Xavier, Ramnik J

    2017-08-21

    Taxonomic and functional changes to the composition of the gut microbiome have been implicated in multiple human diseases. Recent microbiome genome-wide association studies reveal that variants in many human genes involved in immunity and gut architecture are associated with an altered composition of the gut microbiome. Although many factors can affect the microbial organisms residing in the gut, a number of recent findings support the hypothesis that certain host genetic variants predispose an individual towards microbiome dysbiosis. This condition, in which the normal microbiome population structure is disturbed, is a key feature in disorders of metabolism and immunity.

  18. Recent genetic discoveries implicating ion channels in human cardiovascular diseases.

    Science.gov (United States)

    George, Alfred L

    2014-04-01

    The term 'channelopathy' refers to human genetic disorders caused by mutations in genes encoding ion channels or their interacting proteins. Recent advances in this field have been enabled by next-generation DNA sequencing strategies such as whole exome sequencing with several intriguing and unexpected discoveries. This review highlights important discoveries implicating ion channels or ion channel modulators in cardiovascular disorders including cardiac arrhythmia susceptibility, cardiac conduction phenotypes, pulmonary and systemic hypertension. These recent discoveries further emphasize the importance of ion channels in the pathophysiology of human disease and as important druggable targets.

  19. Adult human metapneumonovirus (hMPV) pneumonia mimicking Legionnaire's disease.

    Science.gov (United States)

    Cunha, Burke A; Irshad, Nadia; Connolly, James J

    2016-01-01

    In adults hospitalized with viral pneumonias the main differential diagnostic consideration is influenza pneumonia. The respiratory viruses causing viral influenza like illnesses (ILIs), e.g., RSV may closely resemble influenza. Rarely, extrapulmonary findings of some ILIs may resemble Legionnaire's disease (LD), e.g., adenovirus, human parainfluenza virus (HPIV-3). We present a most unusual case of human metapneumonovirus pneumonia (hMPV) with some characteristic extrapulmonary findings characteristic of LD, e.g., relative bradycardia, as well as mildly elevated serum transaminases and hyphosphatemia. We believe this is the first reported case of hMPV pneumonia in a hospitalized adult that had some features of LD.

  20. Cellular reprogramming for understanding and treating human disease.

    Directory of Open Access Journals (Sweden)

    Riya Rajan Kanherkar

    2014-11-01

    Full Text Available In the last two decades we have witnessed a paradigm shift in our understanding of cells so radical that it has rewritten the rules of biology. The study of cellular reprogramming has gone from little more than a hypothesis, to applied bioengineering, with the creation of a variety of important cell types. By way of metaphor, we can compare the discovery of reprogramming with the archaeological discovery of the Rosetta stone. This stone slab made possible the initial decipherment of Egyptian hieroglyphics because it allowed us to see this language in a way that was previously impossible. We propose that cellular reprogramming will have an equally profound impact on understanding and curing human disease, because it allows us to perceive and study molecular biological processes such as differentiation, epigenetics, and chromatin in ways that were likewise previously impossible. Stem cells could be called cellular Rosetta stones because they allow also us to perceive the connections between development, disease, cancer, aging, and regeneration in novel ways. Here we present a comprehensive historical review of stem cells and cellular reprogramming, and illustrate the developing synergy between many previously unconnected fields. We show how stem cells can be used to create in vitro models of human disease and provide examples of how reprogramming is being used to study and treat such diverse diseases as cancer, aging and accelerated aging syndromes, infectious diseases such as AIDS, and epigenetic diseases such as polycystic ovary syndrome. While the technology of reprogramming is being developed and refined there have also been significant ongoing developments in other complementary technologies such as gene editing, progenitor cell production, and tissue engineering. These technologies are the foundations of what is becoming a fully-functional field of regenerative medicine and are converging to a point that will allow us to treat almost any

  1. Grape Polyphenols’ Effects in Human Cardiovascular Diseases and Diabetes

    Directory of Open Access Journals (Sweden)

    Zuriñe Rasines-Perea

    2017-01-01

    Full Text Available The consumption of fruits and vegetables, as well as foods enriched in bioactive compounds and nutraceuticals, has increased due to consumers’ interest in the relevance of food composition for human health. Considerable recent interest has focused on bioactive phenolic compounds in grape, as they possess many biological activities, such as antioxidant, cardioprotective, anticancer, anti-inflammation, anti-ageing and antimicrobial properties. Observational studies indicate that the intake of polyphenol-rich foods improves vascular health, thereby significantly reducing the risk of hypertension, and cardiovascular disease (CVD. Other researchers have described the benefits of a grape polyphenol-rich diet for other types of maladies such as diabetes mellitus. This is a comprehensive review on the consumption of polyphenolic grape compounds, concerning their potential benefits for human health in the treatment of cardiovascular diseases and diabetes.

  2. Grape Polyphenols' Effects in Human Cardiovascular Diseases and Diabetes.

    Science.gov (United States)

    Rasines-Perea, Zuriñe; Teissedre, Pierre-Louis

    2017-01-01

    The consumption of fruits and vegetables, as well as foods enriched in bioactive compounds and nutraceuticals, has increased due to consumers' interest in the relevance of food composition for human health. Considerable recent interest has focused on bioactive phenolic compounds in grape, as they possess many biological activities, such as antioxidant, cardioprotective, anticancer, anti-inflammation, anti-ageing and antimicrobial properties. Observational studies indicate that the intake of polyphenol-rich foods improves vascular health, thereby significantly reducing the risk of hypertension, and cardiovascular disease (CVD). Other researchers have described the benefits of a grape polyphenol-rich diet for other types of maladies such as diabetes mellitus. This is a comprehensive review on the consumption of polyphenolic grape compounds, concerning their potential benefits for human health in the treatment of cardiovascular diseases and diabetes.

  3. Mitochondrial protein import and human health and disease.

    Science.gov (United States)

    MacKenzie, James A; Payne, R Mark

    2007-05-01

    The targeting and assembly of nuclear-encoded mitochondrial proteins are essential processes because the energy supply of humans is dependent upon the proper functioning of mitochondria. Defective import of mitochondrial proteins can arise from mutations in the targeting signals within precursor proteins, from mutations that disrupt the proper functioning of the import machinery, or from deficiencies in the chaperones involved in the proper folding and assembly of proteins once they are imported. Defects in these steps of import have been shown to lead to oxidative stress, neurodegenerative diseases, and metabolic disorders. In addition, protein import into mitochondria has been found to be a dynamically regulated process that varies in response to conditions such as oxidative stress, aging, drug treatment, and exercise. This review focuses on how mitochondrial protein import affects human health and disease.

  4. Assessing the human gut microbiota in metabolic diseases.

    Science.gov (United States)

    Karlsson, Fredrik; Tremaroli, Valentina; Nielsen, Jens; Bäckhed, Fredrik

    2013-10-01

    Recent findings have demonstrated that the gut microbiome complements our human genome with at least 100-fold more genes. In contrast to our Homo sapiens-derived genes, the microbiome is much more plastic, and its composition changes with age and diet, among other factors. An altered gut microbiota has been associated with several diseases, including obesity and diabetes, but the mechanisms involved remain elusive. Here we discuss factors that affect the gut microbiome, how the gut microbiome may contribute to metabolic diseases, and how to study the gut microbiome. Next-generation sequencing and development of software packages have led to the development of large-scale sequencing efforts to catalog the human microbiome. Furthermore, the use of genetically engineered gnotobiotic mouse models may increase our understanding of mechanisms by which the gut microbiome modulates host metabolism. A combination of classical microbiology, sequencing, and animal experiments may provide further insights into how the gut microbiota affect host metabolism and physiology.

  5. Genetic control of human brain transcript expression in Alzheimer disease.

    Science.gov (United States)

    Webster, Jennifer A; Gibbs, J Raphael; Clarke, Jennifer; Ray, Monika; Zhang, Weixiong; Holmans, Peter; Rohrer, Kristen; Zhao, Alice; Marlowe, Lauren; Kaleem, Mona; McCorquodale, Donald S; Cuello, Cindy; Leung, Doris; Bryden, Leslie; Nath, Priti; Zismann, Victoria L; Joshipura, Keta; Huentelman, Matthew J; Hu-Lince, Diane; Coon, Keith D; Craig, David W; Pearson, John V; Heward, Christopher B; Reiman, Eric M; Stephan, Dietrich; Hardy, John; Myers, Amanda J

    2009-04-01

    We recently surveyed the relationship between the human brain transcriptome and genome in a series of neuropathologically normal postmortem samples. We have now analyzed additional samples with a confirmed pathologic diagnosis of late-onset Alzheimer disease (LOAD; final n = 188 controls, 176 cases). Nine percent of the cortical transcripts that we analyzed had expression profiles correlated with their genotypes in the combined cohort, and approximately 5% of transcripts had SNP-transcript relationships that could distinguish LOAD samples. Two of these transcripts have been previously implicated in LOAD candidate-gene SNP-expression screens. This study shows how the relationship between common inherited genetic variants and brain transcript expression can be used in the study of human brain disorders. We suggest that studying the transcriptome as a quantitative endo-phenotype has greater power for discovering risk SNPs influencing expression than the use of discrete diagnostic categories such as presence or absence of disease.

  6. Diagnosis of human heritable diseases--laboratory approaches and outcomes.

    Science.gov (United States)

    Dowton, S B; Slaugh, R A

    1995-05-01

    Detection of mutant human genes is rapidly becoming an integral part of clinical practice. Human disease may arise by genetic deletion, insertion, fusion, point mutation, or amplification of unstable sequences. Such changes in structure may occur in germ cells or somatically. Rapid advances in understanding the complex nuclear and mitochondrial genomes necessitates deployment of a variety of methods to identify aberrant genes. These techniques include polymerase chain reaction, Southern transfer, and allele-specific hybridization studies, as well as methods to unmask mismatches between mutant and normal sequences. Development of protein truncation tests has added a vehicle for assessing larger DNA segments for mutations that cause premature translational termination. Linkage analysis remains an important tool where direct assay of disease-causing mutations is not possible. Considerations of confidentiality, informed consent, and insurability are important whenever genetic testing is used. These issues will assume increasing importance as presymptomatic testing for heritable predispositions emerges for common conditions.

  7. Disease Ontology 2015 update: an expanded and updated database of human diseases for linking biomedical knowledge through disease data.

    Science.gov (United States)

    Kibbe, Warren A; Arze, Cesar; Felix, Victor; Mitraka, Elvira; Bolton, Evan; Fu, Gang; Mungall, Christopher J; Binder, Janos X; Malone, James; Vasant, Drashtti; Parkinson, Helen; Schriml, Lynn M

    2015-01-01

    The current version of the Human Disease Ontology (DO) (http://www.disease-ontology.org) database expands the utility of the ontology for the examination and comparison of genetic variation, phenotype, protein, drug and epitope data through the lens of human disease. DO is a biomedical resource of standardized common and rare disease concepts with stable identifiers organized by disease etiology. The content of DO has had 192 revisions since 2012, including the addition of 760 terms. Thirty-two percent of all terms now include definitions. DO has expanded the number and diversity of research communities and community members by 50+ during the past two years. These community members actively submit term requests, coordinate biomedical resource disease representation and provide expert curation guidance. Since the DO 2012 NAR paper, there have been hundreds of term requests and a steady increase in the number of DO listserv members, twitter followers and DO website usage. DO is moving to a multi-editor model utilizing Protégé to curate DO in web ontology language. This will enable closer collaboration with the Human Phenotype Ontology, EBI's Ontology Working Group, Mouse Genome Informatics and the Monarch Initiative among others, and enhance DO's current asserted view and multiple inferred views through reasoning. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. Under the lash: Demodex mites in human diseases.

    Science.gov (United States)

    Lacey, Noreen; Kavanagh, Kevin; Tseng, Scheffer C G

    2009-08-01

    Demodex mites, class Arachnida and subclass Acarina, are elongated mites with clear cephalothorax and abdomens, the former with four pairs of legs. There are more than 100 species of Demodex mite, many of which are obligatory commensals of the pilosebaceous unit of mammals including cats, dogs, sheep, cattle, pigs, goats, deer, bats, hamsters, rats and mice. Among them, Demodex canis, which is found ubiquitously in dogs, is the most documented and investigated. In excessive numbers D. canis causes the inflammatory disease termed demodicosis (demodectic mange, follicular mange or red mange), which is more common in purebred dogs and has a hereditary predisposition in breeding kennels1. Two distinct Demodex species have been confirmed as the most common ectoparasite in man. The larger Demodex folliculorum, about 0.3-0.4 mm long, is primarily found as a cluster in the hair follicle (Figure 1a), while the smaller Demodex brevis, about 0.2-0.3 mm long with a spindle shape and stubby legs, resides solitarily in the sebaceous gland (Figure 1b). These two species are also ubiquitously found in all human races without gender preference. The pathogenic role of Demodex mites in veterinary medicine is not as greatly disputed as in human diseases. In this article, we review the key literature and our joint research experience regarding the pathogenic potential of these two mites in causing inflammatory diseases of human skin and eye. We hope that the evidence summarized herein will invite readers to take a different look at the life of Demodex mites in several common human diseases.

  9. Does biodiversity protect humans against infectious disease? Reply

    Science.gov (United States)

    Wood, Chelsea L.; Lafferty, Kevin D.; DeLeo, Giulio; Young, Hillary S.; Hudson, Peter J.; Kuris, Armand M.

    2016-01-01

    The dilution effect is the sort of idea that everyone wants to be true. If nature protects humans against infectious disease, imagine the implications: nature's value could be tallied in terms of human suffering avoided. This makes a potent argument for conservation, convincing even to those who would otherwise be disinclined to support conservation initiatives. The appeal of the dilution effect has been recognized by others: “the desire to make the case for conservation has led to broad claims regarding the benefits of nature conservation for human health” (Bauch et al. 2015). Randolph and Dobson (2012) were among the first to critique these claims, making the case that promotion of conservation to reduce Lyme disease risk, although well intentioned, was flawed. Along with Randolph and Dobson's critique, there have been several calls for a more nuanced scientific assessment of the relationship between biodiversity and disease transmission (Dunn 2010, Salkeld et al. 2013, Wood and Lafferty 2013, Young et al. 2013). In response, supporters of the dilution effect have instead increased the scope of their generalizations with review papers, press releases, and, like Levi et al. (2015), letters. These responses have been successful; it is not uncommon to read papers that repeat the assertion that biodiversity generally interferes with disease transmission and that conservation will therefore generally benefit human health. Here, we explain how Levi et al. (2015) and other, similar commentaries use selective interpretation and shifting definitions to argue for the generality of the dilution effect hypothesis.

  10. Molecular basis of telomere dysfunction in human genetic diseases.

    Science.gov (United States)

    Sarek, Grzegorz; Marzec, Paulina; Margalef, Pol; Boulton, Simon J

    2015-11-01

    Mutations in genes encoding proteins required for telomere structure, replication, repair and length maintenance are associated with several debilitating human genetic disorders. These complex telomere biology disorders (TBDs) give rise to critically short telomeres that affect the homeostasis of multiple organs. Furthermore, genome instability is often a hallmark of telomere syndromes, which are associated with increased cancer risk. Here, we summarize the molecular causes and cellular consequences of disease-causing mutations associated with telomere dysfunction.

  11. Molecular clocks and the human condition: approaching their characterization in human physiology and disease.

    Science.gov (United States)

    Fitzgerald, G A; Yang, G; Paschos, G K; Liang, X; Skarke, C

    2015-09-01

    Molecular clockworks knit together diverse biological networks and compelling evidence from model systems infers their importance in metabolism, immunological and cardiovascular function. Despite this and the diurnal variation in many aspects of human physiology and the phenotypic expression of disease, our understanding of the role and importance of clock function and dysfunction in humans is modest. There are tantalizing hints of connection across the translational divide and some correlative evidence of gene variation and human disease but most of what we know derives from forced desynchrony protocols in controlled environments. We now have the ability to monitor quantitatively ex vivo or in vivo the genome, metabolome, proteome and microbiome of humans in the wild. Combining this capability, with the power of mobile telephony and the evolution of remote sensing, affords a new opportunity for deep phenotyping, including the characterization of diurnal behaviour and the assessment of the impact of the clock on approved drug function.

  12. Identification of susceptibility genes and genetic modifiers of human diseases

    Science.gov (United States)

    Abel, Kenneth; Kammerer, Stefan; Hoyal, Carolyn; Reneland, Rikard; Marnellos, George; Nelson, Matthew R.; Braun, Andreas

    2005-03-01

    The completion of the human genome sequence enables the discovery of genes involved in common human disorders. The successful identification of these genes is dependent on the availability of informative sample sets, validated marker panels, a high-throughput scoring technology, and a strategy for combining these resources. We have developed a universal platform technology based on mass spectrometry (MassARRAY) for analyzing nucleic acids with high precision and accuracy. To fuel this technology, we generated more than 100,000 validated assays for single nucleotide polymorphisms (SNPs) covering virtually all known and predicted human genes. We also established a large DNA sample bank comprised of more than 50,000 consented healthy and diseased individuals. This combination of reagents and technology allows the execution of large-scale genome-wide association studies. Taking advantage of MassARRAY"s capability for quantitative analysis of nucleic acids, allele frequencies are estimated in sample pools containing large numbers of individual DNAs. To compare pools as a first-pass "filtering" step is a tremendous advantage in throughput and cost over individual genotyping. We employed this approach in numerous genome-wide, hypothesis-free searches to identify genes associated with common complex diseases, such as breast cancer, osteoporosis, and osteoarthritis, and genes involved in quantitative traits like high density lipoproteins cholesterol (HDL-c) levels and central fat. Access to additional well-characterized patient samples through collaborations allows us to conduct replication studies that validate true disease genes. These discoveries will expand our understanding of genetic disease predisposition, and our ability for early diagnosis and determination of specific disease subtype or progression stage.

  13. Forward-time simulations of human populations with complex diseases.

    Directory of Open Access Journals (Sweden)

    Bo Peng

    2007-03-01

    Full Text Available Due to the increasing power of personal computers, as well as the availability of flexible forward-time simulation programs like simuPOP, it is now possible to simulate the evolution of complex human diseases using a forward-time approach. This approach is potentially more powerful than the coalescent approach since it allows simulations of more than one disease susceptibility locus using almost arbitrary genetic and demographic models. However, the application of such simulations has been deterred by the lack of a suitable simulation framework. For example, it is not clear when and how to introduce disease mutants-especially those under purifying selection-to an evolving population, and how to control the disease allele frequencies at the last generation. In this paper, we introduce a forward-time simulation framework that allows us to generate large multi-generation populations with complex diseases caused by unlinked disease susceptibility loci, according to specified demographic and evolutionary properties. Unrelated individuals, small or large pedigrees can be drawn from the resulting population and provide samples for a wide range of study designs and ascertainment methods. We demonstrate our simulation framework using three examples that map genes associated with affection status, a quantitative trait, and the age of onset of a hypothetical cancer, respectively. Nonadditive fitness models, population structure, and gene-gene interactions are simulated. Case-control, sibpair, and large pedigree samples are drawn from the simulated populations and are examined by a variety of gene-mapping methods.

  14. Beyond the zebrafish: diverse fish species for modeling human disease

    Directory of Open Access Journals (Sweden)

    Manfred Schartl

    2014-02-01

    Full Text Available In recent years, zebrafish, and to a lesser extent medaka, have become widely used small animal models for human diseases. These organisms have convincingly demonstrated the usefulness of fish for improving our understanding of the molecular and cellular mechanisms leading to pathological conditions, and for the development of new diagnostic and therapeutic tools. Despite the usefulness of zebrafish and medaka in the investigation of a wide spectrum of traits, there is evidence to suggest that other fish species could be better suited for more targeted questions. With the emergence of new, improved sequencing technologies that enable genomic resources to be generated with increasing efficiency and speed, the potential of non-mainstream fish species as disease models can now be explored. A key feature of these fish species is that the pathological condition that they model is often related to specific evolutionary adaptations. By exploring these adaptations, new disease-causing and disease-modifier genes might be identified; thus, diverse fish species could be exploited to better understand the complexity of disease processes. In addition, non-mainstream fish models could allow us to study the impact of environmental factors, as well as genetic variation, on complex disease phenotypes. This Review will discuss the opportunities that such fish models offer for current and future biomedical research.

  15. Fractional Flow Reserve-Guided Multivessel Angioplasty in Myocardial Infarction.

    Science.gov (United States)

    Smits, Pieter C; Abdel-Wahab, Mohamed; Neumann, Franz-Josef; Boxma-de Klerk, Bianca M; Lunde, Ketil; Schotborgh, Carl E; Piroth, Zsolt; Horak, David; Wlodarczak, Adrian; Ong, Paul J; Hambrecht, Rainer; Angerås, Oskar; Richardt, Gert; Omerovic, Elmir

    2017-03-30

    Background In patients with ST-segment elevation myocardial infarction (STEMI), the use of percutaneous coronary intervention (PCI) to restore blood flow in an infarct-related coronary artery improves outcomes. The use of PCI in non-infarct-related coronary arteries remains controversial. Methods We randomly assigned 885 patients with STEMI and multivessel disease who had undergone primary PCI of an infarct-related coronary artery in a 1:2 ratio to undergo complete revascularization of non-infarct-related coronary arteries guided by fractional flow reserve (FFR) (295 patients) or to undergo no revascularization of non-infarct-related coronary arteries (590 patients). The FFR procedure was performed in both groups, but in the latter group, both the patients and their cardiologist were unaware of the findings on FFR. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, revascularization, and cerebrovascular events at 12 months. Clinically indicated elective revascularizations performed within 45 days after primary PCI were not counted as events in the group receiving PCI for an infarct-related coronary artery only. Results The primary outcome occurred in 23 patients in the complete-revascularization group and in 121 patients in the infarct-artery-only group that did not receive complete revascularization, a finding that translates to 8 and 21 events per 100 patients, respectively (hazard ratio, 0.35; 95% confidence interval [CI], 0.22 to 0.55; Pratio, 0.80; 95% CI, 0.25 to 2.56), myocardial infarction in 7 and 28 patients, respectively (2.4% vs. 4.7%) (hazard ratio, 0.50; 95% CI, 0.22 to 1.13), revascularization in 18 and 103 patients (6.1% vs. 17.5%) (hazard ratio, 0.32; 95% CI, 0.20 to 0.54), and cerebrovascular events in 0 and 4 patients (0 vs. 0.7%). An FFR-related serious adverse event occurred in 2 patients (both in the group receiving infarct-related treatment only). Conclusions In patients with STEMI and multivessel

  16. Evaluation of cat brain infarction model using microPET

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J. J.; Lee, D. S.; Kim, J. H.; Hwang, D. W.; Jung, J. G.; Lee, M. C [College of Medicine, Seoul National University, Seoul (Korea, Republic of); Lim, S. M [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2004-07-01

    PET has some disadvantage in the imaging of small animal due to poor resolution. With the advance of microPET scanner, it is possible to image small animals. However, the image quality was not so much satisfactory as human image. As cats have relatively large sized brain, cat brain imaging was superior to mice or rat. In this study, we established the cat brain infarction model and evaluate it and its temporal change using microPET scanner. Two adult male cats were used. Anesthesia was done with xylazine and ketamine HCl. A burr hole was made at 1cm right lateral to the bregma. Collagenase type IV 10 ul was injected using 30G needle for 5 minutes to establish the infarction model. F-18 FDG microPET (Concorde Microsystems Inc., Knoxville. TN) scans were performed 1. 11 and 32 days after the infarction. In addition. 18F-FDG PET scans were performed using Gemini PET scanner (Philips medical systems. CA, USA) 13 and 47 days after the infarction. Two cat brain infarction models were established. The glucose metabolism of an infraction lesion improved with time. An infarction lesion was also distinguishable in the Gemini PET scan. We successfully established the cat brain infarction model and evaluated the infarcted lesion and its temporal change using F-18 FDG microPET scanner.

  17. Cardiac Disease Associated with Human Immunodeficiency Virus Infection.

    Science.gov (United States)

    Bloomfield, Gerald S; Leung, Claudia

    2017-02-01

    Over the last 2 decades human immunodeficiency virus (HIV) infection has become a chronic disease requiring long-term management. Aging, antiretroviral therapy, chronic inflammation, and several other factors contribute to the increased risk of cardiovascular disease in patients infected with HIV. In low-income and middle-income countries where antiretroviral therapy access is limited, cardiac disease is most commonly related to opportunistic infections and end-stage manifestations of HIV/acquired immunodeficiency syndrome, including HIV-associated cardiomyopathy, pericarditis, and pulmonary arterial hypertension. Cardiovascular screening, prevention, and risk factor management are important factors in the management of patients infected with HIV worldwide. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. The human gut microbiome impacts health and disease.

    Science.gov (United States)

    Ehrlich, Stanislav Dusko

    2016-01-01

    The human gut microbiome can now be characterized in unprecedented detail by an approach based on high-throughput sequencing of total stool DNA, that we name quantitative metagenomics. Central to the approach is a catalog that lists all the genes of intestinal microbes that are known - 9.9 millions, identified by the analysis of 1267 stool samples. Beyond the gene list, genetic units that carry them begun to be known; many of these correspond to bacterial species that were never isolated and cultured yet. Quantitative metagenomics allows developing powerful algorithms to diagnose a disease, monitor patients and identify individuals at risk to progress towards a disease. This lays ground for developing new approaches to better restore and even preserve the health by modulation of the altered microbiome, which contributes to promote or aggravate a disease.

  19. Nutrition, epigenetics, and developmental plasticity: implications for understanding human disease.

    Science.gov (United States)

    Burdge, Graham C; Lillycrop, Karen A

    2010-08-21

    There is considerable evidence for induction of differential risk of noncommunicable diseases in humans by variation in the quality of the early life environment. Studies in animal models show that induction and stability of induced changes in the phenotype of the offspring involve altered epigenetic regulation by DNA methylation and covalent modifications of histones. These findings indicate that such epigenetic changes are highly gene specific and function at the level of individual CpG dinucleotides. Interventions using supplementation with folic acid or methyl donors during pregnancy, or folic acid after weaning, alter the phenotype and epigenotype induced by maternal dietary constraint during gestation. This suggests a possible means for reducing risk of induced noncommunicable disease, although the design and conduct of such interventions may require caution. The purpose of this review is to discuss recent advances in understanding the mechanism that underlies the early life origins of disease and to place these studies in a broader life-course context.

  20. DRUMS: a human disease related unique gene mutation search engine.

    Science.gov (United States)

    Li, Zuofeng; Liu, Xingnan; Wen, Jingran; Xu, Ye; Zhao, Xin; Li, Xuan; Liu, Lei; Zhang, Xiaoyan

    2011-10-01

    With the completion of the human genome project and the development of new methods for gene variant detection, the integration of mutation data and its phenotypic consequences has become more important than ever. Among all available resources, locus-specific databases (LSDBs) curate one or more specific genes' mutation data along with high-quality phenotypes. Although some genotype-phenotype data from LSDB have been integrated into central databases little effort has been made to integrate all these data by a search engine approach. In this work, we have developed disease related unique gene mutation search engine (DRUMS), a search engine for human disease related unique gene mutation as a convenient tool for biologists or physicians to retrieve gene variant and related phenotype information. Gene variant and phenotype information were stored in a gene-centred relational database. Moreover, the relationships between mutations and diseases were indexed by the uniform resource identifier from LSDB, or another central database. By querying DRUMS, users can access the most popular mutation databases under one interface. DRUMS could be treated as a domain specific search engine. By using web crawling, indexing, and searching technologies, it provides a competitively efficient interface for searching and retrieving mutation data and their relationships to diseases. The present system is freely accessible at http://www.scbit.org/glif/new/drums/index.html.

  1. Migraine Infarction. Case Report

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    Yoany Mesa Barrera

    2015-03-01

    Full Text Available Migraine is considered like a risk factor for ischemic ictus in adult young people. In spite of the criteria established for the treatment of the migraine infarct, they are not always fulfilled strictly, permitting certain flexibility in the aforementioned treatment. The case of a patient with a background of migraine with auras, who suffers an ischemic cerebral migraine infarct at the course of a migraine crisis, is presented. The ictus was manifested like an especial right hemiparesis of the female sex in fertile age. The prognosis is good with low risk of recurrence, with unstable disorders and dysarthria. The laboratories studies were normal and the cerebral infarct was detected in the magnetic resonance, at the half left cerebral artery's territory. The patient had favorable evolution without sequel.

  2. Occipital lobe infarctions are different

    OpenAIRE

    Naess, Halvor; Waje-Andreassen, Ulrikke; Thomassen, Lars

    2007-01-01

    Objectives We hypothesized that occipital lobe infarctions differ from infarctions in other locations as to etiology, risk factors and prognosis among young adults. Methods Location, etiology, risk factors and long-term outcome were evaluated among all young adults 15–49 years suffering from cerebral infarction in Hordaland County, Norway between 1988 and 1997. Results The following variables were more frequent among patients with occipital lobe infarction compared with patients with infarcti...

  3. MORPHIN: a web tool for human disease research by projecting model organism biology onto a human integrated gene network.

    Science.gov (United States)

    Hwang, Sohyun; Kim, Eiru; Yang, Sunmo; Marcotte, Edward M; Lee, Insuk

    2014-07-01

    Despite recent advances in human genetics, model organisms are indispensable for human disease research. Most human disease pathways are evolutionally conserved among other species, where they may phenocopy the human condition or be associated with seemingly unrelated phenotypes. Much of the known gene-to-phenotype association information is distributed across diverse databases, growing rapidly due to new experimental techniques. Accessible bioinformatics tools will therefore facilitate translation of discoveries from model organisms into human disease biology. Here, we present a web-based discovery tool for human disease studies, MORPHIN (model organisms projected on a human integrated gene network), which prioritizes the most relevant human diseases for a given set of model organism genes, potentially highlighting new model systems for human diseases and providing context to model organism studies. Conceptually, MORPHIN investigates human diseases by an orthology-based projection of a set of model organism genes onto a genome-scale human gene network. MORPHIN then prioritizes human diseases by relevance to the projected model organism genes using two distinct methods: a conventional overlap-based gene set enrichment analysis and a network-based measure of closeness between the query and disease gene sets capable of detecting associations undetectable by the conventional overlap-based methods. MORPHIN is freely accessible at http://www.inetbio.org/morphin.

  4. Infarct healing is a dynamic process following acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Pokorney Sean D

    2012-09-01

    Full Text Available Abstract Background The role of infarct size on left ventricular (LV remodeling in heart failure after an acute ST-segment elevation myocardial infarction (STEMI is well recognized. Infarct size, as determined by cardiovascular magnetic resonance (CMR, decreases over time. The amount, rate, and duration of infarct healing are unknown. Methods A total of 66 patients were prospectively enrolled after reperfusion for an acute STEMI. Patients underwent a CMR evaluation within 1 week, 4 months, and 14 months after STEMI. Results Mean infarct sizes for the 66 patients at baseline (acute necrosis, early follow-up (early scar, and late follow-up (late scar were 25 ± 17 g, 17 ± 12 g, and 15 ± 11 g, respectively. Patients were stratified in tertiles, based on infarct size, with the largest infarcts having the greatest absolute decrease in mass at early and late scar. The percent reduction of infarct mass was independent of initial infarct size. There was an 8 g or 32% decrease in infarct mass between acute necrosis and early scar (p  Conclusions Infarct healing is a continuous process after reperfusion for STEMI, with greatest reduction in infarct size in the first few months. The dynamic nature of infarct healing through the first year after STEMI indicates that decisions based on infarct size, and interventions to reduce infarct size, must take into consideration the time frame of measurement.

  5. 人性化护理对急性心肌梗塞患者急性期心理状态的影响%Impact of humane care for patients with acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    朱桂萍

    2015-01-01

    Objective: To analyze mental state of patients with acute myocardial infarction during nursing interventions. Methods: 101 patients with acute myocardial infarction were treated as research subjects; the observation group and the control group took nursing interventions. 7 days after the intervention, two groups of pain scores and morbidity were compared. Results: In groups pain scores were significantly different, with statistical significance (P<0.05). Humane nursing intervention for 7 days, the incidence of heart failure, arrhythmias, acute angina clearly decreased, with statistical significance (P<0.05). Conclusion: Acute myocardial infarction with nursing intervention, patients can significantly improve physical and mental state.%目的:分析急性心肌梗塞患者行人性化护理干预的心理状态.方法:将我院2013年3月-2014年10月收治的急性心肌梗塞患者101人作为研究对象,观察组与对照组均行人性化护理干预.干预7d后,对比两组疼痛评分及发病率.结果:行人性化护理干预7d后,对照组与观察组疼痛评分值对比,其差异显著,具有统计学意义(P<0.05).人性化护理干预7d后,对照组与观察组在心力衰竭、心律失常、急性心绞痛等发病率方面显著下降,具有统计学意义(P<0.05).结论:对急性心肌梗塞行人性化护理干预,可使患者身心状态明显改善.

  6. Prophylactic lidocaine for myocardial infarction.

    Science.gov (United States)

    Martí-Carvajal, Arturo J; Simancas-Racines, Daniel; Anand, Vidhu; Bangdiwala, Shrikant

    2015-08-21

    Coronary artery disease is a major public health problem affecting both developed and developing countries. Acute coronary syndromes include unstable angina and myocardial infarction with or without ST-segment elevation (electrocardiogram sector is higher than baseline). Ventricular arrhythmia after myocardial infarction is associated with high risk of mortality. The evidence is out of date, and considerable uncertainty remains about the effects of prophylactic use of lidocaine on all-cause mortality, in particular, in patients with suspected myocardial infarction. To determine the clinical effectiveness and safety of prophylactic lidocaine in preventing death among people with myocardial infarction. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 3), MEDLINE Ovid (1946 to 13 April 2015), EMBASE (1947 to 13 April 2015) and Latin American Caribbean Health Sciences Literature (LILACS) (1986 to 13 April 2015). We also searched Web of Science (1970 to 13 April 2013) and handsearched the reference lists of included papers. We applied no language restriction in the search. We included randomised controlled trials assessing the effects of prophylactic lidocaine for myocardial infarction. We considered all-cause mortality, cardiac mortality and overall survival at 30 days after myocardial infarction as primary outcomes. We performed study selection, risk of bias assessment and data extraction in duplicate. We estimated risk ratios (RRs) for dichotomous outcomes and measured statistical heterogeneity using I(2). We used a random-effects model and conducted trial sequential analysis. We identified 37 randomised controlled trials involving 11,948 participants. These trials compared lidocaine versus placebo or no intervention, disopyramide, mexiletine, tocainide, propafenone, amiodarone, dimethylammonium chloride, aprindine and pirmenol. Overall, trials were underpowered and had high risk of bias. Ninety-seven per cent of trials (36

  7. Functions of NOD-like receptors (NLRs in human diseases

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    Yifei eZhong

    2013-10-01

    Full Text Available Nucleotide-binding and oligomerization domain (NOD-like receptors (NLRs are highly conserved cytosolic pattern recognition receptors that perform critical functions in surveying the intracellular environment for the presence of infection, noxious substances, and metabolic perturbations. Sensing of these danger signals by NLRs leads to their oligomerization into large macromolecular scaffolds and the rapid deployment of effector signaling cascades to restore homeostasis. While some NLRs operate by recruiting and activating inflammatory caspases into inflammasomes, others trigger inflammation via alternative routes including the NF-κB, MAPK and IRF pathways. The critical role of NLRs in development and physiology is demonstrated by their clear implications in human diseases. Mutations in the genes encoding NLRP3 or NLRP12 lead to hereditary periodic fever syndromes, while mutations in CARD15 that encodes NOD2 are linked to Crohn’s disease or Blau’s syndrome. Genome-wide association studies (GWAS have identified a number of risk alleles encompassing NLR genes in a host of diseases including allergic rhinitis, multiple sclerosis, inflammatory bowel disease, asthma, multi-bacillary leprosy, vitiligo, early-onset menopause, and bone density loss in elderly women. Animal models have allowed the characterization of underlying effector mechanisms in a number of cases. In this review, we highlight the functions of NLRs in health and disease and discuss how the characterization of their molecular mechanisms provides new insights into therapeutic strategies for the management of inflammatory pathologies.

  8. Diagnosis of Alzheimer's disease based on disease-specific autoantibody profiles in human sera.

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    Eric Nagele

    Full Text Available After decades of Alzheimer's disease (AD research, the development of a definitive diagnostic test for this disease has remained elusive. The discovery of blood-borne biomarkers yielding an accurate and relatively non-invasive test has been a primary goal. Using human protein microarrays to characterize the differential expression of serum autoantibodies in AD and non-demented control (NDC groups, we identified potential diagnostic biomarkers for AD. The differential significance of each biomarker was evaluated, resulting in the selection of only 10 autoantibody biomarkers that can effectively differentiate AD sera from NDC sera with a sensitivity of 96.0% and specificity of 92.5%. AD sera were also distinguishable from sera obtained from patients with Parkinson's disease and breast cancer with accuracies of 86% and 92%, respectively. Results demonstrate that serum autoantibodies can be used effectively as highly-specific and accurate biomarkers to diagnose AD throughout the course of the disease.

  9. Assessment of Myocardial Infarction by Cardiac Magnetic Resonance Imaging and Long-Term Mortality

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    João Luiz Fernandes Petriz

    2015-02-01

    Full Text Available Background: Cardiac magnetic resonance imaging provides detailed anatomical information on infarction. However, few studies have investigated the association of these data with mortality after acute myocardial infarction. Objective: To study the association between data regarding infarct size and anatomy, as obtained from cardiac magnetic resonance imaging after acute myocardial infarction, and long-term mortality. Methods: A total of 1959 reports of “infarct size” were identified in 7119 cardiac magnetic resonance imaging studies, of which 420 had clinical and laboratory confirmation of previous myocardial infarction. The variables studied were the classic risk factors – left ventricular ejection fraction, categorized ventricular function, and location of acute myocardial infarction. Infarct size and acute myocardial infarction extent and transmurality were analyzed alone and together, using the variable named “MET-AMI”. The statistical analysis was carried out using the elastic net regularization, with the Cox model and survival trees. Results: The mean age was 62.3 ± 12 years, and 77.3% were males. During the mean follow-up of 6.4 ± 2.9 years, there were 76 deaths (18.1%. Serum creatinine, diabetes mellitus and previous myocardial infarction were independently associated with mortality. Age was the main explanatory factor. The cardiac magnetic resonance imaging variables independently associated with mortality were transmurality of acute myocardial infarction (p = 0.047, ventricular dysfunction (p = 0.0005 and infarcted size (p = 0.0005; the latter was the main explanatory variable for ischemic heart disease death. The MET-AMI variable was the most strongly associated with risk of ischemic heart disease death (HR: 16.04; 95%CI: 2.64-97.5; p = 0.003. Conclusion: The anatomical data of infarction, obtained from cardiac magnetic resonance imaging after acute myocardial infarction, were independently associated with long

  10. Assessment of Myocardial Infarction by Cardiac Magnetic Resonance Imaging and Long-Term Mortality

    Energy Technology Data Exchange (ETDEWEB)

    Petriz, João Luiz Fernandes, E-mail: jlpetriz@cardiol.br [Universidade Federal do Rio de Janeiro (UFRJ) / Instituto do Coração Edson Saad - Programa de Pós Graduação em Medicina (Cardiologia), Rio de Janeiro, RJ (Brazil); Hospital Barra D’Or, Rio de Janeiro, RJ (Brazil); Instituto D’Or de Pesquisa e Ensino, Rio de Janeiro, RJ (Brazil); Gomes, Bruno Ferraz de Oliveira; Rua, Braulio Santos [Hospital Barra D’Or, Rio de Janeiro, RJ (Brazil); Azevedo, Clério Francisco [Instituto D’Or de Pesquisa e Ensino, Rio de Janeiro, RJ (Brazil); Hadlich, Marcelo Souza [Universidade Federal do Rio de Janeiro (UFRJ) / Instituto do Coração Edson Saad - Programa de Pós Graduação em Medicina (Cardiologia), Rio de Janeiro, RJ (Brazil); Instituto D’Or de Pesquisa e Ensino, Rio de Janeiro, RJ (Brazil); Mussi, Henrique Thadeu Periard [Universidade Federal do Rio de Janeiro (UFRJ) / Instituto do Coração Edson Saad - Programa de Pós Graduação em Medicina (Cardiologia), Rio de Janeiro, RJ (Brazil); Hospital Barra D’Or, Rio de Janeiro, RJ (Brazil); Taets, Gunnar de Cunto [Instituto D’Or de Pesquisa e Ensino, Rio de Janeiro, RJ (Brazil); Nascimento, Emília Matos do; Pereira, Basílio de Bragança; Silva, Nelson Albuquerque de Souza e [Universidade Federal do Rio de Janeiro (UFRJ) / Instituto do Coração Edson Saad - Programa de Pós Graduação em Medicina (Cardiologia), Rio de Janeiro, RJ (Brazil)

    2015-02-15

    Cardiac magnetic resonance imaging provides detailed anatomical information on infarction. However, few studies have investigated the association of these data with mortality after acute myocardial infarction. To study the association between data regarding infarct size and anatomy, as obtained from cardiac magnetic resonance imaging after acute myocardial infarction, and long-term mortality. A total of 1959 reports of “infarct size” were identified in 7119 cardiac magnetic resonance imaging studies, of which 420 had clinical and laboratory confirmation of previous myocardial infarction. The variables studied were the classic risk factors – left ventricular ejection fraction, categorized ventricular function, and location of acute myocardial infarction. Infarct size and acute myocardial infarction extent and transmurality were analyzed alone and together, using the variable named “MET-AMI”. The statistical analysis was carried out using the elastic net regularization, with the Cox model and survival trees. The mean age was 62.3 ± 12 years, and 77.3% were males. During the mean follow-up of 6.4 ± 2.9 years, there were 76 deaths (18.1%). Serum creatinine, diabetes mellitus and previous myocardial infarction were independently associated with mortality. Age was the main explanatory factor. The cardiac magnetic resonance imaging variables independently associated with mortality were transmurality of acute myocardial infarction (p = 0.047), ventricular dysfunction (p = 0.0005) and infarcted size (p = 0.0005); the latter was the main explanatory variable for ischemic heart disease death. The MET-AMI variable was the most strongly associated with risk of ischemic heart disease death (HR: 16.04; 95%CI: 2.64-97.5; p = 0.003). The anatomical data of infarction, obtained from cardiac magnetic resonance imaging after acute myocardial infarction, were independently associated with long-term mortality, especially for ischemic heart disease death.

  11. Human Gut Microbiota: Toward an Ecology of Disease

    Science.gov (United States)

    Selber-Hnatiw, Susannah; Rukundo, Belise; Ahmadi, Masoumeh; Akoubi, Hayfa; Al-Bizri, Hend; Aliu, Adelekan F.; Ambeaghen, Tanyi U.; Avetisyan, Lilit; Bahar, Irmak; Baird, Alexandra; Begum, Fatema; Ben Soussan, Hélène; Blondeau-Éthier, Virginie; Bordaries, Roxane; Bramwell, Helene; Briggs, Alicia; Bui, Richard; Carnevale, Matthew; Chancharoen, Marisa; Chevassus, Talia; Choi, Jin H.; Coulombe, Karyne; Couvrette, Florence; D'Abreau, Samantha; Davies, Meghan; Desbiens, Marie-Pier; Di Maulo, Tamara; Di Paolo, Sean-Anthony; Do Ponte, Sabrina; dos Santos Ribeiro, Priscyla; Dubuc-Kanary, Laure-Anne; Duncan, Paola K.; Dupuis, Frédérique; El-Nounou, Sara; Eyangos, Christina N.; Ferguson, Natasha K.; Flores-Chinchilla, Nancy R.; Fotakis, Tanya; Gado Oumarou H D, Mariam; Georgiev, Metodi; Ghiassy, Seyedehnazanin; Glibetic, Natalija; Grégoire Bouchard, Julien; Hassan, Tazkia; Huseen, Iman; Ibuna Quilatan, Marlon-Francis; Iozzo, Tania; Islam, Safina; Jaunky, Dilan B.; Jeyasegaram, Aniththa; Johnston, Marc-André; Kahler, Matthew R.; Kaler, Kiranpreet; Kamani, Cedric; Karimian Rad, Hessam; Konidis, Elisavet; Konieczny, Filip; Kurianowicz, Sandra; Lamothe, Philippe; Legros, Karina; Leroux, Sebastien; Li, Jun; Lozano Rodriguez, Monica E.; Luponio-Yoffe, Sean; Maalouf, Yara; Mantha, Jessica; McCormick, Melissa; Mondragon, Pamela; Narayana, Thivaedee; Neretin, Elizaveta; Nguyen, Thi T. T.; Niu, Ian; Nkemazem, Romeo B.; O'Donovan, Martin; Oueis, Matthew; Paquette, Stevens; Patel, Nehal; Pecsi, Emily; Peters, Jackie; Pettorelli, Annie; Poirier, Cassandra; Pompa, Victoria R.; Rajen, Harshvardhan; Ralph, Reginald-Olivier; Rosales-Vasquez, Josué; Rubinshtein, Daria; Sakr, Surya; Sebai, Mohammad S.; Serravalle, Lisa; Sidibe, Fily; Sinnathurai, Ahnjana; Soho, Dominique; Sundarakrishnan, Adithi; Svistkova, Veronika; Ugbeye, Tsolaye E.; Vasconcelos, Megan S.; Vincelli, Michael; Voitovich, Olga; Vrabel, Pamela; Wang, Lu; Wasfi, Maryse; Zha, Cong Y.; Gamberi, Chiara

    2017-01-01

    Composed of trillions of individual microbes, the human gut microbiota has adapted to the uniquely diverse environments found in the human intestine. Quickly responding to the variances in the ingested food, the microbiota interacts with the host via reciprocal biochemical signaling to coordinate the exchange of nutrients and proper immune function. Host and microbiota function as a unit which guards its balance against invasion by potential pathogens and which undergoes natural selection. Disturbance of the microbiota composition, or dysbiosis, is often associated with human disease, indicating that, while there seems to be no unique optimal composition of the gut microbiota, a balanced community is crucial for human health. Emerging knowledge of the ecology of the microbiota-host synergy will have an impact on how we implement antibiotic treatment in therapeutics and prophylaxis and how we will consider alternative strategies of global remodeling of the microbiota such as fecal transplants. Here we examine the microbiota-human host relationship from the perspective of the microbial community dynamics. PMID:28769880

  12. CRISPR-mediated genome editing and human diseases

    Directory of Open Access Journals (Sweden)

    Liquan Cai

    2016-12-01

    Full Text Available CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats technology has emerged as a powerful technology for genome editing and is now widely used in basic biomedical research to explore gene function. More recently, this technology has been increasingly applied to the study or treatment of human diseases, including Barth syndrome effects on the heart, Duchenne muscular dystrophy, hemophilia, β-Thalassemia, and cystic fibrosis. CRISPR/Cas9 (CRISPR-associated protein 9 genome editing has been used to correct disease-causing DNA mutations ranging from a single base pair to large deletions in model systems ranging from cells in vitro to animals in vivo. In addition to genetic diseases, CRISPR/Cas9 gene editing has also been applied in immunology-focused applications such as the targeting of C-C chemokine receptor type 5, the programmed death 1 gene, or the creation of chimeric antigen receptors in T cells for purposes such as the treatment of the acquired immune deficiency syndrome (AIDS or promoting anti-tumor immunotherapy. Furthermore, this technology has been applied to the genetic manipulation of domesticated animals with the goal of producing biologic medical materials, including molecules, cells or organs, on a large scale. Finally, CRISPR/Cas9 has been teamed with induced pluripotent stem (iPS cells to perform multiple tissue engineering tasks including the creation of disease models or the preparation of donor-specific tissues for transplantation. This review will explore the ways in which the use of CRISPR/Cas9 is opening new doors to the treatment of human diseases.

  13. Exploring the potential relevance of human-specific genes to complex disease

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    Cooper David N

    2011-01-01

    Full Text Available Abstract Although human disease genes generally tend to be evolutionarily more ancient than non-disease genes, complex disease genes appear to be represented more frequently than Mendelian disease genes among genes of more recent evolutionary origin. It is therefore proposed that the analysis of human-specific genes might provide new insights into the genetics of complex disease. Cross-comparison with the Human Gene Mutation Database (http://www.hgmd.org revealed a number of examples of disease-causing and disease-associated mutations in putatively human-specific genes. A sizeable proportion of these were missense polymorphisms associated with complex disease. Since both human-specific genes and genes associated with complex disease have often experienced particularly rapid rates of evolutionary change, either due to weaker purifying selection or positive selection, it is proposed that a significant number of human-specific genes may play a role in complex disease.

  14. A simple method for assessment of human anti-Neu5Gc antibodies applied to Kawasaki disease.

    Directory of Open Access Journals (Sweden)

    Vered Padler-Karavani

    Full Text Available N-glycolylneuraminic acid (Neu5Gc is an immunogenic sugar of dietary origin that metabolically incorporates into diverse native glycoconjugates in humans. Anti-Neu5Gc antibodies are detected in all human sera, though with variable levels and epitope-recognition profiles. These antibodies likely play a role in several inflammation-mediated pathologies including cardiovascular diseases and cancer. In cancer, they have dualistic and opposing roles, either stimulating or repressing disease, as a function of their dose, and some of these antibodies serve as carcinoma biomarkers. Thus, anti-Neu5Gc antibodies may signify risk of inflammation-mediated diseases, and changes in their levels could potentially be used to monitor disease progression and/or response to therapy. Currently, it is difficult to determine levels of anti-Neu5Gc antibodies in individual human samples because these antibodies recognize multiple Neu5Gc-epitopes. Here we describe a simple and specific method for detection and overall estimation of human anti-Neu5Gc antibodies. We exploit the difference between two mouse models that differ only by Neu5Gc-presence (wild-type or Neu5Gc-absence (Cmah(-/- knockout. We characterize mouse serum from both strains by HPLC, lectin and mass-spectrometry analysis and show the target Neu5Gc-epitopes. We then use Cmah(-/- knockout sera to inhibit all non-Neu5Gc-reactivity followed by binding to wild-type sera to detect overall anti-Neu5Gc response in a single assay. We applied this methodology to characterize and quantify anti-Neu5Gc IgG and IgA in sera of patients with Kawasaki disease (KD at various stages compared to controls. KD is an acute childhood febrile disease characterized by inflammation of coronary arteries that untreated may lead to coronary artery aneurysms with risk of thrombosis and myocardial infarction. This estimated response is comparable to the average of detailed anti-Neu5Gc IgG profile analyzed by a sialoglycan microarray

  15. Zoonotic disease surveillance--inventory of systems integrating human and animal disease information.

    Science.gov (United States)

    Wendt, A; Kreienbrock, L; Campe, A

    2015-02-01

    Although 65% of recent major disease outbreaks throughout the world have a zoonotic origin, there is still a sharp division among the disciplines into the human and animal health sectors. In the last few decades, a global integrative concept, often referred to as 'One Health', has been strongly endorsed. Surveillance and monitoring efforts are major components for effective disease prevention and control. As human health and animal health are inextricably linked, it is assumed that a cross-sectoral data interpretation of zoonotic disease information will improve their prevention, prediction and control. To provide an overview of existing systems throughout the world which integrate information from humans and animals on zoonotic diseases, a literature review was conducted. Twenty projects were identified and described regarding their concepts and realization. They all vary widely depending on their surveillance purpose, their structure and the source of information they use. What they have in common is that they quite often use data which have already been collected for another purpose. Therefore, the challenges of how to make use of such secondary data are of great interest.

  16. Cerebral infarction in patient with minimal change nephrotic syndrome.

    Science.gov (United States)

    Babu, A; Boddana, P; Robson, S; Ludeman, L

    2013-01-01

    We report a case of 68-year-old Caucasian man who presented with cerebral infarcts secondary to arterial thrombosis associated with nephrotic syndrome. His initial presentation included edema of legs, left hemiparesis, and right-sided cerebellar signs. Investigations with computed tomography and magnetic resonance imaging of brain showed multiple cerebral infarcts in middle cerebral and posterior cerebral artery territory. Blood and urine investigations also showed impaired renal function, hypercholesterolemia, hypoalbuminaemia, and nephrotic range proteinuria. Renal biopsy showed minimal change disease. Cerebral infarcts were treated with antiplatelet agents and nephrotic syndrome was treated with high dose steroids. Patient responded well to the treatment and is all well till date.

  17. Does FXIII deficiency impair wound healing after myocardial infarction?

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    Matthias Nahrendorf

    Full Text Available Inadequate healing of myocardial infarction may contribute to local expansion of the infarct, frequently leading to chamber dilation, heart failure, or myocardial rupture. Experimental evidence in mouse models suggests that Factor XIII might play a key role in wound healing, and low persistent values lead to increased incidence of cardiac rupture following myocardial infarction. Here we would like to share our initial clinical experiences with strikingly similar observations in patients with this grave disease, and compare these observations to experimental findings.

  18. Inferior ST-Elevation Myocardial Infarction Associated with Takotsubo Cardiomyopathy

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    Oliver Koeth

    2010-01-01

    Full Text Available Takotsubo cardiomyopathy (TCM is usually characterized by transient left ventricular apical ballooning. Due to the clinical symptoms which include chest pain, electrocardiographic changes, and elevated myocardial markers, Takotsubo cardiomyopathy is frequently mimicking ST-elevation myocardial infarction in the absence of a significant coronary artery disease. Otherwise an acute occlusion of the left anterior descending coronary artery can produce a typical Takotsubo contraction pattern. ST-elevation myocardial infarction (STEMI is frequently associated with emotional stress, but to date no cases of STEMI triggering TCM have been reported. We describe a case of a female patient with inferior ST-elevation myocardial infarction complicated by TCM.

  19. Inferior ST-Elevation Myocardial Infarction Associated with Takotsubo Cardiomyopathy

    Science.gov (United States)

    Koeth, Oliver; Zeymer, Uwe; Schiele, Rudolf; Zahn, Ralf

    2010-01-01

    Takotsubo cardiomyopathy (TCM) is usually characterized by transient left ventricular apical ballooning. Due to the clinical symptoms which include chest pain, electrocardiographic changes, and elevated myocardial markers, Takotsubo cardiomyopathy is frequently mimicking ST-elevation myocardial infarction in the absence of a significant coronary artery disease. Otherwise an acute occlusion of the left anterior descending coronary artery can produce a typical Takotsubo contraction pattern. ST-elevation myocardial infarction (STEMI) is frequently associated with emotional stress, but to date no cases of STEMI triggering TCM have been reported. We describe a case of a female patient with inferior ST-elevation myocardial infarction complicated by TCM. PMID:20811565

  20. Cardiovascular disease in human immunodeficiency virus-infection as a cause of hospitalization: a case-series in a General Hospital in Peru.

    Science.gov (United States)

    Valenzuela-Rodríguez, Germán; Mezones-Holguín, Edward; Mendo-Urbina, Fernando; Rodríguez-Morales, Alfonso J

    2015-01-01

    Cardiovascular disease in the context of human immunodeficiency virus infection has become a major clinical concern in recent years. In the current report we assess hospitalizations due to cardiovascular disease in human immunodeficiency virus patients in a Social Security reference hospital in Peru. A retrospective study was carried out between January 1996 and December 2012 in a General Hospital in Lima, Peru. We included 26 patients hospitalized due to cardiovascular disease. Mean age was 46.3 years (SD 12.5), predominantly male (57.7%). Ten patients (38.4%) were in Acquired Immunodeficiency Syndrome stages. Seventeen (65.4%) received high-active-antiretroviral therapy. Eleven (42.3%) had cardiac involvement and 15 (57.7%) had non-cardiac vascular involvement. The most frequent causes of cardiac involvement were pericardial effusion and myocardial infarction. On the other hand, deep vein thrombosis and stroke were the most frequent for non-cardiac vascular involvement. Cardiovascular disease is an important cause of hospitalization in Peruvian human immunodeficiency virus patients, with differences between immunosuppression stages. Further studies analyzing associated factors are warranted. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

  1. Comparison of Cockcroft-Gault and modification of diet in renal disease formulas as predictors of cardiovascular outcomes in patients with myocardial infarction treated with primary percutaneous coronary intervention.

    Science.gov (United States)

    Ekmekci, Ahmet; Uluganyan, Mahmut; Gungor, Baris; Tufan, Fatih; Cekirdekci, Elif Iclal; Ozcan, Kazim Serhan; Erer, Hatice Betul; Orhan, Ahmet; Osmanov, Damir; Bozbay, Mehmet; Cicek, Gokhan; Sayar, Nurten; Eren, Mehmet

    2014-10-01

    We prospectively assessed the value of estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (C-G) equations in predicting inhospital adverse outcomes after primary coronary intervention for acute ST-segment elevation myocardial infarction. We classified 647 patients into 3 categories according to eGFR, 90 mL/min/1.73 m(2). The eGFRC-G classified 17 patients in the >90 mL/min/1.73 m(2) subgroup and 6 and 11 patients in the 60 to 90 and 90 mL/min/1.73 m(2) (P = .01 and P = .01, respectively); the eGFRMDRD was not predictive. Although the MDRD equation more accurately estimates GFR in certain populations, the CG formula may be a better predictor of adverse events. © The Author(s) 2013.

  2. Clinical analysis of sixteen cases of cerebral watershed infarction caused by other diseases%16例疾病诱发分水岭脑梗死病例的临床分析

    Institute of Scientific and Technical Information of China (English)

    杨志强; 林秀英; 甘淑娟

    2014-01-01

    Objective:To investigate the pathogenesis,onset of forms,induced factors,clinical features and preventation and treatment measures.Methods:To analyze the clinical materials,onset of forms, induced factors,imaging features,and preventation and treatment measures,sixteen patients presenting with cerebral watershed infarction induced by other diseases were col ected.Result:Artery atheroscle-rosis stenosis or blocking is the major pathological basis of cerebral watershed infarction,while hypotention,circulatory disturbance,and hypovolemia are important induced factors.Conclusion:We must pay more attention to old patients with high risk factors.We should foresee the possibility and prevent the cerebral watershed infarction when we treat with other diseases which may result in hypotention or hy-povolemia.%目的::探讨分水岭脑梗死的病因、发病形式与诱发因素、临床特点及防治措施。方法:分析16例疾病诱发的分水岭脑梗死患者的临床资料、发病形式、诱发因素、影像学特点及相应的预防及治疗措施。结果:大动脉粥样硬化狭窄或闭塞是分水岭脑梗死最主要病理基础,低血压、循环障碍、血容量不足是重要诱发因素。结论:临床上对年老、存在危险因素的高危患者,应高度重视,在治疗可能诱发低血压及低血容量的疾病时,应能够提前预见及积极防控分水岭脑梗死的发生。

  3. Myeloid dendritic cells are potential players in human neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Paola eBossù

    2015-12-01

    Full Text Available Alzheimer’s (AD and Parkinson’s (PD diseases are devastating neurodegenerative disturbances wherein neuroinflammation is a chronic pathogenic process with high therapeutic potential. Major mediators of AD/PD neuroimmune processes are resident immune cells, but immune cells derived from periphery may also participate and to some extent modify neuroinflammation. Specifically, blood borne myeloid cells emerge as crucial components of AD/PD progression and susceptibility. Among these, dendritic cells (DCs are key immune orchestrators and players of brain immune surveillance: we candidate them as potential mediators of both AD and PD and as relevant cell model for unraveling myeloid cell role in neurodegeneration. Hence, we recapitulate and discuss emerging data suggesting that blood-derived DCs play a role in experimental and human neurodegenerative diseases. In humans, in particular, DCs are modified by in vitro culture with neurodegeneration-associated pathogenic factors and dysregulated in AD patients, while the levels of DC precursors are decreased in AD and PD patients’ blood, possibly as an index of their recruitment to the brain. Overall, we emphasize the need to explore the impact of DCs on neurodegeneration to uncover peripheral immune mechanisms of pathogenic importance, recognize potential biomarkers and improve therapeutic approaches for neurodegenerative diseases.

  4. Africa: the next frontier for human disease gene discovery?

    Science.gov (United States)

    Ramsay, Michèle; Tiemessen, Caroline T; Choudhury, Ananyo; Soodyall, Himla

    2011-10-15

    The populations of Africa harbour the greatest human genetic diversity following an evolutionary history tracing its beginnings on the continent to time before the emergence of Homo sapiens. Signatures of selection are detectable as responses to ancient environments and cultural practices, modulated by more recent events including infectious epidemics, migrations, admixture and, of course, chance. The age of high-throughput biology is not passing Africa by. African-based cohort studies and networks with an African footprint are ideal springboards for disease-related genetic and genomic studies. Initiatives like HapMap, the 1000 Genomes Project, MalariaGEN, the INDEPTH network and Human Heredity and Health in Africa are catalysts to exploring African genetic diversity and its role in the spectrum from health to disease. The challenges are abundant in dissecting biological questions in the light of linguistic, cultural, geographic and political boundaries and their respective roles in shaping health-related profiles. Will studies based on African populations lead to a new wave of discovery of genetic contributors to disease?

  5. Malarial birds: modeling infectious human disease in animals.

    Science.gov (United States)

    Slater, Leo B

    2005-01-01

    Through the examination of avian malarias as models of infectious human disease, this paper reveals the kinds of claims that scientists and physicians made on the basis of animal models-biological systems in the laboratory and the field-and what characteristics made for congruence between these models and human malaria. The focus is on the period between 1895 and 1945, and on the genesis and trajectory of certain animal models of malaria within specific locations, such as the Johns Hopkins School of Hygiene and Public Health in Baltimore and Bayer (I. G. Farben) in Elberfeld. These exemplars illustrate a diversity of approaches to malaria-as-disease, and the difficulties of framing aspects of this disease complex within an animal or laboratory system. The diversity and nearness to wild types of the birds, protozoan parasites, and mosquitoes that made up these malaria models contributed a great deal to the complexity of the models. Avian malarias, adopted with enthusiasm, were essential to the success of the U.S. antimalarial program during World War II.

  6. Transcriptome Profiling in Human Diseases: New Advances and Perspectives

    Directory of Open Access Journals (Sweden)

    Amelia Casamassimi

    2017-07-01

    Full Text Available In the last decades, transcriptome profiling has been one of the most utilized approaches to investigate human diseases at the molecular level. Through expression studies, many molecular biomarkers and therapeutic targets have been found for several human pathologies. This number is continuously increasing thanks to total RNA sequencing. Indeed, this new technology has completely revolutionized transcriptome analysis allowing the quantification of gene expression levels and allele-specific expression in a single experiment, as well as to identify novel genes, splice isoforms, fusion transcripts, and to investigate the world of non-coding RNA at an unprecedented level. RNA sequencing has also been employed in important projects, like ENCODE (Encyclopedia of the regulatory elements and TCGA (The Cancer Genome Atlas, to provide a snapshot of the transcriptome of dozens of cell lines and thousands of primary tumor specimens. Moreover, these studies have also paved the way to the development of data integration approaches in order to facilitate management and analysis of data and to identify novel disease markers and molecular targets to use in the clinics. In this scenario, several ongoing clinical trials utilize transcriptome profiling through RNA sequencing strategies as an important instrument in the diagnosis of numerous human pathologies.

  7. Justification for intravenous magnesium therapy in acute myocardial infarction

    DEFF Research Database (Denmark)

    Rasmussen, H S

    1988-01-01

    Recent studies have shown that patients with acute myocardial infarction (AMI) are magnesium-deficient and develop an additional transient decrease in serum magnesium concentrations (S-Mg c) during the acute phase of the infarct. Animal experiments, as well as studies on humans, have indicated...... of routine practice for patients with acute myocardial infarction....... that the acute decrease in S-Mg c as well as a more chronic magnesium (Mg) deficiency state are harmful to the myocardium in the setting of acute ischaemia. This knowledge has led during the last couple of years to the performance of four double-blind placebo controlled studies in which the effect of i...

  8. [Segmental testicular infarction].

    Science.gov (United States)

    Ripa Saldías, L; Guarch Troyas, R; Hualde Alfaro, A; de Pablo Cárdenas, A; Ruiz Ramo, M; Pinós Paul, M

    2006-02-01

    We report the case of a 47 years old man previously diagnosed of left hidrocele. After having a recent mild left testicular pain, an ultrasonografic study revealed a solid hipoecoic testicular lesion rounded by a big hidrocele, suggesting a testicular neoplasm. Radical inguinal orchiectomy was made and pathologic study showed segmental testicular infarction. No malignancy was found. We review the literature of the topic.

  9. Endothelial cells overexpressing IL-8 receptor reduce cardiac remodeling and dysfunction following myocardial infarction.

    Science.gov (United States)

    Zhao, Xiangmin; Zhang, Wei; Xing, Dongqi; Li, Peng; Fu, Jinyan; Gong, Kaizheng; Hage, Fadi G; Oparil, Suzanne; Chen, Yiu-Fai

    2013-08-15

    The endothelium is a dynamic component of the cardiovascular system that plays an important role in health and disease. This study tested the hypothesis that targeted delivery of endothelial cells (ECs) overexpressing neutrophil membrane IL-8 receptors IL8RA and IL8RB reduces acute myocardial infarction (MI)-induced left ventricular (LV) remodeling and dysfunction and increases neovascularization in the area at risk surrounding the infarcted tissue. MI was created by ligating the left anterior descending coronary artery in 12-wk-old male Sprague-Dawley rats. Four groups of rats were studied: group 1: sham-operated rats without MI or EC transfusion; group 2: MI rats with intravenous vehicle; group 3: MI rats with transfused ECs transduced with empty adenoviral vector (Null-EC); and group 4: MI rats with transfused ECs overexpressing IL8RA/RB (1.5 × 10⁶ cells post-MI). Two weeks after MI, LV function was assessed by echocardiography; infarct size was assessed by triphenyltetrazolium chloride (live tissue) and picrosirus red (collagen) staining, and capillary density and neutrophil infiltration in the area at risk were measured by CD31 and MPO immunohistochemical staining, respectively. When compared with the MI + vehicle and MI-Null-EC groups, transfusion of IL8RA/RB-ECs decreased neutrophil infiltration and pro-inflammatory cytokine expression and increased capillary density in the area at risk, decreased infarct size, and reduced MI-induced LV dysfunction. These findings provide proof of principle that targeted delivery of ECs is effective in repairing injured cardiac tissue. Targeted delivery of ECs to infarcted hearts provides a potential novel strategy for the treatment of acute MI in humans.

  10. Acute myocardial infarction and infarct size: do circadian variations play a role?

    Directory of Open Access Journals (Sweden)

    Ibáñez B

    2012-08-01

    Full Text Available Aída Suárez-Barrientos,1 Borja Ibáñez1,21Cardiovascular Institute, Hospital Clínico San Carlos, 2Centro Nacional de Investigaciones Cardiovasculares, Madrid, SpainAbstract: The circadian rhythm influences cardiovascular system physiology, inducing diurnal variations in blood pressure, heart rate, cardiac output, endothelial functions, platelet aggregation, and coronary arterial flow, among other physiological parameters. Indeed, an internal circadian network modulates cardiovascular physiology by regulating heart rate, metabolism, and even myocyte growth and repair ability. Consequently, cardiovascular pathology is also controlled by circadian oscillations, with increased morning incidence of cardiovascular events. The potential circadian influence on the human tolerance to ischemia/reperfusion has not been systematically scrutinized until recently. It has since been proven, in both animals and humans, that infarct size varies during the day depending on the symptom onset time, while circadian fluctuations in spontaneous cardioprotection in humans with ST-segment elevation myocardial infarction (STEMI have also been demonstrated. Furthermore, several studies have proposed that the time of day at which revascularization occurs in patients with STEMI may also influence infarct size and reperfusion outcomes. The potential association of the circadian clock with infarct size advocates the acknowledgment of time of day as a new prognostic factor in patients suffering acute myocardial infarction, which would open up a new field for chronotherapeutic targets and lead to the inclusion of time of day as a variable in clinical trials that test novel cardioprotective strategies.Keywords: cardioprotection, circadian rhythm, reperfusion injury, ST-segment elevation myocardial infarction

  11. Traffic jam: a compendium of human diseases that affect intracellular transport processes.

    Science.gov (United States)

    Aridor, M; Hannan, L A

    2000-11-01

    As sequencing of the human genome nears completion, the genes that cause many human diseases are being identified and functionally described. This has revealed that many human diseases are due to defects of intracellular trafficking. This 'Toolbox' catalogs and briefly describes these diseases.

  12. Unaltered mRNA expression of calcitonin-like receptor and receptor activity modifying proteins in human arteries in stroke and myocardial infarction

    DEFF Research Database (Denmark)

    Eskesen, Karen; János, Tajti; Tibor, Hortobágyi;

    2007-01-01

    -dependent change in total RNA and level of mRNA for p-actin or GAPDH could be detected in vessels removed from 1 and 5 days post mortem. The expression of beta-actin appears lower in coronary artery than in pulmonary artery and middle cerebral artery with no significant difference for GAPDH; both worked well......-R and RAMPs in arteries from patients with hemorrhagic stroke, arteriosclerosis and acute myocardial infarction when compared to patients without these diagnoses. Thus the mRNA expression seems to be unaltered in these disorders....

  13. CT features of renal infarction

    Energy Technology Data Exchange (ETDEWEB)

    Suzer, Okan; Shirkhoda, Ali; Jafri, S. Zafar; Madrazo, Beatrice L.; Bis, Kostaki G.; Mastromatteo, James F

    2002-10-01

    Purpose: To demonstrate the different patterns of renal infarction to avoid pitfalls. To present 'flip-flop enhancement' pattern in renal infarction. Materials and methods: Retrospective review of a total of 41 renal infarction in 37 patients were done. These patients underwent initial CT and the diagnosis of renal infarction was confirmed with either follow up CT or at surgery. Results: Twenty-three patients had wedge-shaped focal infarcts, nine patients had global and five patients had multifocal infarcts of the kidneys. Cortical rim sign was seen predominantly with global infarcts. In five patients, a 'flip-flop enhancement' pattern was observed. In two patients, planned renal biopsies due to tumefactive renal lesions were cancelled because of 'flip-flop enhancement' pattern on follow up CTs. Conclusion: Although most of our cases were straightforward for the diagnosis of renal infarction, cases with tumefactive lesions and global infarctions without the well-known cortical rim sign were particularly challenging. We describe a new sign, flip-flop enhancement pattern, which we believe solidified the diagnosis of renal infarction in five of our cases. The authors recommend further investigations for association of flip-flop enhancement and renal infarction.

  14. 老年急性脑梗死合并冠心病的危险因素分析%Risk factors for coronary heart disease in elderly patients with acute cere-bral infarction analysis

    Institute of Scientific and Technical Information of China (English)

    黄丽

    2014-01-01

    Objective To analyze the risk factors for coronary heart disease in elderly patients with acute cerebral infarction , ex-ploration for the prevention of coronary heart disease in elderly patients with acute cerebral infarction reference.Methods January 2013-2014 in March in our hospital 93 cases of acute cerebral infarction in elderly patients with coronary heart disease as a clin-ical research object, select the same period another 90 cases of simple treatment of elderly patients with acute cerebral infarction as a control group to compare the two of hypertension , diabetes, lipids and blood glucose and other biochemical differences, ap-plication Logistic regression analysis of clinical risk factors for coronary heart disease in elderly patients with acute cerebral in-farction.Results BMI observation group was(28.7±4.6)kg/m2, SBP was(170.6±17.5)mmHg,TG was(2.9±0.6)mmol/L, LDL-C was (4.3±0.5)mmol/L,TC was(5.8±1.9)mmol/L,FBG was(8.4±2.5)mmol/L,2hPG was(14.3±2.9)mmol/L,age was(71.86±7.96)years old , smoking a total of 68 cases , a total of 74 cases of hypertension , diabetes, a total of 46 cases , a total of 39 cases of dyslipidemia was significantly higher related to the level of the control group (P<0.05); Logistic regression analysis showed that age,smoking, obesity, high blood pressure , high blood sugar and high cholesterol are elderly patients with acute cerebral infarction and coronary heart disease. Conclusion An independent risk elderly patients with acute cerebral infarction and coronary heart disease because of diabetes,and high LDL-C viremia , early intervention risk factors have contributed to the prevention of cardiovascular events.%目的:分析老年急性脑梗死合并冠心病的危险因素,为防治老年急性脑梗死合并冠心病提供参考。方法选取2013年1月-2014年3月我院治疗的93例老年急性脑梗死合并冠心病患者作为临床研究对象,另选取同期治疗的90例单纯老年急性脑梗死患者

  15. Record linked retrospective cohort study of 4.6 million people exploring ethnic variations in disease: myocardial infarction in South Asians

    Directory of Open Access Journals (Sweden)

    Mueller G

    2007-07-01

    Full Text Available Abstract Background Law and policy in several countries require health services to demonstrate that they are promoting racial/ethnic equality. However, suitable and accurate data are usually not available. We demonstrated, using acute myocardial infarction, that linkage techniques can be ethical and potentially useful for this purpose. Methods The linkage was based on probability matching. Encryption of a unique national health identifier (the Community Health Index (CHI ensured that information about health status and census-based ethnicity could not be ascribed to an identified individual. We linked information on individual ethnic group from the 2001 Census to Scottish hospital discharge and mortality data. Results Overall, 94% of the 4.9 million census records were matched to a CHI record with an estimated false positive rate of less than 0.1 %, with 84.9 – 87.6% of South Asians being successfully linked. Between April 2001 and December 2003 there were 126 first episodes of acute myocardial infarction (AMI among South Asians and 30,978 among non-South Asians. The incidence rate ratio was 1.45 (95% CI 1.17, 1.78 for South Asian compared to non-South Asian men and 1.80 (95% CI 1.31, 2.48 for South Asian women. After adjustment for age, sex and any previous admission for diabetes the hazard ratio for death following AMI was 0.59 (95% CI 0.43, 0.81, reflecting better survival among South Asians. Conclusion The technique met ethical, professional and legal concerns about the linkage of census and health data and is transferable internationally wherever the census (or population register contains ethnic group or race data. The outcome is a retrospective cohort study. Our results point to increased incidence rather than increased case fatality in explaining high CHD mortality rate. The findings open up new methods for researchers and health planners.

  16. Network Medicine: A Network-based Approach to Human Diseases

    Science.gov (United States)

    Ghiassian, Susan Dina

    With the availability of large-scale data, it is now possible to systematically study the underlying interaction maps of many complex systems in multiple disciplines. Statistical physics has a long and successful history in modeling and characterizing systems with a large number of interacting individuals. Indeed, numerous approaches that were first developed in the context of statistical physics, such as the notion of random walks and diffusion processes, have been applied successfully to study and characterize complex systems in the context of network science. Based on these tools, network science has made important contributions to our understanding of many real-world, self-organizing systems, for example in computer science, sociology and economics. Biological systems are no exception. Indeed, recent studies reflect the necessity of applying statistical and network-based approaches in order to understand complex biological systems, such as cells. In these approaches, a cell is viewed as a complex network consisting of interactions among cellular components, such as genes and proteins. Given the cellular network as a platform, machinery, functionality and failure of a cell can be studied with network-based approaches, a field known as systems biology. Here, we apply network-based approaches to explore human diseases and their associated genes within the cellular network. This dissertation is divided in three parts: (i) A systematic analysis of the connectivity patterns among disease proteins within the cellular network. The quantification of these patterns inspires the design of an algorithm which predicts a disease-specific subnetwork containing yet unknown disease associated proteins. (ii) We apply the introduced algorithm to explore the common underlying mechanism of many complex diseases. We detect a subnetwork from which inflammatory processes initiate and result in many autoimmune diseases. (iii) The last chapter of this dissertation describes the

  17. The possible mechanisms of the human microbiome in allergic diseases.

    Science.gov (United States)

    Ipci, Kagan; Altıntoprak, Niyazi; Muluk, Nuray Bayar; Senturk, Mehmet; Cingi, Cemal

    2017-02-01

    In the present paper, we discuss the importance of the microbiome in allergic disease. In this review paper, the data from the Medline (PubMed) and search engine of Kirikkale University were systematically searched for all relevant articles in June 15th, 2015 for the past 30 years. The keywords of "microbiome", "dysbiosis", "allergy", "allergic rhinitis", "allergic disease", "mechanisms" and "treatment" were used alone or together. In this paper, microbiomes were presented in terms of "Definition", "Influence of \\the human microbiome on health", "The microbiome and allergic diseases", and "Modulation of the gut microbiota in terms of treatment and prevention". Microbiological dysbiosis is also reviewed. The microbiome is the genetic material of all microbes (bacteria, fungi, protozoa, and viruses) that live on or in the human body. Microbes outnumber human cells in a 10:1 ratio. Most microbes live in the gut, particularly the large intestine. Changes in the immune function of the respiratory tract are (at least in theory) linked to the immunomodulatory activity of the gut microbiota via the concept of a "common mucosal response". The gut microbiota shapes systemic immunity, thus affecting the lung mucosa. Alternatively, changes in the gut microbiota may reflect alterations in the oropharyngeal microbiota, which may in turn directly affect the lung microbiota and host immune responses via microaspiration. Dysbiosis is defined as qualitative and quantitative changes in the intestinal flora; and modern diet and lifestyle, antibiotics, psychological and physical stress result in alterations in bacterial metabolism, as well as the overgrowth of potentially pathogenic microorganisms. All immune system components are directly or indirectly regulated by the microbiota. The nature of microbial exposure early in life appears to be important for the development of robust immune regulation; disruption of either the microbiota or the host response can trigger chronic

  18. Human RECQ helicases: roles in cancer, aging, and inherited disease

    Directory of Open Access Journals (Sweden)

    Sidorova JM

    2014-12-01

    Full Text Available Julia M Sidorova,1,* Raymond J Monnat Jr,1,2,* 1Department of Pathology, 2Department of Genome Sciences, University of Washington, Seattle, WA, USA *The authors contributed equally to this review Abstract: DNA helicases use the energy of ATP hydrolysis to disrupt DNA base pairing and displace proteins from DNA in order to facilitate replication, recombination, transcription, and repair. This article focuses on the human RECQ helicases, five DNA-dependent helicases that play key roles in cellular physiology and disease. Loss of function of three RECQ helicases causes the cancer predisposition syndromes Bloom syndrome, Werner syndrome, and Rothmund–Thomson and related syndromes. We summarize recent work on these syndromes and proteins and discuss disease pathogenesis in light of RECQ helicase biochemical activities and in vivo functions. Keywords: ATP-dependent DNA helicase, Bloom syndrome, Werner syndrome, Rothmund–Thomson syndrome, DNA replication, DNA repair, genetic instability, cancer predisposition syndrome

  19. Mutations that Cause Human Disease: A Computational/Experimental Approach

    Energy Technology Data Exchange (ETDEWEB)

    Beernink, P; Barsky, D; Pesavento, B

    2006-01-11

    International genome sequencing projects have produced billions of nucleotides (letters) of DNA sequence data, including the complete genome sequences of 74 organisms. These genome sequences have created many new scientific opportunities, including the ability to identify sequence variations among individuals within a species. These genetic differences, which are known as single nucleotide polymorphisms (SNPs), are particularly important in understanding the genetic basis for disease susceptibility. Since the report of the complete human genome sequence, over two million human SNPs have been identified, including a large-scale comparison of an entire chromosome from twenty individuals. Of the protein coding SNPs (cSNPs), approximately half leads to a single amino acid change in the encoded protein (non-synonymous coding SNPs). Most of these changes are functionally silent, while the remainder negatively impact the protein and sometimes cause human disease. To date, over 550 SNPs have been found to cause single locus (monogenic) diseases and many others have been associated with polygenic diseases. SNPs have been linked to specific human diseases, including late-onset Parkinson disease, autism, rheumatoid arthritis and cancer. The ability to predict accurately the effects of these SNPs on protein function would represent a major advance toward understanding these diseases. To date several attempts have been made toward predicting the effects of such mutations. The most successful of these is a computational approach called ''Sorting Intolerant From Tolerant'' (SIFT). This method uses sequence conservation among many similar proteins to predict which residues in a protein are functionally important. However, this method suffers from several limitations. First, a query sequence must have a sufficient number of relatives to infer sequence conservation. Second, this method does not make use of or provide any information on protein structure, which

  20. [Human and animal parasitic diseases in the New Hebrides].

    Science.gov (United States)

    Bourée, P; Léon, J J

    1976-01-01

    New-Hebrides Condominium, an archipelago in the South Pacific, is a country with a special socio-political environment, due to the duality of its French-British regime. This state of affairs is felt in all areas including Public Health, where we find French, British and Condominial personnel. The pathology of parasitic diseases is essentially tropical with a strong predominance of paludism, at times fatal, and intestinal nematodes; however we rarely find amibiasis or human hydatid disease. Strongyloidiasis as well as specific ascaris of each species are very frequent in animals. In general cattle is relatively healthy, which is fortunate for a country whose economy is turning more and more to breeding.

  1. Therapeutics Targeting FGF Signaling Network in Human Diseases.

    Science.gov (United States)

    Katoh, Masaru

    2016-12-01

    Fibroblast growth factor (FGF) signaling through its receptors, FGFR1, FGFR2, FGFR3, or FGFR4, regulates cell fate, angiogenesis, immunity, and metabolism. Dysregulated FGF signaling causes human diseases, such as breast cancer, chondrodysplasia, gastric cancer, lung cancer, and X-linked hypophosphatemic rickets. Recombinant FGFs are pro-FGF signaling therapeutics for tissue and/or wound repair, whereas FGF analogs and gene therapy are under development for the treatment of cardiovascular disease, diabetes, and osteoarthritis. FGF traps, anti-FGF/FGFR monoclonal antibodies (mAbs), and small-molecule FGFR inhibitors are anti-FGF signaling therapeutics under development for the treatment of cancer, chondrodysplasia, and rickets. Here, I discuss the benefit-risk and cost-effectiveness issues of precision medicine targeting FGFRs, ALK, EGFR, and FLT3. FGFR-targeted therapy should be optimized for cancer treatment, focusing on genomic tests and recurrence.

  2. Motor unit involvement in human acute Chagas' disease

    Directory of Open Access Journals (Sweden)

    O. R. Benavente

    1989-09-01

    Full Text Available Thirty five patients with acute Chagas' disease who demonstrated parasitaemia at the time of the investigation were submitted to a detailed electromyographical study. With their muscles at rest, 12 patients showed fibrillation potentials and/or positive sharp waves. On volitional contraction, 7 had short duration motor unit potentials (MUPs and low polyphasic MUPs. On motor and sensory nerve fibers conduction studies, 20 disclosed values below the lower control limit within one or more nerves. Finally, 12 patients produced a muscle, decremental response on nerve supramaximal repetitive stimulation. The findings signal that primary muscle involvement, neuropathy and impairement of the neuromuscular transmission, either isolated or combined, may be found in the acute stage of human Chagas' disease.

  3. Human papillomavirus infection and disease in men: Impact of HIV

    Directory of Open Access Journals (Sweden)

    Sinead Delany-Moretlwe

    2013-12-01

    Full Text Available There is growing evidence of a significant burden of human papillomavirus (HPV infection and associated disease in men. High rates of HPV infection have been observed in men from sub-Saharan Africa where HIV prevalence is high. HIV infection increases HPV prevalence, incidence and persistence and is strongly associated with the development of anogenital warts and anal, penile and head and neck cancers in men. Despite increasing access to antiretroviral therapy, there appears to be little benefit in preventing the development of these cancers in HIV-positive men, making prevention of infection a priority. New prevention options that are being introduced in many African countries include male circumcision and HPV vaccination. However, more data are needed on the burden of HPV disease in men before boys are included in HPV vaccination programmes.

  4. Mitochondrial regulation of epigenetics and its role in human diseases

    DEFF Research Database (Denmark)

    Minocherhomji, Sheroy; Tollefsbol, Trygve O; Singh, Keshav K

    2012-01-01

    Most pathogenic mitochondrial DNA (mtDNA) mutations induce defects in mitochondrial oxidative phosphorylation (OXPHOS). However, phenotypic effects of these mutations show a large degree of variation depending on the tissue affected. These differences are difficult to reconcile with OXPHOS...... as the sole pathogenic factor suggesting that additional mechanisms contribute to lack of genotype and clinical phenotype correlationship. An increasing number of studies have identified a possible effect on the epigenetic landscape of the nuclear genome as a consequence of mitochondrial dysfunction...... to epigenetic changes causing genomic instability in the nuclear genome. We propose that "mitocheckpoint" mediated epigenetic and genetic changes may play key roles in phenotypic variation related to mitochondrial diseases or host of human diseases in which mitochondrial defect plays a primary role....

  5. Human embryonic stem cell therapies for neurodegenerative diseases.

    Science.gov (United States)

    Tomaskovic-Crook, Eva; Crook, Jeremy M

    2011-06-01

    There is a renewed enthusiasm for the clinical translation of human embryonic stem (hES) cells. This is abetted by putative clinically-compliant strategies for hES cell maintenance and directed differentiation, greater understanding of and accessibility to cells through formal cell registries and centralized cell banking for distribution, the revised US government policy on funding hES cell research, and paradoxically the discovery of induced pluripotent stem (iPS) cells. Additionally, as we consider the constraints (practical and fiscal) of delivering cell therapies for global healthcare, the more efficient and economical application of allogeneic vs autologous treatments will bolster the clinical entry of hES cell derivatives. Neurodegenerative disorders such as Parkinson's disease are primary candidates for hES cell therapy, although there are significant hurdles to be overcome. The present review considers key advances and challenges to translating hES cells into novel therapies for neurodegenerative diseases, with special consideration given to Parkinson's disease and Alzheimer's disease. Importantly, despite the focus on degenerative brain disorders and hES cells, many of the issues canvassed by this review are relevant to systemic application of hES cells and other pluripotent stem cells such as iPS cells.

  6. Use of rodents as models of human diseases

    Directory of Open Access Journals (Sweden)

    Thierry F Vandamme

    2014-01-01

    Full Text Available Advances in molecular biology have significantly increased the understanding of the biology of different diseases. However, these discoveries have not yet been fully translated into improved treatments for patients with diseases such as cancers. One of the factors limiting the translation of knowledge from preclinical studies to the clinic has been the limitations of in vivo diseases models. In this brief review, we will discuss the advantages and disadvantages of rodent models that have been developed to simulate human pathologies, focusing in models that employ xenografts and genetic modification. Within the framework of genetically engineered mouse (GEM models, we will review some of the current genetic strategies for modeling diseases in the mouse and the preclinical studies that have already been undertaken. We will also discuss how recent improvements in imaging technologies may increase the information derived from using these GEMs during early assessments of potential therapeutic pathways. Furthermore, it is interesting to note that one of the values of using a mouse model is the very rapid turnover rate of the animal, going through the process of birth to death in a very short timeframe relative to that of larger mammalian species.

  7. Non-photic solar associations of heart rate variability and myocardial infarction

    Science.gov (United States)

    Cornélissen, Germaine; Halberg, Franz; Breus, Tamara; Syutkina, Elena V.; Baevsky, Roman; Weydahl, Andi; Watanabe, Yoshihiko; Otsuka, Kuniaki; Siegelova, Jarmila; Fiser, Bohumil; Bakken, Earl E.

    2002-03-01

    Alignment of serial epidemiological, physiological, including electrocardiographic data with variations in galactic cosmic rays, geomagnetic activity, and atmospheric pressure suggests the possibility of links among these physical environmental variations and health risks, such as myocardial infarctions and ischemic strokes, among others. An increase in the incidence of myocardial infarction in association with magnetic storms, reported by several investigators from Russia, Israel, Italy and Mexico, accounts in Minnesota for a 5% (220cases/year) increase in mortality during years of maximal solar activity by comparison with years of minimal solar activity. Magnetic storms are also found to decrease heart rate variability (HRV), indicating a possible mechanism since a reduced HRV is a prognostic factor for coronary artery disease and myocardial infarction. Longitudinal electrocardiographic monitoring for a week or much longer spans in different geographic locations, notably in the auroral oval, further suggests that the decrease in HRV affects spectral regions other than that around 3.6s (0.15-0.40Hz), reportedly associated with the parasympathetic nervous system. Differences in some associations are observed from solar cycle to solar cycle, and as a function of solar cycle stage, a finding resolving controversies. Coordinated physiological and physical monitoring, the scope of an international project on the Biosphere and the Cosmos, seeks reference values for a better understanding of environmental effects on human health and for testing the merit of space weather reports that could prompt countermeasures in space and on earth. Physiological data being collected systematically worldwide and morbidity/mortality statistics from causes such as myocardial infarction and stroke constitute invaluable data bases for assessing changes within the physiological range, for detecting environmental effects and for recognizing endogenous as well as exogenous disease

  8. Complement regulators in human disease: lessons from modern genetics.

    Science.gov (United States)

    K Liszewski, M; Atkinson, J P

    2015-03-01

    First identified in human serum in the late 19th century as a 'complement' to antibodies in mediating bacterial lysis, the complement system emerged more than a billion years ago probably as the first humoral immune system. The contemporary complement system consists of nearly 60 proteins in three activation pathways (classical, alternative and lectin) and a terminal cytolytic pathway common to all. Modern molecular biology and genetics have not only led to further elucidation of the structure of complement system components, but have also revealed function-altering rare variants and common polymorphisms, particularly in regulators of the alternative pathway, that predispose to human disease by creating 'hyperinflammatory complement phenotypes'. To treat these 'complementopathies', a monoclonal antibody against the initiator of the membrane attack complex, C5, has received approval for use. Additional therapeutic reagents are on the horizon.

  9. Aquaporin water channels: molecular mechanisms for human diseases.

    Science.gov (United States)

    Agre, Peter; Kozono, David

    2003-11-27

    Although water is the major component of all biological fluids, the molecular pathways for water transport across cell membranes eluded identification until the discovery of the aquaporin family of water channels. The atomic structure of mammalian AQP1 illustrates how this family of proteins is freely permeated by water but not protons (hydronium ions, H3O+). Definition of the subcellular sites of expression predicted their physiological functions and potential clinical disorders. Analysis of several human disease states has confirmed that aquaporins are involved in multiple different illnesses including abnormalities of kidney function, loss of vision, onset of brain edema, starvation, and arsenic toxicity.

  10. Melanopsin-expressing retinal ganglion cells: implications for human diseases

    DEFF Research Database (Denmark)

    La Morgia, Chiara; Ross-Cisneros, Fred N; Hannibal, Jens

    2011-01-01

    interest on these cells, mainly focused on animal models. Only recently, a few studies have started to address the relevance of the mRGC system in humans and related diseases. We recently discovered that mRGCs resist neurodegeneration in two inherited mitochondrial disorders that cause blindness, i.......e. Leber hereditary optic neuropathy and dominant optic atrophy. The mechanism leading to mRGCs sparing in these blinding disorders, characterized by extensive and selective loss of RGCs, is currently unknown and under investigation. Other studies reported on mRGCs in glaucoma, on genetic variation...

  11. Metalloprotein Inhibitors for the Treatment of Human Diseases.

    Science.gov (United States)

    Yang, Yang; Hu, Xue-Qin; Li, Qing-Shan; Zhang, Xing-Xing; Ruan, Ban-Feng; Xu, Jun; Liao, Chenzhong

    2016-01-01

    Metalloproteins have attracted momentous attentions for the treatment of many human diseases, including cancer, HIV, hypertension, etc. This article reviews the progresses that have been made in the field of drug development of metalloprotein inhibitors, putting emphasis on the targets of carbonic anhydrase, histone deacetylase, angiotensin converting enzyme, and HIV-1 integrase. Many other important metalloproteins are also briefly discussed. The binding and coordination modes of different marketed metalloprotein inhibitors are stated, providing insights to design novel metal binding groups and further novel inhibitors for metalloproteins.

  12. Glycogen Storage Disease Type Ia in Canines: A Model for Human Metabolic and Genetic Liver Disease

    Directory of Open Access Journals (Sweden)

    Andrew Specht

    2011-01-01

    Full Text Available A canine model of Glycogen storage disease type Ia (GSDIa is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including “lactic acidosis”, larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases.

  13. Regulatory Role of Small Nucleolar RNAs in Human Diseases

    Directory of Open Access Journals (Sweden)

    Grigory A. Stepanov

    2015-01-01

    Full Text Available Small nucleolar RNAs (snoRNAs are appreciable players in gene expression regulation in human cells. The canonical function of box C/D and box H/ACA snoRNAs is posttranscriptional modification of ribosomal RNAs (rRNAs, namely, 2′-O-methylation and pseudouridylation, respectively. A series of independent studies demonstrated that snoRNAs, as well as other noncoding RNAs, serve as the source of various short regulatory RNAs. Some snoRNAs and their fragments can also participate in the regulation of alternative splicing and posttranscriptional modification of mRNA. Alterations in snoRNA expression in human cells can affect numerous vital cellular processes. SnoRNA level in human cells, blood serum, and plasma presents a promising target for diagnostics and treatment of human pathologies. Here we discuss the relation between snoRNAs and oncological, neurodegenerative, and viral diseases and also describe changes in snoRNA level in response to artificial stress and some drugs.

  14. Control of human parasitic diseases: Context and overview.

    Science.gov (United States)

    Molyneux, David H

    2006-01-01

    The control of parasitic diseases of humans has been undertaken since the aetiology and natural history of the infections was recognized and the deleterious effects on human health and well-being appreciated by policy makers, medical practitioners and public health specialists. However, while some parasitic infections such as malaria have proved difficult to control, as defined by a sustained reduction in incidence, others, particularly helminth infections can be effectively controlled. The different approaches to control from diagnosis, to treatment and cure of the clinically sick patient, to control the transmission within the community by preventative chemotherapy and vector control are outlined. The concepts of eradication, elimination and control are defined and examples of success summarized. Overviews of the health policy and financing environment in which programmes to control or eliminate parasitic diseases are positioned and the development of public-private partnerships as vehicles for product development or access to drugs for parasite disease control are discussed. Failure to sustain control of parasites may be due to development of drug resistance or the failure to implement proven strategies as a result of decreased resources within the health system, decentralization of health management through health-sector reform and the lack of financial and human resources in settings where per capita government expenditure on health may be less than $US 5 per year. However, success has been achieved in several large-scale programmes through sustained national government investment and/or committed donor support. It is also widely accepted that the level of investment in drug development for the parasitic diseases of poor populations is an unattractive option for pharmaceutical companies. The development of partnerships to specifically address this need provides some hope that the intractable problems of the treatment regimens for the trypanosomiases and

  15. CORRELATION BETWEEN FIBRINOGEN LEVEL AND CEREBRAL INFARCTION

    Institute of Scientific and Technical Information of China (English)

    Yi-cheng Zhu; Li-ying Cui; Bao-lai Hua; Jia-qi Pan

    2006-01-01

    Objective To investigate the correlation between plasma fibrinogen level and cerebral infarction (CI) as well as the difference of fibrinogen among subtypes of CI.Methods A case-controlled study was conducted with 131 cases of CI and 148 controls. Plasma fibrinogen levels were detected by the Clauss method.Results High fibrinogen level (3.09±0.94 g/L) was correlated with CI (OR=2.47, 95% CI:1.51-4.04,P<0.005) at the onset stage of the disease. Persistent high fibrinogen level (3.14±0.81 g/L) at 6-month after stroke onset was detected and correlated with CI (OR=4.34, 95% CI: 1.80-10. 51,P=0.001). Higher fibrinogen level was correlated with total anterior circulation infarction (TACI), partial anterior circulation infarction (PACI), and posterior circulation infarction (POCI) (OR = 4.008, P<0.001). Higher fibrinogen level was correlated with extracranial atherosclerosis (OR=3.220, P<0.05), but not with intracranial atherosclerosis.Conclusion Fibrinogen level may be a risk factor of CI and probably correlates with subtypes of CI and distributions of atherosclerosis.

  16. The role of nanotechnology in control of human diseases: perspectives in ocular surface diseases.

    Science.gov (United States)

    Rai, Mahendra; Ingle, Avinash P; Gaikwad, Swapnil; Padovani, Felipe Hering; Alves, Monica

    2016-10-01

    Nanotechnology is the creation and use of materials and devices on the same scale as molecules and intracellular structures, typically less than 100 nm in size. It is an emerging science and has made its way into pharmaceuticals to significantly improve the delivery and efficacy of drugs in a number of therapeutic areas, due to development of various nanoparticle-based products. In recent years, there has been increasing evidence that nanotechnology can help to overcome many of the ocular diseases and hence researchers are keenly interested in this science. Nanomedicines offer promise as viable alternatives to conventional drops, gels or ointments to improve drug delivery to the eye. Because of their small size, they are well tolerated, thus preventing washout, increase bioavailability and also help in specific drug delivery. This review describes the application of nanotechnology in the control of human diseases with special emphasis on various eye and ocular surfaces diseases.

  17. Human keratin diseases: the increasing spectrum of disease and subtlety of the phenotype-genotype correlation.

    Science.gov (United States)

    Irvine, A D; McLean, W H

    1999-05-01

    Keratins are obligate heterodimer proteins that form the intermediate filament cytoskeleton of all epithelial cells. Keratins are tissue and differentiation specific and are expressed in pairs of types I and II proteins. The spectrum of inherited human keratin diseases has steadily increased since the causative role of mutations in the basal keratinocyte keratins 5 and 14 in epidermolysis bullosa simplex (EBS) was first reported in 1991. At the time of writing, mutations in 15 epithelial keratins and two trichocyte keratins have been associated with human diseases which include EBS, bullous congenital ichthyosiform erythroderma, epidermolytic palmoplantar keratoderma, ichthyosis bullosa of Siemens, diffuse and focal non-epidermolytic palmoplantar keratoderma, pachyonychia congenita and monilethrix. Mutations in extracutaneous keratins have been reported in oral white sponge naevus and Meesmann's corneal dystrophy. New subtleties of phenotype-genotype correlation are emerging within the keratin diseases with widely varying clinical presentations attributable to similar mutations within the same keratin. Mutations in keratin-associated proteins have recently been reported for the first time. This article reviews clinical, ultrastructural and molecular aspects of all the keratin diseases described to date and delineates potential future areas of research in this field.

  18. DiseaseMeth version 2.0: a major expansion and update of the human disease methylation database

    Science.gov (United States)

    Xiong, Yichun; Wei, Yanjun; Gu, Yue; Zhang, Shumei; Lyu, Jie; Zhang, Bin; Chen, Chuangeng; Zhu, Jiang; Wang, Yihan; Liu, Hongbo; Zhang, Yan

    2017-01-01

    The human disease methylation database (DiseaseMeth, http://bioinfo.hrbmu.edu.cn/diseasemeth/) is an interactive database that aims to present the most complete collection and annotation of aberrant DNA methylation in human diseases, especially various cancers. Recently, the high-throughput microarray and sequencing technologies have promoted the production of methylome data that contain comprehensive knowledge of human diseases. In this DiseaseMeth update, we have increased the number of samples from 3610 to 32 701, the number of diseases from 72 to 88 and the disease–gene associations from 216 201 to 679 602. DiseaseMeth version 2.0 provides an expanded comprehensive list of disease–gene associations based on manual curation from experimental studies and computational identification from high-throughput methylome data. Besides the data expansion, we also updated the search engine and visualization tools. In particular, we enhanced the differential analysis tools, which now enable online automated identification of DNA methylation abnormalities in human disease in a case-control or disease–disease manner. To facilitate further mining of the disease methylome, three new web tools were developed for cluster analysis, functional annotation and survival analysis. DiseaseMeth version 2.0 should be a useful resource platform for further understanding the molecular mechanisms of human diseases. PMID:27899673

  19. Economic burden of human papillomavirus-related diseases in Italy.

    Directory of Open Access Journals (Sweden)

    Gianluca Baio

    Full Text Available INTRODUCTION: Human papilloma virus (HPV genotypes 6, 11, 16, and 18 impose a substantial burden of direct costs on the Italian National Health Service that has never been quantified fully. The main objective of the present study was to address this gap: (1 by estimating the total direct medical costs associated with nine major HPV-related diseases, namely invasive cervical cancer, cervical dysplasia, cancer of the vulva, vagina, anus, penis, and head and neck, anogenital warts, and recurrent respiratory papillomatosis, and (2 by providing an aggregate measure of the total economic burden attributable to HPV 6, 11, 16, and 18 infection. METHODS: For each of the nine conditions, we used available Italian secondary data to estimate the lifetime cost per case, the number of incident cases of each disease, the total economic burden, and the relative prevalence of HPV types 6, 11, 16, and 18, in order to estimate the aggregate fraction of the total economic burden attributable to HPV infection. RESULTS: The total direct costs (expressed in 2011 Euro associated with the annual incident cases of the nine HPV-related conditions included in the analysis were estimated to be €528.6 million, with a plausible range of €480.1-686.2 million. The fraction attributable to HPV 6, 11, 16, and 18 was €291.0 (range €274.5-315.7 million, accounting for approximately 55% of the total annual burden of HPV-related disease in Italy. CONCLUSIONS: The results provided a plausible estimate of the significant economic burden imposed by the most prevalent HPV-related diseases on the Italian welfare system. The fraction of the total direct lifetime costs attributable to HPV 6, 11, 16, and 18 infections, and the economic burden of noncervical HPV-related diseases carried by men, were found to be cost drivers relevant to the making of informed decisions about future investments in programmes of HPV prevention.

  20. [Environmental pollution with lead and myocardial infarction morbidity].

    Science.gov (United States)

    Dulskiene, Virginija

    2003-01-01

    The aim of the study was to assess the effect of exposure to ambient lead and other environmental factors on first myocardial infarction incidence. Epidemiological case-control study comprised 579 male cases (25-64 year old) of myocardial infarction, treated in Kaunas hospitals and 1777 controls of the same age group without ischemic heart disease. Myocardial infarction incidence in the area of low exposure to lead was 2.34 per 1000, while in the high exposure area it was 2.61 per 1000. We determined the distribution of potential myocardial infarction risk factors among cases and controls and calculated corresponding crude odds ratios. Variables considered for inclusion in multivariate logistic regression model were those with higher prevalence among cases and values of odds ratios greater than 1.5. The analysis revealed that smoking, arterial hypertension and stress significantly increased the risk of first myocardial infarction among 25-64 year old men. Occupational exposure to chemical substances increased myocardial infarction risk by 26%, while residential exposure to ambient lead concentrations, exceeding 0.225 microg/m (3), tended to increase myocardial infarction risk by 12% (95% PI 0.94-1.34).

  1. Topoisomerase I in Human Disease Pathogenesis and Treatments

    Directory of Open Access Journals (Sweden)

    Min Li

    2016-06-01

    Full Text Available Mammalian topoisomerase 1 (TOP1 is an essential enzyme for normal development. TOP1 relaxes supercoiled DNA to remove helical constraints that can otherwise hinder DNA replication and transcription and thus block cell growth. Unfortunately, this exact activity can covalently trap TOP1 on the DNA that could lead to cell death or mutagenesis, a precursor for tumorigenesis. It is therefore important for cells to find a proper balance between the utilization of the TOP1 catalytic activity to maintain DNA topology and the risk of accumulating the toxic DNA damages due to TOP1 trapping that prevents normal cell growth. In an apparent contradiction to the negative attribute of the TOP1 activity to genome stability, the detrimental effect of the TOP1-induced DNA lesions on cell survival has made this enzyme a prime target for cancer therapies to kill fast-growing cancer cells. In addition, cumulative evidence supports a direct role of TOP1 in promoting transcriptional progression independent of its topoisomerase activity. The involvement of TOP1 in transcriptional regulation has recently become a focus in developing potential new treatments for a subtype of autism spectrum disorders. Clearly, the impact of TOP1 on human health is multifold. In this review, we will summarize our current understandings on how TOP1 contributes to human diseases and how its activity is targeted for disease treatments.

  2. Topoisomerase I in Human Disease Pathogenesis and Treatments

    Institute of Scientific and Technical Information of China (English)

    Min Li; Yilun Liu

    2016-01-01

    Mammalian topoisomerase 1 (TOP1) is an essential enzyme for normal development. TOP1 relaxes supercoiled DNA to remove helical constraints that can otherwise hinder DNA repli-cation and transcription and thus block cell growth. Unfortunately, this exact activity can covalently trap TOP1 on the DNA that could lead to cell death or mutagenesis, a precursor for tumorigenesis. It is therefore important for cells to find a proper balance between the utilization of the TOP1 cat-alytic activity to maintain DNA topology and the risk of accumulating the toxic DNA damages due to TOP1 trapping that prevents normal cell growth. In an apparent contradiction to the negative attribute of the TOP1 activity to genome stability, the detrimental effect of the TOP1-induced DNA lesions on cell survival has made this enzyme a prime target for cancer therapies to kill fast-growing cancer cells. In addition, cumulative evidence supports a direct role of TOP1 in pro-moting transcriptional progression independent of its topoisomerase activity. The involvement of TOP1 in transcriptional regulation has recently become a focus in developing potential new treat-ments for a subtype of autism spectrum disorders. Clearly, the impact of TOP1 on human health is multifold. In this review, we will summarize our current understandings on how TOP1 contributes to human diseases and how its activity is targeted for disease treatments.

  3. Human Brucellosis: Still an Unfamiliar and Misdiagnosed Disease in India

    Directory of Open Access Journals (Sweden)

    Smita Mangalgi

    2015-01-01

    Full Text Available Background: Human brucellosis is a disease with protean clinical manifestations. Despite many awareness programmes, it is still missed or wrongly diagnosed. This leads to chronic morbidity leading to misery and loss of working days. Aim and Objectives: To assess the microbiological, clinical and epidemiological aspects of human brucellosis. Materials and Methods: Patients with positive brucella screening test constituted the study material. A detailed laboratory, clinical, epidemiological study along with response to the treatment was analyzed. Results: Seroprevalence of brucellosis was found to be 1.75%. Brucellosis was clinically diagnosed in only 12.73% of cases. Fever, joint pain and low backache were the commonest symptoms. Close contact with animals and raw milk ingestion were the major sources of infection. Knowledge regarding brucellosis and its prevention was lacking in patients. Brucellosis was not considered as one of the differential diagnosis by the treating physicians. Conclusion: Brucellosis should be considered as one of the differential diagnosis in cases presenting with fever, low backache, arthritis and arthralgia. Laboratories should screen all the serum samples for brucella agglutinins by Rose Bengal Plate Test. Awareness regarding the prevention of brucellosis in the general population and regarding the existence of the disease among the doctors practicing in rural areas is needed

  4. Hsp10: anatomic distribution, functions, and involvement in human disease.

    Science.gov (United States)

    David, Sabrina; Bucchieri, Fabio; Corrao, Simona; Czarnecka, Anna M; Campanella, Claudia; Farina, Felicia; Peri, Giovanni; Tomasello, Giovanni; Sciumè, Carmelo; Modica, Giuseppe; La Rocca, Giampiero; Anzalone, Rita; Giuffrè, Mario; Conway De Macario, Everly; Macario, Alberto J L; Cappello, Francesco; Zummo, Giovanni

    2013-01-01

    There is growing evidence that molecular chaperones/heat shock proteins are involved in the pathogenesis of a number of human diseases, known as chaperonopathies. A better molecular understanding of the pathogenetic mechanisms is essential for addressing new strategies in diagnostics, therapeutics and clinical management of chaperonopathies, including those in which Hsp10 is involved. This chaperonin has been studied for a long time as a member of the mitochondrial protein-folding machine. However, although in normal cells Hsp10 is mainly localized in the mitochondrial matrix, it has also been found during and after stress in other subcellular compartments, such as cytosol, vesicles and secretory granules, alone or in combination with other proteins. In these extramitochondrial locales, Hsp10 plays an active role in cell signalling. For example, cancer cells often show altered levels of Hsp10, compared to normal cells. Hsp10 may also be found in the extracellular space and in the bloodstream, with a possible immunomodulatory activity. This minireview focuses on some studies to date on the involvement of Hsp10 in human disease pathogenesis.

  5. Human endogenous retrovirus-K contributes to motor neuron disease.

    Science.gov (United States)

    Li, Wenxue; Lee, Myoung-Hwa; Henderson, Lisa; Tyagi, Richa; Bachani, Muzna; Steiner, Joseph; Campanac, Emilie; Hoffman, Dax A; von Geldern, Gloria; Johnson, Kory; Maric, Dragan; Morris, H Douglas; Lentz, Margaret; Pak, Katherine; Mammen, Andrew; Ostrow, Lyle; Rothstein, Jeffrey; Nath, Avindra

    2015-09-30

    The role of human endogenous retroviruses (HERVs) in disease pathogenesis is unclear. We show that HERV-K is activated in a subpopulation of patients with sporadic amyotrophic lateral sclerosis (ALS) and that its envelope (env) protein may contribute to neurodegeneration. The virus was expressed in cortical and spinal neurons of ALS patients, but not in neurons from control healthy individuals. Expression of HERV-K or its env protein in human neurons caused retraction and beading of neurites. Transgenic animals expressing the env gene developed progressive motor dysfunction accompanied by selective loss of volume of the motor cortex, decreased synaptic activity in pyramidal neurons, dendritic spine abnormalities, nucleolar dysfunction, and DNA damage. Injury to anterior horn cells in the spinal cord was manifested by muscle atrophy and pathological changes consistent with nerve fiber denervation and reinnervation. Expression of HERV-K was regulated by TAR (trans-activation responsive) DNA binding protein 43, which binds to the long terminal repeat region of the virus. Thus, HERV-K expression within neurons of patients with ALS may contribute to neurodegeneration and disease pathogenesis. Copyright © 2015, American Association for the Advancement of Science.

  6. Small teleost fish provide new insights into human skeletal diseases.

    Science.gov (United States)

    Witten, P E; Harris, M P; Huysseune, A; Winkler, C

    2017-01-01

    Small teleost fish such as zebrafish and medaka are increasingly studied as models for human skeletal diseases. Efficient new genome editing tools combined with advances in the analysis of skeletal phenotypes provide new insights into fundamental processes of skeletal development. The skeleton among vertebrates is a highly conserved organ system, but teleost fish and mammals have evolved unique traits or have lost particular skeletal elements in each lineage. Several unique features of the skeleton relate to the extremely small size of early fish embryos and the small size of adult fish used as models. A detailed analysis of the plethora of interesting skeletal phenotypes in zebrafish and medaka pushes available skeletal imaging techniques to their respective limits and promotes the development of new imaging techniques. Impressive numbers of zebrafish and medaka mutants with interesting skeletal phenotypes have been characterized, complemented by transgenic zebrafish and medaka lines. The advent of efficient genome editing tools, such as TALEN and CRISPR/Cas9, allows to introduce targeted deficiencies in genes of model teleosts to generate skeletal phenotypes that resemble human skeletal diseases. This review will also discuss other attractive aspects of the teleost skeleton. This includes the capacity for lifelong tooth replacement and for the regeneration of dermal skeletal elements, such as scales and fin rays, which further increases the value of zebrafish and medaka models for skeletal research. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Electrocardiogram changes in acute cerebral infarction patients

    Institute of Scientific and Technical Information of China (English)

    Jing Fang; Weihong Yan

    2006-01-01

    BACKGROUND: Comparison of different stroke locations had been focused in past researches in electrocardiogram (ECG) changes of cerebral stroke patients. Some researches neglected the heart disease in the illness history.OBJECTIVE: To discuss ECG changes in different infarction locations and size of acute cerebral infarction and compare with healthy people.DESIGN: Contrast observation.SETrING: Shanghai Ninth People's Hospital.PARTICIPANTS: A total of 57 patients with cerebral infarction were selected from the Neurological Department of Ninth People's Hospital of Shanghai from March 2003 to September 2005. They were diagnosed according to the criteria revised in the 4th National Cerebral Disease Conference and b