Characterization of the positive and negative inotropic effects of acetylcholine in the human myocardium

NARCIS (Netherlands)

X.Y. Du (Xiaoyi); R.G. Schoemaker (Regien); E. Bos (Egbert); P.R. Saxena (Pramod Ranjan)

1995-01-01

textabstractIn the human isolated myocardium, acetylcholine (10−9 to 10−3 M) elicited a biphasic inotropic effect (a decrease in the lower and an increase in the higher concentration range) in atrial and a positive inotropic effect in ventricular trabeculae. However, under conditions of raised

Pathological mechanism for delayed hyperenhancement of chronic scarred myocardium in contrast agent enhanced magnetic resonance imaging.

Directory of Open Access Journals (Sweden)

Jian Wang

Full Text Available OBJECTIVES: To evaluate possible mechanism for delayed hyperenhancement of scarred myocardium by investigating the relationship of contrast agent (CA first pass and delayed enhancement patterns with histopathological changes. MATERIALS AND METHODS: Eighteen pigs underwent 4 weeks ligation of 1 or 2 diagonal coronary arteries to induce chronic infarction. The hearts were then removed and perfused in a Langendorff apparatus. The hearts firstly experienced phosphorus 31 MR spectroscopy. The hearts in group I (n = 9 and II (n = 9 then received the bolus injection of Gadolinium diethylenetriamine pentaacetic acid (0.05 mmol/kg and gadolinium-based macromolecular agent (P792, 15 µmol/kg, respectively. First pass T2* MRI was acquired using a gradient echo sequence. Delayed enhanced T1 MRI was acquired with an inversion recovery sequence. Masson's trichrome and anti- von Willebrand Factor (vWF staining were performed for infarct characterization. RESULTS: Wash-in of both kinds of CA caused the sharp and dramatic T2* signal decrease of scarred myocardium similar to that of normal myocardium. Myocardial blood flow and microvessel density were significantly recovered in 4-week-old scar tissue. Steady state distribution volume (ΔR1 relaxation rate of Gd-DTPA was markedly higher in scarred myocardium than in normal myocardium, whereas ΔR1 relaxation rate of P792 did not differ significantly between scarred and normal myocardium. The ratio of extracellular volume to the total water volume was significantly greater in scarred myocardium than in normal myocardium. Scarred myocardium contained massive residual capillaries and dilated vessels. Histological stains indicated the extensively discrete matrix deposition and lack of cellular structure in scarred myocardium. CONCLUSIONS: Collateral circulation formation and residual vessel effectively delivered CA into scarred myocardium. However, residual vessel without abnormal hyperpermeability allowed Gd

99mTc-glucarate kinetics differentiate normal, stunned, hibernating, and nonviable myocardium in a perfused rat heart model

International Nuclear Information System (INIS)

Okada, David R.; Liu, Zhonglin; Johnson, Gerald; Okada, Robert D.; Beju, Delia; Khaw, Ban An

2010-01-01

99m Tc-glucarate is an infarct-avid imaging agent. However, patients may have mixtures of normal, irreversibly injured, stunned, and hibernating myocardium. The purposes were to determine 99m Tc-glucarate uptake and clearance kinetics in these four conditions, and its ability to determine the extent of injury. Twenty-two perfused rat hearts were studied: controls (n = 5), stunned (n = 5; 20-min no-flow followed by 5-min reflow), hibernating (n = 6; 120-min low flow at 4 ml/min), and ischemic-reperfused (n = 6; 120-min no-flow followed by reflow). 99m Tc-glucarate was then infused. Tracer activity was monitored using a NaI scintillation detector and a multichannel analyzer. Creatine kinase, electron microscopy, and triphenyltetrazolium chloride determined viability. 99m Tc-glucarate 10-min myocardial uptake was significantly greater in ischemic-reperfused (2.50 ± 0.09) (cpm, SEM) than in control (1.74 ± 0.07), stunned (1.68 ± 0.11), and hibernating (1.59 ± 0.11) (p 99m Tc-glucarate 60-min myocardial uptake was significantly greater in ischemic-reperfused (7.60 ± 0.63) than in control (1.98 ± 0.15), stunned (1.79 ± 0.08), and hibernating (2.33 ± 0.15) (p 99m Tc-glucarate activity continually and progressively increased in irreversibly injured myocardium. 99m Tc-glucarate uptake was strongly correlated with myocardial necrosis as determined by three independent assessments of viability. There were minimal and similar 99m Tc-glucarate uptakes in control, stunned, and hibernating myocardium. (orig.)

Preliminary applied study of assessment ischemic/viable myocardium by 99Tcm-HL91

International Nuclear Information System (INIS)

Liu Gang; Wu Hua

2004-01-01

Objective: To investigate the representation of 99 Tc m -HL91 in the ischemic myocardium, evaluate the diagnosis value of 99 Tc m -HL91 on hypoxic but viable myocardium. Methods: Six patients with cardiac infarction all underwent 99 Tc m -MIBI SPECT and 99 Tc m -HL91 SPECT. Average radioactivity of ischemic area and normal area were respectively obtained by ROI (2 x 2 pixels) on heart minor axis of images, And the radioactivity ratios of target (ischemic area)-to-non target(normal area)were calculated. Results: In image of 99 Tc m -HL91 SPECT, two patients who's radioactivity coloboma of 99 Tc m -MIBI image could be filled with 99 Tc m -HL91, four patients were not caught sight of obvious filling up. Conclusion 99 Tc m -HL91 can be selectively uptaken by ischemic and hypoxic but viable myocardium. it combination of 99 Tc m -MIBI SPECT may be good for accurate diagnosis and differentiation of viable myocardium. (authors)

Dynamic MRI of ferumoxide-labeled bone mesenchmal stem cells after transplantation in infarcted myocardium

International Nuclear Information System (INIS)

Liu Qiong; Zhao Shihua; Lu Minjie; Jiang Shiliang; Yan Chaowu; Zhang Yan; Meng Liang; Tang Yue; Meng Xianmin; Wei Yingjie; Wang Qingzhi

2009-01-01

Objective: To investigate the ability of magnetic resonance imaging (MRI) in tracking magnetically labeled mesenchymal stem cells (MR-MSCs) in a swine myocardial infarction (MI) model. Methods: Adult Chinese mini-pigs (n=6) were subjected to open-chest experimental MI operation. Their autogeneic bone marrow-derived mesenchymal stem cells (MSCs) was cultured and doubly labeled with ferumoxides and DAPI. On the 14 th day after MSCs transplantation, the size and location of the myocardial infarction were assessed by using delayed-enhancement MRI (DE-MRI). Then the labeled MSCs were injected intramyocardially into peri-infarct zone and normal myocardium. At 24 hrs and 3 weeks after injection, the contrast and the volume of the MR-MSCs hypointense lesion from the MR images were acquired, and the contrast was determined using the difference in signal intensity between the hypointense and normal myocardium divided by signal intensity of the normal region. After humane euthanasia, the heart was excised and histology corresponding to MRI slices that demonstrated MR-MSCs lesions was performed. Repeated-measures ANOVA and a paired t test were used for comparison of the contrast and the volume of the MR-MSCs hypointense lesion at different time points. Comparisons between independent groups were performed with the standard Student t test. Results: The labeling efficiency of ferumoxides and DAPI was 100%. On the 14 th day after the MI operation, the average percentage of infracted myocardial area was (33.6±8.9)%. Twenty- four hours after MSCs transplantation, MSCs injection sites appeared as ovoid hypointensive lesions with sharp border on T 2 * images. At 24 h after injection, the signal contrast [(67.00±5.48)% vs (61.92±7.76)%,t=1.65, P=0.1158] and the size [(0.56±0.24) cm 2 vs (0.52±0.25) cm 2 , t=0.39, P=0.7044] of the lesions showed no statistical difference between the peri-infarct zone and the normal myocardium. At 3 weeks after injection, the signal contrast

Remote Ischaemic PrEconditioning of Human Myocardium (RIPE): study protocol for a double-blinded randomised controlled trial.

Science.gov (United States)

Deja, Marek A; Wiaderkiewicz, Ryszard; Czekaj, Piotr; Czech, Ewa; Malinowski, Marcin; Machej, Leszek; Węglarzy, Andrzej; Kowalówka, Adam; Piekarska, Magda; Szurlej, Bartosz; Latusek, Tomasz

2018-01-01

Remote preconditioning has been shown to be a potent protective phenomenon in many animals. Several studies aimed to demonstrate it was feasible in humans by trying to show its protective effect during cardiac surgery. Of these, some small studies and one larger trial were positive while two other bigger studies showed no effectiveness of remote preconditioning as assessed by levels of postoperatively released cardiac markers. Recently, two large clinical trials also failed to prove the benefit of remote preconditioning in cardiac surgery. No study showed that remote preconditioning actually increases resistance of human myocardium to standardised ischaemic and reperfusion stimulus in experimental settings. In animal studies, remote preconditioning was shown to improve mitochondrial function and structure, but such data on human myocardium are scarce. The aim of the study is to determine whether remote preconditioning protects human myocardium against ischaemia-reperfusion injury in both in vivo and in vitro conditions. The trial is designed as a single-centre, double-blinded, sham-controlled trial of 120 patients. We randomise (1:1) patients referred for coronary artery bypass grafting for stable coronary artery disease to remote preconditioning or "sham" intervention. The remote preconditioning is obtained by three cycles of 5 min inflation and 5 min deflation of a blood pressure cuff on the right arm. Postoperative course including myocardial enzymes profile will be analysed. Moreover, in the in-vitro arm the clinically preconditioned myocardium will be assessed for function, mitochondria structure, and mitochondria-dependent apoptosis. The informed consent of all patients is obtained before enrolment into the study by the investigator. The study conforms to the spirit and the letter of the declaration of Helsinki. In case the effect of remote preconditioning is not measurable in ex-vivo assessment, any future attempt at implementing this phenomenon in clinical

Pyrophosphate scan of the temporarily ischemized dog myocardium

Energy Technology Data Exchange (ETDEWEB)

Duska, F.; Novak, J.; Vizda, J.; Kubicek, J.; Kafka, P.; Veverkova, O.

1981-12-01

In 9 dogs a transient myocardial ischemia was provoked using complete occlusion of the ramus interventricularis anterior of the left coronary artery. The occlusion was removed after 5, 10 or 15 min. Four hrs after removal of the occlusion a scan of the myocardium was carried out using sup(99m)Tc-labelled pyrophosphate. In 7 out of 9 dogs under study the scan was markedly positive, in 2 dogs negative. ECG demonstrated ischemic changes practically in all dogs; the changes became normal after removal of the occlusion, namely in 5 to 35 min. The histological examination of the tissue demonstrated in all 9 dogs only a slight impairment of the myocardium.

Kinetics of thallium-201 in reperfused canine myocardium after coronary artery occlusion

International Nuclear Information System (INIS)

Okada, R.D.

1984-01-01

To study the kinetics of thallium-201 in nonsalvaged acutely infarcted myocardium and salvaged myocardium, the tracer was administered after experimental left anterior descending coronary artery reperfusion 2 hours after occlusion. In 19 dogs, thallium activity was then monitored for 4 hours in the reperfused anterior wall and normal posterior wall using miniature cadmium telluride radiation detectors. After sacrifice, 13 of the dogs were found to have an infarcted anterior wall by triphenyltetrazolium-chloride staining. In these dogs, mean (+/- standard deviation) fractional 4 hour thallium clearance was 0.33 +/- 0.08 for the infarct zone and 0.15 +/- 0.06 for the normal control zone (p less than 0.001). When computer-modeled, the clearance curve from the infarct zone was biexponential. The second exponential clearance curve from the infarct zone began 19.1 +/- 3.2 minutes after tracer administration, and was indistinguishable from the monoexponential clearance curve from the normal control zone. Thallium clearance from the blood pool was triexponential, the final exponential clearance curve being indistinguishable from the normal control zone clearance curve. Six dogs were found to have a salvaged noninfarcted anterior wall by triphenyltetrazolium-chloride staining. In these dogs, mean fractional 4 hour thallium clearance was 0.20 +/- 0.07 for the reperfused zone, and 0.19 +/- 0.08 for the normal control zone (p . NS). When computer-modeled, clearance curves for the reperfused and control zones were monoexponential. The monoexponential clearance curve for the salvaged reperfused zone was indistinguishable from the monoexponential clearance curve for normal myocardium

Characterization of the positive and negative inotropic effects of acetylcholine in the human myocardium

OpenAIRE

Du, Xiaoyi; Schoemaker, Regien; Bos, Egbert; Saxena, Pramod Ranjan

1995-01-01

textabstractIn the human isolated myocardium, acetylcholine (10−9 to 10−3 M) elicited a biphasic inotropic effect (a decrease in the lower and an increase in the higher concentration range) in atrial and a positive inotropic effect in ventricular trabeculae. However, under conditions of raised contractility achieved by exposure to noradrenaline (10−5 M), only negative inotropic effects were observed in both atria and ventricles. Atropine (10−6 M), but not propranolol (10−6 M), antagonized bot...

Analysis of the influence factors on myocardium to liver ratio of 99Tcm-MIBI

International Nuclear Information System (INIS)

Zhang Jinming; Tian Jiahe; Zhao Xiaoguang; Liu Zilai; Wang Shengcai

1995-01-01

The resting myocardial SPECT by different MIBI kits for 113 cases of normal and ischemic heart disease is performed. The preparation of kits, reducing agents, and the time of imaging are checked using myocardium to liver (M/L) ratio as the parameter of myocardium uptake of MIBI. It shows that MIBI uptake of myocardium has no relation with the reducing agents, the time of imaging between 60-120 min, while M/L ratio varied in every individual case. The ratio of M/L has also no relation to the Radiochemical Purity (RCP) as long as RCP is more than 95%

Proteomic analysis identifies mitochondrial metabolic enzymes as major discriminators between different stages of the failing human myocardium

DEFF Research Database (Denmark)

Urbonavicius, Sigitas; Wiggers, Henrik; Bøtker, Hans Erik

2009-01-01

Our aim was to identify patterns in differentially regulated proteins associated with the progression of chronic heart failure. We specifically studied proteomics in chronic reversibly (RDM) and irreversibly dysfunctional myocardium (IRDM), as well as end-stage failing myocardium (ESFM).......Our aim was to identify patterns in differentially regulated proteins associated with the progression of chronic heart failure. We specifically studied proteomics in chronic reversibly (RDM) and irreversibly dysfunctional myocardium (IRDM), as well as end-stage failing myocardium (ESFM)....

Myocardium scanning with 201TL-chloride in ischemic heart disease

International Nuclear Information System (INIS)

Shejretova, E.; Beloev, J.; Kaloyanova, A.; Trindev, P.

1979-01-01

Results of myocardial scanning with 210 TL-chloride in ischemic herart disease are repoorted. An avearge dose of 500 microcurie and antero-posterior or lateral projection scanning with coloured registration are recommended. The scintigraphic pattern of the normal myocardium and the pathological changes, manifested by reduced isotope fixation, depending on the severity of the damage, are described. The diffuse pathological changes in the myocardium in ischemic heart disease are manifested by diffuse hypofixation of the radionuclide. The focal lesions in ischemic heart disease were manifested by characteristic changes: the infarctions of the posterior wall show a relatively clear scanographic picture on antero-posterior projection, with cold or cool zones in the median sections of the myocardium picture. Infarctions of the anterior myocardial wall, depending on how sizable they are, on antero-posterior projection are seen to occupy the lateral and central parts of the heart muscle. In the left oblique projection the pathologic process is projected frontally and centrally. (A.B.)

[Effect of compound danshen dripping pill combined with intravenous transplantation of human umbilical cord blood mononuclear cells on local inflammatory response in the myocardium of rabbits with acute myocardial infarction].

Science.gov (United States)

Deng, Liu-xia; Yu, Guo-long; Al, Qi; Yuan, Chun-ju

2013-11-01

To investigate effect of Compound Danshen Dripping Pill (CDDP) on the inflammatory response of the myocardium of acute myocardial infarction (AMI) rabbits, to observe the therapeutic effect of CDDP combined intravenous transplantation of human umbilical cord blood mononuclear cells (HUCBMCs) on inflammatory response, pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) , and heart function in the myocardium of AMI rabbits, and to explore the possible protective mechanisms of the combined therapy. The AMI model was successfully established by ligation of the left anterior coronary artery (LAD) in 40 healthy rabbits.Then they were randomly divided into four groups, i.e., the control group, the CDDP group, the transplantation group, and the combined group, 10 in each group. Rabbits in the control group received intravenous injection of 0.5 mL normal saline via ear vein within 24 h after AMI and then intragastric infusion of normal saline at 5 mL per day. Rabbits in the CDDP group received intravenous injection of 0.5 mL normal saline via ear vein within 24 h after AMI and then intragastric infusion of solution obtained by solving 270 mg CDDP in 5 mL normal saline per day. Rabbits in the transplantation group received intravenous injection of 0.5 mL normal saline labeled with green fluorescent protein (GFP) containing 3 x 10(7) of HUCBMCs via ear vein within 24 h after AMI and then intragastric infusion of normal saline at 5 mL per day. Rabbits in the combined group received intravenous injection of 0.5 mL normal saline labeled with GFP containing 3 x 10(7) of HUCBMCs via ear vein within 24 h after AMI and then intragastric infusion of solution obtained by solving 270 mg CDDP in 5 mL normal saline per day. At week 1 and 4 after treatment, cardiac function indices such as left ventricular fractional shorting (LVFS) and left ventricular ejection fraction (LVEF) were performed by echocardiography; the number of transplanted cells in the myocardium was found

Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip

Science.gov (United States)

Zhang, Yu Shrike; Arneri, Andrea; Bersini, Simone; Shin, Su-Ryon; Zhu, Kai; Goli-Malekabadi, Zahra; Aleman, Julio; Colosi, Cristina; Busignani, Fabio; Dell'Erba, Valeria; Bishop, Colin; Shupe, Thomas; Demarchi, Danilo; Moretti, Matteo; Rasponi, Marco; Dokmeci, Mehmet Remzi; Atala, Anthony; Khademhosseini, Ali

2016-01-01

Engineering cardiac tissues and organ models remains a great challenge due to the hierarchical structure of the native myocardium. The need of integrating blood vessels brings additional complexity, limiting the available approaches that are suitable to produce integrated cardiovascular organoids. In this work we propose a novel hybrid strategy based on 3D bioprinting, to fabricate endothelialized myocardium. Enabled by the use of our composite bioink, endothelial cells directly bioprinted within microfibrous hydrogel scaffolds gradually migrated towards the peripheries of the microfibers to form a layer of confluent endothelium. Together with controlled anisotropy, this 3D endothelial bed was then seeded with cardiomyocytes to generate aligned myocardium capable of spontaneous and synchronous contraction. We further embedded the organoids into a specially designed microfluidic perfusion bioreactor to complete the endothelialized-myocardium-on-a-chip platform for cardiovascular toxicity evaluation. Finally, we demonstrated that such a technique could be translated to human cardiomyocytes derived from induced pluripotent stem cells to construct endothelialized human myocardium. We believe that our method for generation of endothelialized organoids fabricated through an innovative 3D bioprinting technology may find widespread applications in regenerative medicine, drug screening, and potentially disease modeling. PMID:27710832

{sup 99m}Tc-glucarate kinetics differentiate normal, stunned, hibernating, and nonviable myocardium in a perfused rat heart model

Energy Technology Data Exchange (ETDEWEB)

Okada, David R. [University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Liu, Zhonglin [University of Arizona School of Medicine, Tucson, AZ (United States); Johnson, Gerald; Okada, Robert D. [University of Oklahoma Health Sciences Center, Oklahoma, OK (United States); University of Tulsa, Tulsa, OK (United States); Beju, Delia [Oklahoma State University School of Medicine, Tulsa, OK (United States); Khaw, Ban An [Northeastern University, Boston, MA (United States)

2010-10-15

{sup 99m}Tc-glucarate is an infarct-avid imaging agent. However, patients may have mixtures of normal, irreversibly injured, stunned, and hibernating myocardium. The purposes were to determine {sup 99m}Tc-glucarate uptake and clearance kinetics in these four conditions, and its ability to determine the extent of injury. Twenty-two perfused rat hearts were studied: controls (n = 5), stunned (n = 5; 20-min no-flow followed by 5-min reflow), hibernating (n = 6; 120-min low flow at 4 ml/min), and ischemic-reperfused (n = 6; 120-min no-flow followed by reflow). {sup 99m}Tc-glucarate was then infused. Tracer activity was monitored using a NaI scintillation detector and a multichannel analyzer. Creatine kinase, electron microscopy, and triphenyltetrazolium chloride determined viability. {sup 99m}Tc-glucarate 10-min myocardial uptake was significantly greater in ischemic-reperfused (2.50 {+-} 0.09) (cpm, SEM) than in control (1.74 {+-} 0.07), stunned (1.68 {+-} 0.11), and hibernating (1.59 {+-} 0.11) (p < 0.05). Tracer retention curves for ischemic-reperfused were elevated at all time points as compared with the other groups. {sup 99m}Tc-glucarate 60-min myocardial uptake was significantly greater in ischemic-reperfused (7.60 {+-} 0.63) than in control (1.98 {+-} 0.15), stunned (1.79 {+-} 0.08), and hibernating (2.33 {+-} 0.15) (p < 0.05). The 60-min well-counted tracer activity ratio of ischemic-reperfused to control was 9:1 and corroborated the NaI detector results. Creatine kinase, triphenyltetrazolium chloride, and electron microscopy all demonstrated significantly greater injury in ischemic-reperfused compared to the other groups. An excellent correlation was observed between viability markers and tracer activity (r = 0.99 triphenyltetrazolium chloride; r = 0.90 creatine kinase). {sup 99m}Tc-glucarate activity continually and progressively increased in irreversibly injured myocardium. {sup 99m}Tc-glucarate uptake was strongly correlated with myocardial necrosis as

Free Radical Oxidation in Rat Myocardium after Maximum Permissible Hepatic Resection.

Science.gov (United States)

Ermolaev, P A; Khramykh, T P; Barskaya, L O

2016-03-01

Free radical oxidation in rat myocardial homogenate was studied by chemiluminescent assay during the early terms after maximum permissible liver resection. During this period, activation of free radical oxidation was biphasic. The critical terms characterized by dramatic intensification of free radical oxidation in the myocardium are the first hour and the first day after surgery. The period from 3 to 12 h after surgery, in which the indices of chemiluminescence decrease, can be tentatively termed as the period of "putative wellbeing". Normalization of the free radical oxidation processes in the myocardium occurred by day 7 after surgery.

Incidence of stunned, hibernating and scarred myocardium in ischaemic cardiomyopathy

International Nuclear Information System (INIS)

Hernandez-Pampaloni, Miguel; Morita, Koichi; Dutka, David P.; Camici, Paolo G.; Bax, Jeroen J.

2005-01-01

Different criteria to identify residual viability in chronically dysfunctioning myocardium in patients with coronary artery disease (CAD) can be derived by the combined assessment of myocardial blood flow (MBF) and glucose utilisation (MRG) using positron emission tomography (PET). The aim of this study was to evaluate, in a large number of patients, the prevalence of these different patterns by purely quantitative means. One hundred and sixteen consecutive patients with ischaemic cardiomyopathy (LVEF ≤40%) underwent resting 2D echocardiography to assess regional contractile function (16-segment model). PET with 15 O-labelled water (H 2 15 O) and 18 F-fluorodeoxyglucose (FDG) was used to quantify MBF and MRG during hyperinsulinaemic euglycaemic clamp. Dysfunctional segments with normal MBF (≥0.6 ml min -1 g -1 ) were classified as stunned, and segments with reduced MBF ( -1 g -1 ) as hibernating if MRG was ≥0.25 μmol min -1 g -1 . Segments with reduced MBF and MRG -1 g -1 were classified as transmural scars and segments with reduced MBF and MRG between 0.20 and 0.25 μmol min -1 g -1 as non-transmural scars. Eight hundred and thirty-four (46%) segments were dysfunctional. Of these, 601 (72%) were chronically stunned, with 368 (61%) having normal MRG (0.47±0.20 μmol min -1 g -1 ) and 233 (39%) reduced MRG (0.16±0.05 μmol min -1 g -1 ). Seventy-four (9%) segments with reduced MBF had preserved MRG (0.40±0.18 μmol min -1 g -1 ) and were classified as hibernating myocardium. In addition, 15% of segments were classified as transmural and 4% as non-transmural scar. The mean MBF was highest in stunned myocardium (0.95±0.32 ml min -1 g -1 ), intermediate in hibernating myocardium and non-transmural scars (0.47±0.09 ml min -1 g -1 and 0.48±0.08 ml min -1 g -1 , respectively), and lowest in transmural scars (0.40±0.14 ml min -1 g -1 , P -1 g -1 vs 0.46±0.20 μmol min -1 g -1 , NS), and lowest in stunned myocardium with reduced MRG and transmural scars

Increased cross-bridge recruitment contributes to transient increase in force generation beyond maximal capacity in human myocardium.

Science.gov (United States)

Milani-Nejad, Nima; Chung, Jae-Hoon; Canan, Benjamin D; Fedorov, Vadim V; Whitson, Bryan A; Kilic, Ahmet; Mohler, Peter J; Janssen, Paul M L

2018-01-01

Cross-bridge attachment allows force generation to occur, and rate of tension redevelopment (k tr ) is a commonly used index of cross-bridge cycling rate. Tension overshoots have been observed briefly after a slack-restretch k tr maneuver in various species of animal models and humans. In this study, we set out to determine the properties of these overshoots and their possible underlying mechanism. Utilizing human cardiac trabeculae, we have found that tension overshoots are temperature-dependent and that they do not occur at resting states. In addition, we have found that myosin cross-bridge cycle is vital to these overshoots as inhibition of the cycle results in the blunting of the overshoots and the magnitude of the overshoots are dependent on the level of myofilament activation. Lastly, we show that the number of cross-bridges transiently increase during tension overshoots. These findings lead us to conclude that tension overshoots are likely due to a transient enhancement of the recruitment of myosin heads into the cross-bridge cycling, regulated by the myocardium, and with potential physiological significance in determining cardiac output. We show that isolated human myocardium is capable of transiently increasing its maximal force generation capability by increasing cross-bridge recruitment following slack-restretch maneuver. This process can potentially have important implications and significance in cardiac contraction in vivo. Copyright © 2017 Elsevier Ltd. All rights reserved.

The alteration of interelemental ratios in myocardium under the congenital heart disease (SRXRF)

International Nuclear Information System (INIS)

Trunova, V.A.; Zvereva, V.V.; Okuneva, G.N.; Levicheva, E.N.

2007-01-01

It is the myocardium that bears the basic functional loading during heart working, including muscle contractility and enzyme activity. The elemental concentrations in myocardium tissue of heart were determined by SRXRF technique. Our investigation is systematical: the elemental content in each compartment (left and right ventricles, left and right auricles) of hearts of healthy and diseased children (congenital heart diseases, transposition of main vessels (TMV)) was analyzed. The elemental distribution in myocardium of four heart chambers of human fetuses was also analyzed. Following elements were determined: S, Cl, K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Br, Rb, Sr. It was revealed that the elemental concentrations in myocardium of both ventricles are almost constant in heart of fetuses and healthy children. The transition from pre-natal study (fetus) to post-natal study is accompanied by the redistribution of chemical elements in myocardium. The higher concentrations of S, Fe, Ca, Sr and Cu in myocardium of children are observed, the content of K, Br, Rb and especially Se is lower than in heart of fetuses. The elemental distribution in myocardium of children TMV is considerably different in comparison with the healthy children: the higher levels of Cu are observed. The content of Se is lower

Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip.

Science.gov (United States)

Zhang, Yu Shrike; Arneri, Andrea; Bersini, Simone; Shin, Su-Ryon; Zhu, Kai; Goli-Malekabadi, Zahra; Aleman, Julio; Colosi, Cristina; Busignani, Fabio; Dell'Erba, Valeria; Bishop, Colin; Shupe, Thomas; Demarchi, Danilo; Moretti, Matteo; Rasponi, Marco; Dokmeci, Mehmet Remzi; Atala, Anthony; Khademhosseini, Ali

2016-12-01

Engineering cardiac tissues and organ models remains a great challenge due to the hierarchical structure of the native myocardium. The need of integrating blood vessels brings additional complexity, limiting the available approaches that are suitable to produce integrated cardiovascular organoids. In this work we propose a novel hybrid strategy based on 3D bioprinting, to fabricate endothelialized myocardium. Enabled by the use of our composite bioink, endothelial cells directly bioprinted within microfibrous hydrogel scaffolds gradually migrated towards the peripheries of the microfibers to form a layer of confluent endothelium. Together with controlled anisotropy, this 3D endothelial bed was then seeded with cardiomyocytes to generate aligned myocardium capable of spontaneous and synchronous contraction. We further embedded the organoids into a specially designed microfluidic perfusion bioreactor to complete the endothelialized-myocardium-on-a-chip platform for cardiovascular toxicity evaluation. Finally, we demonstrated that such a technique could be translated to human cardiomyocytes derived from induced pluripotent stem cells to construct endothelialized human myocardium. We believe that our method for generation of endothelialized organoids fabricated through an innovative 3D bioprinting technology may find widespread applications in regenerative medicine, drug screening, and potentially disease modeling. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mismatched regional myocardial uptake between [sup 123]I-BMIPP and [sup 201]Tl SPECT; Comparison between hypertrophic myocardium and dilated myocardium

Energy Technology Data Exchange (ETDEWEB)

Otsuka, Makoto; Ichiya, Yuichi; Kuwabara, Yasuo; Sasaki, Masayuki; Fukumura, Toshimitsu; Masuda, Kouji; Ejima, Junichi; Tsuda, Yasuo (Kyushu Univ., Fukuoka (Japan). Faculty of Medicine)

1992-07-01

The distribution of a new myocardial fatty acid metabolic agent [sup 123]I-BMIPP was compared in 6 each patients with hypertrophic myocardium (4 cases of hypertensive heart disease and 2 of hypertrophic cardiomyopathy) and dilated myocardium (4 of dilated type of valvular heart disease and 2 of dilated cardiomyopathy) with that of [sup 201]Tl. Mismatched regional myocardial uptake between [sup 123]I-BMIPP and [sup 201]Tl SPECT was observed in all of the hypertrophic myocardium, however no but one in the dilated myocardium. Relative increase or decrease in regional BMIPP from the images of 20 min and to those of 4 h was observed in 3 cases of the hypertrophic myocardium. FDG-PET was performed in 2 cases of the hypertrophic myocardium. The distribution of FDG was different from neither those of BMIPP nor Tl in a hypertrophic cardiomyopathy case with the reserved distribution of BMIPP and Tl. Although more investigations are necessary, we concluded that [sup 123]I-BMIPP is a promising radiopharmaceutical for evaluating myocardial fatty acid metabolism in hypertrophic myocardium. (author).

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

Subacute ghrelin administration inhibits apoptosis and improves ultrastructural abnormalities in remote myocardium post-myocardial infarction.

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Eid, Refaat A; Zaki, Mohamed Samir Ahmed; Al-Shraim, Mubarak; Eleawa, Samy M; El-Kott, Attalla Farag; Al-Hashem, Fahaid H; Eldeen, Muhammad Alaa; Ibrahim, Hoja; Aldera, Hussain; Alkhateeb, Mahmoud A

2018-05-01

This study investigated the effect of ghrelin on cardiomyocytes function, apoptosis and ultra-structural alterations of remote myocardium of the left ventricle (LV) of rats, 21 days post myocardial infarction (MI). Rats were divided into 4 groups as a control, a sham-operated rats, a sham-operated+ghrelin, an MI + vehicle and an MI + ghrelin-treated rats. MI was induced by LAD ligation and then rats were recievd a concomitant doe of either normal saline as a vehicle or treated with ghrelin (100 μg/kg S.C., 2x/day) for 21 consecutive days. Ghrelin enhanced myocardial contractility in control rats and reversed the decreases in myocardial contractility and the increases in the serum levels of CK-MB and LDH in MI-induced rats. Additionally, it inhibited the increases in levels of Bax and cleaved caspase 3 and increased those for Bcl-2 in the remote myocardium of rat's LV, post-MI. At ultra-structural level, while ghrelin has no adverse effects on LV myocardium obtained from control or sham-treated rats, ghrelin post-administration to MI-induced rats reduced vascular formation, restored normal microfilaments appearance and organization, preserved mitochondria structure, and prevented mitochondrial swelling, collagen deposition and number of ghost bodies in the remote areas of their LV. Concomitantly, in remote myocardium of MI-induced rats, ghrelin enhanced endoplasmic reticulum intracellular organelles count, decreased number of atrophied nuclei and phagocytes, diminished the irregularity in the nuclear membranes and inhibited chromatin condensation. In conclusion, in addition to the physiological, biochemical and molecular evidence provided, this is the first study that confirms the anti-apoptotic effect of ghrelin in the remote myocardium of the LV during late MI at the level of ultra-structural changes. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Healing human myocardial infarction associated with increased chymase immunoreactivity

NARCIS (Netherlands)

Daemen, M. J.; Urata, H.

1997-01-01

We studied the immunoreactivity of the chymase protein in normal human myocardium and in human myocardial infarctions at various postinfarction times using immuno-histochemistry. In noninfarcted hearts chymase was mainly present in cardiomyocytes and endothelial cells. At 6 h after infarction the

Myocardial kinetics of thallium-201 after stress in normal and perfusion-reduced canine myocardium

International Nuclear Information System (INIS)

Okada, R.D.

1985-01-01

Despite the emerging use of quantitative computer programs for assessing myocardial thallium uptake and clearance after exercise, little is known about the kinetics of thallium after exercise stress. Accordingly, 11 mongrel dogs with experimental left anterior descending coronary stenoses were given thallium during norepinephrine infusion to simulate exercise. The infusion was discontinued and thallium activity was monitored regionally using miniature radiation detectors for 3 hours. Heart rate, arterial pressure and double product all increased significantly during norepinephrine infusion. The mean fractional myocardial thallium clearance was lower (0.47 +/- 0.03 [+/- standard error of the mean]) for the stenosis zone than for the no-stenosis zone (0.57 +/- 0.03) (p less than 0.0001). The stress blood flow ratio (stenosis/no-stenosis zone = 0.27 +/- 0.06) was significantly lower than the final thallium activity ratio (0.68 +/- 0.07) (p less than 0.001), consistent with thallium redistribution occurring over the 3-hour period. Myocardial thallium activity in the stenosis zone peaked in a mean of 2.2 minutes, then washed out biexponentially with a final decay constant of 0.0035 +/- 0.0005 min-1. Myocardial thallium activity in the no-stenosis zone peaked within 1 minute in all dogs, then washed out biexponentially, with a final decay constant of 0.0043 +/- 0.0003 (p less than 0.001 compared with stenosis zone). In conclusion, fractional clearance of thallium can differentiate myocardium distal to a coronary artery stenosis from that supplied by a normal coronary vessel

Myocardium tracking via matching distributions.

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Ben Ayed, Ismail; Li, Shuo; Ross, Ian; Islam, Ali

2009-01-01

The goal of this study is to investigate automatic myocardium tracking in cardiac Magnetic Resonance (MR) sequences using global distribution matching via level-set curve evolution. Rather than relying on the pixelwise information as in existing approaches, distribution matching compares intensity distributions, and consequently, is well-suited to the myocardium tracking problem. Starting from a manual segmentation of the first frame, two curves are evolved in order to recover the endocardium (inner myocardium boundary) and the epicardium (outer myocardium boundary) in all the frames. For each curve, the evolution equation is sought following the maximization of a functional containing two terms: (1) a distribution matching term measuring the similarity between the non-parametric intensity distributions sampled from inside and outside the curve to the model distributions of the corresponding regions estimated from the previous frame; (2) a gradient term for smoothing the curve and biasing it toward high gradient of intensity. The Bhattacharyya coefficient is used as a similarity measure between distributions. The functional maximization is obtained by the Euler-Lagrange ascent equation of curve evolution, and efficiently implemented via level-set. The performance of the proposed distribution matching was quantitatively evaluated by comparisons with independent manual segmentations approved by an experienced cardiologist. The method was applied to ten 2D mid-cavity MR sequences corresponding to ten different subjects. Although neither shape prior knowledge nor curve coupling were used, quantitative evaluation demonstrated that the results were consistent with manual segmentations. The proposed method compares well with existing methods. The algorithm also yields a satisfying reproducibility. Distribution matching leads to a myocardium tracking which is more flexible and applicable than existing methods because the algorithm uses only the current data, i.e., does not

Liposome kinetics in infarcted canine myocardium

International Nuclear Information System (INIS)

Caride, V.J.; Twickler, J.; Zaret, B.L.

1984-01-01

To study the mechanisms and kinetics of liposome deposition in the region of the experimental myocardial infarction, the myocardial distribution of positive and negative liposomes was determined as a function of regional myocardial blood flow and time after administration. The study was performed in dogs at 1 and 24 h following experimental myocardial infarction. Twenty-four hours after coronary artery occlusion, the initial myocardial distribution of positive and negative liposomes (2 min) is directly proportional to regional myocardial blood flow. With time, there is reduction of the radiotracer associated with negative liposomes from all myocardial regions (p less than 0.01). In contrast, in areas of moderate and severe blood flow reduction, there is progressive accumulation of tracers entrapped or incorporated in positive liposomes. This increment becomes significant in 120 min (p less than 0.005). Similar findings are observed in studies performed 1 h after coronary artery occlusion. Dual-label liposomes [( 3 H]cholesterol and [99mTc]diethylenetriamine pentaacetic acid) were used to study the integrity of liposomes in normal and ischemic myocardium. Significant dissociation of the aqueous and lipid labels of positive liposomes is observed 1 h following coronary artery occlusion. In the 24-h myocardial infarction model, dissociation of the aqueous and lipid labels in ischemic myocardium is also observed. This phenomenon is more pronounced with positive than with negative liposomes (p less than 0.02)

Anisotropy of the Elastic Properties of Normal and Pathological Myocardium: Angular Dependence of Ultrasonic Backscatter, Attenuation, and Velocity.

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Verdonk, Edward Dennis

The focus of this thesis is the measurement of anisotropies in the ultrasonic parameters of soft tissues. The goal is to contribute to a better understanding of the physics which underlies the interaction of ultrasonic waves with inhomogeneous and anisotropic media. Broadband measurements using a piezoelectric transducer are reported for investigations of excised specimens of human and canine myocardial tissue. Emphasis is placed on identifying the effect that the muscle fiber orientation, relative to the direction of insonification, has on the propagation and scattering properties of ultrasonic waves. Results of the anisotropy of backscatter, the anisotropy of attenuation, and the anisotropy of quasilongitudinal velocity are presented for data obtained in 2^ circ increments through the full 360 ^circ relative to the myofibers. Measured velocities are used in conjunction with measured specimen densities to determine the elastic stiffness constants c_{11} and c_ {33} and to estimate specific mechanical moduli for thin layers of myocardium.

Development of an in vivo method for determining material properties of passive myocardium

Directory of Open Access Journals (Sweden)

Espen Remme

2004-10-01

Full Text Available Calculation of mechanical stresses and strains in the left ventricular (LV myocardium by the finite element (FE method relies on adequate knowledge of the material properties of myocardial tissue. In this paper we present a model-based estimation procedure to characterize the stress-strain relationship in passive LV myocardium. A 3D FE model of the LV myocardium was used, which included morphological fiber and sheet structure and a nonlinear orthotropic constitutive law with different stiffness in the fiber, sheet and sheet-normal directions. The estimation method was based on measured wall strains. We analyzed the method's ability to estimate the material parameters by generating a set of synthetic strain data by simulating the LV inflation phase with known material parameters. In this way we were able to verify the correctness of the solution and to analyze the effects of measurement and model error on the solution accuracy and stability. A sensitivity analysis was performed to investigate the observability of the material parameters and to determine which parameters to estimate. The results showed a high degree of coupling between the parameters governing the stiffness in each direction. Thus, only one parameter in each of the three directions was estimated. For the tested magnitudes of added noise and introduced model errors, the resulting estimated stress-strain characteristics in the fiber and sheet directions converged with good accuracy to the known relationship. The sheet-normal stress-strain relationship had a higher degree of uncertainty as more noise was added and model error was introduced.

Contribution to the study of thallium 201 myocardium scintigraphy

International Nuclear Information System (INIS)

Annweiler, Marc.

1976-01-01

In this work a new isotope was tested in the field of myocardium scintigraphy: thallium 201. The different radioisotopes used so far in myocardium scintigraphy are reviewed to begin with. The main biological and physical characteristics of thallium and the scintillation camera used for this work are described next. In our opinion thallium 201 owing to its biological behavior similar to that of potassium and to its physical characteristics, appears as one of the better -if not the best- known tracer suitable for use in myocardium scintigraphy. Its properties are suited to the use of a scintillation camera, which considerably shortens the examination time and thus allows an isotopic exploration of the myocardium from several incidences. The only disadvantage of this cyclotron-produced isotope seems to be its high price which will probably limit its use on a large scale. Fifty thallium 201 myocardium scintigraphs were practised on forty-eight coronary thrombosis patients. From this was established a precise topographic correlation between the electrocardiographic diagnosis and the scintigraph. The two corresponded in 47 cases out of 50. The few disagreements between ECG and scintigraphic results seem to be due either to poor-quality images or to an overall myocardium hypofixation connected with a very extensive necrosis. This means that thallium 201 myocardium scintigraphy is a reliable method of examination in the great majority of cases, giving a direct picture of the heart muscle and its necrotic lesions [fr

Tropical diseases of the myocardium: a review

Directory of Open Access Journals (Sweden)

Groom ZC

2017-04-01

Full Text Available Zoe C Groom,1 Aristotle D Protopapas,2 Vasileios Zochios3,4 1Costello Medical Consulting Limited, Cambridge, 2Department of Surgery, Division of Surgery and Cancer, Imperial College London, London, 3Department of Intensive Care Medicine, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, 4College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK Abstract: Cardiovascular diseases are widely distributed throughout the world. Human parasitic infections are ubiquitous. Tropical parasites are increasingly recognized as causes of cardiovascular diseases. In this review, we address the most frequently reported parasites that directly infect the myocardium, including Trypanosoma cruzi, the protozoal causative agent of American trypanosomiasis (Chagas disease, and Taenia solium, the cestode causative agent of taeniasis and cysticercosis. We also discuss tropical endomyocardial fibrosis, trichinellosis and schistosomiasis. Health systems, attitudes, the perceptions of both patients and physicians as well as socioeconomic factors should all be explored and recognized as crucial factors for improving the control of cardiovascular diseases in the tropics. Clinicians throughout the world must remain aware of imported parasites as potential causes of cardiac diseases. Keywords: cardiomyopathy, Chagas disease, myocardium, parasitic infection, tropical infections

Focalized contractile impairment at hypertrophied myocardium proven in consideration of wall stress in patients with hypertrophic cardiomyopathy

International Nuclear Information System (INIS)

Yamazaki, Tadashi; Suzuki, Jun-ichi; Shimamoto, Ryoichi; Tsuji, Taeko; Ohmoto, Yuki; Toyo-oka, Teruhiko; Omata, Masao; Ohtomo, Kuni; Nagai, Ryozo

2006-01-01

In hypertrophic cardiomyopathy (HCM) a hyperkinetic state is sometimes observed in spite of impaired systolic function in the hypertrophied myocardium. The aim of the present study was to determine the mechanism of this paradox. Seventeen patients with HCM and 10 normal subjects underwent cine magnetic resonance (MR) imaging to measure percent systolic wall thickening and percent fractional shortening. The ratio of systolic radial wall stress of the LV at the hypertrophied myocardium over that at the nonhypertrophied myocardium was evaluated to describe the focal advantageous condition for wall thickening. The ratio was 0.66±0.36 at the start of contraction and 0.78±0.31 at early-systole, indicating consistently smaller radial wall stress at the hypertrophied myocardium. Although the condition for contraction was favorable (a ratio less than 1.00), percent systolic wall thickening at the hypertrophied myocardium (23.0±11.8%) was smaller than that at the nonhypertrophied myocardium (70.5±32.3%). Smaller end-diastolic dimension (HCM group; 45.2±4.2 mm, reference group; 48.9±4.1 mm, P=0.04) with a statistically identical value of systolic decrease in intraventricular dimension (HCM group; 19.7±3.9 mm, reference group; 18.9±3.2 mm, P=0.60) yielded high percent fractional shortening in patients with HCM (43.5±7.6%). Although contractile impairment was proven at the hypertrophied region with low radial wall stress in the HCM group, the smaller end-diastolic dimension in this group resulted in high percent fractional shortening. (author)

Experimental basis of metabolic imaging of the myocardium with radioiodinated aromatic free fatty acids

International Nuclear Information System (INIS)

Reske, S.N.; Knapp, F.F. Jr.; Winkler, C.

1986-01-01

For the investigation of myocardial perfusion and left ventricular pump function, advanced radioisotopic techniques have been established. New developments in radiopharmacology and single-photon emission computed tomography have recently enabled the investigation of parameters of regional energy metabolism in well defined areas of the heart muscle. For this purpose, various iodine ( 123 I)-labeled free fatty acids (FFA) have been synthesized. The diagnostic application of labeled FFA in heart disease may be important, since FFA are the preferred substrates for cardiac energy production at rest in the fasting state. In addition, regional myocardial FFA uptake and regional myocardial blood flow are tightly coupled in normal myocardium with beta-oxidation which is extremely sensitive to oxygen deprivation. This article outlines the basic physiologic pathways of FFA in normal and ischemic myocardium and reviews the results of animal experiments validating the application of these principles for metabolic imaging of the heart by means of the aromatic radioiodinated FFA, 15-(p-iodophenyl)pentadecanoic acid. In addition, the development, physiologic properties, and potential applications of a new generation of 3-methyl-substituted radioiodinated fatty acids that show high myocardial uptake but prolonged retention are discussed. 64 references

Observation of 99Tcm-MIBI uptake of ischemic myocardium in dog models after left circumflex coronary artery constriction

International Nuclear Information System (INIS)

Cheng Guanghua; Dai Yunhai; Wu Kefang; Xu Quanfeng

2008-01-01

Objective: To observe 99 Tc m -MIBI uptake of ischemic myocardium at different times (1h, 4h) in dog models after left circumflex coronary artery constriction. Methods: 12 dog models of coronary artery stenosis were prepared by left circumflex coronary ligation, and were given injection of 99 Tc m -MIBI at the dosage of 185 MBq (5 mCi). Six models were sacrificed at one hour and four hours after the injection respectively. Radio-uptake in about 100 mg myocardium from both ischemic and non-ischemic sites were measured with r-counter. Results: No significant differences were found between ratios of radioactive count of ischemic over normal myocardial tissues at 1h and 4h after injection of 99 Tc m -MIBI (0.726±0.054 and 0.673±0.080, respective, t=1.3452, P >0.05). Conclusion: The extension of post-injection time would not increase 99 Tc m -MIBI uptake in ischemic myocardium. (authors)

The effect of percutaneous transmyocardial laser revascularization on left ventricular function in a porcine model of hibernating myocardium

International Nuclear Information System (INIS)

Almeda, Francis Q.; Glock, Dana; Sandelski, Joanne; Ibrahim, Osama; Macioch, James E.; Allen, Trisha; Dainauskas, John R.; Parrillo, Joseph E.; Snell, R. Jeffrey; Schaer, Gary L.

2004-01-01

Background: Hibernating myocardium is defined as a state of persistently impaired myocardial function at rest due to reduced coronary blood flow that can partially or completely be restored to normal if the myocardial oxygen supply/demand relationship is favorably altered. Percutaneous laser revascularization (PMR) is an emerging catheter-based technique that involves creating channels in the myocardium, directly through a percutaneous approach with a laser delivery system, and has been shown to reduce symptoms in patients with severe refractory angina; however, its effect on improving regional wall motion abnormalities in hibernating myocardium has not been clearly established. We sought to determine the effect of PMR using the Eclipse System (Cardiogenesis) on left ventricular function in a porcine model of hibernating myocardium. Methods: A model of hibernating myocardium was created by placement of an ameroid constrictor in the proximal left anterior descending artery of a 35 kg male Yorkshire pig. The presence of hibernating myocardium was confirmed with dobutamine stress echocardiography (DSE) and defined as severe hypocontractility at rest, with an improvement in systolic wall thickening with low-dose dobutamine in myocardial regions with a subsequent deterioration in function at peak stress (biphasic response). After the demonstration of hibernating myocardium, PMR was performed in the area of hypocontractile function, and the serial echocardiography was performed. The echocardiograms were reviewed by an experienced echocardiologist blinded to the results, and regional wall motion was assessed using the American Society of Echocardiography Wall Motion Score. Six weeks after PMR, the animal was sacrificed and the heart sent for histopathologic studies. Results: A comparison of the regional wall motion function of the area distal to the ameroid constrictor and in the contralateral wall at baseline, post-ameroid placement, and post-PMR was performed

Native T1 value in the remote myocardium is independently associated with left ventricular dysfunction in patients with prior myocardial infarction.

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Nakamori, Shiro; Alakbarli, Javid; Bellm, Steven; Motiwala, Shweta R; Addae, Gifty; Manning, Warren J; Nezafat, Reza

2017-10-01

To compare remote myocardium native T 1 in patients with chronic myocardial infarction (MI) and controls without MI and to elucidate the relationship of infarct size and native T 1 in the remote myocardium for the prediction of left ventricular (LV) systolic dysfunction after MI. A total of 41 chronic MI (18 anterior MI) patients and 15 age-matched volunteers with normal LV systolic function and no history of MI underwent cardiac magnetic resonance imaging (MRI) at 1.5T. Native T 1 map was performed using a slice interleaved T 1 mapping and late gadolinium enhancement (LGE) imaging. Cine MR was acquired to assess LV function and mass. The remote myocardium native T 1 time was significantly elevated in patients with prior MI, compared to controls, for both anterior MI and nonanterior MI (anterior MI: 1099 ± 30, nonanterior MI: 1097 ± 39, controls: 1068 ± 25 msec, P Remote myocardium native T 1 moderately correlated with LV volume, mass index, and ejection fraction (r = 0.38, 0.50, -0.49, respectively, all P remote myocardium was independently associated with reduced LV ejection fraction, after adjusting for age, gender, infarct size, and comorbidity (β = -0.34, P = 0.03). In chronic MI, the severity of LV systolic dysfunction after MI is independently associated with native T 1 in the remote myocardium. Diffuse myocardial fibrosis in the remote myocardium may play an important pathophysiological role of post-MI LV dysfunction. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1073-1081. © 2017 International Society for Magnetic Resonance in Medicine.

Volume of myocardium perfused by coronary artery branches as estimated from 3D micro-CT images of rat hearts

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Lund, Patricia E.; Naessens, Lauren C.; Seaman, Catherine A.; Reyes, Denise A.; Ritman, Erik L.

2000-04-01

Average myocardial perfusion is remarkably consistent throughout the heart wall under resting conditions and the velocity of blood flow is fairly reproducible from artery to artery. Based on these observations, and the fact that flow through an artery is the product of arterial cross-sectional area and blood flow velocity, we would expect the volume of myocardium perfused to be proportional to the cross-sectional area of the coronary artery perfusing that volume of myocardium. This relationship has been confirmed by others in pigs, dogs and humans. To test the body size-dependence of this relationship we used the hearts from rats, 3 through 25 weeks of age. The coronary arteries were infused with radiopaque microfil polymer and the hearts scanned in a micro- CT scanner. Using these 3D images we measured the volume of myocardium and the arterial cross-sectional area of the artery that perfused that volume of myocardium. The average constant of proportionality was found to be 0.15 +/- 0.08 cm3/mm2. Our data showed no statistically different estimates of the constant of proportionality in the rat hearts of different ages nor between the left and right coronary arteries. This constant is smaller than that observed in large animals and humans, but this difference is consistent with the body mass-dependence on metabolic rate.

Stereoselective handling of perhexiline: implications regarding accumulation within the human myocardium.

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Chong, Cher-Rin; Drury, Nigel E; Licari, Giovanni; Frenneaux, Michael P; Horowitz, John D; Pagano, Domenico; Sallustio, Benedetta C

2015-12-01

Perhexiline is a prophylactic anti-ischaemic agent with weak calcium antagonist effect which has been increasingly utilised in the management of refractory angina. The metabolic clearance of perhexiline is modulated by CYP2D6 metaboliser status and stereoselectivity. The current study sought to (1) determine whether the acute accumulation of perhexiline in the myocardium is stereoselective and (2) investigate the relationship between duration of short-term therapy and the potential stereoselective effects of perhexiline within myocardium. Patients (n = 129) from the active arm of a randomised controlled trial of preoperative perhexiline in cardiac surgery were treated with oral perhexiline for a median of 9 days. Correlates of atrial and ventricular concentrations of enantiomers were sought via univariate followed by multivariate analyses. Myocardial uptake of both (+) and (-) perhexiline was greater in ventricles than in atria, and there was more rapid clearance of (-) than (+) perhexiline. The main determinants of atrial uptake of both (+) and (-) perhexiline were the plasma concentrations [(+) perhexiline: β = -0.256, p = 0.015; (-) perhexiline: β = -0.347, p = 0.001] and patients' age [(+) perhexiline: β = 0.300, p = 0.004; (-) perhexiline: β = 0.288, p = 0.005]. Atrial uptake of (+) enantiomer also varied directly with duration of therapy (β = 0.228, p = 0.025), while atrial uptake of (-) perhexiline varied inversely with simultaneous heart rate (β = -0.240, p = 0.015). (1) Uptake of both perhexiline enantiomers into atrium is greater with advanced age and displays evidence of both saturability and minor stereoselectivity. (2) Atrial uptake of (-) perhexiline may selectively modulate heart rate reduction.

Detection of the myocardium ischemia in scintigraphy

International Nuclear Information System (INIS)

Faraggi, M.; Pierquet-Ghazzar, N.; Maunoury, C.

2005-01-01

The myocardium scintigraphy (SPECT) gives excellent elements of prognosis allowing to select at the best, the patients having a revascularization, and then an angiography examination. It appears complementary of the coronaries tree imaging and should (in theory) be practised in first in an organisation chart of taking over. In the search of practicable myocardium, the PET with 18 FDG, although being competitive, is more and more forsaken to the MRI profit. In retaliation, the PET with 82 Rb with test of pharmacology stimulation could develop in detection of coronaries disease. (N.C.)

Myocardium scintigraphy and coronaries scanner: results and respective contribution of these two examinations; Scintigraphie myocardique et scanner coronaire: resultats et apport respectif des deux examens

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Songy, B.; Balestrini, V.; Sablayrolles, J.L.; Vigoni, F.; Lussato, D. [Centre cardiologique du Nord (CCN), Saint-Denis, (France); Faccio, F. [fondation San Geronimo, Santa Fe, (Argentina)

2009-05-15

The objective were to evaluate the results and the respective contribution of the myocardium scintigraphy and the coro-scanner. It exists an excellent correlation between a normal scanner and a normal scintigraphy (97%). 30% of patients having non tight stenosis at scanner and 60% of these ones having tight stenosis have a scintigraphy ischemia; An abnormal scanner, whatever be the the degree of stenosis must be completed by a test of myocardium ischemia. The actual limitations of the coro-scanner (64 gills) are in relation with its spatial resolution (quantification) and temporal resolution (right coronary). The choice of the diagnosis examination to realize in first intention must depend on the age and prevalence of the coronary disease. (N.C.)

Synchronous In Situ ATPase Activity, Mechanics, and Ca2+ Sensitivity of Human and Porcine Myocardium

Czech Academy of Sciences Publication Activity Database

Griffiths, P. J.; Isackson, H.; Pelc, Radek; Redwood, C.S.; Funari, S.S.; Watkins, H.; Ashley, C. C.

2009-01-01

Roč. 97, č. 9 (2009), s. 2503-2512 ISSN 0006-3495 R&D Projects: GA MŠk(CZ) LC06063 Grant - others:EC(XE) RII3-CT-2004-506008 Institutional research plan: CEZ:AV0Z50110509 Keywords : myocardium * actomyosin- ATPase * synchrotron-radiation Subject RIV: ED - Physiology Impact factor: 4.390, year: 2009

Probability mapping of scarred myocardium using texture and intensity features in CMR images

Science.gov (United States)

2013-01-01

Background The myocardium exhibits heterogeneous nature due to scarring after Myocardial Infarction (MI). In Cardiac Magnetic Resonance (CMR) imaging, Late Gadolinium (LG) contrast agent enhances the intensity of scarred area in the myocardium. Methods In this paper, we propose a probability mapping technique using Texture and Intensity features to describe heterogeneous nature of the scarred myocardium in Cardiac Magnetic Resonance (CMR) images after Myocardial Infarction (MI). Scarred tissue and non-scarred tissue are represented with high and low probabilities, respectively. Intermediate values possibly indicate areas where the scarred and healthy tissues are interwoven. The probability map of scarred myocardium is calculated by using a probability function based on Bayes rule. Any set of features can be used in the probability function. Results In the present study, we demonstrate the use of two different types of features. One is based on the mean intensity of pixel and the other on underlying texture information of the scarred and non-scarred myocardium. Examples of probability maps computed using the mean intensity of pixel and the underlying texture information are presented. We hypothesize that the probability mapping of myocardium offers alternate visualization, possibly showing the details with physiological significance difficult to detect visually in the original CMR image. Conclusion The probability mapping obtained from the two features provides a way to define different cardiac segments which offer a way to identify areas in the myocardium of diagnostic importance (like core and border areas in scarred myocardium). PMID:24053280

Enhanced detection of ischemic but viable myocardium by the reinjection of thallium after stress-redistribution imaging

International Nuclear Information System (INIS)

Dilsizian, V.; Rocco, T.P.; Freedman, N.M.; Leon, M.B.; Bonow, R.O.

1990-01-01

The identification of ischemic but viable myocardium by thallium exercise scintigraphy is often imprecise, since many of the perfusion defects that develop in ischemic myocardium during exercise do not fill in on subsequent redistribution images. We hypothesized that a second injection of thallium given after the redistribution images were taken might improve the detection of ischemic but viable myocardium. We studied 100 patients with coronary artery disease, using thallium exercise tomographic imaging and radionuclide angiography. Patients received 2 mCi of thallium intravenously during exercise, redistribution imaging was performed three to four hours later, and a second dose of 1 mCi of thallium was injected at rest immediately thereafter. The three sets of images (stress, redistribution, and reinjection) were then analyzed. Ninety-two of the 100 patients had exercise-induced perfusion defects. Of the 260 abnormal myocardial regions identified by stress imaging, 85 (33 percent) appeared to be irreversible on redistribution imaging three to four hours later. However, 42 of these apparently irreversible defects (49 percent) demonstrated improved or normal thallium uptake after the second injection of thallium, with an increase in mean regional uptake from 56 +/- 12 percent on redistribution studies to 64 +/- 10 percent on reinjection imaging (P less than 0.001). Twenty patients were restudied three to six months after coronary angioplasty. Of the 15 myocardial regions with defects on redistribution studies that were identified as viable by reinjection studies before angioplasty, 13 (87 percent) had normal thallium uptake and improved regional wall motion after angioplasty. In contrast, all eight regions with persistent defects on reinjection imaging before angioplasty had abnormal thallium uptake and abnormal regional wall motion after angioplasty

Evaluation of noncoronary sources of left ventricular perfusion to intercoronary collateral-dependent myocardium due to chronic major vessel occlusion: absent contribution of luminal and extracardiac channels

International Nuclear Information System (INIS)

Crystal, G.J.; Downey, H.F.; Bashour, F.A.

1981-01-01

Liminal contribution to perfusion of collateral-dependent left ventricular (LV) myocardium was evaluated in six dogs. A portion of LV free wall was rendered collateral-dependent by gradual occlusion of left circumflex artery with Ameroid constrictor. Eight to 10 weeks after implantation of constrictor, measurements of LV myocardial flow were made by left atrial injections of 9-10 micro radioactive microspheres. To measure total collateral flow, microspheres were injected under control conditions, and to measure luminal contribution to collateral flow, microspheres were injected after ligation of right coronary artery during extracorporeal perfusion of left common coronary artery (LCCA) with microsphere-free arterial blood, and during stoppage of flow through LCCA. Under control conditions, myocardial blood flow in collateral-dependent region, 1.01 +/- 0.31 ml/min/gm, was not significantly different from that in normal region, 1.06 +/- 0.32 ml/min/gm. Flow from luminal collateral vessels was negligible (less than 0.005 ml/min/gm) in both collateral-dependent and normal myocardium, and was not affected by stoppage of flow through LCCA. These results indicate that luminal collateral vessels, as well as collateral vessels originating from other noncoronary sources, do not contribute significantly to perfusion of normal or collateral-dependent LV myocardium

Angiogenesis with intramyocardial administration of basic fibroblast growth factor in canine ischemic myocardium

International Nuclear Information System (INIS)

Sun Lijun; Liu Ying; Zhao Haitao; Huan Yi; Ge Yali; Gao Fabao

2004-01-01

Objective: To evaluate the effect of intramyocardial administration of basic fibroblast growth factor on angiogenesis of infarcted myocardium in dogs. Methods: Twenty-four mongrel dogs were randomized into control group and therapeutic group. Acute myocardial infarction was made by ligation of the left anterior descending coronary artery distal to its first diagonal branch. As soon as coronary artery was occluded, 50 mg of basic fibroblast growth factor in 15 ml of saline was injected into the infarcted and border zone in therapeutic group, whereas 15 ml saline alone was used in the same way in control dogs. Every 3 dogs in each group was studied on the 1 st day, the 3 rd day, the 10 th day, and the 17 th day, respectively. Electron microscope was used to observe the growth of capillaries. Angiogenesis was evaluated by immunohistochemical studies with VIII factor. With sensitivity encoded technique, cine MR and MR perfusion imaging were performed on each dog within 3 hours after surgery and before euthanasia to evaluate cardiac function and the characteristics of myocardial perfusion. Results: In therapeutic group, LVEF improved markedly since the 10 th day (on the 10 th day: control group 24.09 ± 3.32, therapeutic group 45.71 ± 6.27; on the 17 th day: control group 31.46 ± 4.60, therapeutic group 53.46 ± 5.24). Hypoenhancement on first pass and hyperenhancement on delayed phase appeared in infarcted myocardium. There were significant differences for the time of upslope, peak time of signal intensity, upslope curves ratio, and contrast enhancement ratio between infarcted and normal myocardium. The size of infarcted myocardium was markedly decreased on the 17 th day [control group (9.04 ± 1.59)%, therapeutic group (4.07 ± 1.20)%]. The capillaries grew actively in therapeutic group and microvessel density was higher in therapeutic group than in control group except the first day (control group and therapeutic group respectively on the 3 rd day: 92.3 ± 11

Diagnosis of Non-compacted Myocardium of the Left Ventricle in Children

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I.B. Yershova

2014-05-01

Full Text Available The authors presented a review of published literature data on rare congenital abnormalities in children — a non-compacted myocardium of the left ventricle, which refers to unclassified cardiomyopathy. This pathology by the American Heart Association classification relates to genetic cardiomyopathy. Non-compacted myocardium of the left ventricle in children develops due to violation of myocardial induration of the fetus in utero. Diagnosis of the disease is difficult due to the lack of specific clinical signs. The authors also presented a clinical case of non-compacted left ventricular myocardium in 6-year-old girl.

The possibilities of using scale-selective polarization cartography in diagnostics of myocardium pathologies

Science.gov (United States)

Ushenko, Yu. A.; Wanchuliak, O. Y.

2013-06-01

The optical model of polycrystalline networks of myocardium protein fibrils is presented. The technique of determining the coordinate distribution of polarization azimuth of the points of laser images of myocardium histological sections is suggested. The results of investigating the interrelation between the values of statistical (statistical moments of the 1st-4th order) parameters are presented which characterize distributions of wavelet-coefficients polarization maps of myocardium layers and death reasons.

The Impact of Energy Substrates, Hormone Level and Subject-Related Factors on Physiologic Myocardial {sup 18}F-FDG Uptake in Normal Humans

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Jeong, Juhye; Kong, Eunjung; Chun, Kyungah; Cho, Ihnho [Yeung-Nam Univ. Hoepital, Daegu (Korea, Republic of)

2013-12-15

In a whole-body {sup 18}F-FDG PET/CT, non-specific {sup 18}F-FDG uptake of the myocardium is a common finding and can be very variable, ranging from background activity to intense accumulation and inhomogeneity. We investigated the effect of energy substrates and plasma/serum hormones that may have an influence on myocardial {sup 18}F-FDG uptake. F-FDG PET/CT was performed on 100 normal volunteers from November 2007 to August 2008. Blood samples were taken just before {sup 18}F-FDG injection from all subjects. Myocardial {sup 18}F-FDG uptake was measured as the mean (SUVmean) and maximal (SUV{sub max}) standardized uptake value. The myocardium was delineated on the PET/CT image by a manual volume of interest (VOI).We analyzed the influence of age, sex, presence of diabetes, fasting duration, insulin, glucagon, fasting glucose, lactate, free fatty acid (FFA), epinephrine (EPi), norepinephrine (NEp), free triiodothyronine (T3), free thyroxine (T4), thyroid-stimulating hormone (TSH) and body mass index (BMI). Overall, 92 subjects (mean age 50.28±8.30, male 57) were enrolled. The average of myocardial SUVmean was 2.08 and of myocardial SUV{sub max} was 4.57, respectively and there was a strong linear correlation between SUVmean and SUV{sub max} (r =0.98). FFA and fasting duration showed significant negative correlation with myocardial {sup 18}F-FDG uptake, respectively (r =-0.40 in FFA; r =-0.41 in fasting duration). No significant relationships were observed between myocardial uptake and age, sex, presence of diabetics, insulin, glucagon, fasting glucose, lactate, EPi, NEp, free T3, free T4, TSH and BMI. Myocardial {sup 18}F-FDG uptake decreases with longer fasting duration and higher FFA level in normal humans. Modulating myocardial uptake could improve {sup 18}F-FDG PET/CT imaging for specific oncologic and cardiovascular indications.

Study on the kinetics of high-energy phosphates in myocardium by phosphorous nuclear magnetic resonance

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Kusuoka, Hideo; Tsuneoka, Yutaka; Inoue, Michitoshi; Abe, Hiroshi [Osaka Univ. (Japan). Faculty of Medicine; Watari, Hiroshi

1982-12-01

Effect of artificial blood, FC 43 (Perfluorochemicals) on the kinetics of high-energy phosphate in the myocardium was evaluated by /sup 31/P-NMR which permits a continuous and non-invasive assessment of in vivo phosphorus compounds. Cardiac perfusion was carried out on a excised rat heart with a Krebs-Henseleit modified solution and FC 43 alternately. Under the normal condition, ischemic condition, and at second perfusion amounts of intramyocardial creatine phosphoric acid, ATP, and inorganic phosphorus were determined by /sup 31/P-NMR. Coronary flow was simultaneously estimated. The ischemic state due to interruption of perfusion resulted in a decrease in creatine phosphoric acid, which was associated with an increase in inorganic phosphorus and intracellular acidosis. No change of ATP amount was observed under ischemic state. With resumption of perfusion, the levels of creatine phosphoric acid and inorganic phosphorus rapidly returned to the normal. In the group of FC 43, coronary flow was 2.68 ml/min/g of the heart weight, about 1/2 of that of the Krebs-Henseleit group (5.68 ml/min/g of the heart weight). In controls, there was no difference between the two groups concerning creatine phosphoric acid level and recovery of creatine phospohric acid level after ischemia. These results showed that FC 43 supplies sufficient oxygen, and has no effect on the kinetics of energy in the myocardium.

Multimodality imaging demonstrates trafficking of liposomes preferentially to ischemic myocardium

International Nuclear Information System (INIS)

Lipinski, Michael J.; Albelda, M. Teresa; Frias, Juan C.; Anderson, Stasia A.; Luger, Dror; Westman, Peter C.; Escarcega, Ricardo O.; Hellinga, David G.; Waksman, Ron; Arai, Andrew E.; Epstein, Stephen E.

2016-01-01

Introduction: Nanoparticles may serve as a promising means to deliver novel therapeutics to the myocardium following myocardial infarction. We sought to determine whether lipid-based liposomal nanoparticles can be shown through different imaging modalities to specifically target injured myocardium following intravenous injection in an ischemia–reperfusion murine myocardial infarction model. Methods: Mice underwent ischemia–reperfusion surgery and then either received tail-vein injection with gadolinium- and fluorescent-labeled liposomes or no injection (control). The hearts were harvested 24 h later and underwent T1 and T2-weighted ex vivo imaging using a 7 Tesla Bruker magnet. The hearts were then sectioned for immunohistochemistry and optical fluorescent imaging. Results: The mean size of the liposomes was 100 nm. T1-weighted signal intensity was significantly increased in the ischemic vs. the non-ischemic myocardium for mice that received liposomes compared with control. Optical imaging demonstrated significant fluorescence within the infarct area for the liposome group compared with control (163 ± 31% vs. 13 ± 14%, p = 0.001) and fluorescent microscopy confirmed the presence of liposomes within the ischemic myocardium. Conclusions: Liposomes traffic to the heart and preferentially home to regions of myocardial injury, enabling improved diagnosis of myocardial injury and could serve as a vehicle for drug delivery.

Multimodality imaging demonstrates trafficking of liposomes preferentially to ischemic myocardium

Energy Technology Data Exchange (ETDEWEB)

Lipinski, Michael J., E-mail: mjlipinski12@gmail.com [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States); Albelda, M. Teresa [GIBI2" 3" 0, Grupo de Investigación Biomédica en Imagen, IIS La Fe, Valencia (Spain); Frias, Juan C. [Departamento de Ciencias Biomédicas, Universidad CEU Cardenal Herrera, Valencia (Spain); Anderson, Stasia A. [Advanced Cardiovascular Imaging Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (United States); Luger, Dror; Westman, Peter C.; Escarcega, Ricardo O.; Hellinga, David G.; Waksman, Ron [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States); Arai, Andrew E. [Advanced Cardiovascular Imaging Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (United States); Epstein, Stephen E. [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States)

2016-03-15

Introduction: Nanoparticles may serve as a promising means to deliver novel therapeutics to the myocardium following myocardial infarction. We sought to determine whether lipid-based liposomal nanoparticles can be shown through different imaging modalities to specifically target injured myocardium following intravenous injection in an ischemia–reperfusion murine myocardial infarction model. Methods: Mice underwent ischemia–reperfusion surgery and then either received tail-vein injection with gadolinium- and fluorescent-labeled liposomes or no injection (control). The hearts were harvested 24 h later and underwent T1 and T2-weighted ex vivo imaging using a 7 Tesla Bruker magnet. The hearts were then sectioned for immunohistochemistry and optical fluorescent imaging. Results: The mean size of the liposomes was 100 nm. T1-weighted signal intensity was significantly increased in the ischemic vs. the non-ischemic myocardium for mice that received liposomes compared with control. Optical imaging demonstrated significant fluorescence within the infarct area for the liposome group compared with control (163 ± 31% vs. 13 ± 14%, p = 0.001) and fluorescent microscopy confirmed the presence of liposomes within the ischemic myocardium. Conclusions: Liposomes traffic to the heart and preferentially home to regions of myocardial injury, enabling improved diagnosis of myocardial injury and could serve as a vehicle for drug delivery.

Reductions in mitochondrial O(2) consumption and preservation of high-energy phosphate levels after simulated ischemia in chronic hibernating myocardium.

Science.gov (United States)

Hu, Qingsong; Suzuki, Gen; Young, Rebeccah F; Page, Brian J; Fallavollita, James A; Canty, John M

2009-07-01

We performed the present study to determine whether hibernating myocardium is chronically protected from ischemia. Myocardial tissue was rapidly excised from hibernating left anterior descending coronary regions (systolic wall thickening = 2.8 +/- 0.2 vs. 5.4 +/- 0.3 mm in remote myocardium), and high-energy phosphates were quantified by HPLC during simulated ischemia in vitro (37 degrees C). At baseline, ATP (20.1 +/- 1.0 vs. 26.7 +/- 2.1 micromol/g dry wt, P < 0.05), ADP (8.1 +/- 0.4 vs. 10.3 +/- 0.8 micromol/g, P < 0.05), and total adenine nucleotides (31.2 +/- 1.3 vs. 40.1 +/- 2.9 micromol/g, P < 0.05) were depressed compared with normal myocardium, whereas total creatine, creatine phosphate, and ATP-to-ADP ratios were unchanged. During simulated ischemia, there was a marked attenuation of ATP depletion (5.6 +/- 0.9 vs. 13.7 +/- 1.7 micromol/g at 20 min in control, P < 0.05) and mitochondrial respiration [145 +/- 13 vs. 187 +/- 11 ng atoms O(2).mg protein(-1).min(-1) in control (state 3), P < 0.05], whereas lactate accumulation was unaffected. These in vitro changes were accompanied by protection of the hibernating heart from acute stunning during demand-induced ischemia. Thus, despite contractile dysfunction at rest, hibernating myocardium is ischemia tolerant, with reduced mitochondrial respiration and slowing of ATP depletion during simulated ischemia, which may maintain myocyte viability.

Quantitative stress-redistribution planar T1-201 scintigraphy: Assessment of the extent of hypoperfused myocardium by relationship to angiographic findings

International Nuclear Information System (INIS)

Bassir, R.; Maddahi, J.; Garcia, E.

1984-01-01

The size of hypoperfused myocardium (HM) in coronary artery (CA) disease (D) potentially provides a prognostic index that may not be accurately assess by conventional angiographic classification. The authors studied 62 consecutive patients (pts) with planar stress-redistribution T1-201 scintigraphy (T1-201) and coronary arteriography who did not have prior myocardial infarction and achieved 85% predicted maximum heart rate on exercise. Of 62 pts, 42 had CAD (>50% stenosis). For T1-201 quantification of the size of HM, maximum count circumferential profiles of initial distribution and % washout were obtained and compared to previously established normal limits. The area enclosed between the normal limits and the abnormal portion of the pt's profiles represented a quantitative T1-201 jeopardy score (JS). Despite increasing T1-201 JS from 1 to 3 vessel (V) and left-main (LM) D, significant overlap between the different angiographic groups was observed; of 45 pts with mild JS (<300), 14 (31%) had 3VD and/or LMD. The angiographic extent of CAD was also analyzed using a method (CLASS) proposed by Gensini et al based on the CA territory, location and severity of stenosis, and collateral circulation. T1-201 JS correlated significantly with CLASS (r=.78, p<.01). Of the 45 pts with mild JS, only 5 (11%) had severe CLASS score. Thus, the size of the hypoperfused myocardium by quantitative stress- and redistribution T1-201 correlates better with a more complex angiographic estimate of myocardium at risk than conventional 1, 2, and 3 vessel disease classification

Blood flow, flow reserve, and glucose utilization in viable and nonviable myocardium in patients with ischemic cardiomyopathy.

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Zhang, Xiaoli; Schindler, Thomas H; Prior, John O; Sayre, James; Dahlbom, Magnus; Huang, Sung-Cheng; Schelbert, Heinrich R

2013-04-01

The aim of the study was to determine whether glucose uptake in viable myocardium of ischemic cardiomyopathy patients depends on rest myocardial blood flow (MBF) and the residual myocardial flow reserve (MFR). Thirty-six patients with ischemic cardiomyopathy (left ventricular ejection fraction 25 ± 10 %) were studied with (13)N-ammonia and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Twenty age-matched normals served as controls. Regional MBF was determined at rest and during dipyridamole hyperemia and regional FDG extraction was estimated from regional FDG to (13)N-ammonia activity ratios. Rest MBF was reduced in viable (0.42 ± 0.18 ml/min per g) and nonviable regions (0.32 ± 0.09 ml/min per g) relative to remote regions (0.68 ± 0.23 ml/min per g, p MFRs did not differ significantly (p > 0.05). Compared to MFR in remote myocardium, MFRs in viable regions were similar (1.39 ± 0.56 vs 1.70 ± 0.45, p > 0.05) but were significantly lower in nonviable regions (1.23 ± 0.43, p MFRs (r =-0.424, p MFRs in viable myocardium are associated with increasing glucose extraction that likely reflects a metabolic adaptation of remodeling hibernating myocytes.

Protective Effect of Ischemic Postconditioning against Ischemia Reperfusion-Induced Myocardium Oxidative Injury in IR Rats

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Jiangwei Ma

2012-03-01

Full Text Available Brief episodes of myocardial ischemia-reperfusion (IR employed during reperfusion after a prolonged ischemic insult may attenuate the total ischemia-reperfusion injury. This phenomenon has been termed ischemic postconditioning. In the present study, we studied the possible effect of ischemic postconditioning on an ischemic reperfusion (IR-induced myocardium oxidative injury in rat model. Results showed that ischemic postconditioning could improve arrhythmia cordis, reduce myocardium infarction and serum creatin kinase (CK, lactate dehydrogenase (LDH and aspartate transaminase (AST activities in IR rats. In addition, ischemic postconditioning could still decrease myocardium malondialdehyde (MDA level, and increased myocardium Na+-K+-ATPase, Ca2+-Mg2+-ATPase, superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GSH-Px and glutathione reductase (GR activities. It can be concluded that ischemic postconditioning possesses strong protective effects against ischemia reperfusion-induced myocardium oxidative injury in IR rats.

A study on the kinetics of high-energy phosphates in myocardium by phosphorous nuclear magnetic resonance

International Nuclear Information System (INIS)

Kusuoka, Hideo; Tsuneoka, Yutaka; Inoue, Michitoshi; Abe, Hiroshi; Watari, Hiroshi.

1982-01-01

Effect of artificial blood, FC 43 (Perfluorochemicals) on the kinetics of high-energy phosphate in the myocardium was evaluated by 31 P-NMR which permits a continuous and non-invasive assessment of in vivo phosphorus compounds. Cardiac perfusion was carried out on a excised rat heart with a Krebs-Henseleit modified solution and FC 43 alternately. Under the normal condition, ischemic condition, and at second perfusion amounts of intramyocardial creatine phosphoric acid, ATP, and inorganic phosphorus were determined by 31 P-NMR. Coronary flow was simultaneously estimated. The ischemic state due to interruption of perfusion resulted in a decrease in creatine phosphoric acid, which was associated with an increase in inorganic phosphorus and intracellular acidosis. No change of ATP amount was observed under ischemic state. With resumption of perfusion, the levels of creatine phosphoric acid and inorganic phosphorus rapidly returned to the normal. In the group of FC 43, coronary flow was 2.68 ml/min/g of the heart weight, about 1/2 of that of the Krebs-Henseleit group (5.68 ml/min/g of the heart weight). In controls, there was no difference between the two groups concerning creatine phosphoric acid level and recovery of creatine phospohric acid level after ischemia. These results showed that FC 43 supplies sufficient oxygen, and has no effect on the kinetics of energy in the myocardium. (Ueda, J.)

99m Technetium pyrophosphate myocardium scintigraphy. First results

International Nuclear Information System (INIS)

Toussaint, Paul.

1976-01-01

99m technetium pyrophosphate myocardium scintigraphy is a very recent examination technique. This work gives the results obtained on 61 patients. As a vector of the isotope, pyrophosphate has the advantage over polyphosphate of a fast bone uptake there it should be stressed that a 90 minute pause is necessary between the intraveinous injection of the isotope and the photographic recording so that the reading is not troubled by the labelled intracardiac blood pool image, an image quality criterion being the estimation of a good costal fixation which in fact appears sooner or later according to the subject. The role of pyrophosphate, chelator of calcium in fixation of the isotope on the myocardium, could be explained by the fast appearance of 'dense bodies', made up of calcium hydroxyapathice crystals, in the mitochondria of myocardium cells having undergone an irreversible necrotic process. The choice of 99 m technetium is based on its ease of use: 6 hour half-life, high-energy pure gamma emission at 140 keV. The fixed image studied under two incidences, front and left anterior oblique, is obtained from mobile images given by the scintillation camera used in connection with a data processing system. Several facts are underlined, explaining the disadvantages, advantages and indications of the method [fr

Effects of acute and chronic uremia on active cation transport in rat myocardium

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Druml, W.; Kelly, R.A.; England, B.K.; O' Hara, D.S.; Mitch, W.E. (Brigham and Women' s Hospital, Boston, MA (USA))

1990-12-01

As abnormalities of active cation transport could contribute to the genesis of uremic cardiomyopathy, we investigated myocardial sodium pump function in rats with acute renal failure (ARF) and with a model of experimental chronic renal failure (CRF) that has metabolic similarities to advanced chronic uremia in humans. CRF rats were hypertensive and had left ventricular hypertrophy (33% higher heart:body weight ratio; P less than 0.01) at four weeks compared to pair-fed sham-operated rats. Importantly, both ouabain- and furosemide-sensitive 86Rb uptake rates were unchanged in left ventricular myocardial slices from CRF, and the intracellular sodium concentration was not different from that of control rats even though skeletal muscle sodium was increased, as we found previously. Insulin-stimulated, ouabain-sensitive 86Rb influx was also preserved. There also were no abnormalities in myocardium cation transport in rats with ARF. However, (3H)ouabain binding was decreased 45% in CRF rats (P less than 0.01); it was unchanged in acute uremia. Decreased ouabain binding in chronic uremia was due entirely to fewer low affinity (3H)ouabain binding sites (the binding affinity for ouabain was unaffected). We conclude that in chronic, (but not acute) renal failure, sodium pump number is reduced in myocardium but intracellular sodium is unchanged and active cation flux rates are maintained. These results emphasize that in rats with chronic uremia, intracellular sodium homeostasis is preserved in myocardium, despite the presence of marked abnormalities of active cation transport in skeletal muscle that are characteristic of chronic uremia.

Detection of viable myocardium in canine model with myocardial ischemia and ischemia-reperfusion by 125I-BMIPP: relation to regional blood flow

International Nuclear Information System (INIS)

Huang Gang; Zhao Huiyang; Shen Xuedong; Li Qing; Yuan Jimin; Zhu Cuiying

1999-01-01

Objective: The effects of BMIPP (β-methyl-iodophenyl pentadecanoic acid) on detecting viable myocardium and the relation between regional blood flow and the uptake of BMIPP were evaluated in canine model of myocardial ischemia and ischemia-reperfusion. Methods: 12 open-chest dogs under anesthesia were divided into two groups. Group I (ischemia group) had left circumflex coronary arterial occlusion for 2 h and group II (ischemia-reperfusion group) was occluded for 1 h and followed by 2 h reperfusion. Myocardial blood flow was measured with 99 Tc m -microspheres. 30 min after intravenous injection of 125 I-BMIPP and 99 Tc m -microspheres, the heart was excised rapidly and stained with Evans blue and NBT. Tissue samples (divided into approximately 1 g) of left ventricle were obtained, weighed and counted for 125 I and 99 Tc m . Regional blood flow and the uptake of BMIPP were expressed as percentages of average values in non-ischemic myocardium (two to three tissue samples) from the normal myocardium. Results: In ischemic myocardium (NBT positive samples), the uptake of BMIPP was relatively higher compared with regional blood flow [(67 +- 23)% vs (42 +- 19)%, P 0.05]. In ischemia-reperfusion group, regional blood flow was increased in ischemic and necrotic tissues, but the uptake of BMIPP was not enhanced with the increasing blood flow. Conclusions: BMIPP uptake seems to provide metabolic information independent of regional blood flow. The mismatching between regional blood flow and BMIPP uptake may indicate myocardial viability in the regions of hypoperfusion and the uptake of BMIPP in ischemic myocardium was related to existence of cellular metabolism

Fiber architecture in remodeled myocardium revealed with a quantitative diffusion CMR tractography framework and histological validation.

Science.gov (United States)

Mekkaoui, Choukri; Huang, Shuning; Chen, Howard H; Dai, Guangping; Reese, Timothy G; Kostis, William J; Thiagalingam, Aravinda; Maurovich-Horvat, Pal; Ruskin, Jeremy N; Hoffmann, Udo; Jackowski, Marcel P; Sosnovik, David E

2012-10-12

The study of myofiber reorganization in the remote zone after myocardial infarction has been performed in 2D. Microstructural reorganization in remodeled hearts, however, can only be fully appreciated by considering myofibers as continuous 3D entities. The aim of this study was therefore to develop a technique for quantitative 3D diffusion CMR tractography of the heart, and to apply this method to quantify fiber architecture in the remote zone of remodeled hearts. Diffusion Tensor CMR of normal human, sheep, and rat hearts, as well as infarcted sheep hearts was performed ex vivo. Fiber tracts were generated with a fourth-order Runge-Kutta integration technique and classified statistically by the median, mean, maximum, or minimum helix angle (HA) along the tract. An index of tract coherence was derived from the relationship between these HA statistics. Histological validation was performed using phase-contrast microscopy. In normal hearts, the subendocardial and subepicardial myofibers had a positive and negative HA, respectively, forming a symmetric distribution around the midmyocardium. However, in the remote zone of the infarcted hearts, a significant positive shift in HA was observed. The ratio between negative and positive HA variance was reduced from 0.96 ± 0.16 in normal hearts to 0.22 ± 0.08 in the remote zone of the remodeled hearts (p layers of the myocardium. Tractography-based quantification, performed here for the first time in remodeled hearts, may provide a framework for assessing regional changes in the left ventricle following infarction.

Isolated noncompaction of myocardium associated with calcification in the interventricular septum.

Science.gov (United States)

Nil, M; Mori, K; Yuasa, Y; Ichida, F

2003-01-01

We describe a 12-year-old male with isolated noncompaction of the myocardium and associated abnormal calcification in the basal interventricular septum, and we present a review of the literature. The patient has been healthy and free of symptoms. The electrocardiogram showed abnormal Q waves in III, V1, V2, and ST elevation in V1-V3. Exercise testing demonstrated ST depression in V4 and V5. Myocardial scintigraphic examination showed a regional reduction in iodine-1,2,3-beta-methyl-iodophenylpentadecanoic acid uptake in the basal interventricular septum. Since coronary angiography demonstrated normal coronary vessels and the trabeculations were not prominent in this region, we hypothesize that coronary microcirculatory dysfunction may cause subendocardial infarction associated with calcification in the same area.

The myocardium functional reserve indicators in junior children with recurrent acute upper respiratory tract infection

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L.S. Ovcharenko

2017-02-01

Full Text Available Background. The problem of early diagnosis of cardiovascular diseases in children is relevant throughout the world and in Ukraine, as in childhood the health and quality of life of an adult are formed. The psychoemotional stress in junior children as well as increasingly complicating school curriculum, information overload with electronic gadgets, increased frequency of colds in children cause physical inactivity. In addition, infectious agents have a toxic effect on the myocardium, altering its functional state. All these together adversely affect the formation and development of the cardiovascular and respiratory systems of children. The aim was to study the functional reserve of the myocardium in junior children, depending on the frequency of upper respiratory tract infection (URTI. Materials and methods. The study examined 1109 children aged 6 to 9 years old. The URTI incidence was analyzed depending on the age. In the study, the children were divided into two groups. Group 1 consisted of the children with URTI — 210. Group 2 involved the children with occasional URTI — 899. Results. Among 210 surveyed children with upper respiratory infections 171 schoolboys (81.4 % had reduced functional reserve of the myocardium, which is consistent with findings from other studies. In children aged 7 and 9 years old, the number of reduced functional reserve of the myocardium varies from 70 to 82 % in seven-year children, among the schoolboys aged 6 and 8 years old the incidence of reduced functional reserve of the myocardium increased from 83 to 100 % in six-year children. Conclusions. Children with URTI have a reduced functional reserve of the myocardium. Children with episodic URTI have higher rates of functional reserve of the myocardium, therefore reducing the incidence of URTI will lead to the improvement of the myocardium functional state.

Perfusion single photon emission computed tomography of myocardium with 99mTc-tetra-phosmine (Myoview)

International Nuclear Information System (INIS)

Khusainova, Sh.K.; Zholdybaj, Zh.; Potapov, A.V.; Karaev, O.S.; Akhmetova, G.R.

2003-01-01

The aim of the work is study of diagnostic valuation of myocardium scintigraphy with help of the 99m Tc-tetrophosmin, Myoview in determination of latent coronary blood-circulation destabilization in liquidators of the Chernobyl accident (LChA) and persons living in the Semipalatinsk test site (STS) region. The perfusion myocardium scintigraphy was made to 71 patients (5 women and 66 men) from those - 33 LChA and 37 - residents of STS region. The examination was carried out in 'ADAC Genesys Epic' apparatus (USA). Mean age of the patients was 46.3±2.3 years old. In the result of examination the left ventricle myocardium perfusion reduction on 30 % and more was revealed. The distribution of radiopharmaceutical by the myocardium parts were relatively proportional both with pharmacologic load (ATF, dipiridamol) and the rest in 48 (67.7 %) patients. So, the 99m Tc-tetrophosmin, Myoview pharmaceutical allows with high rate estimate the myocardium perfusion and get a high qualitative images, that permits to identify localization, character and distribution of myocardium perfusion reduction in the revealed areas. In the result of myocardine scintigraphy with the pharmacologic load trial conducting the both the latent coronary blood-circulation destabilization forms and the incoming ones were differentiated

Immunohistochemical evidence for expression of fast-twitch type sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA1) in German shepherd dogs with dilated cardiomyopathy myocardium.

Science.gov (United States)

Summerfield, Nuala; Peters, Mary E; Hercock, Carol A; Mobasheri, Ali; Young, Iain S

2010-04-01

Dilated cardiomyopathy (DCM) is one of the most common acquired canine heart diseases. It is particularly common in large and giant breed dogs. Although a great deal is known about the clinical progression and manifestations of the disease, the underlying cellular and molecular mechanisms remain poorly understood. One widely held belief is that calcium-handling abnormalities are critically involved in the disease process. This study investigates the changes in expression of the sarco(endo)plasmic reticulum calcium ATPase (SERCA) isoforms in DCM myocardium from German shepherd dogs. Affected tissue samples were obtained from German shepherd dogs with DCM, euthanized for intractable congestive heart failure while normal myocardial tissue samples were obtained from German shepherd dogs, euthanized for non-cardiovascular reasons. Tissue microarrays containing normal and DCM myocardium samples were prepared, immunostained with SERCA1 and SERCA2 antibodies and analyzed. We were able to demonstrate, for the first time, that while there is little change in the expression of the cardiac isoform (SERCA2), there is clear expression of the fast-twitch skeletal muscle isoform SERCA1 in the myocardium of dogs diagnosed with DCM. We propose that SERCA1 expression is evidence of a natural adaptive response to the impaired Ca2+ handling thought to occur in German shepherd dogs with DCM and heart failure. Copyright 2010 Elsevier B.V. All rights reserved.

Measurement of infarct size and percentage myocardium infarcted in a dog preparation with single photon-emission computed tomography, thallium-201, and indium 111-monoclonal antimyosin Fab

International Nuclear Information System (INIS)

Johnson, L.L.; Lerrick, K.S.; Coromilas, J.

1987-01-01

Single photon-emission tomography (SPECT) and indium 111-labeled monoclonal antimyosin Fab fragments were used to measure myocardial infarct size in 12 dogs, six subjected to balloon catheter-induced coronary artery occlusion for 6 hr (late reperfusion) and six subjected to occlusion with reperfusion at 2 hr (early reperfusion). Tomographic imaging was performed 24 hr after the intravenous injection of labeled Fab fragments with the use of a dual-head SPECT camera with medium-energy collimators. Immediately after the first tomographic scan, thallium-201 was injected into nine of 12 dogs and imaging was repeated. Estimated infarct size in grams was calculated from transaxially reconstructed, normalized, and background-corrected indium SPECT images with the use of a threshold technique for edge detection. Estimated noninfarcted myocardium in grams was calculated from obliquely reconstructed thallium SPECT images by a similar method. The animals were killed and infarct size in grams and true infarct size as a percentage of total left ventricular myocardial volume were measured by triphenyl tetrazolium chloride staining. Estimated infarct size from indium SPECT images showed an excellent correlation with true infarct size (r = .95, SEE = 4.1 g). Estimated percentage myocardium infarcted was calculated by dividing estimated infarct size from indium images by the sum of estimated infarct size plus estimated noninfarcted myocardium obtained from thallium images. Correlation between the estimated percentage of myocardium infarcted and true percentage of myocardium infarcted was excellent

MRI in the diagnosis of non-compacted ventricular Myocardium (NCVM) compared to echocardiography

International Nuclear Information System (INIS)

Weiss, F.; Habermann, C.R.; Sievers, J.; Weil, J.; Adam, G.; Lilje, C.; Razek, W.

2003-01-01

Purpose: To report the detection of con-compacted ventricular myocardium (NVCM) with MRI compared to echocardiography in 8 patients. Material and methods: Non-compaction of the ventricular myocardium is a congenital disorder characterized by an altered structure of the myocardial wall resulting from an intrauterine arrest in endomyocardial embryogenesis. The morphological findings consist of a prominent meshwork of multiple myocardial trabeculations and deep intertrabecular recesses, communicating with the left ventricular cavity. 8 consecutive patients (mean age 7.3 years) with clinical and echocardiographic signs of NCVM were examined by MRI (1.5 T, Vision, Siemens) in short axis and 2- and 4-chamber views, using T 1 -weighted TSE and Cine-GRE in 6 patients and true FISP sequences in 2 patients. MRI and echocardiography were evaluated for visibility, signs of NCVM and involvement of myocardial wall segments. Thickness was measured for non-compacted and compacted myocardium and the non-compacted to compacted (N/C) ratio calculated. Results: MRI diagnosed 6 of 8 patients of having NCVM. Myocardial thickness as measured by echocardiography and MRI showed a good correlation in compacted myocardium (r = 0.82) and no correlation in non-compacted myocardium (r = 0.4). In 2 cases, non-compacted myocardium was detected, but echocardiography did not reach the N/C ratio > 2 as required to diagnose NCVM in accordance with the criteria found in the literature. Both patients were also misdiagnosed by MRI performed with Cine-GRE. MRI reached a N/C ratio > 2 in only three patients. Newer TruFisp sequences showed no definite advantages. Extent of non-compaction could be visualized correctly with MRI. (orig.) [de

Comparative study between MRI and echocardiography in noncompaction of ventricular myocardium

International Nuclear Information System (INIS)

Sun Ziyan; Xia Liming; Wang Chengyuan; Rao Jingjing; Shenyu Weihui

2007-01-01

Objective: To investigate the MRI and echocardiography manifestations of noncompaction of ventricular myocardium(NVM) and assess the role of MR1 in the diagnosis of NVM by comparing it with echocardiography. Methods: Fourteen cases of NVM diagnosed by echocardiography were examined with MRI, including scanning of black-blood sequences, double inversion recovery fast spin echo (DIBFSE) and triple inversion recovery fast spin echo (TIRFSE), and white blood sequence: fast imaging employ steady state acquisition (FIESTA). Scanning plane includes short axis view, four-chamber view and long axis view. Results: Both MRI and echocardiography displayed involvement of left ventricles in thirteen cases and involvement of double ventricles in one case. Apexes of heart and the intermedius are commonly affected. MRI showed 54 segments and echocardiography showed 53 segments affected, and there is no significant difference between the capability of MRI and echocardiography (P=1,000). The affected myocardium consisted of two layers: subendocardial noncompacted myocardium and epicardial compacted myocardium, and the ratio measurement of N/C by MRI was 3.37±0.89 and it was 3.19±0.82 by echocardiography. Noncompacted myocardium was characterized by prominent and excessive myocardial trabeculations and deep intratrabecular recesses, in which the blood flow was communicated with the ventricle. One case was complicated with ventricular aneurysm, and coronary arteriography was performed with unremarkable findings. One case underwent heart transplantation because of progressive heart failure, Gross findings demonstrated prominent muscular' trabeculations with deep intratrabecular recesses, which coincided well with MRI findings. Conclusion: The MRI manifestation of NVM is characteristic, and MRI with multiple series and planes is helpful in the diagnose of NVM. Compared with echocardiography, MRI could display the pathological cardiac muscle more clearly, because of its high soft

In vitro cultured progenitors and precursors of cardiac cell lineages from human normal and post-ischemic hearts

Directory of Open Access Journals (Sweden)

F Di Meglio

2009-08-01

Full Text Available The demonstration of the presence of dividing primitive cells in damaged hearts has sparked increased interest about myocardium regenerative processes. We examined the rate and the differentiation of in vitro cultured resident cardiac primitive cells obtained from pathological and normal human hearts in order to evaluate the activation of progenitors and precursors of cardiac cell lineages in post-ischemic human hearts. The precursors and progenitors of cardiomyocyte, smooth muscle and endothelial lineage were identified by immunocytochemistry and the expression of characteristic markers was studied by western blot and RT-PCR. The amount of proteins characteristic for cardiac cells (a-SA and MHC, VEGFR-2 and FVIII, SMA for the precursors of cardiomyocytes, endothelial and smooth muscle cells, respectively inclines toward an increase in both a-SA and MHC. The increased levels of FVIII and VEGFR2 are statistically significant, suggesting an important re-activation of neoangiogenesis. At the same time, the augmented expression of mRNA for Nkx 2.5, the trascriptional factor for cardiomyocyte differentiation, confirms the persistence of differentiative processes in terminally injured hearts. Our study would appear to confirm the activation of human heart regeneration potential in pathological conditions and the ability of its primitive cells to maintain their proliferative capability in vitro. The cardiac cell isolation method we used could be useful in the future for studying modifications to the microenvironment that positively influence cardiac primitive cell differentiation or inhibit, or retard, the pathological remodeling and functional degradation of the heart.

Experimental study of 31P MR spectroscopy in vitro canine myocardium

International Nuclear Information System (INIS)

Gao Fabao; Zhao Haitao; Suo Liping; Zhang Yushun; Fang Hong; Huang Zhilan

1999-01-01

Objective: To conduct a dynamic survey of the metabolism of high-energy phosphates in myocardium in order to define, the relationship between the changes in myocardial energy metabolism and the duration of ischemia. Methods: A dynamic survey of isolated heart of 8 dogs was done with the use of 31 P MRS. Results: Myocardial PCr level decreased rapidly after the heart was isolated and was reduced to zero in 2-3 hours. ATP level diminished progressively to its depletion at 6 hours following isolation. Conclusions: After the heart was isolated, the PCr level rapidly decreased and was reduced to zero in 2-3 hours whereas ATP was not depleted until 4-6 hours after isolation. The ATP level remained within normal limits as long as PCr had not been depleted

Stereological Cell Morphometry In Right Atrium Myocardium Of Primates

Science.gov (United States)

Mandarim-De-Lacerda, Carlos A...; Hureau, Jacques

1986-07-01

The mechanism by which the cardiac impulse is propagated in normal hearts from its origin in the sinus node to the atrio-ventricular node has not been agreed on fully. We studied the "internodal posterior tract" through the crista terminalis by light microscopy and stereological morphometry. The hearts of 12 Papio cynocephalus were perfused , after sacrifice,with phosphate-buffered formol saline. The regions of the crista terminalis (CT), interatrial septum (IAS), atrioventricular bundle (AVB) and interventricular septum (IVS) were cut off and embedded in paraplast and sectioned (10 4m). The multipurpose test system M 42 was superimposed over the photomicrographs (1,890 points test, ESR = 2%) to the stereological computing. The quantitative results show that the cells from CT were more closely relationed with IAS cells than others cells (IVS and AVB cells). This results are not a morphological evidence to establish the specificity of the "internodal posterior tract". The cellular arrangement and anatomical variation in CT myocardium is very important.

Study of shape memory alloy fibers for the development of artificial myocardium.

Science.gov (United States)

Hassoulas, Ioannis A; Ladopoulos, Vlassios S; Kalogerakos, Paris-Dimitrios K

2010-01-01

Circulatory support devices are employed to treat heart failure. Such a device could be made from shape memory alloy (SMA) fibers. These Ni-Ti fibers contract when electric current flows through them, thus resembling artificial muscles. An artificial myocardium device made from SMA fibers can directly compress the epicardial surface of a failing heart, thus contributing to the pumping action. Unlike modern mechanical circulatory support devices, there is no blood-contacting surface to provoke thromboembolism, hemorrhage, inflammatory response or hemolysis. The experimental setup permitted a detailed study of a sample SMA fiber with great accuracy while the ambient temperature was controlled to resemble that of the human body. The current profile through the fiber was controlled (current shaping, CS) by a microcontroller and a portable computer. Parameters such as strain, contraction and relaxation velocities and the effect of ambient temperature were measured. The contraction and relaxation velocities were measured after applying various effective currents. It was found that the contraction velocity could be manipulated to reach that of the healthy myocardium through CS. On the other hand, the relaxation velocity was independent of the contraction velocity. A cardiac assist device can be made from SMA fibers. More studies need to be conducted in this direction.

Radiolabeled Rhein as Small-Molecule Necrosis Avid Agents for Imaging of Necrotic Myocardium.

Science.gov (United States)

Luo, Qi; Jin, Qiaomei; Su, Chang; Zhang, Dongjian; Jiang, Cuihua; Fish, Anne Folta; Feng, Yuanbo; Ni, Yicheng; Zhang, Jian; Yin, Zhiqi

2017-01-17

A rapid and accurate identification of necrotic myocardium is of great importance for diagnosis, risk stratification, clinical decision-making, and prognosis evaluation of myocardial infarction. Here, we explored technetium-99m labeled rhein derivatives for rapid imaging of the necrotic myocardium. Three hydrazinonicotinic acid-linker-rhein (HYNIC-linker-rhein) derivatives were synthesized, and then, these synthetic compounds were labeled with technetium-99m using ethylenediaminediacetic acid (EDDA) and tricine as coligands [ 99m Tc(EDDA)-HYNIC-linker-rhein]. The necrosis avidity of the three 99m Tc-labeled rhein derivatives was tested in a mouse model of ethanol-induced muscular necrosis by gamma counting, histochemical staining, and autoradiography. A lead tracer for visualization of necrotic myocardium was assessed by single photon emission computed tomography/computed tomography (SPECT/CT) imaging in a rat model with reperfused myocardial infarction. The necrosis avidity mechanism of the tracer was explored by DNA binding studies in vitro and blocking experiments in vivo. Results showed that the uptake in necrotic muscles of the three 99m Tc-compounds was higher than that in viable muscles (P EDDA)-HYNIC-ethylenediamine-rhein [ 99m Tc(EDDA)-HYNIC-2C-rhein] displayed the best distribution profiles for imaging. The necrotic myocardium lesions were clearly visualized by SPECT/CT using 99m Tc(EDDA)-HYNIC-2C-rhein at 1 h after injection. The necrotic-to-viable myocardium and necrotic myocardium-to-blood uptake ratios of 99m Tc(EDDA)-HYNIC-2C-rhein were 4.79 and 3.02 at 1 h after injection. DNA binding studies suggested HYNIC-linker-rhein bound to DNA through intercalation. The uptake of 99m Tc(EDDA)-HYNIC-2C-rhein in necrotic muscle was significantly blocked by excessive unlabeled rhein, with 77.61% decline at 1 h after coinjection. These findings suggested 99m Tc(EDDA)-HYNIC-2C-rhein emerged as a "hot spot" imaging probe that has a potential for rapid imaging of

Probing myocardium biomechanics using quantitative optical coherence elastography

Science.gov (United States)

Wang, Shang; Lopez, Andrew L.; Morikawa, Yuka; Tao, Ge; Li, Jiasong; Larina, Irina V.; Martin, James F.; Larin, Kirill V.

2015-03-01

We present a quantitative optical coherence elastographic method for noncontact assessment of the myocardium elasticity. The method is based on shear wave imaging optical coherence tomography (SWI-OCT), where a focused air-puff system is used to induce localized tissue deformation through a low-pressure short-duration air stream and a phase-sensitive OCT system is utilized to monitor the propagation of the induced tissue displacement with nanoscale sensitivity. The 1-D scanning of M-mode OCT imaging and the application of optical phase retrieval and mapping techniques enable the reconstruction and visualization of 2-D depth-resolved shear wave propagation in tissue with ultra-high frame rate. The feasibility of this method in quantitative elasticity measurement is demonstrated on tissue-mimicking phantoms with the estimated Young's modulus compared with uniaxial compression tests. We also performed pilot experiments on ex vivo mouse cardiac muscle tissues with normal and genetically altered cardiomyocytes. Our results indicate this noncontact quantitative optical coherence elastographic method can be a useful tool for the cardiac muscle research and studies.

Neurogenic Stunned Myocardium Associated with Acute Spinal Cord Infarction: A Case Report

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Gillian A. Beauchamp

2012-01-01

Full Text Available Introduction. Neurogenic stunned myocardium (NSM is a reversible cardiomyopathy resulting in transient left ventricular apical ballooning presumed to result from catecholamine surge occurring under physiologic stress. Acute spinal cord ischemia is a rare ischemic vascular lesion. We report a case of neurogenic stunned myocardium occurring in the setting of acute spinal cord infarction. Methods. Singe case report was used. Results. We present the case of a 63-year-old female with a history of prior lacunar stroke, hypertension, chronic back pain, and hypothyroidism who presented with a brief episode of diffuse abdominal and bilateral lower extremity pain which progressed within minutes to bilateral lower extremity flaccid paralysis. MRI of the spinal cord revealed central signal hyperintensity of T2-weighted imaging from conus to T8 region, concerning for acute spinal cord ischemia. Transthoracic echocardiogram was performed to determine if a cardiac embolic phenomenon may have precipitated this ischemic event and showed left ventricular apical hypokinesis and ballooning concerning for NSM. Conclusion. Neurogenic stunned myocardium is a reversible cardiomyopathy which has been described in patients with physiologic stress resulting in ventricular apical ballooning. Our case suggests that it is possible for neurogenic stunned myocardium to occur in the setting of acute spinal cord ischemia.

A Review of Neurogenic Stunned Myocardium

OpenAIRE

Biso, Sylvia; Wongrakpanich, Supakanya; Agrawal, Akanksha; Yadlapati, Sujani; Kishlyansky, Marina; Figueredo, Vincent

2017-01-01

Neurologic stunned myocardium (NSM) is a phenomenon where neurologic events give rise to cardiac abnormalities. Neurologic events like stroke and seizures cause sympathetic storm and autonomic dysregulation that result in myocardial injury. The clinical presentation can involve troponin elevation, left ventricular dysfunction, and ECG changes. These findings are similar to Takotsubo cardiomyopathy and acute coronary syndrome. It is difficult to distinguish NSM from acute coronary syndrome bas...

Immunolocalization of transforming growth factor alpha in normal human tissues

DEFF Research Database (Denmark)

Christensen, M E; Poulsen, Steen Seier

1996-01-01

anchorage-independent growth of normal cells and was, therefore, considered as an "oncogenic" growth factor. Later, its immunohistochemical presence in normal human cells as well as its biological effects in normal human tissues have been demonstrated. The aim of the present investigation was to elucidate...... the distribution of the growth factor in a broad spectrum of normal human tissues. Indirect immunoenzymatic staining methods were used. The polypeptide was detected with a polyclonal as well as a monoclonal antibody. The polyclonal and monoclonal antibodies demonstrated almost identical immunoreactivity. TGF......-alpha was found to be widely distributed in cells of normal human tissues derived from all three germ layers, most often in differentiated cells. In epithelial cells, three different kinds of staining patterns were observed, either diffuse cytoplasmic, cytoplasmic in the basal parts of the cells, or distinctly...

Application of cine cardiac MR imaging in normal subjects and patients with valvular, coronary artery, and aortic disease

International Nuclear Information System (INIS)

Maddahi, J.; Ostrzega, E.; Crues, J.; Honma, H.; Siegel, R.; Charuzi, Y.; Berman, D.

1987-01-01

Cine MR imaging was performed on 15 normal subjects and 27 patients with cardiac disease. In normal subjects, high signal intensity of flowing blood contrasted with that of the myocardium. In 16 patients with valvular regurgitation, signal void jet due to turbulence was visualized across the diseased valves. In three IHSS patients, thickened LV myocardium, mitral regurgitant jets, and systolic LV outflow jets were noted. Five patients with myocardial infarction (MI) showed thinning and/or hypokinesis of MI regions. In three patients with Marfan syndrome, aortic dilatation, insufficiency, and flap (one pt) were identified. Cine MR imaging is potentially useful for evaluation of a variety of cardiac diseases

DNA amplification is rare in normal human cells

International Nuclear Information System (INIS)

Wright, J.A.; Watt, F.M.; Hudson, D.L.; Stark, G.R.; Smith, H.S.; Hancock, M.C.

1990-01-01

Three types of normal human cells were selected in tissue culture with three drugs without observing a single amplification event from a total of 5 x 10 8 cells. No drug-resistant colonies were observed when normal foreskin keratinocytes were selected with N-(phosphonacetyl)-L-aspartate or with hydroxyurea or when normal mammary epithelial cells were selected with methotrexate. Some slightly resistant colonies with limited potential for growth were obtained when normal diploid fibroblast cells derived from fetal lung were selected with methotrexate or hydroxyurea but careful copy-number analysis of the dihydrofolate reductase and ribonucleotide reductase genes revealed no evidence of amplification. The rarity of DNA amplification in normal human cells contrasts strongly with the situation in tumors and in established cell lines, where amplification of onogenes and of genes mediating drug resistance is frequent. The results suggest that tumors and cell lines have acquired the abnormal ability to amplify DNA with high frequency

Review of the emerging role of optical polarimetry in characterization of pathological myocardium.

Science.gov (United States)

Ahmad, Iftikhar

2017-10-01

Myocardial infarction (MI), a cause of significant morbidity and mortality, is typically followed by microstructural alterations where the necrotic myocardium is steadily replaced with a collagen scar. Engineered remodeling of the fibrotic scar via stem cell regeneration has been shown to improve/restore the myocardium function after MI. Nevertheless, the heterogeneous nature of the scar patch may impair the myocardial electrical integrity, leading to the formation of arrhythmogenesis. Radiofrequency ablation (RFA) offers an effective treatment for focal arrhythmias where local heating generated via electric current at specific spots in the myocardium ablate the arrhythmogenic foci. Characterization of these myocardial pathologies (i.e., infarcted, stem cell regenerated, and RFA-ablated myocardial tissues) is of potential clinical importance. Optical polarimetry, the use of light to map and characterize the polarization signatures of a sample, has emerged as a powerful imaging tool for structural characterization of myocardial tissues, exploiting the underlying highly fibrous tissue nature. This study aims to review the recent progress in optical polarimetry pertaining to the characterization of myocardial pathologies while describing the underlying biological rationales that give rise to the optical imaging contrast in various pathologies of the myocardium. Future possibilities of and challenges to optical polarimetry in cardiac imaging clinics are also discussed. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Saffold virus infection associated with human myocarditis

DEFF Research Database (Denmark)

Nielsen, Trine Skov; Nielsen, Alex Yde; Banner, Jytte

2016-01-01

BACKGROUND: Saffold virus was described in 2007 as one of the first human viruses within the genus cardioviruses. Cardioviruses may cause severe infections of the myocardium in animals, and several studies have associated saffold virus with human disease. As a result, saffold virus has been...... isolated from different anatomical compartments, including the myocardium, but, until now, it has not been possible to demonstrate the accompanying histopathological signs of inflammation. OBJECTIVES: The aim of the study was to examine if saffold virus is capable of causing invasive infection in the human...... myocardium. STUDY DESIGN: Using real-time PCR, we retrospectively examined formalin-fixed paraffin embedded cardiac tissue specimens from 150 deceased individuals diagnosed with myocarditis at autopsy. The results were compared with histological findings. RESULTS AND CONCLUSIONS: Saffold virus was detected...

Activin receptor subunits in normal and dysfunctional adult human testis

DEFF Research Database (Denmark)

Dias, V; Meachem, S; Rajpert-De Meyts, E

2008-01-01

The cellular sites of activin action and its regulation in the normal and dysfunctional adult human testis are unknown.......The cellular sites of activin action and its regulation in the normal and dysfunctional adult human testis are unknown....

Radioimmunoassay of human cardiac tropomyosin in acute myocardial infarction

International Nuclear Information System (INIS)

Cummins, P.; McGurk, B.; Littler, W.A.

1981-01-01

Tropomyosin was prepared from fresh human myocardium and antisera raised in rabbits. A sensitive radioimmunoassay was developed for the detection of human cardiac 125 I-labelled tropomyosin in human sera down to levels of 1 ng/ml. Values for human cardiac tropomyosin in normal patients ranged from less than 1 to 3 ng/ml. In 18 patients with acute myocardial infarction all had elevated tropomyosin levels ranging from 41 to above 200 ng/ml with a mean peak level of 101 ng/ml. In this study there were no false positive or false negative results. In the initial stages of infarction the time course of appearance and peak levels of cardiac tropomyosin, total creatine kinase and creatine kinase MB isoenzyme were similar. Although total creatine kinase and creatine kinase MB isoenzyme levels were normal after 72 h in patients with single, uncomplicated infarction, cardiac tropomyosin levels were still significantly elevated above normal after this time, being 30-60% of peak values. Radioimmunoassay of human cardiac tropomyosin may prove useful in the diagnosis and in the management of patients with acute myocardial infarction, particularly in the long-term postinfarction period. (author)

Imaging of the myocardium using {sup 18}F-FDG-PET/MRI

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Ferda, Jiří, E-mail: ferda@fnplzen.cz [Clinic of the Imaging Methods, University Hospital Plzen, Alej Svobody 80, 304 60 Plzeň (Czech Republic); Hromádka, Milan, E-mail: hromadkam@fnplzen.cz [Department of Cardiology, University Hospital Plzen, Alej Svobody 80, 304 60 Plzeň (Czech Republic); Baxa, Jan, E-mail: baxaj@fnplzen.cz [Clinic of the Imaging Methods, University Hospital Plzen, Alej Svobody 80, 304 60 Plzeň (Czech Republic)

2016-10-15

Highlights: • The natural combination of the metabolic and structural information is the most important strenghtof myocardial PET/MRI. • Metabolic conversion to glycolysis is needed in the assesment ov the viable myocardium. • Metabolic conversion to the fatty acid metabolism is the crucial in the assesment of the ischemic memory and myocardial inflammation. - Abstract: The introduction of the integrated hybrid PET/MRI equipment creates the possibility to perform PET and MRI simultaneously. Depending on the clinical question, the metabolic conversion to glycolytic activity or beta-oxidation is performed before the application of FDG. Since FDG aids to evaluate the energetic metabolism of the myocytes and myocardial MRI reaches the imaging capabilities of perfusion and tissue characterization in the daily routine, FDG-PET/MRI looks to be a promising method of PET/MRI exploitation in cardiac imaging. When myocardial FDG uptake should be evaluated in association with the perfusion distribution, the cross-evaluation of FDG accumulation distribution and perfusion distribution pattern is necessary. The different scenarios may be used in the assessment of myocardium, the conversion to glycolytic activity is used in the imaging of the viable myocardium, but the glycolytic activity suppression might be used in the indications of the identification of injured myocardium by ischemia or inflammation. FDG-PET/MRI might aid to answer the clinical tasks according to the structure, current function and possibilities to improve the function in ischemic heart disease or to display the extent or activity of myocardial inflammation in sarcoidosis. The tight coupling between metabolism, perfusion and contractile function offers an opportunity for the simultaneous assessment of cardiac performance using one imaging modality.

Deterministic Encapsulation of Human Cardiac Stem Cells in Variable Composition Nanoporous Gel Cocoons To Enhance Therapeutic Repair of Injured Myocardium.

Science.gov (United States)

Kanda, Pushpinder; Alarcon, Emilio I; Yeuchyk, Tanya; Parent, Sandrine; de Kemp, Robert A; Variola, Fabio; Courtman, David; Stewart, Duncan J; Davis, Darryl R

2018-04-20

Although cocooning explant-derived cardiac stem cells (EDCs) in protective nanoporous gels (NPGs) prior to intramyocardial injection boosts long-term cell retention, the number of EDCs that finally engraft is trivial and unlikely to account for salutary effects on myocardial function and scar size. As such, we investigated the effect of varying the NPG content within capsules to alter the physical properties of cocoons without influencing cocoon dimensions. Increasing NPG concentration enhanced cell migration and viability while improving cell-mediated repair of injured myocardium. Given that the latter occurred with NPG content having no detectable effect on the long-term engraftment of transplanted cells, we found that changing the physical properties of cocoons prompted explant-derived cardiac stem cells to produce greater amounts of cytokines, nanovesicles, and microRNAs that boosted the generation of new blood vessels and new cardiomyocytes. Thus, by altering the physical properties of cocoons by varying NPG content, the paracrine signature of encapsulated cells can be enhanced to promote greater endogenous repair of injured myocardium.

Effects of isoproterenol on myocardium

International Nuclear Information System (INIS)

Barker, M.E.; Lieber, J.G.; Budinger, T.F.

1982-01-01

In the course of autoradiographic studies designed to localize 14 C-taurine within the cells of the rat myocardium, severe tissue damage was noted after stimulation by very low levels of isoproterenol. This β-adrenergic agonist had previously been shown by others to modulate taurine uptake by what appeared to be a very specific mechanism, but our studies have led to a different mechanism. Within four hours after injection of isoproterenol at all concentrations used, pronounced edema of myocytes in the subendocardium was noted; this was followed by an inflammatory reation and degeneration of mitochondria and myofilaments

Distinction of salvaged and infarcted myocardium within the ischaemic area-at-risk with T2 mapping

DEFF Research Database (Denmark)

Hammer-Hansen, Sophia; Ugander, Martin; Hsu, Li-Yueh

2014-01-01

values from T2 maps and signal intensities on T2-weighted images were measured in the corresponding areas. RESULTS: At both imaging time points, the T2 of the salvaged myocardium was longer than of remote (66.0 ± 6.9 vs. 51.4 ± 3.5 ms, P ...AIM: Area-at-risk (AAR) measurements often rely on T2-weighted images, but subtle differences in T2 may be overlooked with this method. To determine the differences in oedema between salvaged and infarcted myocardium, we performed quantitative T2 mapping of the AAR. We also aimed to determine...... (14.7 ± 5.6 vs. 8.7 ± 5.1 ms, P = 0.02). CONCLUSIONS: T2 relaxation parameters are different in the infarcted and salvaged myocardium, and both are significantly longer than remote. Furthermore, the magnitude of increase in T2 was less in the salvaged myocardium after longer reperfusion, indicating...

Bacteriostatic enterochelin-specific immunoglobulin from normal human serum

Energy Technology Data Exchange (ETDEWEB)

Moore, D.G.; Yancey, R.J.; Lankford, C.E.; Earhart, C.F.

1980-02-01

Heat-inactivated normal human serum produces iron-reversible bacteriostasis of a number of microorganisms. This inhibitory effect was abolished by adsorption of serum with ultraviolet-killed cells of species that produce the siderophore enterochelin. Bacteriostasis also was alleviated by asorption of serum with 2,3-dihydroxy-N-benzoyl-L-serine, a degradation product of enterochelin, bound to the insoluble matrix AH-Sepharose 4B. Our results indicate that enterochelin-specific immunoglobulins exist in normal human serum. These immunoglobulins may act synergistically with transferrin to effect bacteriostasis of enterochelin-producing pathogens.

Bile acids induce arrhythmias in human atrial myocardium--implications for altered serum bile acid composition in patients with atrial fibrillation.

Science.gov (United States)

Rainer, Peter P; Primessnig, Uwe; Harenkamp, Sandra; Doleschal, Bernhard; Wallner, Markus; Fauler, Guenter; Stojakovic, Tatjana; Wachter, Rolf; Yates, Ameli; Groschner, Klaus; Trauner, Michael; Pieske, Burkert M; von Lewinski, Dirk

2013-11-01

High bile acid serum concentrations have been implicated in cardiac disease, particularly in arrhythmias. Most data originate from in vitro studies and animal models. We tested the hypotheses that (1) high bile acid concentrations are arrhythmogenic in adult human myocardium, (2) serum bile acid concentrations and composition are altered in patients with atrial fibrillation (AF) and (3) the therapeutically used ursodeoxycholic acid has different effects than other potentially toxic bile acids. Multicellular human atrial preparations ('trabeculae') were exposed to primary bile acids and the incidence of arrhythmic events was assessed. Bile acid concentrations were measured in serum samples from 250 patients and their association with AF and ECG parameters analysed. Additionally, we conducted electrophysiological studies in murine myocytes. Taurocholic acid (TCA) concentration-dependently induced arrhythmias in atrial trabeculae (14/28 at 300 µM TCA, pursodeoxycholic acid did not. Patients with AF had significantly decreased serum levels of ursodeoxycholic acid conjugates and increased levels of non-ursodeoxycholic bile acids. In isolated myocytes, TCA depolarised the resting membrane potential, enhanced Na(+)/Ca(2+) exchanger (NCX) tail current density and induced afterdepolarisations. Inhibition of NCX prevented arrhythmias in atrial trabeculae. High TCA concentrations induce arrhythmias in adult human atria while ursodeoxycholic acid does not. AF is associated with higher serum levels of non-ursodeoxycholic bile acid conjugates and low levels of ursodeoxycholic acid conjugates. These data suggest that higher levels of toxic (arrhythmogenic) and low levels of protective bile acids create a milieu with a decreased arrhythmic threshold and thus may facilitate arrhythmic events.

Fiber architecture in remodeled myocardium revealed with a quantitative diffusion CMR tractography framework and histological validation

Directory of Open Access Journals (Sweden)

Mekkaoui Choukri

2012-10-01

Full Text Available Abstract Background The study of myofiber reorganization in the remote zone after myocardial infarction has been performed in 2D. Microstructural reorganization in remodeled hearts, however, can only be fully appreciated by considering myofibers as continuous 3D entities. The aim of this study was therefore to develop a technique for quantitative 3D diffusion CMR tractography of the heart, and to apply this method to quantify fiber architecture in the remote zone of remodeled hearts. Methods Diffusion Tensor CMR of normal human, sheep, and rat hearts, as well as infarcted sheep hearts was performed ex vivo. Fiber tracts were generated with a fourth-order Runge-Kutta integration technique and classified statistically by the median, mean, maximum, or minimum helix angle (HA along the tract. An index of tract coherence was derived from the relationship between these HA statistics. Histological validation was performed using phase-contrast microscopy. Results In normal hearts, the subendocardial and subepicardial myofibers had a positive and negative HA, respectively, forming a symmetric distribution around the midmyocardium. However, in the remote zone of the infarcted hearts, a significant positive shift in HA was observed. The ratio between negative and positive HA variance was reduced from 0.96 ± 0.16 in normal hearts to 0.22 ± 0.08 in the remote zone of the remodeled hearts (p Conclusions A significant reorganization of the 3D fiber continuum is observed in the remote zone of remodeled hearts. The positive (rightward shift in HA in the remote zone is greatest in the subepicardium, but involves all layers of the myocardium. Tractography-based quantification, performed here for the first time in remodeled hearts, may provide a framework for assessing regional changes in the left ventricle following infarction.

The Histological Effects of L-arginine on Ventricular Myocardium in Iron Treated Male Rats

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M Sofiabadi

2012-05-01

Full Text Available

Background and Objectives: Iron overload is detrimental for the body and can create damage to different body tissues, such as myocardium by producing oxidative stress. Therefore, the antioxidant factors can neutralize iron induced damages. According to available reports, L-arginine as a precursor nitric oxide production has antioxidant effects. This study was carried out to evaluate the histological effects of iron overload on ventricular muscle and preventive role of L-arginine in male rats.

Methods: In this experiment, 40 male rats with weight range of 300-250g were divided at random into five equal groups including:1- Control, 2- Iron (10mg/kg, ip, 3- Iron(10mg/kg, ip+L-arginine (1mg/ml, po, 4- Iron (50mg/kg, ip and 5- Iron (50mg/kg,ip+L-arginine(1mg/ml,po. After treatment (6 weeks, the animals were anesthetized and the samples of left apical ventricular myocardium were taken out and morphological studies were done following fixation with 10% formalin and H&E staining. Microscopic parameters under study were cell swelling, vessel dilatation and hypercongestion, cell necrosis and tissue deformity. The type and severity of damage to the tissue were also noted. Data were analyzed using chi-square statistical procedure, and Pvalue≤0.05 were considered to be significant. 

Results: The data showed moderate changes in the ventricular myocardium of group 2 that was significant in comparison to the control group (P<0.05. The ventricular myocardium of group 3 showed low changes and wasn't significant in comparison to control group (P=0.84. The ventricular myocardium of the group 4 showed severe changes in comparison to the control group (P<0.01. The low change showed in the ventricular myocardium of group 5 that wasn't significant in comparison to the control group.

Conclusion: This study showed

Study of rNIS as a reporter gene monitoring rBMSC transplanted to rat myocardium

International Nuclear Information System (INIS)

Hu Shou; Lan Xiaoli; Cao Wei; Cao Guoxiang; Zhang Guopeng; Zhang Binqing; Wu Tao; Chang Wei; Zhang Yongxue

2010-01-01

Objective: To investigate the feasibility of rat sodium/iodide symporter (rNIS) as a reporter gene monitoring rat bone marrow mesenchymal cells (rBMSC) transplanted to rat myocardium in vivo. Methods: Recombinated adenovirus vector was constructed by rNIS/enhanced green fluorescence protein (EGFP) (Ad-rNIS/EGFP). rBMSC transfected by Ad-rNIS/EGFP were studied using fluorescence microscope. Fifteen rats were transplanted with rBMSC and randomly divided into three groups: rNIS group (with rNIS transfection), blocked group (with rNIS transfection) by oral intake of perchloric sodium before planar imaging (GE Millennium MPR SPECT), and control group (without rNIS transfection). All rats underwent 99 Tc m -pertechnetate planar imaging. The biological distribution of 99 Tc m -pertechnetate was studied. The expressions of rNIS gene and protein in myocardium were measured by real time polymerase chain reaction (PCR) and western blot, respectively. The expressions of CD 29 , CD 44 , CD 90 , CD 11 b, CD 34 and CD 45 were measured by immunohistochemistry. Results: rBMSC transfected by Ad-rNIS/EGFP showed EGFP expression under fluorescence microscope. The transplanted rat myocardium could be visualized on 99 Tc m -pertechnetate planar imaging in rNIS group. The relative uptake ratio (R heart /R hmb , RUR) was 6.7 ±0.4. RUR in control group (3.0 ±0.2) was lower than that in rNIS group (t =2.78, P=0.03). The percentage injection dose per gram of tissue (% ID/g) of the transplanted myocardium was 60.2 ± 20.8 in rNIS group, which was higher than that (2.5 ± 0.4) % ID/g of control group ( t = 7.13, P 29 , CD 44 and CD 90 were positive, CD 45 and CD 45 negative CD 11 b mildly positive in the myocardium transplanted with infective rBMSC. Conclusion: rNIS can efficiently monitor rBMSC transplanted to rat myocardium. (authors)

New perspectives in the treatment of damaged myocardium using autologous skeletal myoblasts

International Nuclear Information System (INIS)

Rigatelli, Gianluca; Rossini, Katia; Vindigni, Vincenzo; Mazzoleni, Francesco; Rigatelli, Giorgio; Carraro, Ugo

2004-01-01

Autologous skeletal myoblast transplantation may be used to ameliorate the healing process following myocardium infarct and, hopefully, cardiomyopathies. Despite successful animal experimentation, several issues need to be addressed in clinical settings, i.e., the impact of the delivery route, the extent of short- and long-term survival, and differentiation of the injected skeletal myoblasts. The authors offer some new hypotheses resulting from basic research, i.e., where and when to inject the myogenic cells, whatever their source, how to decrease new myofiber atrophy and improve their regeneration. Although these new hypotheses still need to be tested in humans, they may be decisive for future experimental studies and will lead to making endovascular cell implantation a more effective way to treat ischemic heart disease and failure

Genetic modification of stem cells for improved therapy of the infarcted myocardium.

Science.gov (United States)

Haider, Husnain Kh; Mustafa, Anique; Feng, Yuliang; Ashraf, Muhammad

2011-10-03

The conventional treatment modalities for ischemic heart disease only provide symptomatic relief to the patient without repairing and regenerating the damaged myocardium. Stem cell transplantation has emerged as a promising alternative therapeutic approach for cardiovascular diseases. Stem cells possess the potential of differentiation to adopt morphofunctional cardiac and vasculogenic phenotypes to repopulate the scar tissue and restore regional blood flow in the ischemic myocardium. These beneficial therapeutic effects make stem cell transplantation the method of choice for the treatment of ischemic heart disease. The efficacy of stem cell transplantation may be augmented by genetic manipulation of the cells prior to transplantation. Not only will insertion of therapeutic transgene(s) into the stem cells support the survival and differentiation of cells in the unfavorable microenvironment of the ischemic myocardium, but also the genetically manipulated stem cells will serve as a source of the transgene expression product in the heart for therapeutic benefits. We provide an overview of the extensively studied stem cell types for cardiac regeneration, the various methods in which these cells have been genetically manipulated and rationale of genetic modification of stem cells for use in regenerative cardiovascular therapeutics.

The effect of rigor mortis on the passage of erythrocytes and fluid through the myocardium of isolated dog hearts.

Science.gov (United States)

Nevalainen, T J; Gavin, J B; Seelye, R N; Whitehouse, S; Donnell, M

1978-07-01

The effect of normal and artificially induced rigor mortis on the vascular passage of erythrocytes and fluid through isolated dog hearts was studied. Increased rigidity of 6-mm thick transmural sections through the centre of the posterior papillary muscle was used as an indication of rigor. The perfusibility of the myocardium was tested by injecting 10 ml of 1% sodium fluorescein in Hanks solution into the circumflex branch of the left coronary artery. In prerigor hearts (20 minute incubation) fluorescein perfused the myocardium evenly whether or not it was preceded by an injection of 10 ml of heparinized dog blood. Rigor mortis developed in all hearts after 90 minutes incubation or within 20 minutes of perfusing the heart with 50 ml of 5 mM iodoacetate in Hanks solution. Fluorescein injected into hearts in rigor did not enter the posterior papillary muscle and adjacent subendocardium whether or not it was preceded by heparinized blood. Thus the vascular occlusion caused by rigor in the dog heart appears to be so effective that it prevents flow into the subendocardium of small soluble ions such as fluorescein.

[Influence of pacing site on myocardial transmural dispersion of repolarization in intact normal and dilated cardiomyopathy dogs].

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Bai, Rong; Pu, Jun; Liu, Nian; Lu, Jia-Gao; Zhou, Qiang; Ruan, Yan-Fei; Niu, Hui-Yan; Wang, Lin

2003-12-25

In order to verify the hypothesis that left ventricular epicardial (LV-Epi) pacing and biventricular (BiV) pacing unavoidably influence the myocardial electrophysiological characters and may result in high risk of malignant ventricular arrhythmia, we calculated, in both normal mongrel dogs and dog models with rapid-right-ventricular-pacing induced dilated cardiomyopathy congestive heart failure (DCM-CHF), the monophasic action potential duration (MAPD) and the transmural dispersion of repolarization (TDR) in intracardiac electrogram together with the QT interval and T(peak)-T(end) (T(p(-T(e)) interval in surface electrocardiogram (ECG) during LV-Epi and BiV pacing, compared with those during right ventricular endocardial (RV-Endo) pacing. To prepare the DCM-CHF dog model, rapid right ventricular pacing (250 bpm) was performed for 23.6+/-2.57 days to the dog. All the normal and DCM-CHF dogs were given radio frequency catheter ablation (RFCA) to His bundle with the guide of X-ray fluoroscopy. After the RFCA procedures, the animals were under the situation of complete atrioventricular block so that the canine heart rates could be voluntarily controlled in the following experiments. After a thoracotomy, ECG and monophasic action potentials (MAP) of subendocardial, subepicardial and mid-layer myocardium were recorded synchronously in 8 normal and 5 DCM-CHF dogs during pacing from endocardium of RV apex (RV-Endo), epicardium of LV anterior wall (LV-Epi) and simultaneously both of the above (biventricular, BiV), the later was similar to the ventricular resynchronization therapy to congestive heart failure patients in clinic. The Tp-Te) meant the interval from the peak to the end of T wave, which was a representative index of TDR in surface ECG. The TDR was defined as the difference between the longest and the shortest MAPD of subendocardial, subepicardial and mid-layer myocardium. Our results showed that in normal dogs, pacing participating of LV (LV-Epi, BiV) prolonged

Parietal podocytes in normal human glomeruli.

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Bariety, Jean; Mandet, Chantal; Hill, Gary S; Bruneval, Patrick

2006-10-01

Although parietal podocytes along the Bowman's capsule have been described by electron microscopy in the normal human kidney, their molecular composition remains unknown. Ten human normal kidneys that were removed for cancer were assessed for the presence and the extent of parietal podocytes along the Bowman's capsule. The expression of podocyte-specific proteins (podocalyxin, glomerular epithelial protein-1, podocin, nephrin, synaptopodin, and alpha-actinin-4), podocyte synthesized proteins (vascular endothelial growth factor and novH), transcription factors (WT1 and PAX2), cyclin-dependent kinase inhibitor p57, and intermediate filaments (cytokeratins and vimentin) was tested. In addition, six normal fetal kidneys were studied to track the ontogeny of parietal podocytes. The podocyte protein labeling detected parietal podocytes in all of the kidneys, was found in 76.6% on average of Bowman's capsule sections, and was prominent at the vascular pole. WT1 and p57 were expressed in some parietal cells, whereas PAX2 was present in all or most of them, so some parietal cells coexpressed WT1 and PAX2. Furthermore, parietal podocytes coexpressed WT1 and podocyte proteins. Cytokeratin-positive cells covered a variable part of the capsule and did not express podocyte proteins. Tuft-capsular podocyte bridges were present in 15.5 +/- 3.7% of the glomerular sections. Parietal podocytes often covered the juxtaglomerular arterioles and were present within the extraglomerular mesangium. Parietal podocytes were present in fetal kidneys. Parietal podocytes that express the same epitopes as visceral podocytes do exist along Bowman's capsule in the normal adult kidney. They are a constitutive cell type of the Bowman's capsule. Therefore, their role in physiology and pathology should be investigated.

Fractal analysis of phasic laser images of the myocardium for the purpose of diagnostics of acute coronary insufficiency

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Wanchuliak, O. Y.; Bachinskyi, V. T.

2011-09-01

In this work on the base of Mueller-matrix description of optical anisotropy, the possibility of monitoring of time changes of myocardium tissue birefringence, has been considered. The optical model of polycrystalline networks of myocardium is suggested. The results of investigating the interrelation between the values correlation (correlation area, asymmetry coefficient and autocorrelation function excess) and fractal (dispersion of logarithmic dependencies of power spectra) parameters are presented. They characterize the distributions of Mueller matrix elements in the points of laser images of myocardium histological sections. The criteria of differentiation of death coming reasons are determined.

Semi-automatic segmentation of myocardium at risk in T2-weighted cardiovascular magnetic resonance

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Sjögren Jane

2012-01-01

Full Text Available Abstract Background T2-weighted cardiovascular magnetic resonance (CMR has been shown to be a promising technique for determination of ischemic myocardium, referred to as myocardium at risk (MaR, after an acute coronary event. Quantification of MaR in T2-weighted CMR has been proposed to be performed by manual delineation or the threshold methods of two standard deviations from remote (2SD, full width half maximum intensity (FWHM or Otsu. However, manual delineation is subjective and threshold methods have inherent limitations related to threshold definition and lack of a priori information about cardiac anatomy and physiology. Therefore, the aim of this study was to develop an automatic segmentation algorithm for quantification of MaR using anatomical a priori information. Methods Forty-seven patients with first-time acute ST-elevation myocardial infarction underwent T2-weighted CMR within 1 week after admission. Endocardial and epicardial borders of the left ventricle, as well as the hyper enhanced MaR regions were manually delineated by experienced observers and used as reference method. A new automatic segmentation algorithm, called Segment MaR, defines the MaR region as the continuous region most probable of being MaR, by estimating the intensities of normal myocardium and MaR with an expectation maximization algorithm and restricting the MaR region by an a priori model of the maximal extent for the user defined culprit artery. The segmentation by Segment MaR was compared against inter observer variability of manual delineation and the threshold methods of 2SD, FWHM and Otsu. Results MaR was 32.9 ± 10.9% of left ventricular mass (LVM when assessed by the reference observer and 31.0 ± 8.8% of LVM assessed by Segment MaR. The bias and correlation was, -1.9 ± 6.4% of LVM, R = 0.81 (p Conclusions There is a good agreement between automatic Segment MaR and manually assessed MaR in T2-weighted CMR. Thus, the proposed algorithm seems to be a

Semi-automatic segmentation of myocardium at risk in T2-weighted cardiovascular magnetic resonance.

Science.gov (United States)

Sjögren, Jane; Ubachs, Joey F A; Engblom, Henrik; Carlsson, Marcus; Arheden, Håkan; Heiberg, Einar

2012-01-31

T2-weighted cardiovascular magnetic resonance (CMR) has been shown to be a promising technique for determination of ischemic myocardium, referred to as myocardium at risk (MaR), after an acute coronary event. Quantification of MaR in T2-weighted CMR has been proposed to be performed by manual delineation or the threshold methods of two standard deviations from remote (2SD), full width half maximum intensity (FWHM) or Otsu. However, manual delineation is subjective and threshold methods have inherent limitations related to threshold definition and lack of a priori information about cardiac anatomy and physiology. Therefore, the aim of this study was to develop an automatic segmentation algorithm for quantification of MaR using anatomical a priori information. Forty-seven patients with first-time acute ST-elevation myocardial infarction underwent T2-weighted CMR within 1 week after admission. Endocardial and epicardial borders of the left ventricle, as well as the hyper enhanced MaR regions were manually delineated by experienced observers and used as reference method. A new automatic segmentation algorithm, called Segment MaR, defines the MaR region as the continuous region most probable of being MaR, by estimating the intensities of normal myocardium and MaR with an expectation maximization algorithm and restricting the MaR region by an a priori model of the maximal extent for the user defined culprit artery. The segmentation by Segment MaR was compared against inter observer variability of manual delineation and the threshold methods of 2SD, FWHM and Otsu. MaR was 32.9 ± 10.9% of left ventricular mass (LVM) when assessed by the reference observer and 31.0 ± 8.8% of LVM assessed by Segment MaR. The bias and correlation was, -1.9 ± 6.4% of LVM, R = 0.81 (p Segment MaR, -2.3 ± 4.9%, R = 0.91 (p Segment MaR and manually assessed MaR in T2-weighted CMR. Thus, the proposed algorithm seems to be a promising, objective method for standardized MaR quantification in T2

Capillary permeability of 99mTc-DTPA and blood flow rate in the human myocardium determined by intracoronary bolus injection and residue detection

DEFF Research Database (Denmark)

Svendsen, Jesper Hastrup; Efsen, F; Haunsø, S

1992-01-01

.7 ml.(100 g.min)-1 (SD 13.0). Similar values of blood flow rate, capillary extraction fraction and the PS product were determined in 6 patients with localized coronary atheroma without hemodynamically significant coronary artery stenosis (25-50% luminal narrowing). The values for the regional......The aims of the present study were to quantitate blood flow rate and capillary permeability of 99mTc-DTPA in the human myocardium and to assess whether capillary permeability is influenced by the presence of small degree atherosclerotic lesions. Myocardial blood flow rate and capillary permeability......, a mean value of the capillary permeability-surface area (PS) product of 54.0 ml.(100 g.min)-1 (SD 13.0) was determined from a capillary extraction of 55.0% (SD 9.4%) and a regional myocardial plasma flow rate of 74.6 ml.(100 g.min)-1 (SD 6.3) equivalent with a regional myocardial blood flow rate of 121...

Imaging gene expression in human mesenchymal stem cells: from small to large animals

DEFF Research Database (Denmark)

Willmann, Jürgen K; Paulmurugan, Ramasamy; Rodriguez-Porcel, Martin

2009-01-01

To evaluate the feasibility of reporter gene imaging in implanted human mesenchymal stem cells (MSCs) in porcine myocardium by using clinical positron emission tomography (PET)-computed tomography (CT) scanning.......To evaluate the feasibility of reporter gene imaging in implanted human mesenchymal stem cells (MSCs) in porcine myocardium by using clinical positron emission tomography (PET)-computed tomography (CT) scanning....

Collateral circulation as a marker of the presence of viable myocardium in patients with recent myocardial infarction

International Nuclear Information System (INIS)

Fujita, M.; Ohno, A.; Wada, O.; Miwa, K.; Nozawa, T.; Yamanishi, K.; Sasayama, S.

1991-01-01

The relationship between the presence of viable myocardium and the extent of coronary collateral circulation to the infarct area was evaluated in 20 patients with a recent anterior myocardial infarction who had complete obstruction of the left anterior descending coronary artery. The viability of myocardial tissue was assessed by exercise thallium-201 myocardial scintigraphy, and the collateral circulation was angiographically evaluated by means of a collateral index ranging from 0 to 3. Patients were divided into two groups according to the presence (group 1, n = 10) or absence (group 2, n = 10) of viable myocardium in the perfusion territory of the infarct-related artery. The collateral index in group 1 was 2.5 ± 0.5 (SD), which was significantly higher than the 0.7 ± 0.8 in group 2. These findings indicate that the presence of ischemic but viable myocardium is intimately related to the development of collateral circulation in patients with myocardial infarction, and the existence of well-developed collateral channels predicts the presence of viable myocardium in the infarct area

Effects of Cordyceps sinensis on the Expressions of NF-κB and TGF-β1 in Myocardium of Diabetic Rats

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You-you Gu

2015-01-01

Full Text Available Objective. To investigate the effect of Cordyceps sinensis (CS on the expressions of NF-κB and TGF-β1 in myocardium of streptozotocin-induced diabetic rats. Methods. A total of 53 healthy male SD rats, mice age of 8 weeks and weight of 220 ± 20 g, were randomly divided into five groups by randomized block design: normal control group (n=10, diabetic group (n=10, low dose of CS group (n=12; CS 0.6 g·kg−1·d−1, middle dose of CS group (n=11; CS 2.5 g·kg−1·d−1, and high dose of CS group (n=10; CS 5 g·kg−1·d−1. The diabetic models with tail intravenous injection by streptozotocin (45 mg·kg−1. Diabetic rats were sacrificed after 8 weeks; the expressions of NF-κB and TGF-β1 proteins and mRNA in the cardiac muscle were determined by using immunohistochemistry staining and reverse transcription polymerase chain reaction (RT-PCR method. The data were analyzed using one factor analysis of variance. Result. The expressions of NF-κB and TGF-β1 proteins and mRNA in the cardiac muscle of diabetic rats were significantly raised (P<0.05, which could be decreased by CS (P<0.05. Conclusions. The changes on the expressions of NF-κB and TGF-β1 in myocardium may be involved in the occurrence of diabetic cardiomyopathy (DC. CS may play its role on myocardial protection by regulating the expressions of NF-κB and TGF-β1 in myocardium.

Glycoprotein biosynthesis by human normal platelets

International Nuclear Information System (INIS)

Rodriguez, P.; Bello, O.; Apitz-Castro, R.

1987-01-01

Incorporation of radioactive Man, Gal, Fuc, Glc-N, and NANA into washed human normal platelets and endogenous glycoproteins has been found. Both parameters were time dependent. Analysis of hydrolyzed labeled glycoproteins by paper chromatography revealed that the radioactive monosaccharide incubated with the platelets had not been converted into other sugars. Acid hydrolysis demonstrates the presence of a glycosidic linkage. All the effort directed to the demonstration of the existence of a lipid-sugar intermediate in intact human platelets yielded negative results for Man and Glc-N used as precursors. The incorporation of these sugars into glycoproteins is insensitive to bacitracin, suggesting no involvement of lipid-linked saccharides in the synthesis of glycoproteins in human blood platelets. The absence of inhibition of the glycosylation process in the presence of cycloheximide suggests that the sugars are added to proteins present in the intact platelets. These results support the contention that glycoprotein biosynthesis in human blood platelets observed under our experimental conditions is effected through direct sugar nucleotide glycosylation

Decline of Phosphotransfer and Substrate Supply Metabolic Circuits Hinders ATP Cycling in Aging Myocardium.

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Emirhan Nemutlu

Full Text Available Integration of mitochondria with cytosolic ATP-consuming/ATP-sensing and substrate supply processes is critical for muscle bioenergetics and electrical activity. Whether age-dependent muscle weakness and increased electrical instability depends on perturbations in cellular energetic circuits is unknown. To define energetic remodeling of aged atrial myocardium we tracked dynamics of ATP synthesis-utilization, substrate supply, and phosphotransfer circuits through adenylate kinase (AK, creatine kinase (CK, and glycolytic/glycogenolytic pathways using 18O stable isotope-based phosphometabolomic technology. Samples of intact atrial myocardium from adult and aged rats were subjected to 18O-labeling procedure at resting basal state, and analyzed using the 18O-assisted HPLC-GC/MS technique. Characteristics for aging atria were lower inorganic phosphate Pi[18O], γ-ATP[18O], β-ADP[18O], and creatine phosphate CrP[18O] 18O-labeling rates indicating diminished ATP utilization-synthesis and AK and CK phosphotransfer fluxes. Shift in dynamics of glycolytic phosphotransfer was reflected in the diminished G6P[18O] turnover with relatively constant glycogenolytic flux or G1P[18O] 18O-labeling. Labeling of G3P[18O], an indicator of G3P-shuttle activity and substrate supply to mitochondria, was depressed in aged myocardium. Aged atrial myocardium displayed reduced incorporation of 18O into second (18O2, third (18O3, and fourth (18O4 positions of Pi[18O] and a lower Pi[18O]/γ-ATP[18 O]-labeling ratio, indicating delayed energetic communication and ATP cycling between mitochondria and cellular ATPases. Adrenergic stress alleviated diminished CK flux, AK catalyzed β-ATP turnover and energetic communication in aging atria. Thus, 18O-assisted phosphometabolomics uncovered simultaneous phosphotransfer through AK, CK, and glycolytic pathways and G3P substrate shuttle deficits hindering energetic communication and ATP cycling, which may underlie energetic

Kronisk iskaemisk hjerteinsufficiens. Revaskularisering bedrer overlevelsen blandt patienter med hibernating myocardium

DEFF Research Database (Denmark)

Holdgaard, Paw Chr; Nielsen, Søren Steen; Wiggers, Henrik

2007-01-01

imaging was performed with 99mTc-sestamibi and glucose metabolism was visualized with 18F-fluorodeoxyglucose (18F-FDG) gamma camera PET. Medical records and death certificate were reviewed retrospectively. RESULTS: 50 patients were included. We found an increased survival among patients with HIB who......INTRODUCTION: Patients with ischemic heart failure and reversible dysfunctional myocardium (Hibernating myocardium, HIB) can benefit from revascularization. These patients can be selected with nuclear methods. The purpose of this study was to describe the results of the imaging procedures...... in patients tested for HIB and relate the results to the choice of treatment and cause of death. MATERIALS AND METHODS: During a 2-year period 51 patients were referred to determine the amount of HIB. This can be determined with blood flow and metabolic imaging of the heart. Resting-myocardial perfusion...

Object Detection and Tracking-Based Camera Calibration for Normalized Human Height Estimation

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Jaehoon Jung

2016-01-01

Full Text Available This paper presents a normalized human height estimation algorithm using an uncalibrated camera. To estimate the normalized human height, the proposed algorithm detects a moving object and performs tracking-based automatic camera calibration. The proposed method consists of three steps: (i moving human detection and tracking, (ii automatic camera calibration, and (iii human height estimation and error correction. The proposed method automatically calibrates camera by detecting moving humans and estimates the human height using error correction. The proposed method can be applied to object-based video surveillance systems and digital forensic.

Loss of Brain Aerobic Glycolysis in Normal Human Aging.

Science.gov (United States)

Goyal, Manu S; Vlassenko, Andrei G; Blazey, Tyler M; Su, Yi; Couture, Lars E; Durbin, Tony J; Bateman, Randall J; Benzinger, Tammie L-S; Morris, John C; Raichle, Marcus E

2017-08-01

The normal aging human brain experiences global decreases in metabolism, but whether this affects the topography of brain metabolism is unknown. Here we describe PET-based measurements of brain glucose uptake, oxygen utilization, and blood flow in cognitively normal adults from 20 to 82 years of age. Age-related decreases in brain glucose uptake exceed that of oxygen use, resulting in loss of brain aerobic glycolysis (AG). Whereas the topographies of total brain glucose uptake, oxygen utilization, and blood flow remain largely stable with age, brain AG topography changes significantly. Brain regions with high AG in young adults show the greatest change, as do regions with prolonged developmental transcriptional features (i.e., neoteny). The normal aging human brain thus undergoes characteristic metabolic changes, largely driven by global loss and topographic changes in brain AG. Copyright © 2017 Elsevier Inc. All rights reserved.

Hyperthyroidism causes mechanical insufficiency of myocardium with possibly increased SR Ca2+-ATPase activity.

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Takeuchi, Koh; Minakawa, M; Otaki, M; Odagiri, S; Itoh, K; Murakami, A; Yaku, H; Kitamura, N

2003-12-01

Hyperthyroidism is known to affect multiple organ functions, and thyroid hormone has been known to improve myocardial function in a failing heart. The purpose of this study is to elucidate the functional and metabolic effects of thyroid hormone on myocardium in a rat model exposed to long-term excess thyroid hormone, particularly focusing on the SR Ca(2+)-ATPase (SERCA2) function. 3,5,3'-Triiodo-L-thyronine (T3), or the vehicle, was subcutaneously given for 4 weeks (T3 and control [C] group). Bolus I.V. Thapsigargin (TG) was used to test the SERCA2 function (C-TG and T3-TG) in Langendorff perfused heart. Myocardial functions such as LV-developed pressure (LVDP; mmHg), +/- dP/dt (mmHg/s), tau (ms), and oxygen consumption (MVO(2); ml/min/g wt) were measured. SERCA2 and GLUT4 protein level were also evaluated by Western immunoblotting. Left ventricle to body weight (LV/BW) ratio was significantly higher in the T3 group. Both negative dP/dt and tau were significantly decreased by TG. It is interesting that the decrement of negative dP/dt and tau attained by TG was significantly larger in the hyperthyroid group (T3-TG) than in a normal heart (C-TG). SERCA2 and GLUT4 protein levels were not significantly different between control and the T3 group. We conclude that prolonged exposure to thyroid hormone causes hypertrophy of the myocardium and an augmentation of the SR Ca(2+) ATPase activity. Care must be taken in hyperthyroid heart during the ischemia-reperfusion process where the SRECA2 function is inhibited.

ProNormz--an integrated approach for human proteins and protein kinases normalization.

Science.gov (United States)

Subramani, Suresh; Raja, Kalpana; Natarajan, Jeyakumar

2014-02-01

The task of recognizing and normalizing protein name mentions in biomedical literature is a challenging task and important for text mining applications such as protein-protein interactions, pathway reconstruction and many more. In this paper, we present ProNormz, an integrated approach for human proteins (HPs) tagging and normalization. In Homo sapiens, a greater number of biological processes are regulated by a large human gene family called protein kinases by post translational phosphorylation. Recognition and normalization of human protein kinases (HPKs) is considered to be important for the extraction of the underlying information on its regulatory mechanism from biomedical literature. ProNormz distinguishes HPKs from other HPs besides tagging and normalization. To our knowledge, ProNormz is the first normalization system available to distinguish HPKs from other HPs in addition to gene normalization task. ProNormz incorporates a specialized synonyms dictionary for human proteins and protein kinases, a set of 15 string matching rules and a disambiguation module to achieve the normalization. Experimental results on benchmark BioCreative II training and test datasets show that our integrated approach achieve a fairly good performance and outperforms more sophisticated semantic similarity and disambiguation systems presented in BioCreative II GN task. As a freely available web tool, ProNormz is useful to developers as extensible gene normalization implementation, to researchers as a standard for comparing their innovative techniques, and to biologists for normalization and categorization of HPs and HPKs mentions in biomedical literature. URL: http://www.biominingbu.org/pronormz. Copyright © 2013 Elsevier Inc. All rights reserved.

Establishing the proteome of normal human cerebrospinal fluid.

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Steven E Schutzer

2010-06-01

Full Text Available Knowledge of the entire protein content, the proteome, of normal human cerebrospinal fluid (CSF would enable insights into neurologic and psychiatric disorders. Until now technologic hurdles and access to true normal samples hindered attaining this goal.We applied immunoaffinity separation and high sensitivity and resolution liquid chromatography-mass spectrometry to examine CSF from healthy normal individuals. 2630 proteins in CSF from normal subjects were identified, of which 56% were CSF-specific, not found in the much larger set of 3654 proteins we have identified in plasma. We also examined CSF from groups of subjects previously examined by others as surrogates for normals where neurologic symptoms warranted a lumbar puncture but where clinical laboratory were reported as normal. We found statistically significant differences between their CSF proteins and our non-neurological normals. We also examined CSF from 10 volunteer subjects who had lumbar punctures at least 4 weeks apart and found that there was little variability in CSF proteins in an individual as compared to subject to subject.Our results represent the most comprehensive characterization of true normal CSF to date. This normal CSF proteome establishes a comparative standard and basis for investigations into a variety of diseases with neurological and psychiatric features.

Absorption of orally administered 65Zn by normal human subjects

International Nuclear Information System (INIS)

Aamodt, R.L.; Rumble, W.F.; Johnston, G.S.; Markley, E.J.; Henkin, R.I.

1981-01-01

Despite studies by several investigators of human gastrointestinal 65Zn absorption, implications of these data for evaluation of functional zinc status are unclear because limited numbers of normal subjects have been studied. To evaluated zinc absorption in normal humans, 75 subjects (31 women, 44 men, ages 18 to 84 yr) were given 10 micro Ci carrier-free 65Zn orally after an overnight fast. Absorption calculated from total body retention measured 7, 14, and 21 days after administration of tracer was 65 +/- 11% (mean +/- 1 SD), range from 40 to 86%. Comparison of these results with those for patients with a variety of diseases indicate that patients exhibit a wider range of absorption and, in four of six studies patients exhibit decreased mean zinc absorption. These results of gastrointestinal zinc absorption in a large number of normal humans offer a basis for a clearer comparison with data from patients who exhibit abnormalities of zinc absorption

Noninvasive evaluation of sympathetic nervous system in human heart by positron emission tomography

International Nuclear Information System (INIS)

Schwaiger, M.; Kalff, V.; Rosenspire, K.; Haka, M.S.; Molina, E.; Hutchins, G.D.; Deeb, M.; Wolfe, E. Jr.; Wieland, D.M.

1990-01-01

The noninvasive functional characterization of the cardiac sympathetic nervous system by imaging techniques may provide important pathophysiological information in various cardiac disease states. Hydroxyephedrine labeled with carbon 11 has been developed as a new catecholamine analogue to be used in the in vivo evaluation of presynaptic adrenergic nerve terminals by positron emission tomography (PET). To determine the feasibility of this imaging approach in the human heart, six normal volunteers and five patients with recent cardiac transplants underwent dynamic PET imaging after intravenous injection of 20 mCi [11C]hydroxyephedrine. Blood and myocardial tracer kinetics were assessed using a regions-of-interest approach. In normal volunteers, blood 11C activity cleared rapidly, whereas myocardium retained 11C activity with a long tissue half-life. Relative tracer retention in the myocardium averaged 79 +/- 31% of peak activity at 60 minutes after tracer injection. The heart-to-blood 11C activity ratio exceeded 6:1 as soon as 30 minutes after tracer injection, yielding excellent image quality. Little regional variation of tracer retention was observed, indicating homogeneous sympathetic innervation throughout the left ventricle. In the transplant recipients, myocardial [11C]hydroxyephedrine retention at 60 minutes was significantly less (-82%) than that of normal volunteers, indicating only little non-neuronal binding of the tracer in the denervated human heart. Thus, [11C]hydroxyephedrine, in combination with dynamic PET imaging, allows the noninvasive delineation of myocardial adrenergic nerve terminals. Tracer kinetic modeling may permit quantitative assessment of myocardial catecholamine uptake, which will in turn provide insights into the effects of various disease processes on the neuronal integrity of the heart

Survival of human osteosarcoma cells and normal human fibroblasts following alpha particle irradiation

International Nuclear Information System (INIS)

Lloyd, E.L.; Gemmell, M.A.

1981-01-01

Cell survival of human osteosarcoma cells in culture following alpha particle irradiation is reported here for the first time. The osteosarcoma cell line (TE-85) is found to be less sensitive to inactivation by 5.6 MeV alpha particles (LET 86 keV/μm) than normal diploid human fibroblasts (NFS). Values for the mean lethal doses were estimated to be 103 rads for the TE-85 cells compared with 68 rads for the NFS cultures irradiated under identical conditions. It is postulated that the aneuploidy of the tumor cells with increased DNA chromosomal material may confer a selective advantage for the survival of tumor cells relative to normal cells with diploid chromosomes

The influence of the perinatal chronic hyperglycaemia on the pattern of NOS isoforms expression in left ventricle myocardium in male rats of pre-pubertal age

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O. V. Gancheva

2016-12-01

Full Text Available The aim of our study was to find out the features of the nitric oxide synthase (NOS isoforms expression in longitudinal and transversal layers of the myocardium of the left ventricle in male rats of 3 months, which are descendants of female rats with experimental gestational diabetes (EGD. Materials and methods. Study was carried out on 10 male rats descendants of female rats with normal course of pregnancy and 10 descendants of female rats with EGD. We evaluated the expression of neuronal, endothelial and inducible isoforms of NOS in histological sections both of transversal and longitudinal layers of the myocardium of left ventricle. With the aim to analyze the pattern of the NOS isoforms expression in 5 um histological slices of left ventricle myocardium we have carried out a complex of histochemical assays. Slices were allocated to 3 groups: 1st one was incubated with rabbit IgG to neuronal NOS (Santa Cruz Biotechnology, USA in dilution of 1:200; 2nd group underwent the incubation with rabbit IgG to endothelial NOS (eNos (Santa Cruz Biotechnology, USA in dilution 1:200; 3rd group was incubated with mice IgG to inducible NOS (iNos conjugated with FITC (Santa Cruz Biotechnology, USA in dilution of 1:200. The analysis of images was carried out with VIDAS-2.5 application package (Kontron Elektronik, Germany. Microimages of the left ventricle myocardium obtained with AxioScope (Carl Zeiss, Germany and COHU 4922 (COHU Inc., USA camera were processed in the system of digital image analysis VIDAS-386 (Kontron Elektronik, Germany. Results. In the study we have found that prenatal hyperglycaemia leads to the significant changes of the expression of NOS isoforms in the myocardium of left ventricle in male rats descendants of females with EGD, and the contain and the allocation of these enzymes are dependent both on type of the enzyme and its location in muscular layers. For eNOS the increase of the expression and the allocation in both transversal and

Differentiation of recently infarcted myocardium from chronic myocardial scar: the value of contrast-enhanced SSFP-based cine MR imaging

International Nuclear Information System (INIS)

Kim, Kyoung Ah; Seo, Joon Beom; Do, Kyoung Hyun; Heo, Jeong Nam; Lee, Young Kyung; Song, Jae Woo; Lee, Jin Seong; Song, Koun Sik; Lim, Tae Hwan

2006-01-01

The purpose of this study is to demonstrate whether the signal intensity (SI) of myocardial infarction (MI) on contrast enhanced (CE)-cine MRI is useful for differentiating recently infarcted myocardium from chronic scar. This study included 24 patients with acute MI (36-84) years, mean age: 57) and 19 patients with chronic MI (44-80) years, mean age: 64). The diagnosis of acute MI was based on the presence of typical symptoms, i.e. elevation of the cardiac enzymes and the absence of any remote infarction history. The diagnosis of chronic MI was based on a history of MI or coronary artery disease of more than one month duration and on the absence of any recent MI within the previous six months. Retrospectively, the ECG-gated breath-hold cine imaging was performed in the short axis plane using a segmented, balanced, turbo-field, echo-pulse sequence two minutes after the administration of Gd-DTPA at a dose of 0.2 mmol/kg body weight. Delayed contrast-enhanced MRI (DCE MRI) in the same plane was performed 10 to 15 minutes after contrast administration, and this was served as the gold standard of reference. The SI of the infarcted myocardium on the CE-cine MRI was compared with that of the normal myocardium on the same image. The area of abnormal SI on the CE-cine MRI was compared with the area of hyper enhancement on the DCE MRI. The area of high SI on the CE-cine MRI was detected in 23 of 24 patients with acute MI (10 with homogenous high SI, 13 high SI with subendocardial low SI, and one with iso SI). The area of high SI on the CE- cine MRI was larger than that seen on the DCE MRI (ρ < 0.05). In contrast, the areas of chronic MI were seen as iso-SI with thin subendocardial low SI on the CE-cine MR in all the chronic MI patients. The presence of high SI on both the CE-cine MRI and the DCE MRI is more sensitive (95.8%) for determining the age of a MI than the presence of myocardial thinning (66.7%). The study showed the different SI patterns between recently

Metabolic shifts in the myocardium in the long-term effect of atmospheric pollution on the body

Energy Technology Data Exchange (ETDEWEB)

Tsapok, P I; Turdakin, P G; Barkov, L V; Ovcharuk, I N; Protod' iakonova, T N

1981-04-01

Metabolic shifts in the myocardium under conditions of long-term exposure of the body to air pollution were studied in experiments on albino rats. Study of the content of protein, RNA, DNA, glycogen, ATP, lactic and pyruvic acids and the activity of lactate dehydrogenase and creatine kinase in the heart muscle allowed the conclusion that the glycolytic processes are intensified, the bioenergic processes are inhibited and the synthesis of protein and RNA are increased in the myocardium of the experimental animals.

Comparison of radiosensitivities of human autologous normal and neoplastic thyroid epithelial cells

International Nuclear Information System (INIS)

Miller, R.C.; Kopecky, K.J.; Hiraoka, T.; Ezaki, H.; Clifton, K.H.

1986-01-01

Studies were conducted to examine differences between the radiosensitivities of normal and neoplastic epithelial cells of the human thyroid. Freshly excised thyroid tissues from the tumours of eight patients with papillary carcinoma (PC) and five with follicular adenoma (FA) were cultured in vitro separately from normal thyroid tissue obtained from the surgical margins of the same patients. Plating efficiency of unirradiated control tissue was lower, on average for tumour tissue compared with normal tissue. Radiosensitivity, measured by the 37% inactivation dose D 0 , was greater for carcinoma tissue than for normal tissue in seven out of eight PC cases. Adenomatous tissue was less radiosensitive than normal tissue in four out of five FA cases. This is the first report comparing the radiosensitivity of autologous normal and abnormal epithelial tissue from the human thyroid. (author)

Identification of markers for quiescent pancreatic stellate cells in the normal human pancreas.

Science.gov (United States)

Nielsen, Michael Friberg Bruun; Mortensen, Michael Bau; Detlefsen, Sönke

2017-10-01

Pancreatic stellate cells (PSCs) play a central role as source of fibrogenic cells in pancreatic cancer and chronic pancreatitis. In contrast to quiescent hepatic stellate cells (qHSCs), a specific marker for quiescent PSCs (qPSCs) that can be used in formalin-fixed and paraffin embedded (FFPE) normal human pancreatic tissue has not been identified. The aim of this study was to identify a marker enabling the identification of qPSCs in normal human FFPE pancreatic tissue. Immunohistochemical (IHC), double-IHC, immunofluorescence (IF) and double-IF analyses were carried out using a tissue microarray consisting of cores with normal human pancreatic tissue. Cores with normal human liver served as control. Antibodies directed against adipophilin, α-SMA, CD146, CRBP-1, cytoglobin, desmin, GFAP, nestin, S100A4 and vinculin were examined, with special emphasis on their expression in periacinar cells in the normal human pancreas and perisinusoidal cells in the normal human liver. The immunolabelling capacity was evaluated according to a semiquantitative scoring system. Double-IF of the markers of interest together with markers for other periacinar cells was performed. Moreover, the utility of histochemical stains for the identification of human qPSCs was examined, and their ultrastructure was revisited by electron microscopy. Adipophilin, CRBP-1, cytoglobin and vinculin were expressed in qHSCs in the liver, whereas cytoglobin and adipophilin were expressed in qPSCs in the pancreas. Adipophilin immunohistochemistry was highly dependent on the preanalytical time interval (PATI) from removal of the tissue to formalin fixation. Cytoglobin, S100A4 and vinculin were expressed in periacinar fibroblasts (FBs). The other examined markers were negative in human qPSCs. Our data indicate that cytoglobin and adipophilin are markers of qPSCs in the normal human pancreas. However, the use of adipophilin as a qPSC marker may be limited due to its high dependence on optimal PATI

Healthy aging and myocardium: A complicated process with various effects in cardiac structure and physiology.

Science.gov (United States)

Nakou, E S; Parthenakis, F I; Kallergis, E M; Marketou, M E; Nakos, K S; Vardas, P E

2016-04-15

It is known that there is an ongoing increase in life expectancy worldwide, especially in the population older than 65years of age. Cardiac aging is characterized by a series of complex pathophysiological changes affecting myocardium at structural, cellular, molecular and functional levels. These changes make the aged myocardium more susceptible to stress, leading to a high prevalence of cardiovascular diseases (heart failure, atrial fibrillation, left ventricular hypertrophy, coronary artery disease) in the elderly population. The aging process is genetically programmed but modified by environmental influences, so that the rate of aging can vary widely among people. We summarized the entire data concerning all the multifactorial changes in aged myocardium and highlighting the recent evidence for the pathophysiological basis of cardiac aging. Keeping an eye on the clinical side, this review will explore the potential implications of the age-related changes in the clinical management and on novel therapeutic strategies potentially deriving from the scientific knowledge currently acquired on cardiac aging process. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Age-dependent changes in expression of alpha1-adrenergic receptors in rat myocardium

International Nuclear Information System (INIS)

Schaffer, W.; Williams, R.S.

1986-01-01

The expression of alpha 1 -adrenergic receptors within ventricular myocardium of rats ranging in age from 21 days of fetal life to 24 months after birth was measured from [ 125 I] 2-(β hydroxy phenyl) ethylaminomethyl tetralone binding isotherms. No difference was observed in binding affinity between any of the age groups studied. The number of alpha 1 -adrenergic receptors was found to be 60-120% higher in membranes from fetal or immature rats up to 25 days of age when compared with adult animals. The increased expression of alpha 1 -adrenergic receptors in the developing heart relative to that observed in adult heart is consistent with the hypothesis that alpha 1 -adrenergic receptor stimulation may modulate protein synthesis and growth in mammalian myocardium

Importance of scintigraphy of the myocardium with Csup(99m)-Tc-pyrophosphate in the diagnosis of myocardial ischemia

Energy Technology Data Exchange (ETDEWEB)

Botnar' , V I; Dvoskina, I S [Inst. Kardiologii Vsesoyuznogo Kardiologicheskogo Nauchnogo Tsentra AN SSSR

1983-10-01

The following aspects of the method of scintigraphy of the myocardium with sup(99m)Tc-pyrophosphate as test sensitivity, possibility of estimating necrosis focus, prognostic importance of the method, scintigram dynamics in case of acute infarction, pyrophosphate accumulation in myocardial cells are considered. Advantages and prospects of the method for visualization of acute myocardium infarction focus and in cases of other pathological states are pointed out.

Delayed uptake and washout of contrast in non-viable infarcted myocardium shown with dynamic computed tomography

DEFF Research Database (Denmark)

Udholm, Sebastian; Laugesen, Sofie; Agger, Peter

2014-01-01

BACKGROUND: Assessment of ischemic but potentially viable myocardium plays an important role in the planning of coronary revascularization. Until now SPECT, PET, and MRI have been used to identify viable myocardium. Computed tomography (CT) is increasingly used to diagnose coronary atherosclerosis...... descending artery, followed by removal of the balloon and reperfusion. Four pigs died due to refractory ventricular fibrillation. After 6 weeks, dynamic cardiac CT was performed assessing both wall motion and contrast attenuation. Measurements of attenuation values in Hounsfield units (HU) in the infarct...

Gene expression signatures affected by ethanol and/or nicotine in normal human normal oral keratinocytes (NHOKs

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Jeffrey J. Kim

2014-12-01

Full Text Available It has been reported that nicotine/alcohol alters epigenetic control and leads to abrogated DNA methylation and histone modifications, which could subsequently perturb transcriptional regulation critically important in cellular transformation. The aim of this study is to determine the molecular mechanisms of nicotine/alcohol-induced epigenetic alterations and their mechanistic roles in transcriptional regulation in human adult stem cells. We hypothesized that nicotine/alcohol induces deregulation of epigenetic machinery and leads to epigenetic alterations, which subsequently affect transcriptional regulation in oral epithelial stem cells. As an initiating step we have profiled transcriptomic alterations induced by the combinatory administration of EtOH and nicotine in primary normal human oral keratinocytes. Here we provide detailed experimental methods, analysis and information associated with our data deposited into Gene Expression Omnibus (GEO under GSE57634. Our data provide comprehensive transcriptomic map describing molecular changes induced by EtOH and nicotine on normal human oral keratinocytes.

Miocárdio hibernante: uma realidade clínica Hibernant myocardium: a clinical reality

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J.A. Marin-Neto

1997-12-01

Full Text Available O conceito da hibernação miocárdica implica a ocorrência de disfunção ventricular crônica, potencialmente reversível, causada por dissinergia regional, dependente de isquemia prolongada. Não tem fisiopatologia elucidada, em parte porque não existem modelos experimentais satisfatórios para seu estudo. Diversos métodos são capazes de demonstrar viabilidade miocárdica nas regiões que não exibem capacidade contrátil basal. O desmascaramento da hibernação nesses territórios pode ser feito mediante demonstração de reserva contrátil, de funcionamento normal da membrana celular, ou de metabolismo preservado. A correta identificação de miocárdio hibernante reveste-se de especial significado clínico, por suas implicações prognósticas quanto a intervenções de revascularização miocárdica, destinadas a reabilitar a função ventricular em muitos pacientes coronariopatas crônicos.Myocardial hibernation is believed to occur in ventricular dyssynergic regions chronically deprived of coronary flow enough to warrant the preservation of contractile function. Pathophysiology of this condition remains largely unclear, mainly because good experimental models for its study are still lacking. Various methods can be clinically employed to detect hibernation in patients with chronic ventricular dysfunction. These methods use the principle of unmasking contractile reserve, or are based on the demonstration of preserved membrane function or myocardium metabolism in the dyssynergic regions. The correct identification of viable hibernating myocardium is crucial in the process of deciding which coronary disease patients would potentially benefit from revascularization procedures.

Studies concerning the effect of X-rays on electrolytic shifts and on the metabolism of the myocardium. Pt. 6

International Nuclear Information System (INIS)

Prignitz, R.; Saurbier, B.; Hoffmeister, G.

1976-01-01

In the myocardium of guinea-pigs, the behaviour of the catecholamines noradrenalin and adrenalin as well as the monoamine oxidase activity was biochemically studied following a local irradiation with 250 up to 6,000 R surface dose. The noradrenalin content is significantly reduced already after a surface dose of 250 R. This drop of the noradrenalin content is beginning 15 min after irradiation, and not till 72 hours later, a complete normalization of the noradrenalin content is to be shown. A fractionated irradiation with twice 250 R SD in an interval of 24 hours leads to a further reduction. The changes of the adrenalin content are uncharacteristic, the activity of the monoamine oxidase is unaffected. (orig.) [de

Genetic modification of mesenchymal stem cells overexpressing CCR1 increases cell viability, migration, engraftment, and capillary density in the injured myocardium.

Science.gov (United States)

Huang, Jing; Zhang, Zhiping; Guo, Jian; Ni, Aiguo; Deb, Arjun; Zhang, Lunan; Mirotsou, Maria; Pratt, Richard E; Dzau, Victor J

2010-06-11

Although mesenchymal stem cell (MSC) transplantation has been shown to promote cardiac repair in acute myocardial injury in vivo, its overall restorative capacity appears to be restricted mainly because of poor cell viability and low engraftment in the ischemic myocardium. Specific chemokines are upregulated in the infarcted myocardium. However the expression levels of the corresponding chemokine receptors (eg, CCR1, CXCR2) in MSCs are very low. We hypothesized that this discordance may account for the poor MSC engraftment and survival. To determine whether overexpression of CCR1 or CXCR2 chemokine receptors in MSCs augments their cell survival, migration and engraftment after injection in the infarcted myocardium. Overexpression of CCR1, but not CXCR2, dramatically increased chemokine-induced murine MSC migration and protected MSC from apoptosis in vitro. Moreover, when MSCs were injected intramyocardially one hour after coronary artery ligation, CCR1-MSCs accumulated in the infarcted myocardium at significantly higher levels than control-MSCs or CXCR2-MSCs 3 days postmyocardial infarction (MI). CCR1-MSC-injected hearts exhibited a significant reduction in infarct size, reduced cardiomyocytes apoptosis and increased capillary density in injured myocardium 3 days after MI. Furthermore, intramyocardial injection of CCR1-MSCs prevented cardiac remodeling and restored cardiac function 4 weeks after MI. Our results demonstrate the in vitro and in vivo salutary effects of genetic modification of stem cells. Specifically, overexpression of chemokine receptor enhances the migration, survival and engraftment of MSCs, and may provide a new therapeutic strategy for the injured myocardium.

A Review of Neurogenic Stunned Myocardium

Science.gov (United States)

Wongrakpanich, Supakanya; Agrawal, Akanksha; Yadlapati, Sujani; Kishlyansky, Marina; Figueredo, Vincent

2017-01-01

Neurologic stunned myocardium (NSM) is a phenomenon where neurologic events give rise to cardiac abnormalities. Neurologic events like stroke and seizures cause sympathetic storm and autonomic dysregulation that result in myocardial injury. The clinical presentation can involve troponin elevation, left ventricular dysfunction, and ECG changes. These findings are similar to Takotsubo cardiomyopathy and acute coronary syndrome. It is difficult to distinguish NSM from acute coronary syndrome based on clinical presentation alone. Because of this difficulty, a patient with NSM who is at high risk for coronary heart disease may undergo cardiac catheterization to rule out coronary artery disease. The objective of this review of literature is to enhance physician's awareness of NSM and its features to help tailor management according to the patient's clinical profile. PMID:28875040

Response of cultured normal human mammary epithelial cells to X rays

International Nuclear Information System (INIS)

Yang, T.C.; Stampfer, M.R.; Smith, H.S.

1983-01-01

The effect of X rays on the reproductive death of cultured normal human mammary epithelial cells was examined. Techniques were developed for isolating and culturing normal human mammary epithelial cells which provide sufficient cells at second passage for radiation studies, and an efficient clonogenic assay suitable for measuring radiation survival curves. It was found that the survival curves for epithelial cells from normal breast tissue were exponential and had D 0 values of about 109-148 rad for 225 kVp X rays. No consistent change in cell radiosensitivity with the age of donor was observed, and no sublethal damage repair in these cells could be detected with the split-dose technique

Development of Bioartificial Myocardium Using Stem Cells and Nanobiotechnology Templates

Directory of Open Access Journals (Sweden)

Juan Carlos Chachques

2011-01-01

Full Text Available Cell-based regenerative therapy is undergoing experimental and clinical trials in cardiology, in order to limit the consequences of decreased contractile function and compliance of damaged ventricles following myocardial infarction. Over 1000 patients have been treated worldwide with cell-based procedures for myocardial regeneration. Cellular cardiomyoplasty seems to reduce the size and fibrosis of infarct scars, limit adverse postischemic remodelling, and improve diastolic function. The development of a bioartificial myocardium is a new challenge; in this approach, tissue-engineered procedures are associated with cell therapy. Organ decellularization for bioscaffolds fabrication is a new investigated concept. Nanomaterials are emerging as the main candidates to ensure the achievement of a proper instructive cellular niche with good drug release/administration properties. Investigating the electrophysiological properties of bioartificial myocardium is the challenging objective of future research, associating a multielectrode network to provide electrical stimulation could improve the coupling of grafted cells and scaffolds with host cardiomyocytes. In summary, until now stem cell transplantation has not achieved clear hemodynamic benefits for myocardial diseases. Supported by relevant scientific background, the development of myocardial tissue engineering may constitute a new avenue and hope for the treatment of myocardial diseases.

Normal human bone marrow and its variations in MRI

International Nuclear Information System (INIS)

Vahlensieck, M.; Schmidt, H.M.

2000-01-01

Physiology and age dependant changes of human bone marrow are described. The resulting normal distribution patterns of active and inactive bone marrow including the various contrasts on different MR-sequences are discussed. (orig.) [de

A novel generalized normal distribution for human longevity and other negatively skewed data.

Science.gov (United States)

Robertson, Henry T; Allison, David B

2012-01-01

Negatively skewed data arise occasionally in statistical practice; perhaps the most familiar example is the distribution of human longevity. Although other generalizations of the normal distribution exist, we demonstrate a new alternative that apparently fits human longevity data better. We propose an alternative approach of a normal distribution whose scale parameter is conditioned on attained age. This approach is consistent with previous findings that longevity conditioned on survival to the modal age behaves like a normal distribution. We derive such a distribution and demonstrate its accuracy in modeling human longevity data from life tables. The new distribution is characterized by 1. An intuitively straightforward genesis; 2. Closed forms for the pdf, cdf, mode, quantile, and hazard functions; and 3. Accessibility to non-statisticians, based on its close relationship to the normal distribution.

Improved identification of viable myocardium using second harmonic imaging during dobutamine stress echocardiography

NARCIS (Netherlands)

F. Sozzi (Fabiola); D. Poldermans (Don); J.J. Bax (Jeroen); A. Elhendy (Abdou); E.C. Vourvouri (Eleni); R. Valkema (Roelf); J. de Sutter; A.F.L. Schinkel (Arend); A. Borghetti; J.R.T.C. Roelandt (Jos)

2001-01-01

textabstractOBJECTIVE: To determine whether, compared with fundamental imaging, second harmonic imaging can improve the accuracy of dobutamine stress echocardiography for identifying viable myocardium, using nuclear imaging as a reference. PATIENTS: 30 patients with chronic left

Normal 201Tl SPECT myocardial scintigram - a basis for quantification of tomographic data using 1800 rotation

International Nuclear Information System (INIS)

Bock, A.; Frenzel, R.; Meyer, M.; Pink, V.; Reisinger, I.; Strangfeld, D.

1990-01-01

Using 180 0 rotation for 201 Tl myocardial perfusion SPECT the influence of different myocardial wall thickness, depth-dependent resolution, attenuation and other facts is the reason for about 30% inhomogenity from anterolateral to posteroseptal myocardium in polar coordinate Bull's eye. It is very difficult for a visual observer to assess patients without knowledge of the corresponding normal distribution. We studied 25 normal males and calculated pixelwice vitality, washout rate between stress, 2-hr and 3.5-hr delay to obtain a normal Bull's eye reference databank. Before the patient's data can be analysed it is necessary to multiplicate them with the inverse normal Bull's eye. (author)

Statistical and fractal analysis of autofluorescent myocardium images in posthumous diagnostics of acute coronary insufficiency

Science.gov (United States)

Boichuk, T. M.; Bachinskiy, V. T.; Vanchuliak, O. Ya.; Minzer, O. P.; Garazdiuk, M.; Motrich, A. V.

2014-08-01

This research presents the results of investigation of laser polarization fluorescence of biological layers (histological sections of the myocardium). The polarized structure of autofluorescence imaging layers of biological tissues was detected and investigated. Proposed the model of describing the formation of polarization inhomogeneous of autofluorescence imaging biological optically anisotropic layers. On this basis, analytically and experimentally tested to justify the method of laser polarimetry autofluorescent. Analyzed the effectiveness of this method in the postmortem diagnosis of infarction. The objective criteria (statistical moments) of differentiation of autofluorescent images of histological sections myocardium were defined. The operational characteristics (sensitivity, specificity, accuracy) of these technique were determined.

Manifestation of automaticity in the pulmonary-vein myocardium of rats with abdominal aorto-venocaval shunt

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Shogo Hamaguchi

2015-08-01

Full Text Available Effect of abdominal aorto-venocaval shunt (AVS on the automaticity of the pulmonary-vein myocardium was studied in the rat. Spontaneous electrical activity was observed in one third of the isolated pulmonary-vein preparations from the AVS rats, but scarcely in those from sham-operated rats; the activity was induced by tertiapin and suppressed by carbachol or chelation of intracellular Ca2+. The evoked action potentials in AVS rats had less negative resting membrane potential and longer action potential duration than those in sham-operated rats. These results suggest that the automaticity of the rat pulmonary-vein myocardium is manifested under chronic volume overload.

Detection of the human endogenous retrovirus ERV3-encoded Env-protein in human tissues using antibody-based proteomics.

Science.gov (United States)

Fei, Chen; Atterby, Christina; Edqvist, Per-Henrik; Pontén, Fredrik; Zhang, Wei Wei; Larsson, Erik; Ryan, Frank P

2014-01-01

There is growing evidence to suggest that human endogenous retroviruses (HERVs) have contributed to human evolution, being expressed in development, normal physiology and disease. A key difficulty in the scientific evaluation of this potential viral contribution is the accurate demonstration of virally expressed protein in specific human cells and tissues. In this study, we have adopted the endogenous retrovirus, ERV3, as our test model in developing a reliable high-capacity methodology for the expression of such endogenous retrovirus-coded protein. Two affinity-purified polyclonal antibodies to ERV3 Env-encoded protein were generated to detect the corresponding protein expression pattern in specific human cells, tissues and organs. Sampling included normal tissues from 144 individuals ranging from childhood to old age. This included more than forty different tissues and organs and some 216 different cancer tissues representing the twenty commonest forms of human cancer. The Rudbeck Laboratory, Uppsala University and Uppsala University Hospital, Uppsala, Sweden. The potential expression at likely physiological level of the ERV3Env encoded protein in a wide range of human cells, tissues and organs. We found that ERV3 encoded Env protein is expressed at substantive levels in placenta, testis, adrenal gland, corpus luteum, Fallopian tubes, sebaceous glands, astrocytes, bronchial epithelium and the ducts of the salivary glands. Substantive expression was also seen in a variety of epithelial cells as well as cells known to undergo fusion in inflammation and in normal physiology, including fused macrophages, myocardium and striated muscle. This contrasted strongly with the low levels expressed in other tissues types. These findings suggest that this virus plays a significant role in human physiology and may also play a possible role in disease. This technique can now be extended to the study of other HERV genomes within the human chromosomes that may have contributed to

31P MR spectroscopic measurement of intracellular pH in normal human hearts

International Nuclear Information System (INIS)

Kwon, Jae Hyun; Lee, Hui Joong; Jang, Yong Min

2002-01-01

To assess the usefulness of intracellular pH (pHi), calculated by determining the shift of a high-energy metabolite such as inorganic phosphate (Pi) of γ-ATP after performing MRS with ECG-gated two-dimensional 31 P CSI (chemical shift imaging), as a parameter for the overall state of the intracellular milieu. Proto decoupled 31 P CSI was performed on a 1.5-T scanner using a 1 H 31 P dual-tuned surface coil. Cardiac MRS data were obtained from eight normal volunteers aged 24-32 years with no history of heart disease. From the spectra obtained from several regions of the heart, peack position and peak area were estimated. The metabolic ratios of α-, β-, γ-ATP, PCr, Pi, phosphodiester and diphosphoglycerate were calculated, and pHi was estimated from the chemical shift of Pi and γ-ATP resonance. We then compared the data for the anterior myocardium with those previously published. The major phosphorous metabolites identified in these human hearts were as follows: PCr, at -0.1 to +0.1 ppm; three phosphate peaks from ATP, with a chemical shift centered at about -2.7 ppm (γ-ATP), -7.8 ppm (α-ATP), and -16.3 ppm (β-ATP); and phosphodiester (PDE) at 2-3 ppm, inorganic phosphate (Pi) at 4.5-5.4 ppm, and diphosphoglycerate (DPG) at 5.4-6.3 ppm. The PCr/β-ATP ratio was 2.20±0.17 and the PDE/β-ATP ratio, 1.04±0.09 pHi readings were 7.31±0.23 (calculated by the shift of Pi) and 6.81±0.20 (calculated by the shift of γ-ATP). Pi/PCR was 0.539, a ratio higher than that mentioned in previously published reports. The measurement of intracellular metabolism was affected by various kinds of factors. We believe, however, that pHi readings indicate the overall state of the cardiac intracellular milieu. An unexpected pHi readings, seen at MRS, may reflect errors in the MR procedure itself and, or in the analytical method

The expression of Egfl7 in human normal tissues and epithelial tumors.

Science.gov (United States)

Fan, Chun; Yang, Lian-Yue; Wu, Fan; Tao, Yi-Ming; Liu, Lin-Sen; Zhang, Jin-Fan; He, Ya-Ning; Tang, Li-Li; Chen, Guo-Dong; Guo, Lei

2013-04-23

To investigate the expression of Egfl7 in normal adult human tissues and human epithelial tumors.
 RT-PCR and Western blot were employed to detect Egfl7 expression in normal adult human tissues and 10 human epithelial tumors including hepatocellular carcinoma (HCC), lung cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer, malignant glioma, ovarian cancer and renal cancer. Immunohistochemistry and cytoimmunofluorescence were subsequently used to determine the localization of Egfl7 in human epithelial tumor tissues and cell lines. ELISA was also carried out to examine the serum Egfl7 levels in cancer patients. In addition, correlations between Egfl7 expression and clinicopathological features as well as prognosis of HCC and breast cancer were also analyzed on the basis of immunohistochemistry results.
 Egfl7 was differentially expressed in 19 adult human normal tissues and was overexpressed in all 10 human epithelial tumor tissues. The serum Egfl7 level was also significantly elevated in cancer patients. The increased Egfl7 expression in HCC correlated with vein invasion, absence of capsule formation, multiple tumor nodes and poor prognosis. Similarly, upregulation of Egfl7 in breast cancer correlated strongly with TNM stage, lymphatic metastasis, estrogen receptor positivity, Her2 positivity and poor prognosis. 
 Egfl7 is significantly upregulated in human epithelial tumor tissues, suggesting Egfl7 to be a potential biomarker for human epithelial tumors, especially HCC and breast cancer.

In vivo effect of the D-(-) isomer or natural form of 3-hydroxybutyrate on initial release of lactate dehydrogenase from the acutely ischaemic myocardium.

Science.gov (United States)

Lammerant, J; Huynh-Thu, T; Kolanowski, J

1986-07-01

D-(-)-3-hydroxybutyrate, the isomer found in the circulation and in the urine of diabetic patients, generally is believed to be the physiologically important form of 3-hydroxybutyrate [10]. Little is known concerning the effects of an elevated plasma level of the D-(-) isomer of 3-hydroxybutyrate upon the acutely ischaemic heart. Using anaesthetized intact dogs with a balloon catheter inserted into the proximal part of the left anterior descending coronary artery (LAD), we have recently demonstrated that a 1 mM ketonaemia induced with the arginine salt of D-(-)-3-hydroxybutyric acid reduces the uptake of non-esterified fatty acids (NEFA) in the myocardial area distal to the inflated balloon [4]. The question arises as to whether the concomitant increase in ketone uptake in this area could be detrimental to the acutely ischaemic myocardium. Indeed, a previous study on isolated coronary ligated hearts from normal rats has shown that the rate of release of lactate dehydrogenase (LDH) during the first 90 min of ischaemia can be enhanced by replacing glucose (11 mM) in the perfusion fluid with either albumin-bound palmitate (0.9 mM) or sodium DL-3-hydroxybutyrate (10 mM) as the sole energy substrate [11]. This would suggest that the ketone might be as deleterious as its metabolic precursors for membrane integrity in the acutely ischaemic myocardium. In the present report, we examine the effect of arginine D-(-)-3-hydroxybutyrate on LDH release from ischaemic myocardium in our in vivo preparation. The dogs were treated with lidocaine in order to minimize the frequency and, hence, the adverse metabolic effects of ectopic beats.(ABSTRACT TRUNCATED AT 250 WORDS)

Normalized Metadata Generation for Human Retrieval Using Multiple Video Surveillance Cameras

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Jaehoon Jung

2016-06-01

Full Text Available Since it is impossible for surveillance personnel to keep monitoring videos from a multiple camera-based surveillance system, an efficient technique is needed to help recognize important situations by retrieving the metadata of an object-of-interest. In a multiple camera-based surveillance system, an object detected in a camera has a different shape in another camera, which is a critical issue of wide-range, real-time surveillance systems. In order to address the problem, this paper presents an object retrieval method by extracting the normalized metadata of an object-of-interest from multiple, heterogeneous cameras. The proposed metadata generation algorithm consists of three steps: (i generation of a three-dimensional (3D human model; (ii human object-based automatic scene calibration; and (iii metadata generation. More specifically, an appropriately-generated 3D human model provides the foot-to-head direction information that is used as the input of the automatic calibration of each camera. The normalized object information is used to retrieve an object-of-interest in a wide-range, multiple-camera surveillance system in the form of metadata. Experimental results show that the 3D human model matches the ground truth, and automatic calibration-based normalization of metadata enables a successful retrieval and tracking of a human object in the multiple-camera video surveillance system.

Coupling of the Functional Stability of Rat Myocardium and Activity of Lipid Peroxidation in Combined Development of Postinfarction Remodeling and Diabetes Mellitus

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S. A. Afanasiev

2016-01-01

Full Text Available Coupling of the functional stability of rat myocardium and activity of lipid peroxidation processes in combined development of postinfarction remodeling and diabetes mellitus has been studied. The functional stability of myocardium was studied by means of the analysis of inotropic reaction on extrasystolic stimulus, the degree of left ventricular hypertrophy, and the size of scar zone. It was shown that in combined development of postinfarction cardiac remodeling of heart (PICR with diabetes mellitus (DM animal body weight decreased in less degree than in diabetic rats. Animals with combined pathology had no heart hypertrophy. The amplitude of extrasystolic contractions in rats with PICR combined with DM had no differences compared to the control group. In myocardium of rats with PICR combined with DM postextrasystolic potentiation was observed in contrast with the rats with PICR alone. The rats with combined pathology had the decreased value of TBA-active products. Thus, the results of study showed that induction of DM on the stage of the development of postinfarction remodeling increases adaptive ability of myocardium. It is manifested in inhibition of increase of LPO processes activity and maintaining of force-interval reactions of myocardium connected with calcium transport systems of sarcoplasmic reticulum of cardiomyocytes.

Sustained nonoxidative glucose utilization and depletion of glycogen in reperfused canine myocardium

International Nuclear Information System (INIS)

Schwaiger, M.; Neese, R.A.; Araujo, L.

1989-01-01

Ischemically injured reperfused myocardium is characterized by increased 18F-fluorodeoxyglucose uptake as demonstrated by positron emission tomography. To elucidate the metabolic fate of exogenous glucose entering reperfused myocardium, D-[6-14C] glucose and L-[U-13C] lactate were used to determine glucose uptake, glucose oxidation and the contribution of exogenous glucose to lactate production. The pathologic model under investigation consisted of a 3 h balloon occlusion of the left anterior descending coronary artery followed by 24 h of reperfusion in canine myocardium. The extent and severity of myocardial injury after the ischemia and reperfusion were assessed by histochemical evaluation (triphenyltetrazolium chloride and periodic acid-Schiff stains). Thirteen intervention and four control dogs were studied. The glucose uptake in the occluded/reperfused area was significantly enhanced compared with that in control dogs (0.40 +/- 0.14 versus 0.15 +/- 0.10 mumol/ml, respectively). In addition, a significantly greater portion of the glucose extracted immediately entered glycolysis in the intervention group (75%) than in the control dogs (33%). The activity of the nonoxidative glycolytic pathway was markedly increased in the ischemically injured reperfused area, as evidenced by the four times greater lactate release in this area compared with the control value. The dual carbon-labeled isotopes showed that 57% of the exogenous glucose entering glycolysis was being converted to lactate. Exogenous glucose contributed to greater than 90% of the observed lactate production. This finding was confirmed by the histochemical finding of sustained glycogen depletion in the occlusion/reperfusion area. The average area of glycogen depletion (37%) significantly exceeded the average area of necrosis

Insulin binding properties of normal and transformed human epidermal cultured keratinocytes

International Nuclear Information System (INIS)

Verrando, P.; Ortonne, J.P.

1985-01-01

Insulin binding to its receptors was studied in cultured normal and transformed (A431 line) human epidermal keratinocytes. The specific binding was a temperature-dependent, saturable process. Normal keratinocytes possess a mean value of about 80,000 receptors per cell. Fifteen hours exposure of the cells to insulin lowered their receptor number (about 65% loss in available sites); these reappeared when the hormone was removed from the culture medium. In the A431 epidermoid carcinoma cell line, there is a net decrease in insulin binding (84% of the initial bound/free hormone ratio in comparison with normal cells) essentially related to a loss in receptor affinity for insulin. Thus, cultured human keratinocytes which express insulin receptors may be a useful tool in understanding skin pathology related to insulin disorders

Identification of markers for quiescent pancreatic stellate cells in the normal human pancreas

DEFF Research Database (Denmark)

Nielsen, Michael Friberg Bruun; Mortensen, Michael Bau; Detlefsen, Sönke

2017-01-01

cells in the normal human pancreas and perisinusoidal cells in the normal human liver. The immunolabelling capacity was evaluated according to a semiquantitative scoring system. Double-IF of the markers of interest together with markers for other periacinar cells was performed. Moreover, the utility...... of histochemical stains for the identification of human qPSCs was examined, and their ultrastructure was revisited by electron microscopy. Adipophilin, CRBP-1, cytoglobin and vinculin were expressed in qHSCs in the liver, whereas cytoglobin and adipophilin were expressed in qPSCs in the pancreas. Adipophilin...... are markers of qPSCs in the normal human pancreas. However, the use of adipophilin as a qPSC marker may be limited due to its high dependence on optimal PATI. Cytoglobin, on the other hand, is a sensitive marker for qPSCs but is expressed in FBs as well....

Radiosensitivity of normal human epidermal cells in culture

International Nuclear Information System (INIS)

Dover, R.; Potten, C.S.

1983-01-01

Using an in vitro culture system the authors have derived #betta#-radiation survival curves over a dose range 0-8 Gy for the clonogenic cells of normal human epidermis. The culture system used allows the epidermal cells to stratify and form a multi-layered sheet of keratinizing cells. The cultures appear to be a very good model for epidermis in vivo. The survival curves show a population which is apparently more sensitive than murine epidermis in vivo. It remains unclear whether this is an intrinsic difference between the species or is a consequence of the in vitro cultivation of the human cells. (author)

The variability problem of normal human walking

DEFF Research Database (Denmark)

Simonsen, Erik B; Alkjær, Tine

2012-01-01

Previous investigations have suggested considerable inter-individual variability in the time course pattern of net joint moments during normal human walking, although the limited sample sizes precluded statistical analyses. The purpose of the present study was to obtain joint moment patterns from...... a group of normal subjects and to test whether or not the expected differences would prove to be statistically significant. Fifteen healthy male subjects were recorded on video while they walked across two force platforms. Ten kinematic and kinetic parameters were selected and input to a statistical...... cluster analysis to determine whether or not the 15 subjects could be divided into different 'families' (clusters) of walking strategy. The net joint moments showed a variability corroborating earlier reports. The cluster analysis showed that the 15 subjects could be grouped into two clusters of 5 and 10...

Radioimmunoassay of human cardiac tropomyosin in acute myocardial infarction

Energy Technology Data Exchange (ETDEWEB)

Cummins, P; McGurk, B; Littler, W A [Queen Elizabeth Hospital, Birmingham (UK)

1981-03-01

Tropomyosin was prepared from fresh human myocardium and antisera raised in rabbits. A sensitive radioimmunoassay was developed for the detection of human cardiac /sup 125/I-labelled tropomyosin in human sera down to levels of 1 ng/ml. Values for human cardiac tropomyosin in normal patients ranged from less than 1 to 3 ng/ml. In 18 patients with acute myocardial infarction all had elevated tropomyosin levels ranging from 41 to above 200 ng/ml with a mean peak level of 101 ng/ml. In this study there were no false positive or false negative results. In the initial stages of infarction the time course of appearance and peak levels of cardiac tropomyosin, total creatine kinase and creatine kinase MB isoenzyme were similar. Although total creatine kinase and creatine kinase MB isoenzyme levels were normal after 72 h in patients with single, uncomplicated infarction, cardiac tropomyosin levels were still significantly elevated above normal after this time, being 30-60% of peak valuctional hourly rate of absorption and the plasma /sup 32/P radioactivity at 60 min corrected for extracellular fluid volume provided the best app elements, the characteristics of which are determined by employing the Lagrange multiplier concept. Unknowns of the resulting simultaneous equation consist of usual nodal displacements of the whole stru element codes. Therefore, FAST should be useful in several areas for which all other codes are too unwieldy and expensivnt makers was established, in which the investigations and studies have started.

INTESTINAL VIROME AND NORMAL MICROFLORA OF HUMAN: FEATURES OF INTERACTION

Directory of Open Access Journals (Sweden)

Bobyr V.V.

2015-05-01

Full Text Available Summary: Intestinal bacteria defend the host organism and narrow pathogenic bacterial colonization. However, the microbiome effect to enteric viruses is unexplored largely as well as role of microbiota in the pathogenesis of viral infections in general. This review focuses on precisely these issues. Keywords: microbiome, virome, normal microflora, enteric viruses, contagiousness. In this review article, facts about viral persistence in the human gut are summarized. It is described the role of viral populations during health and diseases. After analyzing of the literary facts it was concluded that the gastrointestinal tract is an environment for one from the most complex microbial ecosystems, which requires of more deeper study of its composition, role in physiological processes, as well as the dynamics of changes under influence of the environment. Normal microflora performs a different important functions providing the physiological homeostasis of the human body, including, in particular, an important role in the human metabolic processes, supporting of homeostasis, limiting of colonization by infectious bacteria. The multifactorial significance of the normal gastrointestinal microflora can be divided into immunological, structural and metabolic functions. At the same time, interaction between intestinal microflora and enteric viruses has not been studied largely. In recent years, much attention is paid to study of viruses-bacteria associations, and it is possible, obtained results should change our understanding of microbiota role in the systematic pathogenesis of the diseases with viral etiology. In contrast to the well-known benefits of normal microflora to the host, the viruses can use intestinal microflora as a trigger for replication at the optimal region. Recent studies give a reason for assumption that depletion of normal microflora with antibiotics can determining the antiviral effect. Thus, the role of commensal bacteria in viral

[The protective action of nimodipine on the ischemic myocardium].

Science.gov (United States)

Tsorin, I B; Kazanova, G V; Kirsanova, G Iu; Chirkova, E Iu; Chichkanov, G G

1992-01-01

The experiments with unconscious cats and dogs have demonstrated that the calcium antagonist nimodipine has a profound anti-ischemic property. The drug reduces the average value of ST-segment elevation in multiple epicardial ECG leads, during acute myocardial ischemia. Nimodipine maintains cardiac pump and contractile functions, elevates ATP levels in the arbitrarily intact and ischemic myocardium of the left ventricle during 40-min occlusion and 60-min reperfusion of the coronary artery. The protective action of the drug is unassociated with enhanced collateral coronary circulation.

Kinetics of Tc-99m hexakis t-butyl isonitrile in normal and ischemic canine myocardium

International Nuclear Information System (INIS)

Williams, S.J.; Dragotakos, D.L.

1989-01-01

Hexakis 99m Tc-tertiary butyl isonitrile ( 99m Tc-TBI) was studied as a cardiac perfusion imaging agent in nine dogs with partial occlusion of the LAD. Thirty min after applying the stenosis, 99m Tc-TBI was injected into the right atrium (RA) in five dogs and left atrium (LA) in four dogs. Normal and ischemic zone regional myocardial 99m Tc-TBI activities were monitored continuously for 4 h. Dogs with LA injections had minimal and equivalent 4 h fractional clearance from the normal and ischemic zones. Dogs with RA injections had minimal, but significantly lower 4 h fractional 99m Tc clearances in the ischemic zone (0.08±0.08) compared to the normal zone (0.16±0.07, P 99m Tc-TBI a promising cardiac perfusion imaging agent. (orig.)

Gender-specific changes in laboratory indexes and structural parameters of the left ventricle myocardium in chronic heart failure on the background of diabetes mellitus type 2 and obesity

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P. P. Bidzilya

2015-12-01

Full Text Available Modern studies have shown that the prevalence of cardiovascular disease and chronic heart failure (CHF specifically, in patients with diabetes mellitus (DM is about 50%. Aim. To study gender-specific changes in laboratory indexes and structural myocardial parameters of left ventricle (LV in CHF on the background of diabetes mellitus (DM type 2. 111 patients with I–III functional class of disease with normal, overweight and abdominal obesity I–III degree were examined. Methods and results. Clinical and biochemical blood tests? glomerular filtration rate were used. Structural parameters of the myocardium were estimated with echocardiography. It is established that in CHF on the background of DM type 2 and obesity there is a tendency to develop anemia and renal dysfunction in women. Structural changes of the myocardium is more pronounced in men and presents the prevalence ofLV hypertrophy and dilatation of the heart cavities. Conclusion. This demonstrates different ways of negative impact of gender factor on the laboratory indexes and structural myocardial parameters in CHF on the background of DM type 2 and obesity.

Reduced myocardial perfusion reserve in myocardium having coronary artery aneurysm of Kawasaki disease

International Nuclear Information System (INIS)

Yoon, S. N.; Lee, D. S.; Choi, J. Y.; Kil, H. R.; Jeong, Z. K.; Lee, M. C.; Ko, C. S.

1997-01-01

stenosis or aneurysms on CAG, that is normal. It was concluded that decreased perfusion reserve could be found in myocardium having only aneurysmal coronary arteries without stenosis on CAG in Kawasaki disease, and this result imply that epicardial rest flow assessed by CAG was not enough to ensure tissue perfusion enough to cover coronary flow reserve

Humanized medium (h7H) allows long-term primary follicular thyroid cultures from human normal thyroid, benign neoplasm, and cancer.

Science.gov (United States)

Bravo, Susana B; Garcia-Rendueles, Maria E R; Garcia-Rendueles, Angela R; Rodrigues, Joana S; Perez-Romero, Sihara; Garcia-Lavandeira, Montserrat; Suarez-Fariña, Maria; Barreiro, Francisco; Czarnocka, Barbara; Senra, Ana; Lareu, Maria V; Rodriguez-Garcia, Javier; Cameselle-Teijeiro, Jose; Alvarez, Clara V

2013-06-01

Mechanisms of thyroid physiology and cancer are principally studied in follicular cell lines. However, human thyroid cancer lines were found to be heavily contaminated by other sources, and only one supposedly normal-thyroid cell line, immortalized with SV40 antigen, is available. In primary culture, human follicular cultures lose their phenotype after passage. We hypothesized that the loss of the thyroid phenotype could be related to culture conditions in which human cells are grown in medium optimized for rodent culture, including hormones with marked differences in its affinity for the relevant rodent/human receptor. The objective of the study was to define conditions that allow the proliferation of primary human follicular thyrocytes for many passages without losing phenotype. Concentrations of hormones, transferrin, iodine, oligoelements, antioxidants, metabolites, and ethanol were adjusted within normal homeostatic human serum ranges. Single cultures were identified by short tandem repeats. Human-rodent interspecies contamination was assessed. We defined an humanized 7 homeostatic additives medium enabling growth of human thyroid cultures for more than 20 passages maintaining thyrocyte phenotype. Thyrocytes proliferated and were grouped as follicle-like structures; expressed Na+/I- symporter, pendrin, cytokeratins, thyroglobulin, and thyroperoxidase showed iodine-uptake and secreted thyroglobulin and free T3. Using these conditions, we generated a bank of thyroid tumors in culture from normal thyroids, Grave's hyperplasias, benign neoplasms (goiter, adenomas), and carcinomas. Using appropriate culture conditions is essential for phenotype maintenance in human thyrocytes. The bank of thyroid tumors in culture generated under humanized humanized 7 homeostatic additives culture conditions will provide a much-needed tool to compare similarly growing cells from normal vs pathological origins and thus to elucidate the molecular basis of thyroid disease.

Super Normal Vector for Human Activity Recognition with Depth Cameras.

Science.gov (United States)

Yang, Xiaodong; Tian, YingLi

2017-05-01

The advent of cost-effectiveness and easy-operation depth cameras has facilitated a variety of visual recognition tasks including human activity recognition. This paper presents a novel framework for recognizing human activities from video sequences captured by depth cameras. We extend the surface normal to polynormal by assembling local neighboring hypersurface normals from a depth sequence to jointly characterize local motion and shape information. We then propose a general scheme of super normal vector (SNV) to aggregate the low-level polynormals into a discriminative representation, which can be viewed as a simplified version of the Fisher kernel representation. In order to globally capture the spatial layout and temporal order, an adaptive spatio-temporal pyramid is introduced to subdivide a depth video into a set of space-time cells. In the extensive experiments, the proposed approach achieves superior performance to the state-of-the-art methods on the four public benchmark datasets, i.e., MSRAction3D, MSRDailyActivity3D, MSRGesture3D, and MSRActionPairs3D.

16-Cyclopentadienyl tricarbonyl 99mTc 16-oxo-hexadecanoic acid: synthesis and evaluation of fatty acid metabolism in mouse myocardium.

Science.gov (United States)

Lee, Byung Chul; Kim, Dong Hyun; Lee, Iljung; Choe, Yearn Seong; Chi, Dae Yoon; Lee, Kyung-Han; Choi, Yong; Kim, Byung-Tae

2008-06-26

We synthesized 16-cyclopentadienyl tricarbonyl 99mTc 16-oxo-hexadecanoic acid (99mTc-CpTT-16-oxo-HDA, 1) and investigated its potential as a radiotracer for evaluating fatty acid metabolism in myocardium. Radiotracer 1 was synthesized in 22.6 +/- 6.3% decay-corrected yield by a double ligand transfer reaction between the ferrocene adduct of methyl hexadecanoate ( 2) and Na99mTcO 4 in the presence of Cr(CO)6 and CrCl3, followed by hydrolysis of the methyl ester group. Radiotracer 1 was found to be chemically stable (99% at 6 h) when incubated in human serum. A tissue distribution study in mice showed that high radioactivity accumulated in heart (9.03%ID/g at 1 min and 5.41%ID/g at 5 min postinjection) with rapid clearance and that heart to blood uptake ratios increased with time (2.13 at 5 min and 3.76 at 30 min postinjection). Metabolite analysis of the heart tissues using a simple extraction method showed that 99mTc-CpTT-4-oxo-butyric acid was detected as the major radioactive metabolite by HPLC, suggesting that 1 is metabolized to 99mTc-CpTT-4-oxo-butyric acid via beta-oxidation in myocardium.

Research on Normal Human Plantar Pressure Test

Directory of Open Access Journals (Sweden)

Liu Xi Yang

2016-01-01

Full Text Available FSR400 pressure sensor, nRF905 wireless transceiver and MSP40 SCM are used to design the insole pressure collection system, LabVIEW is used to make HMI of data acquisition, collecting a certain amount of normal human foot pressure data, statistical analysis of pressure distribution relations about five stages of swing phase during walking, using the grid closeness degree to identify plantar pressure distribution pattern recognition, and the algorithm simulation, experimental results demonstrated this method feasible.

From hundreds to thousands: Widening the normal human Urinome

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Laura Santucci

2014-12-01

The data are related to Santucci et al. (in press [1] and available both here and at ChorusProject.org under project name “From hundreds to thousands: widening the normal human Urinome”. The material supplied to Chorus Progect.org includes technical MS spectra data only.

{sup 31}P MR spectroscopic measurement of intracellular pH in normal human hearts

Energy Technology Data Exchange (ETDEWEB)

Kwon, Jae Hyun; Lee, Hui Joong; Jang, Yong Min [Kyungpook National Univ., Taegu (Korea, Republic of)] [and others

2002-05-01

To assess the usefulness of intracellular pH (pHi), calculated by determining the shift of a high-energy metabolite such as inorganic phosphate (Pi) of {gamma}-ATP after performing MRS with ECG-gated two-dimensional {sup 31}P CSI (chemical shift imaging), as a parameter for the overall state of the intracellular milieu. Proto decoupled {sup 31}P CSI was performed on a 1.5-T scanner using a {sup 1}H{sup 31}P dual-tuned surface coil. Cardiac MRS data were obtained from eight normal volunteers aged 24-32 years with no history of heart disease. From the spectra obtained from several regions of the heart, peack position and peak area were estimated. The metabolic ratios of {alpha}-, {beta}-, {gamma}-ATP, PCr, Pi, phosphodiester and diphosphoglycerate were calculated, and pHi was estimated from the chemical shift of Pi and {gamma}-ATP resonance. We then compared the data for the anterior myocardium with those previously published. The major phosphorous metabolites identified in these human hearts were as follows: PCr, at -0.1 to +0.1 ppm; three phosphate peaks from ATP, with a chemical shift centered at about -2.7 ppm ({gamma}-ATP), -7.8 ppm ({alpha}-ATP), and -16.3 ppm ({beta}-ATP); and phosphodiester (PDE) at 2-3 ppm, inorganic phosphate (Pi) at 4.5-5.4 ppm, and diphosphoglycerate (DPG) at 5.4-6.3 ppm. The PCr/{beta}-ATP ratio was 2.20{+-}0.17 and the PDE/{beta}-ATP ratio, 1.04{+-}0.09 pHi readings were 7.31{+-}0.23 (calculated by the shift of Pi) and 6.81{+-}0.20 (calculated by the shift of {gamma}-ATP). Pi/PCR was 0.539, a ratio higher than that mentioned in previously published reports. The measurement of intracellular metabolism was affected by various kinds of factors. We believe, however, that pHi readings indicate the overall state of the cardiac intracellular milieu. An unexpected pHi readings, seen at MRS, may reflect errors in the MR procedure itself and, or in the analytical method.

Metabolic syndrome impairs notch signaling and promotes apoptosis in chronically ischemic myocardium.

Science.gov (United States)

Elmadhun, Nassrene Y; Sabe, Ashraf A; Lassaletta, Antonio D; Chu, Louis M; Kondra, Katelyn; Sturek, Michael; Sellke, Frank W

2014-09-01

Impaired angiogenesis is a known consequence of metabolic syndrome (MetS); however, the mechanism is not fully understood. Recent studies have shown that the notch signaling pathway is an integral component of cardiac angiogenesis. We tested, in a clinically relevant swine model, the effects of MetS on notch and apoptosis signaling in chronically ischemic myocardium. Ossabaw swine were fed either a regular diet (control [CTL], n = 8) or a high-cholesterol diet (MetS, n = 8) to induce MetS. An ameroid constrictor was placed to induce chronic myocardial ischemia. Eleven weeks later, the wine underwent cardiac harvest of the ischemic myocardium. Downregulation of pro-angiogenesis proteins notch2, notch4, jagged2, angiopoietin 1, and endothelial nitric oxide synthase were found in the MetS group compared with the CTL group. Also, upregulation of pro-apoptosis protein caspase 8 and downregulation of anti-angiogenesis protein phosphorylated forkhead box transcription factor 03 and pro-survival proteins phosphorylated P38 and heat shock protein 90 were present in the MetS group. Cell death was increased in the MetS group compared with the CTL group. Both CTL and MetS groups had a similar arteriolar count and capillary density, and notch3 and jagged1 were both similarly concentrated in the smooth muscle wall. MetS in chronic myocardial ischemia significantly impairs notch signaling by downregulating notch receptors, ligands, and pro-angiogenesis proteins. MetS also increases apoptosis signaling, decreases survival signaling, and increases cell death in chronically ischemic myocardium. Although short-term angiogenesis appears unaffected in this model of early MetS, the molecular signals for angiogenesis are impaired, suggesting that inhibition of notch signaling might underlie the decreased angiogenesis in later stages of MetS. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Detection of hibernating myocardium in patients with myocardial infarction by low-dose dobutamine echocardiography. Comparison with thallium-201 scintigraphy with reinjection

International Nuclear Information System (INIS)

Takagi, Tsutomu; Yoshikawa, Junichi; Yoshida, Kiyoshi; Akasaka, Takashi; Honda, Yasuhiro; Yonezawa, Yoshihiro; Shakudo, Masahiro

1995-01-01

The identification of hibernating myocardium is important for selecting patients who will benefit from coronary revascularization. The relationship between echocardiographic and radioisotopic markers of hibernating myocardium and postrevascularization recovery of myocardial function was investigated in 21 patients who underwent successful revascularization. Each patient underwent low-dose dobutamine stress echocardiography and thallium-201 ( 201 Tl) scintigraphy with reinjection before revascularization. The presence of contractile reserve in dobutamine stress echocardiography and Tl uptake in 201 Tl scintigraphy with reinjection were defined as markers of hibernating myocardium. Follow-up echocardiograms were evaluated for improved regional wall motion in all patients at a mean of 8.6 months after revascularization. Sensitivity, specificity, and positive and negative predictive values of low-dose dobutamine stress echocardiography for indicating recovery of function after revascularization were 75.0%, 77.8%, 81.8%, and 70.0%, respectively. Sensitivity, specificity, and positive and negative predictive values of 201 Tl scintigraphy with reinjection for indicating recovery of function after revascularization were 91.7%, 55.6%, 73.3%, and 83.3%, respectively. There were no statistical differences between low-dose dobutamine echocardiography and 201 Tl scintigraphy in predicting postrevascularization recovery of function in patients with hibernating myocardium. (author)

Identification of ischemic and hibernating myocardium: feasibility of post-exercise F-18 deoxyglucose positron emission tomography

International Nuclear Information System (INIS)

Marwick, T.H.; MacIntyre, W.J.; Salcedo, E.E.; Go, R.T.; Saha, G.; Beachler, A.

1991-01-01

The identification of ischemic and hibernating myocardium facilitates the selection of patients most likely to benefit from revascularization. This study examined the feasibility of metabolic imaging, using post-exercise F-18 deoxyglucose positron emission tomography (FDG-PET) for the diagnosis of both ischemia and hibernation in 27 patients with known coronary anatomy. Normal post-exercise FDG uptake was defined in each patient by reference to normal resting perfusion and normal coronary supply. Abnormal elevation of FDG (ischemia or hibernation) was compared in 13 myocardial segments in each patient, with the results of dipyridamole stress perfusion imaging performed by rubidium-82 positron emission tomography (Rb-PET). Myocardial ischemia was diagnosed by either FDG-PET or Rb-PET in 34 segments subtended by significant local coronary stenoses. Increased FDG uptake was present in 32/34 (94%) and a reversible perfusion defect was identified by Rb-PET in 22/34 (65%, p less than .01). In 3 patients, ischemia was identified by metabolic imaging alone. In 16 patients with previous myocardial infarction, perfusion defects were present at rest in 89 regions, 30 of which (34%) demonstrated increased FDG uptake, consistent with the presence of hibernation. Increased post-exercise FDG uptake appears to be a sensitive indicator of ischemia and myocardial hibernation. Increased post-exercise FDG uptake, appears to be a sensitive indicator of ischemia and myocardial hibernation. This test may be useful in selecting post-infarction patients for revascularization

Radioimmunoassay of erythropoietin: circulating levels in normal and polycythemic human beings

International Nuclear Information System (INIS)

Garcia, J.F.; Ebbe, S.N.; Hollander, L.; Cutting, H.O.; Miller, M.E.; Cronkite, E.P.

1982-01-01

Techniques are described in detail for the RIA of human Ep in unextracted plasma or serum. With 100 μl of sample, the assay is sensitive at an Ep concentration of approximately 4 mU/ml, and when required, the sensitivity can be increased to 0.4 mU/ml, a range considerably less than the concentration observed in normal human beings. This is approximately 100 times more sensitive than existing in vivo bioassays for this hormone. Studies concerned with the validation of the Ep RIA show a high degree of correlation with the polycythemic mouse bioassay. Dilutions of a variety of human serum samples show a parallel relationship with the standard reference preparation for Ep. Validation of the RIA is further confirmed by observations of appropriate increases or decreases of circulating Ep levels in physiological and clinical conditions known to be associated with stimulation or suppression of Ep secretion. Significantly different mean serum concentrations of 17.2 mU/ml for normal male subjects and 18.8 mU/ml for normal female subjects were observed. Mean plasma Ep concentrations in patients with polycythemia vera are significantly decreased, and those of patients with secondary polycythemia are significantly increased as compared to plasma levels in normal subjects. These results demonstrate an initial practical value of the Ep RA in the hematology clinic, which will most certainly be expanded with its more extensive use

Quantitative estimation of viable myocardium in the infarcted zone by infarct-redistribution map from images of exercise thallium-201 emission computed tomography

International Nuclear Information System (INIS)

Sekiai, Yasuhiro

1988-01-01

To evaluate, quantitatively, the viable myocardium in the infarcted zone, we invented the infarct-redistribution map which is produced from images of exercise thallium-201 emission computed tomography performed on 10 healthy subjects and 20 patients with myocardial infarction. The map displayed a left ventricle in which the infarcted area both with and without redistribution, the redistribution area without infarction, and normal perfusion area were shown separated in same screen. In these circumstances, the nonredistribution infarct lesion was found as being surrounded by the redistribution area. Indices of infarct and redistribution extent (defect score, % defect, redistribution ratio (RR) and redistribution index (RI)), were induced from the map and were used for quantitative analysis of the redistribution area and as the basis for comparative discussion regarding regional wall motion of the left ventricle. The quantitative indices of defect score, % defect, RR and RI were consistent with the visual assessment of planar images in detecting the extent of redistribution. Furthermore, defect score and % defect had an inverted linear relationship with % shortening (r = -0.573; p < 0.05, r = -0.536; p < 0.05, respectively), and RI had a good linear relationship with % shortening (r = 0.669; p < 0.01). We conclude that the infarct-redistribution map accurately reflects the myocardial viability and therefore may be useful for quantitative estimation of viable myocardium in the infarcted zone. (author)

Evolution of the Sinus Venosus from Fish to Human

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Bjarke Jensen

2014-03-01

Full Text Available The sinus venosus, the cardiac chamber upstream of the (right atrium, is a severely underinvestigated structure. Yet, its myocardium harbors the cardiac pacemaker in all vertebrates. In human, ectopic pacemaking and subsequent pathologies may originate from sinus venosus-derived myocardium surrounding the coronary sinus and the superior caval vein. In ectothermic vertebrates, i.e., fishes, amphibians and reptiles, the sinus venosus aids atrial filling by contracting prior to the atrium (atria. This is facilitated by the sinuatrial delay of approximately the same duration as the atrioventricular delay, which facilitates atrial filling of the ventricles. In mammals, the sinuatrial delay is lost, and the sinus venosus-derived myocardium persists as an extensive myocardial sheet surrounding the caval veins, which is activated in synchrony with the myocardium of the atria. The caval vein myocardium is hardly of significance in the healthy formed heart, but we suggest that the sinus venosus functions as a chamber during development when cardiac output, heart rate, blood pressure and architecture is much more like that of ectothermic vertebrates. The remodeling of the sinus venosus in mammals may be an adaptation associated with the high heart rates necessary for postnatal endothermy. If so, the endothermic birds should exhibit a similar remodeling as mammals, which remains to be investigated.

Muscle protein analysis. II. Two-dimensional electrophoresis of normal and diseased human skeletal muscle

Energy Technology Data Exchange (ETDEWEB)

Giometti, C.S. (Argonne National Lab., IL); Barany, M.; Danon, M.J.; Anderson, N.G.

1980-07-01

High-resolution two-dimensional electrophoresis was used to analyze the major proteins of normal and pathological human-muscle samples. The normal human-muscle pattern contains four myosin light chains: three that co-migrate with the myosin light chains from rabbit fast muscle (extensor digitorum longus), and one that co-migrates with the light chain 2 from rabbit slow muscle (soleus). Of seven Duchenne muscular dystrophy samples, four yielded patterns with decreased amounts of actin and myosin relative to normal muscle, while three samples gave patterns comparable to that for normal muscle. Six samples from patients with myotonic dystrophy also gave normal patterns. In nemaline rod myopathy, in contrast, the pattern was deficient in two of the fast-type myosin light chains.

Infarct-remodeled myocardium is receptive to protection by isoflurane postconditioning: role of protein kinase B/Akt signaling.

Science.gov (United States)

Feng, Jianhua; Fischer, Gregor; Lucchinetti, Eliana; Zhu, Min; Bestmann, Lukas; Jegger, David; Arras, Margarete; Pasch, Thomas; Perriard, Jean-Claude; Schaub, Marcus C; Zaugg, Michael

2006-05-01

Postinfarct remodeled myocardium exhibits numerous structural and biochemical alterations. So far, it is unknown whether postconditioning elicited by volatile anesthetics can also provide protection in the remodeled myocardium. Myocardial infarct was induced in male Wistar rats by ligation of the left anterior descending coronary artery. Six weeks later, hearts were buffer-perfused and exposed to 40 min of ischemia followed by 90 min of reperfusion. Anesthetic postconditioning was induced by 15 min of 2.1 vol% isoflurane. In some experiments, LY294002 (15 microM), a phosphatidylinositol 3-kinase inhibitor, was coadministered with isoflurane. Masson's trichrome staining, immunohistochemistry, Western blot analysis, and reverse-transcription polymerase chain reaction served to confirm remodeling. In buffer-perfused hearts, functional recovery was recorded, and acute infarct size was measured using 1% triphenyltetrazolium chloride staining and lactate dehydrogenase release during reperfusion. Western blot analysis was used to determine phosphorylation of reperfusion injury salvage kinases including protein kinase B/Akt and its downstream targets after 15 min of reperfusion. Infarct hearts exhibited typical macroscopic and molecular changes of remodeling. Isoflurane postconditioning improved functional recovery and decreased acute infarct size, as determined by triphenyltetrazolium (35 +/- 5% in unprotected hearts vs. 8 +/- 3% in anesthetic postconditioning; P protection was abolished by LY294002, which inhibited phosphorylation of protein kinase B/Akt and its downstream targets glycogen synthase kinase 3beta, endothelial nitric oxide synthase, and p70S6 kinase. Infarct-remodeled myocardium is receptive to protection by isoflurane postconditioning via protein kinase B/Akt signaling. This is the first time to demonstrate that anesthetic postconditioning retains its marked protection in diseased myocardium.

Appearance of high signal intensity and gadolinium-DTPA contrast enhancement in hypertrophied myocardium by magnetic resonance imaging

International Nuclear Information System (INIS)

Nishimura, Tsunehiko; Yamada, Naoaki; Nagata, Seiki

1989-01-01

This study was undertaken to examine the potential role of magnetic resonance imaging (MRI) for evaluating myocardial tissue characterization in hypertrophic cardiomyopathy (HCM). ECG-gated MRI images were acquired in 32 HCM patients and 30 patients with hypertensive heart disease (HHD), using a 1.5 T superconducting magnet system. The thickened areas were depicted as high signal intensities in the septum of 12 HCM patients (38%) and the endocardium of 5 HHD patients (17%). Echocardiography revealed that MRI appearance of high signal intensity was associated with more thickened myocardial wall. For evaluable 16 patients receiving i.v. injection of Gd-DTPA in a dose of 0.1 mM/kg, enhancement effects were observed in 10 patients (63%). High signal intensity appearing in the hypertrophied myocardium, as well as contrast enhancement, may not be characteristic of HCM, but reflect the likelihood of myocardial degeneration associated with the hypertrophied myocardium. Although MRI may not be capable of differentiating tissue characterization in HCM from that in HHD, it may provide different information about tissue characterization in the hypertrophied myocardium from that obtained by other techniques. (N.K.)

The skin immune system (SIS): distribution and immunophenotype of lymphocyte subpopulations in normal human skin

NARCIS (Netherlands)

Bos, J. D.; Zonneveld, I.; Das, P. K.; Krieg, S. R.; van der Loos, C. M.; Kapsenberg, M. L.

1987-01-01

The complexity of immune response-associated cells present in normal human skin was recently redefined as the skin immune system (SIS). In the present study, the exact immunophenotypes of lymphocyte subpopulations with their localizations in normal human skin were determined quantitatively. B cells

Skeletal muscle phosphatidylcholine fatty acids and insulin sensitivity in normal humans.

Science.gov (United States)

Clore, J N; Li, J; Gill, R; Gupta, S; Spencer, R; Azzam, A; Zuelzer, W; Rizzo, W B; Blackard, W G

1998-10-01

The fatty acid composition of skeletal muscle membrane phospholipids (PL) is known to influence insulin responsiveness in humans. However, the contribution of the major PL of the outer (phosphatidylcholine, PC) and inner (phosphatidylethanolamine, PE) layers of the sarcolemma to insulin sensitivity is not known. Fatty acid composition of PC and PE from biopsies of vastus lateralis from 27 normal men and women were correlated with insulin sensitivity determined by the hyperinsulinemic euglycemic clamp technique at insulin infusion rates of 0.4, 1.0, and 10.0 mU . kg-1 . min-1. Significant variation in the half-maximal insulin concentration (ED50) was observed in the normal volunteers (range 24.0-146.0 microU/ml), which correlated directly with fasting plasma insulin (r = 0.75, P insulin sensitivity was observed in PE (NS). These studies suggest that the fatty acid composition of PC may be of particular importance in the relationship between fatty acids and insulin sensitivity in normal humans.

Cdx2 modulates proliferation in normal human intestinal epithelial crypt cells

International Nuclear Information System (INIS)

Escaffit, Fabrice; Pare, Frederic; Gauthier, Remy; Rivard, Nathalie; Boudreau, Francois; Beaulieu, Jean-Francois

2006-01-01

The homeobox gene Cdx2 is involved in the regulation of the expression of intestine specific markers such as sucrase-isomaltase and lactase-phlorizin hydrolase. Previous studies performed with immortalized or transformed intestinal cell lines have provided evidence that Cdx2 can promote morphological and functional differentiation in these experimental models. However, no data exist concerning the implication of this factor in normal human intestinal cell physiology. In the present work, we have investigated the role of Cdx2 in normal human intestinal epithelial crypt (HIEC) cells that lack this transcription factor. The establishment of HIEC cells expressing Cdx2 in an inducible manner shows that forced expression of Cdx2 significantly alters the proliferation of intestinal crypt cells and stimulates dipeptidylpeptidase IV expression but is not sufficient to trigger intestinal terminal differentiation. These observations suggest that Cdx2 requires additional factors to activate the enterocyte differentiation program in normal undifferentiated cells

General anesthesia suppresses normal heart rate variability in humans

Science.gov (United States)

Matchett, Gerald; Wood, Philip

2014-06-01

The human heart normally exhibits robust beat-to-beat heart rate variability (HRV). The loss of this variability is associated with pathology, including disease states such as congestive heart failure (CHF). The effect of general anesthesia on intrinsic HRV is unknown. In this prospective, observational study we enrolled 100 human subjects having elective major surgical procedures under general anesthesia. We recorded continuous heart rate data via continuous electrocardiogram before, during, and after anesthesia, and we assessed HRV of the R-R intervals. We assessed HRV using several common metrics including Detrended Fluctuation Analysis (DFA), Multifractal Analysis, and Multiscale Entropy Analysis. Each of these analyses was done in each of the four clinical phases for each study subject over the course of 24 h: Before anesthesia, during anesthesia, early recovery, and late recovery. On average, we observed a loss of variability on the aforementioned metrics that appeared to correspond to the state of general anesthesia. Following the conclusion of anesthesia, most study subjects appeared to regain their normal HRV, although this did not occur immediately. The resumption of normal HRV was especially delayed on DFA. Qualitatively, the reduction in HRV under anesthesia appears similar to the reduction in HRV observed in CHF. These observations will need to be validated in future studies, and the broader clinical implications of these observations, if any, are unknown.

Recommendations to realise and interpret the scintigraphy of myocardium perfusion

International Nuclear Information System (INIS)

Manrique, A.; Marie, P.Y.

2003-06-01

The purpose of these recommendations is to help the physicians in the realization and the interpretation of the tomo-scintigraphies of myocardium perfusion, when this examination is made at the patients having a known or suspected coronary incapacity. These recommendations aim to encourage the practitioners (of nuclear medicine) to reflect and to discuss the procedures applied in their services. These procedures must be also adapted, in every service, to the peculiarities of the environment and to the experiment of each one. (N.C.)

Kinetics of adenylate metabolism in human and rat myocardium

OpenAIRE

Tavenier, M.; Skladanowski, A.C.; Abreu, R.A. de; Jong, J.W. de

1995-01-01

textabstractPathways producing and converting adenosine have hardly been investigated in human heart, contrasting work in other species. We compared the kinetics of enzymes associated with purine degradation and salvage in human and rat heart cytoplasm assaying for adenosine deaminase, nucleoside phosphorylase, xanthine oxidoreductase, AMP deaminase, AMP- and IMP-specific 5′-nucleotidases, adenosine kinase and hypoxanthine guanine phosphoribosyltransferase (HGPRT). Xanthine oxidoreductase was...

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.

Normalization of Deviation: Quotation Error in Human Factors.

Science.gov (United States)

Lock, Jordan; Bearman, Chris

2018-05-01

Objective The objective of this paper is to examine quotation error in human factors. Background Science progresses through building on the work of previous research. This requires accurate quotation. Quotation error has a number of adverse consequences: loss of credibility, loss of confidence in the journal, and a flawed basis for academic debate and scientific progress. Quotation error has been observed in a number of domains, including marine biology and medicine, but there has been little or no previous study of this form of error in human factors, a domain that specializes in the causes and management of error. Methods A study was conducted examining quotation accuracy of 187 extracts from 118 published articles that cited a control article (Vaughan's 1996 book: The Challenger Launch Decision: Risky Technology, Culture, and Deviance at NASA). Results Of extracts studied, 12.8% ( n = 24) were classed as inaccurate, with 87.2% ( n = 163) being classed as accurate. A second dimension of agreement was examined with 96.3% ( n = 180) agreeing with the control article and only 3.7% ( n = 7) disagreeing. The categories of accuracy and agreement form a two by two matrix. Conclusion Rather than simply blaming individuals for quotation error, systemic factors should also be considered. Vaughan's theory, normalization of deviance, is one systemic theory that can account for quotation error. Application Quotation error is occurring in human factors and should receive more attention. According to Vaughan's theory, the normal everyday systems that promote scholarship may also allow mistakes, mishaps, and quotation error to occur.

The distribution of YKL-40 in osteoarthritic and normal human articular cartilage

DEFF Research Database (Denmark)

Volck, B; Ostergaard, K; Johansen, J S

1999-01-01

YKL-40, also called human cartilage glycoprotein-39, is a major secretory protein of human chondrocytes in cell culture. YKL-40 mRNA is expressed by cartilage from patients with rheumatoid arthritis, but is not detectable in normal human cartilage. The aim was to investigate the distribution of YKL......-40 in osteoarthritic (n=9) and macroscopically normal (n=5) human articular cartilage, collected from 12 pre-selected areas of the femoral head, to discover a potential role for YKL-40 in cartilage remodelling in osteoarthritis. Immunohistochemical analysis showed that YKL-40 staining was found...... in chondrocytes of osteoarthritic cartilage mainly in the superficial and middle zone of the cartilage rather than the deep zone. There was a tendency for high number of YKL-40 positive chondrocytes in areas of the femoral head with a considerable biomechanical load. The number of chondrocytes with a positive...

Mitochondrial complex III defects contribute to inefficient respiration and ATP synthesis in the myocardium of Trypanosoma cruzi-infected mice.

Science.gov (United States)

Wen, Jian-Jun; Garg, Nisha Jain

2010-01-01

In this study, we conducted a thorough analysis of mitochondrial bioenergetic function as well as the biochemical and molecular factors that are deregulated and contribute to compromised adenosine triphosphate (ATP) production in the myocardium during Trypanosoma cruzi infection. We show that ADP-stimulated state 3 respiration and ATP synthesis supported by pyruvate/malate (provides electrons to complex I) and succinate (provides electrons to complex II) substrates were significantly decreased in left ventricular tissue and isolated cardiac mitochondria of infected mice. The decreased mitochondrial ATP synthesis in infected murine hearts was not a result of uncoupling between the electron-transport chain and oxidative phosphorylation and decreased availability of the intermediary metabolites (e.g., NADH). The observed decline in the activities of complex-I, -IV, and -V was not physiologically relevant and did not contribute to compromised respiration and ATP synthesis in infected myocardium. Instead, complex III activity was decreased above the threshold level and contributed to respiratory-chain inefficiency and the resulting decline in mitochondrial ATP synthesis in infected myocardium. The loss in complex III activity occurred as a consequence of cytochrome b depletion. Treatment of infected mice with phenyl-alpha-tert-butyl nitrone (PBN, antioxidant) was beneficial in preserving the mtDNA-encoded cytochrome b expression, and subsequently resulted in improved complex III activity, mitochondrial respiration, and ATP production in infected myocardium. Overall, we provide novel data on the mechanism(s) involved in cardiac bioenergetic inefficiency during T. cruzi infection.

Human renin biosynthesis and secretion in normal and ischemic kidneys

International Nuclear Information System (INIS)

Pratt, R.E.; Carleton, J.E.; Richie, J.P.; Heusser, C.; Dzau, V.J.

1987-01-01

The pathway of renin biosynthesis and secretion in normal and ischemic human kidneys has been investigated by pulse-labeling experiments. The results indicate that in normal human kidney, preprorenin is rapidly processed to 47-kDa prorenin. Microradiosequencing showed that this molecule was generated by cleavage between Gly-23 and Leu-24, yielding a 43-amino acid proregion. Analysis of prorenin secreted by the kidney tissue yielded an identical sequence, indicating that prorenin is secreted without any further proteolysis. An examination of the kinetics of processing and secretion suggested that a majority of the newly synthesized prorenin is quickly secreted, while only a small fraction is processed intracellularly to the mature renin. The differences in secretion kinetics between prorenin and mature renin and the selective inhibition of prorenin secretion by monensin suggest that they are secreted independently via two pathways: a constitutive pathway probably from the Golgi or protogranules that rapidly release prorenin and a regulated pathway that secretes mature renin from the mature granules. A comparison of the kinetics of processing between normal and ischemic tissues suggests that renal ischemia leads to an overall increase in the rate of processing or prorenin to mature renin. In addition, prolonged biosynthetic labeling of renin in the ischemic kidney yielded two smaller molecular weight immunoreactive forms suggestive of renin fragments that may be degradative products. These fragments were not detected in normal kidney tissue labeled for similar lengths of time

Gamma-ray excision repair in normal and diseased human cells

International Nuclear Information System (INIS)

Cerutti, P.A.; Remsen, J.F.

1976-01-01

Radiation products of the 5,6-dihydroxy-dihydrothymine type (t') are efficiently removed from the DNA during postirradiation incubation of bacterial and mammalian cells. In this chapter we describe the t'-excision system contained in normal human cells, in human carcinoma HeLa S-3 cells, and in skin fibroblasts from xeroderma pigmentosum (XP) and Fanconi's anemia (FA) patients. The latter diseases are characterized among other symptoms by a genetically increased susceptibility for the development of cancer

The measurement of intrinsic cellular radiosensitivity in human tumours and normal tissues

International Nuclear Information System (INIS)

Lawton, P.A.

1995-01-01

Human tumour and normal cell radiosensitivity are thought to be important factors determining the response of tumour and normal tissues to radiotherapy, respectively. Clonogenic assays are the standard method for measuring radiosensitivity but they are of limited applicability for clinical use with fresh human tumours. The main aim of this work was to evaluate the Adhesive Tumour Cell Culture System (ATCCS), as a method for measuring the radiosensitivity of human tumours. A soft agar clonogenic assay, the modified Courtenay-Mills assay, was used as a standard to compare with the ATCCS. The demonstration that fibroblast contamination could occur with both assay methods led to the investigation of a new technique for removing unwanted fibroblasts from tumour cell suspensions and to the use of a multiwell assay for measuring fibroblast radiosensitivity. (author)

The measurement of intrinsic cellular radiosensitivity in human tumours and normal tissues

Energy Technology Data Exchange (ETDEWEB)

Lawton, P.A.

1995-12-31

Human tumour and normal cell radiosensitivity are thought to be important factors determining the response of tumour and normal tissues to radiotherapy, respectively. Clonogenic assays are the standard method for measuring radiosensitivity but they are of limited applicability for clinical use with fresh human tumours. The main aim of this work was to evaluate the Adhesive Tumour Cell Culture System (ATCCS), as a method for measuring the radiosensitivity of human tumours. A soft agar clonogenic assay, the modified Courtenay-Mills assay, was used as a standard to compare with the ATCCS. The demonstration that fibroblast contamination could occur with both assay methods led to the investigation of a new technique for removing unwanted fibroblasts from tumour cell suspensions and to the use of a multiwell assay for measuring fibroblast radiosensitivity. (author).

Validation of [1-11C]acetate as a tracer for noninvasive assessment of oxidative metabolism with positron emission tomography in normal, ischemic, postischemic, and hyperemic canine myocardium

International Nuclear Information System (INIS)

Armbrecht, J.J.; Buxton, D.B.; Schelbert, H.R.

1990-01-01

Extraction and clearance kinetics of [1-11C]acetate were examined in 65 experiments in 30 open-chest dogs. Twenty-nine studies were performed at control, 13 during ischemia, eight after reperfusion, 13 during dipyridamole-induced hyperemia, and two during alteration of cardiac workload. [1-11C]acetate was injected directly into the left anterior descending coronary artery, and myocardial tissue-time activity curves were recorded with a gamma probe. The single-pass extraction fraction averaged 64.2 +/- 9.7% in control, 65.3 +/- 9.1% in ischemia, 70.0 +/- 4.4% in reperfusion, and 46.5 +/- 7.4% in dipyridamole-induced hyperemia groups. 11C clearance was biexponential in all cases. The rate constant k1 for the first rapid clearance phase correlated closely with myocardial oxygen consumption (r = 0.94) in control, ischemia, reperfusion, and dipyridamole-induced hyperemia groups. Monoexponential fitting of only the first linear part of the clearance curve yielded the rate constant kmono, which also correlated with myocardial oxygen consumption (r = 0.96). Arterial lactate concentrations and the amount of free fatty acid oxygen equivalents consumed by the myocardium were shown to have a small but statistically significant impact on the relation between [1-11C]acetate clearance rate constants and myocardial oxygen consumption. The fraction of 14CO2 activity contributing to overall 14C activity leaving the myocardium after simultaneous injection of [1-14C]acetate (n = 24) was relatively high in all cases , indicating that externally measured 11C clearance corresponds to CO2 production and thus to tricarboxylic acid cycle activity. In conclusion, the results validate the use of [1-11C]acetate as a tracer of oxidative myocardial metabolism for use with positron emission tomography

Stretch-dependent slow force response in isolated rabbit myocardium is Na+ dependent.

Science.gov (United States)

von Lewinski, Dirk; Stumme, Burkhard; Maier, Lars S; Luers, Claus; Bers, Donald M; Pieske, Burkert

2003-03-15

Stretch induces functional and trophic effects in mammalian myocardium via various signal transduction pathways. We tested stretch signal transduction on immediate and slow force response (SFR) in rabbit myocardium. Experiments were performed in isolated right ventricular muscles from adult rabbit hearts (37 degrees C, 1 Hz stimulation rate, bicarbonate-buffer). Muscles were rapidly stretched from 88% of optimal length (L88) to near optimal length (L98) for functional analysis. The resulting immediate and slow increases in twitch force (first phase and SFR, respectively) were assessed at reduced [Na+]o or without and with blockade of stretch activated ion channels (SACs), angiotensin-II (AT1) receptors, endothelin-A (ET(A)) receptors, Na+/H+-exchange (NHE1), reverse mode Na+/Ca2+-exchange (NCX), or Na+/K+-ATPase. The effects of stretch on sarcoplasmic reticulum Ca2+-load were characterized using rapid cooling contractures (RCCs). Intracellular pH was measured in BCECF-AM loaded muscles, and action potential duration (APD) was assessed using floating electrodes. On average, force increased to 216+/-8% of the pre-stretch value during the immediate phase, followed by a further increase to 273+/-10% during the SFR (n=81). RCCs significantly increased during SFR, whereas pH and APD did not change. Neither inhibition of SACs, AT1, or ET(A) receptors affected the stretch-dependent immediate phase nor SFR. In contrast, SFR was reduced by NHE inhibition and almost completely abolished by reduced [Na+]o or inhibition of reverse-mode NCX, whereas increased SFR was seen after raising [Na+]i by Na+/K+-ATPase inhibition. The data demonstrate the existence of a delayed, Na+- and Ca2+-dependent but pH and APD independent SFR to stretch in rabbit myocardium. This inotropic response appears to be independent of autocrine/paracrine AT1 or ET(A) receptor activation, but mediated through stretch-induced activation of NHE and reverse mode NCX.

Pathological prolongation of action potential duration as a cause of the reduced alpha-adrenoceptor-mediated negative inotropy in streptozotocin-induced diabetic mice myocardium.

Science.gov (United States)

Kanae, Haruna; Hamaguchi, Shogo; Wakasugi, Yumi; Kusakabe, Taichi; Kato, Keisuke; Namekata, Iyuki; Tanaka, Hikaru

2017-11-01

Effect of pathological prolongation of action potential duration on the α-adrenoceptor-mediated negative inotropy was studied in streptozotocin-induced diabetic mice myocardium. In streptozotocin-treated mouse ventricular myocardium, which had longer duration of action potential than that in control mice, the negative inotropic response induced by phenylephrine was smaller than that in control mice. 4-Aminopyridine prolonged the action potential duration and decreased the negative inotropy in control mice. Cromakalim shortened the action potential duration and increased the negative inotropy in streptozotocin-treated mice. These results suggest that the reduced α-adrenoceptor-mediated inotropy in the diabetic mouse myocardium is partly due to its prolonged action potential. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Neurogenic stunned myocardium following hemorrhagic cerebral contusion

International Nuclear Information System (INIS)

Deleu, D.; Miyares, F.; Kettern, M.; Kumar, S.; Hassens, Y.; Salim, K.

2007-01-01

Neurogenic stunned myocardium NSM is a well-known complication of subarachnoidal hemorrhage, but has been reported rarely in association with other central nervous system disorders. A case of NSM is described in a patient with hemorrhagic brain contusion associated with cerebral edema. An 18-year-old man was admitted with severe cranial trauma following a car roll-over. Six days after admission, he developed findings suggestive for NSM. The troponin T and creatine kinase-MB level were elevated and echocardiogram showed apical and inferoposterior hypokinesis and diffuse left ventricular akinesis with severely reduced ejection fraction 18%. Invasive measurements confirmed low cardiac output. His cardiac function resolved completely within 6 days after decompressive craniotomy. This case supports the presumed unifying role of the increased intracranial pressure, probably triggering a vigorous sympathetic outflow hyperactivity leading to NSM. (author)

Immortalization of normal human fibroblasts by treatment with 4-nitroquinoline 1-oxide.

Science.gov (United States)

Bai, L; Mihara, K; Kondo, Y; Honma, M; Namba, M

1993-02-01

Normal human fibroblasts (the OUMS-24 strain), derived from a 6-week-old human embryo, were transformed (into the OUMS-24F line) and immortalized by repeated treatments (59 times) with 4-nitroquinoline 1-oxide (4NQO). Treatment began during primary culture and ended at the 51st population doubling level (PDL). At the 57th PDL (146 days after the last treatment), morphologically altered, epithelial-type cells appeared, began to grow and became immortal (now past the 100th PDL). However, the control fibroblasts, which were not treated with 4NQO, senesced at the 62nd PDL. The finding that extensive, repeated treatments with 4NQO are required for the immortalization of normal human cells, indicates that multiple mutational events are involved in the immortalization of human cells in general. In other words, immortalization itself seems to be a multi-step process. Karyotypic analysis showed that many cells were hypodiploid before immortalization, but that afterwards chromosomes were distributed broadly in the diploid to tetraploid regions. The immortalized cells showed amplification and enhanced expression of c-myc. Two-dimensional electrophoretic analysis showed that the number of disappearing cellular proteins was greater than the number of the newly appearing ones after the cells became immortalized. Since the immortalized cells showed neither anchorage-independent growth nor tumorigenicity, they are useful for studying factors that can contribute to multi-step carcinogenesis in human cells. In addition, genetically matched normal (OUMS-24) and immortalized (OUMS-24F) cells will be useful for analyzing the genes related to cellular mortality and immortalization.

Quantitative Differentiation of LV Myocardium with and without Layer-Specific Fibrosis Using MRI in Hypertrophic Cardiomyopathy and Layer-Specific Strain TTE Analysis.

Science.gov (United States)

Funabashi, Nobusada; Takaoka, Hiroyuki; Ozawa, Koya; Kamata, Tomoko; Uehara, Masae; Komuro, Issei; Kobayashi, Yoshio

2018-05-30

To achieve further risk stratification in hypertrophic cardiomyopathy (HCM) patients, we localized and quantified layer-specific LVM fibrosis on MRI in HCM patients using regional layer-specific peak longitudinal strain (PLS) and peak circumferential strain (PCS) in LV myocardium (LVM) on speckle tracking transthoracic echocardiography (TTE). A total of 18 HCM patients (14 males; 58 ± 17 years) underwent 1.5T-MRI and TTE. PLS and PCS in each layer of the LVM (endocardium, epicardium, and whole-layer myocardium) were calculated for 17 AHA-defined lesions. MRI assessment showed that fibrosis was classified as endocardial, epicardial, or whole-layer (= either or both of these). Regional PLS was smaller in fibrotic endocardial lesions than in non-fibrotic endocardial lesions (P = 0.004). To detect LV endocardial lesions with fibrosis, ROC curves of regional PLS revealed an area under the curve (AUC) of 0.609 and a best cut-off point of 13.5%, with sensitivity of 65.3% and specificity of 54.3%. Regional PLS was also smaller in fibrotic epicardial lesions than in non-fibrotic epicardial lesions (P layer myocardium analysis, PLS was smaller in fibrotic lesions than in non-fibrotic lesions (P layer LV lesions with fibrosis, ROC curves of regional PLS revealed an AUC of 0.674 and a best cut-off point of 12.5%, with sensitivity of 79.0% and specificity of 50.7%. There were no significant differences in PCS of LV myocardium (endocardium, epicardium, and whole-layer) between fibrotic and non-fibrotic lesions. Quantitative regional PLS but not PCS in LV endocardium, epicardium, and whole-layer myocardium provides useful non-invasive information for layer-specific localization of fibrosis in HCM patients.

Duchenne Muscular Dystrophy Gene Expression in Normal and Diseased Human Muscle

Science.gov (United States)

Oronzi Scott, M.; Sylvester, J. E.; Heiman-Patterson, T.; Shi, Y.-J.; Fieles, W.; Stedman, H.; Burghes, A.; Ray, P.; Worton, R.; Fischbeck, K. H.

1988-03-01

A probe for the 5' end of the Duchenne muscular dystrophy (DMD) gene was used to study expression of the gene in normal human muscle, myogenic cell cultures, and muscle from patients with DMD. Expression was found in RNA from normal fetal muscle, adult cardiac and skeletal muscle, and cultured muscle after myoblast fusion. In DMD muscle, expression of this portion of the gene was also revealed by in situ RNA hybridization, particularly in regenerating muscle fibers.

The helical ventricular myocardial band: global, three-dimensional, functional architecture of the ventricular myocardium.

Science.gov (United States)

Kocica, Mladen J; Corno, Antonio F; Carreras-Costa, Francesc; Ballester-Rodes, Manel; Moghbel, Mark C; Cueva, Clotario N C; Lackovic, Vesna; Kanjuh, Vladimir I; Torrent-Guasp, Francisco

2006-04-01

We are currently witnessing the advent of new diagnostic tools and therapies for heart diseases, but, without serious scientific consensus on fundamental questions about normal and diseased heart structure and function. During the last decade, three successive, international, multidisciplinary symposia were organized in order to setup fundamental research principles, which would allow us to make a significant step forward in understanding heart structure and function. Helical ventricular myocardial band of Torrent-Guasp is the revolutionary new concept in understanding global, three-dimensional, functional architecture of the ventricular myocardium. This concept defines the principal, cumulative vectors, integrating the tissue architecture (i.e. form) and net forces developed (i.e. function) within the ventricular mass. Here we expose the compendium of Torrent-Guasp's half-century long functional anatomical investigations in the light of ongoing efforts to define the integrative approach, which would lead to new understanding of the ventricular form and function by linking across multiple scales of biological organization, as defined in ongoing Physiome project. Helical ventricular myocardial band of Torrent-Guasp may also, hopefully, allow overcoming some difficulties encountered in contemporary efforts to create a comprehensive mathematical model of the heart.

RhNRG-1β Protects the Myocardium against Irradiation-Induced Damage via the ErbB2-ERK-SIRT1 Signaling Pathway.

Directory of Open Access Journals (Sweden)

Anxin Gu

Full Text Available Radiation-induced heart disease (RIHD, which is a serious side effect of the radiotherapy applied for various tumors due to the inevitable irradiation of the heart, cannot be treated effectively using current clinical therapies. Here, we demonstrated that rhNRG-1β, an epidermal growth factor (EGF-like protein, protects myocardium tissue against irradiation-induced damage and preserves cardiac function. rhNRG-1β effectively ameliorated irradiation-induced myocardial nuclear damage in both cultured adult rat-derived cardiomyocytes and rat myocardium tissue via NRG/ErbB2 signaling. By activating ErbB2, rhNRG-1β maintained mitochondrial integrity, ATP production, respiratory chain function and the Krebs cycle status in irradiated cardiomyocytes. Moreover, the protection of irradiated cardiomyocytes and myocardium tissue by rhNRG-1β was at least partly mediated by the activation of the ErbB2-ERK-SIRT1 signaling pathway. Long-term observations further showed that rhNRG-1β administered in the peri-irradiation period exerts continuous protective effects on cardiac pump function, the myocardial energy metabolism, cardiomyocyte volume and interstitial fibrosis in the rats receiving radiation via NRG/ErbB2 signaling. Our findings indicate that rhNRG-1β can protect the myocardium against irradiation-induced damage and preserve cardiac function via the ErbB2-ERK-SIRT1 signaling pathway.

Distinct p53 genomic binding patterns in normal and cancer-derived human cells

Energy Technology Data Exchange (ETDEWEB)

Botcheva K.; McCorkle S. R.; McCombie W. R.; Dunn J. J.; Anderson C. W.

2011-12-15

We report here genome-wide analysis of the tumor suppressor p53 binding sites in normal human cells. 743 high-confidence ChIP-seq peaks representing putative genomic binding sites were identified in normal IMR90 fibroblasts using a reference chromatin sample. More than 40% were located within 2 kb of a transcription start site (TSS), a distribution similar to that documented for individually studied, functional p53 binding sites and, to date, not observed by previous p53 genome-wide studies. Nearly half of the high-confidence binding sites in the IMR90 cells reside in CpG islands, in marked contrast to sites reported in cancer-derived cells. The distinct genomic features of the IMR90 binding sites do not reflect a distinct preference for specific sequences, since the de novo developed p53 motif based on our study is similar to those reported by genome-wide studies of cancer cells. More likely, the different chromatin landscape in normal, compared with cancer-derived cells, influences p53 binding via modulating availability of the sites. We compared the IMR90 ChIPseq peaks to the recently published IMR90 methylome1 and demonstrated that they are enriched at hypomethylated DNA. Our study represents the first genome-wide, de novo mapping of p53 binding sites in normal human cells and reveals that p53 binding sites reside in distinct genomic landscapes in normal and cancer-derived human cells.

Human-Machine interface for off normal and emergency situations in nuclear power plants

Energy Technology Data Exchange (ETDEWEB)

Kwon, Kee Choon [Korea Atomic Energy Research Institute, Taejeon (Korea)

2000-01-01

Many nuclear power plants (NPPs) have reported that a high percentage of all major failures in the plants are caused by human errors. Therefore, there has been much focus on elimination of human errors, enhancement of human performance, and general improvement of human machine interface (HMI). Both the utility management and the regulators are demanding improvement in this area. The International Atomic Energy Agency (IAEA) Specialists' Meeting on 'Human-Machine Interface for Off Normal and Emergency Situations in Nuclear Power Plants' was co-organized by the Korea Atomic Energy Research Institute (KAERI) and the Korea Power Engineering Company, INC (KOPEC), and took place in Taejeon, Republic of Korea, 1999 October 26-28. Fifty eight participants, representing nine member countries reviewed recent developments and discussed directions for future efforts in the Human-Machine Interface for Off Normal and Emergency Situations in NPPs. Twenty papers were presented, covering a wide spectrum of technical and scientific subjects including recent experience and benefits from Operational Experience with HMI, Development of HMI System, Licensing Issues for HMI and Future Development and Trends. (Author)

Human-Machine interface for off normal and emergency situations in nuclear power plants

Energy Technology Data Exchange (ETDEWEB)

Kwon, Kee Choon [Korea Atomic Energy Research Institute, Taejeon (Korea)

2000-01-01

Many nuclear power plants (NPPs) have reported that a high percentage of all major failures in the plants are caused by human errors. Therefore, there has been much focus on elimination of human errors, enhancement of human performance, and general improvement of human machine interface (HMI). Both the utility management and the regulators are demanding improvement in this area. The International Atomic Energy Agency (IAEA) Specialists' Meeting on 'Human-Machine Interface for Off Normal and Emergency Situations in Nuclear Power Plants' was co-organized by the Korea Atomic Energy Research Institute (KAERI) and the Korea Power Engineering Company, INC (KOPEC), and took place in Taejeon, Republic of Korea, 1999 October 26-28. Fifty eight participants, representing nine member countries reviewed recent developments and discussed directions for future efforts in the Human-Machine Interface for Off Normal and Emergency Situations in NPPs. Twenty papers were presented, covering a wide spectrum of technical and scientific subjects including recent experience and benefits from Operational Experience with HMI, Development of HMI System, Licensing Issues for HMI and Future Development and Trends. (Author)

Heterogeneity of uroplakin localization in human normal urothelium, papilloma and papillary carcinoma

International Nuclear Information System (INIS)

Zupancic, Dasa; Romih, Rok

2013-01-01

Uroplakins are differentiation-related membrane proteins of urothelium. We compared uroplakin expression and ultrastructural localization in human normal urothelium, papilloma and papillary carcinoma. Because of high recurrence rate of these tumours, treated by transurethral resection, we investigated urothelial tumour, resection border and uninvolved urothelium. Urinary bladder samples were obtained from tumour free control subjects and patients with papilloma and papillary carcinoma. Immunohistochemical and immunoelectron labelling of uroplakins were performed. In normal human urothelium with continuous uroplakin-positive superficial cell layer uroplakins were localized to flattened mature fusiform vesicles and apical plasma membrane of umbrella cells. Diverse uroplakin expression was found in papilloma and papillary carcinoma. Three aberrant differentiation stages of urothelial cells, not found in normal urothelium, were recognized in tumours. Diverse uroplakin expression and aberrant differentiation were occasionally found in resection border and in uninvolved urothelium. We demonstrated here that uroplakin expression and localization in urothelial tumours is altered when compared to normal urothelium. In patients with papilloma and papillary carcinoma immunolabelling of uroplakins at ultrastructural level shows aberrant urothelial differentiation. It is possible that aberrant differentiation stages of urothelial cells in resection border and in uninvolved urothelium contribute to high recurrence rate

Stable radioresistance in ataxia-telangiectasia cells containing DNA from normal human cells

International Nuclear Information System (INIS)

Kapp, L.N.; Painter, R.B.

1989-01-01

SV40-transformed ataxia-telangiectasia (AT) cells were transfected with a cosmid containing a normal human DNA library and selectable marker, the neo gene, which endows successfully transformed mammalian cells with resistance to the antibiotic G418. Cells from this line were irradiated with 50 Gy of X-rays and fused with non-transfected AT cells. Among the G418-resistant colonies recovered was one stably resistant to radiation. Resistance to ionizing radiation of both primary transfectant line and its fusion derivative was intermediate between that of AT cells and normal cells, as assayed by colony-forming ability and measurement of radiation-induced G 2 chromatic aberrations; both cell lines retained AT-like radioresistant DNA synthesis. Results suggest that, because radioresistance in transfected cells was not as great as in normal human cells, two hallmarks of AT, radiosensitivity and radioresistant DNA synthesis, may still be the result of a single defective AT gene. (author)

Mr 40,000 and Mr 39,000 pertussis toxin substrates are increased in surgically denervated dog ventricular myocardium

Energy Technology Data Exchange (ETDEWEB)

Hershberger, R.E.; Feldman, A.M.; Anderson, F.L.; Kimball, J.A.; Wynn, J.R.; Bristow, M.R. (Univ. of Utah School of Medicine, Salt Lake City (USA))

1991-04-01

To test the general hypothesis that cardiac innervation may participate in myocardial G protein regulation, we examined the effects of complete intrapericardial surgical denervation or sham operation in dogs. In particulate fractions of dog left ventricular (LV) myocardium harvested 28-33 days after denervation or sham operation, Mr 40,000 and Mr 39,000 pertussis toxin-sensitive substrates (G proteins) were increased by 31% (1.31 +/- 0.084 vs 1.00 +/- 0.058 OD, arbitrary units, p less than 0.01) and 40% (1.40 +/- 0.117 vs. 1.000 +/- 0.084 OD, arbitrary units, p less than 0.02), respectively, as compared with sham-operated controls. The Mr 40,000 pertussis toxin-sensitive band comigrated with a pertussis toxin-sensitive substrate in human erythrocyte membranes known to contain an alpha Gi species. In these same preparations basal, GTP and GppNHp stimulated adenylate cyclase activities were decreased in denervated heart by 20, 26, and 19%, respectively, consistent with increased activity of an inhibitory G protein. In contrast, Gs function was not altered, because cyc(-) membranes reconstituted with membrane extracts and fluoride and beta-receptor-stimulated adenylate cyclase activity were not different between groups. Furthermore, adenylate cyclase catalytic subunit function as assessed with forskolin and manganese stimulation was not different between preparations of control and denervated heart. We conclude that in preparations of surgically denervated dog myocardium Mr 40,000 and Mr 39,000 pertussis toxin-sensitive G proteins are increased by 31 and 40%, respectively, and that functional alterations in adenylate cyclase activity exist, consistent with increased inhibitory G-protein function.

Mr 40,000 and Mr 39,000 pertussis toxin substrates are increased in surgically denervated dog ventricular myocardium

International Nuclear Information System (INIS)

Hershberger, R.E.; Feldman, A.M.; Anderson, F.L.; Kimball, J.A.; Wynn, J.R.; Bristow, M.R.

1991-01-01

To test the general hypothesis that cardiac innervation may participate in myocardial G protein regulation, we examined the effects of complete intrapericardial surgical denervation or sham operation in dogs. In particulate fractions of dog left ventricular (LV) myocardium harvested 28-33 days after denervation or sham operation, Mr 40,000 and Mr 39,000 pertussis toxin-sensitive substrates (G proteins) were increased by 31% (1.31 +/- 0.084 vs 1.00 +/- 0.058 OD, arbitrary units, p less than 0.01) and 40% (1.40 +/- 0.117 vs. 1.000 +/- 0.084 OD, arbitrary units, p less than 0.02), respectively, as compared with sham-operated controls. The Mr 40,000 pertussis toxin-sensitive band comigrated with a pertussis toxin-sensitive substrate in human erythrocyte membranes known to contain an alpha Gi species. In these same preparations basal, GTP and GppNHp stimulated adenylate cyclase activities were decreased in denervated heart by 20, 26, and 19%, respectively, consistent with increased activity of an inhibitory G protein. In contrast, Gs function was not altered, because cyc(-) membranes reconstituted with membrane extracts and fluoride and beta-receptor-stimulated adenylate cyclase activity were not different between groups. Furthermore, adenylate cyclase catalytic subunit function as assessed with forskolin and manganese stimulation was not different between preparations of control and denervated heart. We conclude that in preparations of surgically denervated dog myocardium Mr 40,000 and Mr 39,000 pertussis toxin-sensitive G proteins are increased by 31 and 40%, respectively, and that functional alterations in adenylate cyclase activity exist, consistent with increased inhibitory G-protein function

Dynamic CT perfusion imaging of the myocardium: a technical note on improvement of image quality.

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Daniela Muenzel

Full Text Available OBJECTIVE: To improve image and diagnostic quality in dynamic CT myocardial perfusion imaging (MPI by using motion compensation and a spatio-temporal filter. METHODS: Dynamic CT MPI was performed using a 256-slice multidetector computed tomography scanner (MDCT. Data from two different patients-with and without myocardial perfusion defects-were evaluated to illustrate potential improvements for MPI (institutional review board approved. Three datasets for each patient were generated: (i original data (ii motion compensated data and (iii motion compensated data with spatio-temporal filtering performed. In addition to the visual assessment of the tomographic slices, noise and contrast-to-noise-ratio (CNR were measured for all data. Perfusion analysis was performed using time-density curves with regions-of-interest (ROI placed in normal and hypoperfused myocardium. Precision in definition of normal and hypoperfused areas was determined in corresponding coloured perfusion maps. RESULTS: The use of motion compensation followed by spatio-temporal filtering resulted in better alignment of the cardiac volumes over time leading to a more consistent perfusion quantification and improved detection of the extend of perfusion defects. Additionally image noise was reduced by 78.5%, with CNR improvements by a factor of 4.7. The average effective radiation dose estimate was 7.1±1.1 mSv. CONCLUSION: The use of motion compensation and spatio-temporal smoothing will result in improved quantification of dynamic CT MPI using a latest generation CT scanner.

Magnetic measurements on human erythrocytes: Normal, beta thalassemia major, and sickle

Science.gov (United States)

Sakhnini, Lama

2003-05-01

In this article magnetic measurements were made on human erythrocytes at different hemoglobin states (normal and reduced hemoglobin). Different blood samples: normal, beta thalassemia major, and sickle were studied. Beta thalassemia major and sickle samples were taken from patients receiving lifelong blood transfusion treatment. All samples examined exhibited diamagnetic behavior. Beta thalassemia major and sickle samples showed higher diamagnetic susceptibilities than that for the normal, which was attributed to the increase of membrane to hemoglobin volume ratio of the abnormal cells. Magnetic measurements showed that the erythrocytes in the reduced state showed less diamagnetic response in comparison with erythrocytes in the normal state. Analysis of the paramagnetic component of magnetization curves gave an effective magnetic moment of μeff=7.6 μB per reduced hemoglobin molecule. The same procedure was applied to sickle and beta thalassemia major samples and values for μeff were found to be comparable to that of the normal erythrocytes.

Simple mucin-type carbohydrates in normal and malignant human endometrium

DEFF Research Database (Denmark)

Ravn, V; Mandel, U; Svenstrup, B

1995-01-01

The simple mucin-type carbohydrate antigens, Tn, sialosyl-Tn, and T, are tumor-associated antigens of adenocarcinomas. We evaluated by immunohistochemistry the expression of Tn, sialosyl-Tn (s-Tn), T, and sialosyl-T (s-T) antigens in normal nonsecretory, early gestational, and malignant human...... and malignant endometrium, and the expression of s-T antigen was positively correlated with E2 levels in serum. Our findings suggest a hormonal influence on expression of simple mucin-type carbohydrates in human endometrium. However, the accumulation of Tn and s-Tn antigens in malignant endometrial cells seem...

Hsp60 and p70S6K form a complex in human cardiomyocytes

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Kroupskaya I. V.

2011-02-01

Full Text Available Molecular chaperon Hsp60 and protein kinase p70S6K play an important functional role in the regulation of cardiomyocytes vital function or apoptosis. Aim. To study a possibility of in vivo complex formation between Hsp60 and p70S6K in cardiomyocytes. Methods. Co-immunoprecipitation, Western-blot analysis. Results. We have identified in vivo interaction between molecular chaperone Hsp60 and two isoforms of proteinkinase p70S6K in human myocardium, normal and affected by cardiomyopathy. Conclusions. The results obtained suggest a possible participation of molecular chaperon Hsp60 in regulation of p70S6K activity in stressinduced apoptotic signaling pathway in cardiomyocytes.

Different gene expression in human heart tissue and progenitor cells from control and diabetic subjects: relevance to the pathogenesis of human diabetic cardiomyopathy.

Science.gov (United States)

de Cillis, Emanuela; Leonardini, Anna; Laviola, Luigi; Giorgino, Francesco; Tupputi Schinosa, Luigi de Luca; Bortone, Alessandro Santo

2010-04-01

The The aim of our study is to investigate the molecular mechanisms of diabetic cardiomyopathy through the identification of remarkable genes for the myocardial function that are expressed differently between diabetic and normal subjects. Moreover, we intend to characterize both in human myocardial tissue and in the related cardiac progenitor cells the pattern of gene expression and the levels of expression and protein activation of molecular effectors involved in the regulation of the myocardial function and differentiation to clarify whether in specific human pathological conditions (type 2 diabetes mellitus, cardiac failure, coronary artery disease) specific alterations of the aforementioned factors could take place. Thirty-five patients scheduled for coronary artery bypass grafting (CABG) or for aortic or mitral valve replacement were recruited into the study. There were 13 men and 22 women with a mean age of 64.8 +/- 13.4 years. A list of anamnestic, anthropometric, clinical, and instrumental data required for an optimal phenotypical characterization of the patients is reported. The small cardiac biopsy specimens were placed in the nourishing buffer, in a sterile tube provided the day of the procedure, to maintain the stability of the sample for several hours at room temperature. The cells were isolated by a dedicated protocol and then cultured in vitro. The sample was processed for total RNA extraction and levels of gene expression and protein activation of molecular effectors involved in the regulation of function and differentiation of human myocardium was analyzed. In particular, cardiac genes that modulate the oxidative stress response or the stress induced by pro-inflammatory cytokines (p66Shc, SOCS-1, SOCS-3) were analyzed. From a small sample of myocardium cardiac stem cells and cardiomyoblasts were also isolated and characterized. These cells showed a considerable proliferative capacity due to the fact that they demonstrate stability up to the

Hypoxic regulation of cytoglobin and neuroglobin expression in human normal and tumor tissues

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Emara Marwan

2010-09-01

Full Text Available Abstract Background Cytoglobin (Cygb and neuroglobin (Ngb are recently identified globin molecules that are expressed in vertebrate tissues. Upregulation of Cygb and Ngb under hypoxic and/or ischemic conditions in vitro and in vivo increases cell survival, suggesting possible protective roles through prevention of oxidative damage. We have previously shown that Ngb is expressed in human glioblastoma multiforme (GBM cell lines, and that expression of its transcript and protein can be significantly increased after exposure to physiologically relevant levels of hypoxia. In this study, we extended this work to determine whether Cygb is also expressed in GBM cells, and whether its expression is enhanced under hypoxic conditions. We also compared Cygb and Ngb expression in human primary tumor specimens, including brain tumors, as well as in human normal tissues. Immunoreactivity of carbonic anhydrase IX (CA IX, a hypoxia-inducible metalloenzyme that catalyzes the hydration of CO2 to bicarbonate, was used as an endogenous marker of hypoxia. Results Cygb transcript and protein were expressed in human GBM cells, and this expression was significantly increased in most cells following 48 h incubation under hypoxia. We also showed that Cygb and Ngb are expressed in both normal tissues and human primary cancers, including GBM. Among normal tissues, Cygb and Ngb expression was restricted to distinct cell types and was especially prominent in ductal cells. Additionally, certain normal organs (e.g. stomach fundus, small bowel showed distinct regional co-localization of Ngb, Cygb and CA IX. In most tumors, Ngb immunoreactivity was significantly greater than that of Cygb. In keeping with previous in vitro results, tumor regions that were positively stained for CA IX were also positive for Ngb and Cygb, suggesting that hypoxic upregulation of Ngb and Cygb also occurs in vivo. Conclusions Our finding of hypoxic up-regulation of Cygb/Ngb in GBM cell lines and human

Validation of endogenous normalizing genes for expression analyses in adult human testis and germ cell neoplasms

DEFF Research Database (Denmark)

Svingen, T; Jørgensen, Anne; Rajpert-De Meyts, E

2014-01-01

to define suitable normalizing genes for specific cells and tissues. Here, we report on the performance of a panel of nine commonly employed normalizing genes in adult human testis and testicular pathologies. Our analyses revealed significant variability in transcript abundance for commonly used normalizers......, highlighting the importance of selecting appropriate normalizing genes as comparative measurements can yield variable results when different normalizing genes are employed. Based on our results, we recommend using RPS20, RPS29 or SRSF4 when analysing relative gene expression levels in human testis...... and associated testicular pathologies. OCT4 and SALL4 can be used with caution as second-tier normalizers when determining changes in gene expression in germ cells and germ cell tumour components, but the relative transcript abundance appears variable between different germ cell tumour types. We further...

Cell-surface glycoproteins of human sarcomas: differential expression in normal and malignant tissues and cultured cells

International Nuclear Information System (INIS)

Rettig, W.F.; Garin-Chesa, P.; Beresford, H.R.; Oettgen, H.F.; Melamed, M.R.; Old, L.J.

1988-01-01

Normal differentiation and malignant transformation of human cells are characterized by specific changes in surface antigen phenotype. In the present study, the authors have defined six cell-surface antigens of human sarcomas and normal mesenchymal cells, by using mixed hemadsorption assays and immunochemical methods for the analysis of cultured cells and immunohistochemical staining for the analysis of normal tissues and > 200 tumor specimens. Differential patterns of F19, F24, G171, G253, S5, and Thy-1 antigen expression were found to characterize (i) subsets of cultured sarcoma cell lines, (ii) cultured fibroblasts derived from various organs, (iii) normal resting and activated mesenchymal tissues, and (iv) sarcoma and nonmesenchymal tumor tissues. These results provide a basic surface antigenic map for cultured mesenchymal cells and mesenchymal tissues and permit the classification of human sarcomas according to their antigenic phenotypes

Cyclooxygenase-2 expression in the normal human eye and its expression pattern in selected eye tumours

DEFF Research Database (Denmark)

Wang, Jinmei; Wu, Yazhen; Heegaard, Steffen

2011-01-01

Purpose: Cyclooxygenase-2 (COX-2) is an enzyme involved in neoplastic processes. The purpose of the present study is to investigate COX-2 expression in the normal human eye and the expression pattern in selected eye tumours involving COX-2 expressing cells. Methods: Immunohistochemical staining...... using antibodies against COX-2 was performed on paraffin sections of normal human eyes and selected eye tumours arising from cells expressing COX-2. Results: Cyclooxygenase-2 expression was found in various structures of the normal eye. Abundant expression was seen in the cornea, iris, ciliary body...... and retina. The COX-2 expression was less in tumours deriving from the ciliary epithelium and also in retinoblastoma. Conclusion: Cyclooxygenase-2 is constitutively expressed in normal human eyes. The expression of COX-2 is much lower in selected eye tumours involving COX-2 expressing cells....

Primary pulmonary choriocarcinoma after human chorionic gonadotropin normalization following hydatidiform mole

DEFF Research Database (Denmark)

Maestá, Izildinha; Leite, Fábio Vicente; Michelin, Odair Carlito

2010-01-01

BACKGROUND: Primary pulmonary choriocarcinoma (PPC) is rare and frequently leads to death. CASES: Two young patients presented with previous molar pregnancy and spontaneous serum human chorionic gonadotropin (hCG) normalization. Patient 1 was referred to our center after partial response to chemo...

A radioimmunoassay for erythropoietin: serum levels in normal human subjects and patients with hemopoietic disorders

International Nuclear Information System (INIS)

Rege, A.B.; Brookins, J.; Fisher, J.W.

1982-01-01

An RIA for Ep has been developed that is highly sensitive and specific. A homogeneous Ep preparation was labeled with 125 I by the chloramine-T method to a specific activity of 90 to 136 micro Ci/microgram and immunoreactivity of 80%. Ep antiserum, which was produced to a human urinary Ep preparation (80 U/mg of protein), was adsorbed with normal human urinary and serum proteins without any loss in sensitivity of the RIA to increase the specificity of the assay. A good correlation was seen between the RIA and the exhypoxic polycythemic mouse assay (corr. coef. 0.967; slope 1.05 and y intercept 0.75). Ep titers in sera from 175 hematologically normal human subjects exhibited a normal frequency distribution and ranged between 5.8 and 36.6 mU/ml with a mean of 14.9 +/- 4.7 (S.D.) and median of 14.3 Serum Ep titers were markedly elevated in seven patients with aplastic anemia and one patient with pure red cell aplasia (1350 to 20,640 mU/ml) and were lower than normal in two patients with polycythemia vera (8.1 and 9.4 mU/ml). The serum Ep titers in a prenephrectomy patient with chronic glomerulonephritis (32.1 mU/ml) decreased to below normal levels (9.04 mU/ml) after nephrectomy. The cord serum erythropoietin titers in 10 IDM [90.82 +/- 134.1 (S.D.) mu/ml] returned to values within the normal range (13.86 +/- 5.55) on day 3 after birth, suggesting the utility of the RIA in elucidating the role of hypoxia and/or insulin in increased erythropoiesis in IDM. The serum Ep titers in patients with anemias and polycythemias were compared to those of normal human subjects and agreed well with pathophysiologic mechanisms of these hemopoietic disorders, confirming the validity of the RIA

A radioimmunoassay for erythropoietin: serum levels in normal human subjects and patients with hemopoietic disorders

International Nuclear Information System (INIS)

Rege, A.B.; Brookins, J.; Fisher, J.W.

1982-01-01

An RIA for Ep has been developed that is highly sensitive and specific. A homogeneous Ep preparation was labeled with 125 I by the chloramine-T method to a specific activity of 90 to 136 μCi/μg and immunoreactivity of 80%. Ep antiserum, which was produced to a human urinary Ep preparation (80 U/mg of protein), was adsorbed with normal human urinary and serum proteins without any loss in sensitivity of the RIA to increase the specificity of the assay. A good correlation was seen between the RIA and the exhypoxic polycythemic mouse assay (corr. coef. 0.967; slope 1.05 and ''y'' intercept 0.75). Ep titers in sera from 175 hematologically normal human subjects exhibited a normal frequency distribution and ranged between 5.8 and 36.6 mU/ml with a mean of 14.9 +/- 4.7 (S.D.) and median of 14.3. Serum Ep titers were markedly elevated in seven patients with aplastic anemia and one patient with pure red cell aplasia (1350 to 20,640 mU/ml) and were lower than normal in two patients with polycythemia vera (8.1 and 9.4 mU/ml). The serum Ep titers in a prenephrectomy patient with chronic glomerulonephritis (31.1 mU/ml) decreased to below normal levels (9.04 mU/ml) after nephrectomy. The cord serum erythropoietin titers in 10 IDM [90.82 +/- 134.1 (S.D.) mu/ml] returned to values within the normal range (13.86 +/- 5.55) on day 3 after birth, suggesting the utility of the RIA in elucidating the role of hypoxia and/or insulin in increased erythropoiesis in IDM. The serum Ep titers in patients with anemias and polycythemias were compared to those of normal human subjects and agreed well with pathophysiologic mechanisms of these hemopoietic disorders, confirming the validity of the RIA

Alpha-amidated peptides derived from pro-opiomelanocortin in normal human pituitary

DEFF Research Database (Denmark)

Fenger, M; Johnsen, A H

1988-01-01

Normal human pituitaries were extracted in boiling water and acetic acid, and the alpha-amidated peptide products of pro-opiomelanocortin (POMC), alpha-melanocyte-stimulating hormone (alpha MSH), gamma-melanocyte-stimulating hormone (gamma 1MSH), and amidated hinge peptide (HP-N), as well...... (ACTH)-(1-39), ACTH-(1-14) and alpha MSH immunoreactivity]. alpha MSH and ACTH-(1-14) were only present in non- or mono-acetylated forms. Only large forms of gamma 1MSH and gamma 2MSH were present in partly glycosylated states. The hinge peptides were amidated to an extent two to three orders...... amidated POMC-related peptides are present in normal human pituitary. It also shows that cleavage in vivo at all dibasic amino acids but one, takes place at the N-terminal POMC region; the exception is at the POMC-(49-50) N-terminal of the gamma MSH sequence. The pattern of peptides produced suggests...

Pitx2 confers left morphological, molecular, and functional identity to the sinus venosus myocardium

Czech Academy of Sciences Publication Activity Database

Ammirabile, G.; Tessari, A.; Pignataro, V.; Szumska, D.; Sardo, F.S.; Beneš Jr., Jiří; Balistreri, M.; Bhattacharya, S.; Sedmera, David; Campione, M.

2012-01-01

Roč. 93, č. 2 (2012), s. 291-301 ISSN 0008-6363 R&D Projects: GA ČR(CZ) GA304/08/0615 Institutional research plan: CEZ:AV0Z50110509 Keywords : Pitx2 * sinus venosus myocardium * optical mapping * mouse cardiac development Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 5.940, year: 2012

Oxygen supply and oxidative phosphorylation limitation in rat myocardium in situ.

Science.gov (United States)

Kreutzer, U; Mekhamer, Y; Chung, Y; Jue, T

2001-05-01

The 1H-NMR signal of the proximal histidyl-N(delta)H of deoxymyoglobin is detectable in the in situ rat myocardium and can reflect the intracellular PO2. Under basal normoxic conditions, the cellular PO2 is sufficient to saturate myoglobin (Mb). No proximal histidyl signal of Mb is detectable. On ligation of the left anterior descending coronary artery, the Mb signal at 78 parts/million (ppm) appears, along with a peak shoulder assigned to the corresponding signal of Hb. During dopamine infusion up to 80 microg. kg(-1) x min(-1), both the heart rate-pressure product (RPP) and myocardial oxygen consumption (MVO2) increase by about a factor of 2. Coronary flow increases by 84%, and O2 extraction (arteriovenous O2 difference) rises by 31%. Despite the increased respiration and work, no deoxymyoglobin signal is detected, implying that the intracellular O2 level still saturates MbO2, well above the PO2 at 50% saturation of Mb. The phosphocreatine (PCr) level decreases, however, during dopamine stimulation, and the ratio of the change in P(i) over PCr (DeltaP(i)/PCr) increases by 0.19. Infusion of either pyruvate, as the primary substrate, or dichloroacetate, a pyruvate dehydrogenase activator, abolishes the change in DeltaP(i)/PCr. Intracellular O2 supply does not limit MVO2, and the role of ADP in regulating respiration in rat myocardium in vivo remains an open question.

Effects of a prolonged standardized diet on normalizing the human metabolome123

OpenAIRE

Winnike, Jason H; Busby, Marjorie G; Watkins, Paul B; O'Connell, Thomas M

2009-01-01

Background: Although the effects of acute dietary interventions on the human metabolome have been studied, the extent to which the metabolome can be normalized by extended dietary standardization has not yet been examined.

Generation of hiPSTZ16 (ISMMSi003-A cell line from normal human foreskin fibroblasts

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Marion Dejosez

2018-01-01

Full Text Available Human foreskin fibroblasts from a commercial source were reprogrammed into induced pluripotent stem cells to establish a clonal stem cell line, hiPSTZ16 (ISMMSi003-A. These cells show a normal karyotype and full differentiation potential in teratoma assays. The described cells provide a useful resource in combination with other iPS cell lines generated from normal human foreskin fibroblasts to study source- and reprogramming method-independent effects in downstream applications.

The influence of psycho-emotional stress in children of primary school age on the incidence of recurrent upper respiratory tract infections and the functional state of the myocardium

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L.S. Ovcharenko

2017-10-01

Full Text Available Background. Scientific and technical progress, intensification of educational process and information overload have a negative effect on unformed central nervous system of primary schoolchildren, causing stress, which affects the increase in the incidence of recurrent upper respiratory tract infections (URTI and the functional state of the myocardium. In view of this, we analyzed a functional state of myocardium in children with recurrent URTI. The critical duration of the work of primary school child with electronic means of communication, which affects the quality of nighttime sleep and the nature of awakening in the morning, was established. We have studied the relationship of the above mentioned with the incidence of URTI, the level of school anxiety and functional reserve of the myocardium. The purpose of the study was to evaluate the functional reserve of the myocardium in children of primary school age, depending on the incidence of URTI and the level of psycho-emotional activity. Materials and me­thods. 239 children aged 6 to 9 years were examined. The analysis of the functional reserve of the myocardium was carried out in pupils with different incidence of the URTI, depending on the age. The influence of electronic communications on the quality of nighttime sleep and morning awakening was stu­died, and the level of school anxiety was evaluated. During the study, children were divided into two groups. Group 1 — children with recurrent acute respiratory diseases (n = 143. Group 2 — children who occasionally have URTI (n = 96. Results. Out of 239 children with recurrent acute respiratory infections, we have identified 173 children with reduced functional reserve of the myocardium (72.4 %. Among children with recurrent URTI, the incidence of reduced functional reserve of the myocardium was 76.2 %, and in occasionally ill children — 66.7 %. Children with recurrent URTI use electronic means of communication more often than

An individual urinary proteome analysis in normal human beings to define the minimal sample number to represent the normal urinary proteome

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Liu Xuejiao

2012-11-01

Full Text Available Abstract Background The urinary proteome has been widely used for biomarker discovery. A urinary proteome database from normal humans can provide a background for discovery proteomics and candidate proteins/peptides for targeted proteomics. Therefore, it is necessary to define the minimum number of individuals required for sampling to represent the normal urinary proteome. Methods In this study, inter-individual and inter-gender variations of urinary proteome were taken into consideration to achieve a representative database. An individual analysis was performed on overnight urine samples from 20 normal volunteers (10 males and 10 females by 1DLC/MS/MS. To obtain a representative result of each sample, a replicate 1DLCMS/MS analysis was performed. The minimal sample number was estimated by statistical analysis. Results For qualitative analysis, less than 5% of new proteins/peptides were identified in a male/female normal group by adding a new sample when the sample number exceeded nine. In addition, in a normal group, the percentage of newly identified proteins/peptides was less than 5% upon adding a new sample when the sample number reached 10. Furthermore, a statistical analysis indicated that urinary proteomes from normal males and females showed different patterns. For quantitative analysis, the variation of protein abundance was defined by spectrum count and western blotting methods. And then the minimal sample number for quantitative proteomic analysis was identified. Conclusions For qualitative analysis, when considering the inter-individual and inter-gender variations, the minimum sample number is 10 and requires a balanced number of males and females in order to obtain a representative normal human urinary proteome. For quantitative analysis, the minimal sample number is much greater than that for qualitative analysis and depends on the experimental methods used for quantification.

The contribution of nuclear medicine in the six months following a myocardium infarction

International Nuclear Information System (INIS)

Franken, Ph.R.

2002-01-01

The techniques of nuclear medicine allow to estimate the myocardial infarction size, to measure the ejection fraction and the ventricles volumes and to identify the presence of high-risk and viable myocardium. This information is essential to evaluate the important complications risks after an acute myocardial infarction, that is to say the infarction recurrence and the cardiac death coming from rhythm troubles or a left ventricle failure. (N.C.)

Helium induces preconditioning in human endothelium in vivo

NARCIS (Netherlands)

Smit, Kirsten F.; Oei, Gezina T. M. L.; Brevoord, Daniel; Stroes, Erik S.; Nieuwland, Rienk; Schlack, Wolfgang S.; Hollmann, Markus W.; Weber, Nina C.; Preckel, Benedikt

2013-01-01

Helium protects myocardium by inducing preconditioning in animals. We investigated whether human endothelium is preconditioned by helium inhalation in vivo. Forearm ischemia-reperfusion (I/R) in healthy volunteers (each group n = 10) was performed by inflating a blood pressure cuff for 20 min.

Metabolic borderzone in acutely ischemic canine myocardium demonstrated by positron-CT (PCT)

International Nuclear Information System (INIS)

Schwaiger, M.; Hansen, H.; Selin, C.; Wittmer, S.; Barrio, J.; Schelbert, H.R.

1984-01-01

Acute coronary ligation in dogs results in an area of myocardial dysfunction that exceeds the area of subsequent necrosis suggesting the existence of an ischemic ''borderzone'' of reversibly injured myocardium. The authors tested this hypothesis in 9 closed chest dogs with C-11 plamitate (CPA) and serial PCT imaging after an LAD occlusion. Using a blood flow (MBF) image obtained with iv N-13 ammonia prior to CPA, regions of interest were assigned on the serial CPA cross-sectional images to the center (IC) and border (IB) of the ischemic segment and to control myocardium (CO). CPA uptake was closely related to MBF (r=0.88) implicating flow as a major determinant of CPA uptake. Clearance helftimes (T 1/2) and relative sizes (RS) of the early rapid phase on the C-11 tissue time activity curves were determined for IC, IB and CO. In IC, MBF, RS and T 1/2 were markedly depressed indicating impaired CPA utilization and oxidation. In IB, MBF was less than in CO though only insignificantly, while RS and T 1/2 were highly abnormal. The authors conclude that FFA metabolism in areas adjacent to ischemic segments but without significant MBF decreases in abnormal, presenting evidence for a metabolic borderzone which now can be identified noninvasively with positron emission tomography

Embryonic cardiac morphometry in Carnegie stages 15-23, from the Complutense University of Madrid Institute of Embryology Human Embryo Collection.

Science.gov (United States)

Arráez-Aybar, L A; Turrero-Nogués, A; Marantos-Gamarra, D G

2008-01-01

We performed a morphometric study of cardiac development on human embryos to complement the scarce data on human embryonic cardiac morphometry and to attempt to establish, from these, algorithms describing cardiac growth during the second month of gestation. Thirty human embryos from Carnegie stages 15-23 were included in the study. Shrinkage and compression effects from fixation and inclusion in paraffin were considered in our calculations. Growth of the cardiac (whole heart) volume and volume of ventricular myocardium through the Carnegie stages were analysed by ANOVA. Linear correlation was used to describe the relationship between the ventricular myocardium and cardiac volumes. Comparisons of models were carried out through the R2 statistic. The relationship volume of ventricular myocardium versus cardiac volume is expressed by the equation: cardiac volume = 0.6266 + 2.4778 volume of ventricular myocardium. The relationship cardiac volume versus crown-rump length is expressed by the equation: cardiac volume = 1.3 e(0.126 CR length), where e is the base of natural logarithms. At a clinical level, these results can contribute towards the establishment of a normogram for cardiac development, useful for the design of strategies for early diagnosis of congenital heart disease. They can also help in the study of embryogenesis, for example in the discussion of ventricular trabeculation. Copyright 2007 S. Karger AG, Basel.

Inspiration from heart development: Biomimetic development of functional human cardiac organoids.

Science.gov (United States)

Richards, Dylan J; Coyle, Robert C; Tan, Yu; Jia, Jia; Wong, Kerri; Toomer, Katelynn; Menick, Donald R; Mei, Ying

2017-10-01

Recent progress in human organoids has provided 3D tissue systems to model human development, diseases, as well as develop cell delivery systems for regenerative therapies. While direct differentiation of human embryoid bodies holds great promise for cardiac organoid production, intramyocardial cell organization during heart development provides biological foundation to fabricate human cardiac organoids with defined cell types. Inspired by the intramyocardial organization events in coronary vasculogenesis, where a diverse, yet defined, mixture of cardiac cell types self-organizes into functional myocardium in the absence of blood flow, we have developed a defined method to produce scaffold-free human cardiac organoids that structurally and functionally resembled the lumenized vascular network in the developing myocardium, supported hiPSC-CM development and possessed fundamental cardiac tissue-level functions. In particular, this development-driven strategy offers a robust, tunable system to examine the contributions of individual cell types, matrix materials and additional factors for developmental insight, biomimetic matrix composition to advance biomaterial design, tissue/organ-level drug screening, and cell therapy for heart repair. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sensitization of the Guinea Pig Myocardium through the Mucous Membrane of the Digestive Tract,

Science.gov (United States)

Under certain conditions, sessile antibodies can be bound by the guinea - pig myocardium that had been sensitized by direct introduction of the allergen into the stomach. This is confirmed by the positive anaphylactic reaction in the isolated heart of animals treated in this manner, which reaction manifests itself in a modified heart rate when the isolated heart is challenged by the sensitizing allergen.

99Tcm-MIBI imaging with liposomal prostaglandin E1 infusion to detect viable myocardium in post-myocardial infarction patients

International Nuclear Information System (INIS)

Zheng Yong; Cai Hongbin; Miao Weibing; Lin Jun; Pan Runyang; Lin Haoxue

2007-01-01

Objective: The pharmacological efficiencies of liposomal prostaglandin E 1 (Lipo-PGE 1 ) infusion and nitrate infusion on 99 Tc m -methoxyisobutylisonitrile (MIBI) imaging detection of viable myocardium in post-myocardial infarction (MI) patients were compared in the current study. Methods: Thirty-two patients with MI underwent 99 Tc m -MIBI imaging at rest, nitrate infusion and Lipo-PGE 1 infusion respectively. The semi-quantitative analysis of 99 Tc m -MIBI imaging was carried out in 16 segments over each left ventricle. Results: Abnormal 99 Tc m -MIBI distribution in 216 segments (42.2%) at rest, 178 segments (34.8%) at nitrate infusion, and 184 segments (35.9%) at Lipo-PGE 1 infusion were identified. Among the 216 abnormal segments at rest, 89 (41.2%) and 81 (37.5%) were found improved after nitrate infusion and Lipo-PGE 1 infusion respectively. Detecting viable myocardium with Lipo-PGE 1 infusion imaging was accordant with that of nitrate infusion imaging in 89.8% of the cases. The mean uptake scores of abnormal segments at rest, nitrate infusion, and Lipo-PGE 1 infusion were 15.3 ± 3.3, 10.5 ± 1.4 (P 1 infusion imaging can be used for detection of viable myocardium in patients with MI. (authors)

Arteriosclerotic changes in the myocardium, lung, and kidney in dogs with chronic congestive heart failure and myxomatous mitral valve disease

DEFF Research Database (Denmark)

Falk, Bo Torkel; Jönsson, Lennart; Olsen, Lisbeth Høier

2006-01-01

Background: The occurrence of small vessel arteriosclerosis in the myocardium, kidney, and lung in dogs with naturally occurring myxomatous mitral valve disease has not been previously investigated systematically. Methods: Twenty-one dogs with naturally occurring congestive heart failure and 21 age......-matched, sex-matched, and weight-matched control dogs underwent extensive pathological and histopathological examination. Morphometry and scoring of tissue sections were used to measure arterial narrowing and fibrosis in the myocardium, kidney, and lung; and intimal thickness and plaque formation in the aorta...... and pulmonary artery. Results: Dogs with congestive heart failure had significantly more arterial narrowing in the left ventricle (Pdogs. However...

201Tl scintigraphy of the myocardium in patients with coronary occlusion and normal coronarogram

International Nuclear Information System (INIS)

Ramos, M.; Martin-Comin, J.; Estorch, M.; Freixa, E.; Richart, J.A.; Esplugas, E.

1982-01-01

We have studied 3 young male patients which had had a previous myocardial infarction verified by ECG and enzymes. Selective coronary arteriography was normal in all 3 subjects. Left ventriculography showed segmental wall motion abnormalities, and post-exercise and redistribution scintigraphy demonstrated areas with abnormal thallium uptake in all patients. Those observations as well as literature data suggest that among the factors which modify myocardial thallium uptake, the number of myocardial cells and their functional status play an important role, at least in chronic coronary artery disease. (orig.) [de

Immunohistochemical analysis of Sonic hedgehog signalling in normal human urinary tract development

OpenAIRE

Jenkins, Dagan; Winyard, Paul J D; Woolf, Adrian S.

2007-01-01

Studies of mouse mutants have demonstrated that Sonic hedgehog (SHH) signalling has a functional role in morphogenesis and differentiation at multiple sites within the forming urinary tract, and urinary tract malformations have been reported in humans with mutations that disrupt SHH signalling. However, there is only strikingly sparse and fragmentary information about the expression of SHH and associated signalling genes in normal human urinary tract development. We used immunohistochemistry ...

Higher Leptin but Not Human Milk Macronutrient Concentration Distinguishes Normal-Weight from Obese Mothers at 1-Month Postpartum.

Science.gov (United States)

De Luca, Arnaud; Frasquet-Darrieux, Marine; Gaud, Marie-Agnès; Christin, Patricia; Boquien, Clair-Yves; Millet, Christine; Herviou, Manon; Darmaun, Dominique; Robins, Richard J; Ingrand, Pierre; Hankard, Régis

2016-01-01

Exclusively breastfed infants born to obese mothers have previously been shown to gain less weight by 1-month postpartum than infants of normal-weight mothers. Our hypothesis is that human milk composition and volume may differ between obese and normal-weight mothers. To compare human milk leptin, macronutrient concentration, and volume in obese and normal-weight mothers. Mother and infant characteristics were studied as secondary aims. This cross-sectional observational study compared 50 obese mothers matched for age, parity, ethnic origin, and educational level with 50 normal-weight mothers. Leptin, macronutrient human milk concentration, and milk volume were determined at 1 month in exclusively breastfed infants. Mother characteristics and infant growth were recorded. Human milk leptin concentration was higher in obese mothers than normal-weight mothers (4.8±2.7 vs. 2.5±1.5 ng.mL-1, pobese and normal-weight mothers in protein, lipid, carbohydrate content, and volume, nor in infant weight gain. Leptin concentration was higher in the milk of obese mothers than that of normal-weight mothers, but macronutrient concentration was not. It remains to be established whether the higher leptin content impacts on infant growth beyond the 1-month of the study period.

Low calcium culture condition induces mesenchymal cell-like phenotype in normal human epidermal keratinocytes

International Nuclear Information System (INIS)

Takagi, Ryo; Yamato, Masayuki; Murakami, Daisuke; Sugiyama, Hiroaki; Okano, Teruo

2011-01-01

Highlights: → Normal human epidermal keratinocytes serially cultured under low calcium concentration were cytokeratin and vimentin double positive cells. → The human keratinocytes expressed some epithelial stem/progenitor cell makers, mesenchymal cell markers, and markers of epithelial-mesenchymal transition. → Mesenchymal cell-like phenotype in the keratinocytes was suppressed under high-calcium condition. -- Abstract: Epithelial-mesenchymal transition (EMT) is an important cellular phenomenon in organ developments, cancer invasions, and wound healing, and many types of transformed cell lines are used for investigating for molecular mechanisms of EMT. However, there are few reports for EMT in normal human epithelial cells, which are non-transformed or non-immortalized cells, in vitro. Therefore, normal human epidermal keratinocytes (NHEK) serially cultured in low-calcium concentration medium (LCM) were used for investigating relations between differentiation and proliferation and mesenchymal-like phenotype in the present study, since long-term cultivation of NHEK is achieved in LCM. Interestingly, NHEK serially cultured in LCM consisted essentially of cytokeratin-vimentin double positive cells (98%), although the NHEK exhibited differentiation under high-calcium culture condition with 3T3 feeder layer. The vimentin expression was suppressed under high-calcium condition. These results may indicate the importance of mesenchymal-like phenotype for serially cultivation of NHEK in vitro.

Production of glycosylated physiologically normal human α1-antitrypsin by mouse fibroblasts modified by insertion of a human α1-antitrypsin cDNA using a retroviral vector

International Nuclear Information System (INIS)

Garver, R.I. Jr.; Chytil, A.; Karlsson, S.

1987-01-01

α 2 -Antitrypsin (α 1 AT) deficiency is a hereditary disorder characterized by reduced serum levels of α 1 AT, resulting in destruction of the lower respiratory tract by neutrophil elastase. As an approach to augment α 1 AT levels in this disorder with physiologically normal human α 1 AT, the authors have integrated a full-length normal human α 1 AT cDNA into the genome of mouse fibroblasts. To accomplish this, the retroviral vector N2 was modified by inserting the simian virus 40 early promoter followed by the α 1 AT cDNA. Southern analysis demonstrated that the intact cDNA was present in the genome of selected clones of the transfected murine fibroblasts psi2 and infected NIH 3T3. The clones produced three mRNA transcripts containing human α 1 AT sequences, secreted an α 1 AT molecule recognized by an anti-human α 1 AT antibody, with the same molecular mass as normal human α 1 AT and that complexed with and inhibited human neutrophil elastase. The psi2 produced α 1 AT was glycosylated, and when infused intravenously into mice, it had a serum half-life similar to normal α 1 AT purified from human plasma and markedly longer than that of nonglycosylated human α 1 AT cDNA-directed yeast-produced α 1 AT. These studies demonstrate the feasibility of using a retroviral vector to insert the normal human α 1 AT cDNA into non-α 1 AT-producing cells, resulting in the synthesis and secretion of physiologically normal α 1 AT

Expression of androgen-binding protein (ABP) in human cardiac myocytes.

Science.gov (United States)

Schock, H W; Herbert, Z; Sigusch, H; Figulla, H R; Jirikowski, G F; Lotze, U

2006-04-01

Cardiomyocytes are known to be androgen targets. Changing systemic steroid levels are thought to be linked to various cardiac ailments, including dilated cardiomyopathy (DCM). The mode of action of gonadal steroid hormones on the human heart is unknown to date. In the present study, we used high-resolution immunocytochemistry on semithin sections (1 microm thick), IN SITU hybridization, and mass spectrometry to investigate the expression of androgen-binding protein (ABP) in human myocardial biopsies taken from male patients with DCM. We observed distinct cytoplasmic ABP immunoreactivity in a fraction of the myocytes. IN SITU hybridization with synthetic oligonucleotide probes revealed specific hybridization signals in these cells. A portion of the ABP-positive cells contained immunostaining for androgen receptor. With SELDI TOF mass spectrometry of affinity purified tissue extracts of human myocardium, we confirmed the presence of a 50 kDa protein similar to ABP. Our observations provide evidence of an intrinsic expression of ABP in human heart. ABP may be secreted from myocytes in a paracrine manner perhaps to influence the bioavailabity of gonadal steroids in myocardium.

Pulmonary vein and atrial wall pathology in human total anomalous pulmonary venous connection

NARCIS (Netherlands)

Douglas, Yvonne L.; Jongbloed, Monique R. M.; den Hartog, Wietske C. E.; Bartelings, Margot M.; Bogers, Ad J. J. C.; Ebels, Tjark; DeRuiter, Marco C.; Gittenberger-de Groot, Adriana C.

2009-01-01

Background: Normally, the inside of the left atrial (LA) body and pulmonary veins (PVs) is lined by vessel wall tissue covered by myocardium. In total anomalous pulmonary venous connection (TAPVC), no connection of the PVs with the LA body exists. These veins have an increased incidence of PV

14(R,S)-[18F]Fluoro-6-thia-heptadecanoic acid as a tracer of free fatty acid uptake and oxidation in myocardium and skeletal muscle

International Nuclear Information System (INIS)

Takala, Teemu O.; Nuutila, Pirjo; Pulkki, Kari; Oikonen, Vesa; Groenroos, Tove; Bergman, Joergen; Forsback, Sarita; Knuuti, Juhani; Savunen, Timo; Vaehaesilta, Tommi; Luotolahti, Matti; Kallajoki, Markku

2002-01-01

14(R,S)-[ 18 F]Fluoro-6-thia-heptadecanoic acid ([ 18 F]FTHA) is a long-chain fatty acid substrate for fatty acid metabolism. [ 18 F]FTHA has been used to study fatty acid metabolism in human heart and skeletal muscle. It has been suggested that the rate of radioactivity accumulation in the myocardium reflects the beta-oxidation rate of free fatty acids (FFAs). However, the net accumulation of FFAs in tissue always represents the sum of FFA oxidation and incorporation into triglycerides. The fraction of [ 18 F]FTHA entering directly into mitochondria for oxidation has not been previously measured. Eight anaesthetized pigs were studied with [ 18 F]FTHA and positron emission tomography (PET). Immediately after each PET experiment, tissue samples from myocardium and skeletal muscle were taken for the isolation of mitochondria and measurements of radioactivity accumulation, and for intracellular [ 18 F]FTHA metabolite analysis. Fractional [ 18 F]FTHA uptake rates were calculated both by graphical analysis of PET data and by measuring 18 F in the tissue samples. Fractional [ 18 F]FTHA uptake rates based on the analysis of tissue samples were 0.56±0.17 ml g -1 min -1 and 0.037±0.007 ml g -1 min -1 for myocardium and skeletal muscle (mean ± SD), respectively. The myocardial results obtained from the PET data (0.50±0.11 ml g -1 min -1 ) were similar to the values obtained from the tissue samples (r=0.94, P=0.002). We also found that 89%±23% (mean±SD, n=7) of the 18 F entered mitochondria in myocardium, as compared with only 36%±15% (mean±SD, n=7) in skeletal muscle. Intracellular [ 18 F]FTHA metabolite analysis showed that a major part of [ 18 F]FTHA is metabolized in the mitochondria in the heart. Our data suggest that 89% of [ 18 F]FTHA taken up by the heart enters mitochondria. This supports the hypothesis that [ 18 F]FTHA traces FFA beta-oxidation in the heart. In contrast to this, only 36% of [ 18 F]FTHA accumulated in skeletal muscle appears to directly enter

Enhancer of the rudimentary gene homologue (ERH expression pattern in sporadic human breast cancer and normal breast tissue

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Knüchel Ruth

2008-05-01

Full Text Available Abstract Background The human gene ERH (Enhancer of the Rudimentary gene Homologue has previously been identified by in silico analysis of four million ESTs as a gene differentially expressed in breast cancer. The biological function of ERH protein has not been fully elucidated, however functions in cell cycle progression, pyrimidine metabolism a possible interaction with p21(Cip1/Waf1 via the Ciz1 zinc finger protein have been suggested. The aim of the present study was a systematic characterization of ERH expression in human breast cancer in order to evaluate possible clinical applications of this molecule. Methods The expression pattern of ERH was analyzed using multiple tissue northern blots (MTN on a panel of 16 normal human tissues and two sets of malignant/normal breast and ovarian tissue samples. ERH expression was further analyzed in breast cancer and normal breast tissues and in tumorigenic as well as non-tumorigenic breast cancer cell lines, using quantitative RT-PCR and non-radioisotopic in situ hybridization (ISH. Results Among normal human tissues, ERH expression was most abundant in testis, heart, ovary, prostate, and liver. In the two MTN sets of malignant/normal breast and ovarian tissue,ERH was clearly more abundantly expressed in all tumours than in normal tissue samples. Quantitative RT-PCR analyses showed that ERH expression was significantly more abundant in tumorigenic than in non-tumorigenic breast cancer cell lines (4.5-fold; p = 0.05, two-tailed Mann-Whitney U-test; the same trend was noted in a set of 25 primary invasive breast cancers and 16 normal breast tissue samples (2.5-fold; p = 0.1. These findings were further confirmed by non-radioisotopic ISH in human breast cancer and normal breast tissue. Conclusion ERH expression is clearly up-regulated in malignant as compared with benign breast cells both in primary human breast cancer and in cell models of breast cancer. Since similar results were obtained for ovarian

Preclinical pharmacological study of 99mTcN(NOET)2 and comparison with 201Tl in redistribution of ischemia myocardium

International Nuclear Information System (INIS)

Wang, J.C.; Zhang, J.B.; Wang, Q.; Mi, H.Z.; Wang, X.B.

2002-01-01

Aim: To study the biological properties of the myocardial imaging agent 99m TcN(NOET) 2 and compare with 201 Tl in redistribution of ischemia myocardium. Materials and Methods: To prepared the 99m TcN(NOET) 2 complex, the intermediate [ 99m TcN] 2+ and ligand NOET were synthesized. In the presence of reducer and the doner of N, the [ 99m Tc=N] 2+ could be synthesized at 100, then NOET was added, 99m TcN(NOET) 2 was formed at room temperature. 201 Tl was provided by the Department of Isotope, China Institute of Atomic Energy. Five dogs were from the Fu Wai experimental animal feeding center, two of them were made into ischemia myocardium models by ligating some coronary artery branches were demonstrated by X-ray coronary angiography, the extent of stenosis of those blood vessels was over 90%. Dynamic imaging of rest was performed respectively in three normal dogs after injecting a dose of 555MBq (15mCi) of 99m TcN(NOET) 2 complex up to two hours. The whole body imaging planar and tomography imaging was carried out respectively at fixed time intervals during two hours in order to obtain the time-activity curves of heart, lung and liver, in vivo biodistribution and quality analysis of myocardial images. Moreover, intravenous blood samples were collected at different times to gain the kinetics of blood clearance. Stress and redistribution imaging underwent in two dogs with ischemia myocardium. Dipyridamol was given intravenously at a dose of 0.6mg/Kg in 4 mins. Stress :9 9m TcN(NOET) 2 myocardial SPECT imaging was performed at 30, 70 and 110 min after injection of 99m TcN(NOET) 2 complex, stress 201 Tl myocardial SPECT imaging was carried out 10 min and redistribution imaging 4 hr after injection of 55.5MBq (1.5mCi) 201 Tl chloride. The tests of 99m TcN(NOET) 2 and 201 Tl were performed respectively in the same dog within 10 days, in order to obtain a comparison between two myocardial redistribution imaging. Results: Radiochemical purity of 99m TcN(NOET) 2 was 98.41%�

Effect of vanadate and of removal of extracellular Ca2+ and Na+ on tension development and 45Ca efflux in rat and frog myocardium

DEFF Research Database (Denmark)

Gesser, H; Bonefeld-Jørgensen, Eva Cecilie

1983-01-01

Vanadate in the range 0-5 mM has positive inotropic effects on myocardial strips of frog and to a lesser extent on those of rat. Inhibiting the sarcolemmal Na+, Ca2+ exchange by a solution free of Ca2+ and Na+ caused a drop in 45Ca efflux and a transient increase in resting tension. These effects...... were more expressed for the frog than for the rat myocardium, which suggests that the Na+ for Ca2+ exchange across the cell membrane is more important in the frog than in the rat myocardium. A subsequent addition of vanadate at 2 or 5 mM had no effect on 45Ca efflux, while it increased the resting...... tension. This increase was higher for the frog than for the rat myocardium. These results suggest that the inotropic effects of vanadate may be due to an effect on membrane-bound Ca2+-ATPase....

Validation of endogenous normalizing genes for expression analyses in adult human testis and germ cell neoplasms.

Science.gov (United States)

Svingen, T; Jørgensen, A; Rajpert-De Meyts, E

2014-08-01

The measurement of gene expression levels in cells and tissues typically depends on a suitable point of reference for inferring biological relevance. For quantitative (or real-time) RT-PCR assays, the method of choice is often to normalize gene expression data to an endogenous gene that is stably expressed across the samples analysed: a so-called normalizing or housekeeping gene. Although this is a valid strategy, the identification of stable normalizing genes has proved challenging and a gene showing stable expression across all cells or tissues is unlikely to exist. Therefore, it is necessary to define suitable normalizing genes for specific cells and tissues. Here, we report on the performance of a panel of nine commonly employed normalizing genes in adult human testis and testicular pathologies. Our analyses revealed significant variability in transcript abundance for commonly used normalizers, highlighting the importance of selecting appropriate normalizing genes as comparative measurements can yield variable results when different normalizing genes are employed. Based on our results, we recommend using RPS20, RPS29 or SRSF4 when analysing relative gene expression levels in human testis and associated testicular pathologies. OCT4 and SALL4 can be used with caution as second-tier normalizers when determining changes in gene expression in germ cells and germ cell tumour components, but the relative transcript abundance appears variable between different germ cell tumour types. We further recommend that such studies should be accompanied by additional assessment of histology and cellularity of each sample. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Detection of genomic instability in normal human bronchial epithelial cells exposed to 238Pu

International Nuclear Information System (INIS)

Kennedy, C.H.; Fukushima, N.H.; Neft, R.E.; Lechner, J.F.

1994-01-01

Alpha particle-emitting radon daughters constitute a risk for development of lung cancer in humans. The development of this disease involves multiple genetic alterations. These changes and the time course they follow are not yet defined despite numerous in vitro endeavors to transform human lung cells with various physical or chemical agents. However, genomic instability, characterized both by structural and numerical chromosomal aberrations and by elevated rates of point mutations, is a common feature of tumor cells. Further, both types of genomic instability have been reported in the noncancerous progeny of normal murine hemopoietic cells exposed in vitro to α-particles. The purpose of this investigation was to determine if genomic instability is also a prominent feature of normal human bronchial epithelial cells exposed to α-particle irradiation from the decay of inhaled radon daughters

Analysis of immune cell populations in atrial myocardium of patients with atrial fibrillation or sinus rhythm.

Directory of Open Access Journals (Sweden)

Natalia Smorodinova

Full Text Available Atrial fibrillation (AF is the most common arrhythmia and despite obvious clinical importance remains its pathogenesis only partially explained. A relation between inflammation and AF has been suggested by findings of increased inflammatory markers in AF patients.The goal of this study was to characterize morphologically and functionally CD45-positive inflammatory cell populations in atrial myocardium of patients with AF as compared to sinus rhythm (SR.We examined 46 subjects (19 with AF, and 27 in SR undergoing coronary bypass or valve surgery. Peroperative bioptic samples of the left and the right atrial tissue were examined using immunohistochemistry.The number of CD3+ T-lymphocytes and CD68-KP1+ cells were elevated in the left atrial myocardium of patients with AF compared to those in SR. Immune cell infiltration of LA was related to the rhythm, but not to age, body size, LA size, mitral regurgitation grade, type of surgery, systemic markers of inflammation or presence of diabetes or hypertension. Most of CD68-KP1+ cells corresponded to dendritic cell population based on their morphology and immunoreactivity for DC-SIGN. The numbers of mast cells and CD20+ B-lymphocytes did not differ between AF and SR patients. No foci of inflammation were detected in any sample.An immunohistochemical analysis of samples from patients undergoing open heart surgery showed moderate and site-specific increase of inflammatory cells in the atrial myocardium of patients with AF compared to those in SR, with prevailing population of monocyte-macrophage lineage. These cells and their cytokine products may play a role in atrial remodeling and AF persistence.

Normality and naturalness: a comparison of the meanings of concepts used within veterinary medicine and human medicine.

Science.gov (United States)

Lerner, Henrik; Hofmann, Bjørn

2011-12-01

This article analyses the different connotations of "normality" and "being natural," bringing together the theoretical discussion from both human medicine and veterinary medicine. We show how the interpretations of the concepts in the different areas could be mutually fruitful. It appears that the conceptions of "natural" are more elaborate in veterinary medicine, and can be of value to human medicine. In particular they can nuance and correct conceptions of nature in human medicine that may be too idealistic. Correspondingly, the wide ranging conceptions of "normal" in human medicine may enrich conceptions in veterinary medicine, where the discussions seem to be sparse. We do not argue that conceptions from veterinary medicine should be used in human medicine and vice versa, but only that it could be done and that it may well be fruitful. Moreover, there are overlaps between some notions of normal and natural, and further conceptual analysis on this overlap is needed.

Quantification of Crypt and Stem Cell Evolution in the Normal and Neoplastic Human Colon

Directory of Open Access Journals (Sweden)

Ann-Marie Baker

2014-08-01

Full Text Available Human intestinal stem cell and crypt dynamics remain poorly characterized because transgenic lineage-tracing methods are impractical in humans. Here, we have circumvented this problem by quantitatively using somatic mtDNA mutations to trace clonal lineages. By analyzing clonal imprints on the walls of colonic crypts, we show that human intestinal stem cells conform to one-dimensional neutral drift dynamics with a “functional” stem cell number of five to six in both normal patients and individuals with familial adenomatous polyposis (germline APC−/+. Furthermore, we show that, in adenomatous crypts (APC−/−, there is a proportionate increase in both functional stem cell number and the loss/replacement rate. Finally, by analyzing fields of mtDNA mutant crypts, we show that a normal colon crypt divides around once every 30–40 years, and the division rate is increased in adenomas by at least an order of magnitude. These data provide in vivo quantification of human intestinal stem cell and crypt dynamics.

Normal results of post-race thallium-201 myocardial perfusion imaging in marathon runners with elevated serum MB creatine kinase levels

International Nuclear Information System (INIS)

Siegel, A.J.; Silverman, L.M.; Holman, B.L.

1985-01-01

Elevated cardiac enzyme values in asymptomatic marathon runners after competition can arise from skeletal muscle through exertional rhabdomyolysis, silent injury to the myocardium, or a combined tissue source. Peak post-race levels of the MB isoenzyme of creatine kinase are similar to values in patients with acute myocardial infarction. Previously reported normal results of infarct-avid myocardial scintigraphy with technetium 99m pyrophosphate in runners after competition suggest a non-cardiac source but cannot exclude silent injury to the myocardium. Therefore, thallium 201 myocardial perfusion imaging was performed in runners immediately after competition together with determination of sequential cardiac enzyme levels. Among 15 runners tested, the average peak in serum MB creatine kinase 24 hours after the race was 128 IU/liter with a cumulative MB creatine kinase release of 117 IU/liter; these values are comparable to those in patients with acute transmural myocardial infarction. Thallium 201 myocardial scintigraphic results were normal in five runners randomly selected from those who volunteered for determination of sequential blood levels. It is concluded that elevations of serum MB creatine kinase in marathon runners arise from a skeletal muscle source and that thallium 201 myocardial scintigraphy is useful to assess runners for myocardial injury when clinical questions arise

The distribution of YKL-40 in osteoarthritic and normal human articular cartilage

DEFF Research Database (Denmark)

Volck, B; Ostergaard, K; Johansen, J S

1999-01-01

YKL-40, also called human cartilage glycoprotein-39, is a major secretory protein of human chondrocytes in cell culture. YKL-40 mRNA is expressed by cartilage from patients with rheumatoid arthritis, but is not detectable in normal human cartilage. The aim was to investigate the distribution of YKL...... in chondrocytes of osteoarthritic cartilage mainly in the superficial and middle zone of the cartilage rather than the deep zone. There was a tendency for high number of YKL-40 positive chondrocytes in areas of the femoral head with a considerable biomechanical load. The number of chondrocytes with a positive...

Biological responses of progestogen metabolites in normal and cancerous human breast.

Science.gov (United States)

Pasqualini, Jorge R; Chetrite, Gérard S

2010-12-01

At present, more than 200 progestogen molecules are available, but their biological response is a function of various factors: affinity to progesterone or other receptors, their structure, the target tissues considered, biological response, experimental conditions, dose, method of administration and metabolic transformations. Metabolic transformation is of huge importance because in various biological processes the metabolic product(s) not only control the activity of the maternal hormone but also have an important activity of its own. In this regard, it was observed that the 20-dihydro derivative of the progestogen dydrogesterone (Duphaston®) is significantly more active than the parent compound in inhibiting sulfatase and 17β-hydroxysteroid dehydrogenase in human breast cancer cells. Estrone sulfatase activity is also inhibited by norelgestromin, a norgestimate metabolite. Interesting information was obtained with a similar progestogen, tibolone, which is rapidly metabolized into the active 3α/3β-hydroxy and 4-ene metabolites. All these metabolites can inhibit sulfatase and 17β-hydroxysteroid dehydrogenase and stimulate sulfotransferase in human breast cancer cells. Another attractive aspect is the metabolic transformation of progesterone itself in human breast tissues. In the normal breast progesterone is mainly converted to 4-ene derivatives, whereas in the tumor tissue it is converted mostly to 5α-pregnane derivatives. 20α-Dihydroprogesterone is found mainly in normal breast tissue and possesses antiproliferative properties as well as the ability to act as an anti-aromatase agent. Consequently, this progesterone metabolite could be involved in the control of estradiol production in the normal breast and therefore implicated in one of the multifactorial mechanisms of the breast carcinogenesis process. In conclusion, a better understanding of both natural and synthetic hormone metabolic transformations and their control could potentially provide

Estimation of polyclonal IgG4 hybrids in normal human serum.

Science.gov (United States)

Young, Elizabeth; Lock, Emma; Ward, Douglas G; Cook, Alexander; Harding, Stephen; Wallis, Gregg L F

2014-07-01

The in vivo or in vitro formation of IgG4 hybrid molecules, wherein the immunoglobulins have exchanged half molecules, has previously been reported under experimental conditions. Here we estimate the incidence of polyclonal IgG4 hybrids in normal human serum and comment on the existence of IgG4 molecules with different immunoglobulin light chains. Polyclonal IgG4 was purified from pooled or individual donor human sera and sequentially fractionated using light-chain affinity and size exclusion chromatography. Fractions were analysed by SDS-PAGE, immunoblotting, ELISA, immunodiffusion and matrix-assisted laser-desorption mass spectrometry. Polyclonal IgG4 purified from normal serum contained IgG4κ, IgG4λ and IgG4κ/λ molecules. Size exclusion chromatography showed that IgG4 was principally present in monomeric form (150 000 MW). SDS-PAGE, immunoblotting and ELISA showed the purity of the three IgG4 samples. Immunodiffusion, light-chain sandwich ELISA and mass spectrometry demonstrated that both κ and λ light chains were present on only the IgG4κ/λ molecules. The amounts of IgG4κ/λ hybrid molecules ranged from 21 to 33% from the five sera analysed. Based on the molecular weight these molecules were formed of two IgG4 heavy chains plus one κ and one λ light chain. Polyclonal IgG (IgG4-depleted) was similarly fractionated according to light-chain specificity. No evidence of hybrid IgG κ/λ antibodies was observed. These results indicate that hybrid IgG4κ/λ antibodies compose a substantial portion of IgG4 from normal human serum. © 2014 John Wiley & Sons Ltd.

Distinct patterns of constitutive phosphodiesterase activity in mouse sinoatrial node and atrial myocardium.

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Rui Hua

Full Text Available Phosphodiesterases (PDEs are critical regulators of cyclic nucleotides in the heart. In ventricular myocytes, the L-type Ca(2+ current (I(Ca,L is a major target of regulation by PDEs, particularly members of the PDE2, PDE3 and PDE4 families. Conversely, much less is known about the roles of PDE2, PDE3 and PDE4 in the regulation of action potential (AP properties and I(Ca,L in the sinoatrial node (SAN and the atrial myocardium, especially in mice. Thus, the purpose of our study was to measure the effects of global PDE inhibition with Isobutyl-1-methylxanthine (IBMX and selective inhibitors of PDE2, PDE3 and PDE4 on AP properties in isolated mouse SAN and right atrial myocytes. We also measured the effects of these inhibitors on I(Ca,L in SAN and atrial myocytes in comparison to ventricular myocytes. Our data demonstrate that IBMX markedly increases spontaneous AP frequency in SAN myocytes and AP duration in atrial myocytes. Spontaneous AP firing in SAN myocytes was also increased by the PDE2 inhibitor erythro-9-[2-hydroxy-3-nonyl] adenine (EHNA, the PDE3 inhibitor milrinone (Mil and the PDE4 inhibitor rolipram (Rol. In contrast, atrial AP duration was increased by EHNA and Rol, but not by Mil. IBMX also potently, and similarly, increased I(Ca,L in SAN, atrial and ventricular myocytes; however, important differences emerged in terms of which inhibitors could modulate I(Ca,L in each myocyte type. Consistent with our AP measurements, EHNA, Mil and Rol each increased I(Ca,L in SAN myocytes. Also, EHNA and Rol, but not Mil, increased atrial I(Ca,L. In complete contrast, no selective PDE inhibitors increased I(Ca,L in ventricular myocytes when given alone. Thus, our data show that the effects of selective PDE2, PDE3 and PDE4 inhibitors are distinct in the different regions of the myocardium indicating important differences in how each PDE family constitutively regulates ion channel function in the SAN, atrial and ventricular myocardium.

Dopamine D2 receptor expression in the corticotroph cells of the human normal pituitary gland.

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Pivonello, Rosario; Waaijers, Marlijn; Kros, Johan M; Pivonello, Claudia; de Angelis, Cristina; Cozzolino, Alessia; Colao, Annamaria; Lamberts, Steven W J; Hofland, Leo J

2017-08-01

The dopamine D 2 receptor is the main dopamine receptor expressed in the human normal pituitary gland. The aim of the current study was to evaluate dopamine D 2 receptor expression in the corticotroph cell populations of the anterior lobe and pars intermedia, as well as posterior lobe of the human normal pituitary gland by immunohistochemistry. Human normal pituitary gland samples obtained from routine autopsies were used for the study. In all cases, histology together with immunostaining for adrenocorticotropic hormone, melanocyte-stimulating hormone, prolactin, and neurofilaments were performed and compared to the immunostaining for D 2 receptor. D 2 receptor was heterogeneously expressed in the majority of the cell populations of the anterior and posterior lobe as well as in the area localized between the anterior and posterior lobe, and arbitrary defined as "intermediate zone". This zone, characterized by the presence of nerve fibers included the residual pars intermedia represented by the colloid-filled cysts lined by the remnant melanotroph cells strongly expressing D 2 receptors, and clusters of corticotroph cells, belonging to the anterior lobe but localized within the cysts and adjacent to the posterior lobe, variably expressing D 2 receptors. D 2 dopamine receptor is expressed in the majority of the cell populations of the human normal pituitary gland, and particularly, in the different corticotroph cell populations localized in the anterior lobe and the intermediate zone of the pituitary gland.

Exercise Increases Cystathionine-γ-lyase Expression and Decreases the Status of Oxidative Stress in Myocardium of Ovariectomized Rats.

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Tang, Zhiping; Wang, Yujun; Zhu, Xiaoyan; Ni, Xin; Lu, Jianqiang

2016-01-01

Exercise could be a therapeutic approach for cardiovascular dysfunction induced by estrogen deficiency. Our previous study has shown that estrogen maintains cystathionine-γ-lyase (CSE) expression and inhibits oxidative stress in the myocardium of female rats. In the present study, we investigated whether exercise improves CSE expression and oxidative stress status and ameliorates isoproterenol (ISO)-induced cardiac damage in ovariectomized (OVX) rats. The results showed that treadmill training restored the ovariectomy-induced reduction of CSE and estrogen receptor (ER)α and decrease of total antioxidant capacity (T-AOC) and increase of malondialdehyde (MDA). The level of CSE was positively correlated to T-AOC and ERα while inversely correlated to MDA. OVX rats showed increases in the serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) and the percentage of TUNEL staining in myocardium upon ISO insult compared to sham rats. Exercise training significantly reduced the serum levels of LDH and CK and the percentage of TUNEL staining in myocardium upon ISO insult in OVX rats. In cultured cardiomyocytes, ISO treatment decreased cell viability and increased LDH release, while overexpression of CSE increased cell viability and decreased LDH release in the cells upon ISO insult. The results suggest that exercise training improves the oxidative stress status and ameliorates the cardiac damage induced by oxidative stress in OVX rats. The improvement of oxidative stress status by exercise might be at least partially due to upregulation of CSE/H2S signaling.

Capillary transfer constant of Gd-DTPA in the myocardium at rest and during vasodilation assessed by MRI

DEFF Research Database (Denmark)

Fritz-Hansen, T; Rostrup, Egill; Søndergaard, Lise

1998-01-01

The purpose of this study was to determine whether the capillary transfer constant (Ki) of gadolinium-DTPA was sensitive to perfusion changes and whether ischemic regions in the myocardium could be identified using the modified Kety formula. Ki was measured at rest and during dipyridamole...

Microcapsules engineered to support mesenchymal stem cell (MSC) survival and proliferation enable long-term retention of MSCs in infarcted myocardium.

Science.gov (United States)

Blocki, Anna; Beyer, Sebastian; Dewavrin, Jean-Yves; Goralczyk, Anna; Wang, Yingting; Peh, Priscilla; Ng, Michael; Moonshi, Shehzahdi S; Vuddagiri, Susmitha; Raghunath, Michael; Martinez, Eliana C; Bhakoo, Kishore K

2015-06-01

The limited efficacy of cardiac cell-based therapy is thought to be due to poor cell retention within the myocardium. Hence, there is an urgent need for biomaterials that aid in long-term cell retention. This study describes the development of injectable microcapsules for the delivery of mesenchymal stem cells (MSCs) into the infarcted cardiac wall. These microcapsules comprise of low concentrations of agarose supplemented with extracellular matrix (ECM) proteins collagen and fibrin. Dextran sulfate, a negatively charged polycarbohydrate, was added to mimic glycosaminoglycans in the ECM. Cell viability assays showed that a combination of all components is necessary to support long-term survival and proliferation of MSCs within microcapsules. Following intramyocardial transplantation, microcapsules degraded slowly in vivo and did not induce a fibrotic foreign body response. Pre-labeling of encapsulated MSCs with iron oxide nanoparticles allowed continued cell-tracking by MRI over several weeks following transplantation into infarcted myocardium. In contrast, MSCs injected as cell suspension were only detectable for two days post transplantation by MRI. Histological analysis confirmed integration of transplanted cells at the infarct site. Therefore, microcapsules proved to be suitable for stem cell delivery into the infarcted myocardium and can overcome current limitations of poor cell retention in cardiac cell-based therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Quantification of pulmonary thallium-201 activity after upright exercise in normal persons: importance of peak heart rate and propranolol usage in defining normal values

International Nuclear Information System (INIS)

Brown, K.A.; Boucher, C.A.; Okada, R.D.; Strauss, H.W.; Pohost, G.M.

1984-01-01

Fifty-nine normal patients (34 angiographically normal and 25 clinically normal by Bayesian analysis) underwent thallium-201 imaging after maximal upright exercise. Lung activity was quantitated relative to myocardial activity and a lung/myocardial activity ratio was determined for each patient. Stepwise regression analysis was then used to examine the influence of patient clinical characteristics and exercise variables on the lung/myocardium ratio. Peak heart rate during exercise and propranolol usage both showed significant negative regression coefficients (p less than 0.001). No other patient data showed a significant relation. Using the regression equation and the estimated variance, a 95% confidence level upper limit of normal could be determined for a give peak heart rate and propranolol status. Sixty-one other patients were studied to validate the predicted upper limits of normal based on this model. None of the 27 patients without coronary artery disease had an elevated lung/myocardial ratio, compared with 1 of 8 with 1-vessel disease (difference not significant), 6 of 14 with 2-vessel disease (p less than 0.005), and 6 of 12 with 3-vessel disease (p less than 0.0001). Thus, lung activity on upright exercise thallium-201 studies can be quantitated relative to myocardial activity, and is inversely related to peak heart rate and propranolol use. Use of a regression analysis allows determination of a 95% confidence upper limit of normal to be anticipated in an individual patient

Discovery of Radioiodinated Monomeric Anthraquinones as a Novel Class of Necrosis Avid Agents for Early Imaging of Necrotic Myocardium.

Science.gov (United States)

Wang, Qin; Yang, Shengwei; Jiang, Cuihua; Li, Jindian; Wang, Cong; Chen, Linwei; Jin, Qiaomei; Song, Shaoli; Feng, Yuanbo; Ni, Yicheng; Zhang, Jian; Yin, Zhiqi

2016-02-16

Assessment of myocardial viability is deemed necessary to aid in clinical decision making whether to recommend revascularization therapy for patients with myocardial infarction (MI). Dianthraquinones such as hypericin (Hyp) selectively accumulate in necrotic myocardium, but were unsuitable for early imaging after administration to assess myocardial viability. Since dianthraquinones can be composed by coupling two molecules of monomeric anthraquinone and the active center can be found by splitting chemical structure, we propose that monomeric anthraquinones may be effective functional groups for necrosis targetability. In this study, eight radioiodinated monomeric anthraquinones were evaluated as novel necrosis avid agents (NAAs) for imaging of necrotic myocardium. All (131)I-anthraquinones showed high affinity to necrotic tissues and (131)I-rhein emerged as the most promising compound. Infarcts were visualized on SPECT/CT images at 6 h after injection of (131)I-rhein, which was earlier than that with (131)I-Hyp. Moreover, (131)I-rhein showed satisfactory heart-to-blood, heart-to-liver and heart-to-lung ratios for obtaining images of good diagnostic quality. (131)I-rhein was a more promising "hot spot imaging" tracer for earlier visualization of necrotic myocardium than (131)I-Hyp, which supported further development of radiopharmaceuticals based on rhein for SPECT/CT ((123)I and (99m)Tc) or PET/CT imaging ((18)F and (124)I) of myocardial necrosis.

Conjugation of gold nanoparticles and recombinant human endostatin modulates vascular normalization via interruption of anterior gradient 2-mediated angiogenesis.

Science.gov (United States)

Pan, Fan; Yang, Wende; Li, Wei; Yang, Xiao-Yan; Liu, Shuhao; Li, Xin; Zhao, Xiaoxu; Ding, Hui; Qin, Li; Pan, Yunlong

2017-07-01

Several studies have revealed the potential of normalizing tumor vessels in anti-angiogenic treatment. Recombinant human endostatin is an anti-angiogenic agent which has been applied in clinical tumor treatment. Our previous research indicated that gold nanoparticles could be a nanoparticle carrier for recombinant human endostatin delivery. The recombinant human endostatin-gold nanoparticle conjugates normalized vessels, which improved chemotherapy. However, the mechanism of recombinant human endostatin-gold nanoparticle-induced vascular normalization has not been explored. Anterior gradient 2 has been reported to be over-expressed in many malignant tumors and involved in tumor angiogenesis. To date, the precise efficacy of recombinant human endostatin-gold nanoparticles on anterior gradient 2-mediated angiogenesis or anterior gradient 2-related signaling cohort remained unknown. In this study, we aimed to explore whether recombinant human endostatin-gold nanoparticles could normalize vessels in metastatic colorectal cancer xenografts, and we further elucidated whether recombinant human endostatin-gold nanoparticles could interrupt anterior gradient 2-induced angiogenesis. In vivo, it was indicated that recombinant human endostatin-gold nanoparticles increased pericyte expression while inhibit vascular endothelial growth factor receptor 2 and anterior gradient 2 expression in metastatic colorectal cancer xenografts. In vitro, we uncovered that recombinant human endostatin-gold nanoparticles reduced cell migration and tube formation induced by anterior gradient 2 in human umbilical vein endothelial cells. Treatment with recombinant human endostatin-gold nanoparticles attenuated anterior gradient 2-mediated activation of MMP2, cMyc, VE-cadherin, phosphorylation of p38, and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in human umbilical vein endothelial cells. Our findings demonstrated recombinant human endostatin-gold nanoparticles might normalize

Pathomorphological Changes of the Myocardium in Canine Dilated Cardiomyopathy (DCM

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Janus Izabela

2015-04-01

Full Text Available The study was conducted on ventricular and atrial wall preparations from 11 dogs with clinically diagnosed dilated cardiomyopathy. After fixation, the specimens were stained with haematoxylin and eosin and Masson-Goldner trichrome technique. Parenchymal changes (fibrosis and fatty infiltration, vascular changes (congestion and coronary vessel wall hypertrophy, degenerative changes (loss of striation, changes in cardiomycyte and nuclei structure, and presence of inflammatory infiltrates (mononuclear and polynuclear were estimated. Complex histological changes in both ventricular and atrial muscles were shown. It was not determined whether the processes occurring in the myocardium have a primary character, or are a consequence of developing heart failure. Such issues will be put under further and more detailed examination.

Serial analysis of gene expression (SAGE) in normal human trabecular meshwork.

Science.gov (United States)

Liu, Yutao; Munro, Drew; Layfield, David; Dellinger, Andrew; Walter, Jeffrey; Peterson, Katherine; Rickman, Catherine Bowes; Allingham, R Rand; Hauser, Michael A

2011-04-08

To identify the genes expressed in normal human trabecular meshwork tissue, a tissue critical to the pathogenesis of glaucoma. Total RNA was extracted from human trabecular meshwork (HTM) harvested from 3 different donors. Extracted RNA was used to synthesize individual SAGE (serial analysis of gene expression) libraries using the I-SAGE Long kit from Invitrogen. Libraries were analyzed using SAGE 2000 software to extract the 17 base pair sequence tags. The extracted sequence tags were mapped to the genome using SAGE Genie map. A total of 298,834 SAGE tags were identified from all HTM libraries (96,842, 88,126, and 113,866 tags, respectively). Collectively, there were 107,325 unique tags. There were 10,329 unique tags with a minimum of 2 counts from a single library. These tags were mapped to known unique Unigene clusters. Approximately 29% of the tags (orphan tags) did not map to a known Unigene cluster. Thirteen percent of the tags mapped to at least 2 Unigene clusters. Sequence tags from many glaucoma-related genes, including myocilin, optineurin, and WD repeat domain 36, were identified. This is the first time SAGE analysis has been used to characterize the gene expression profile in normal HTM. SAGE analysis provides an unbiased sampling of gene expression of the target tissue. These data will provide new and valuable information to improve understanding of the biology of human aqueous outflow.

14(R,S)-[{sup 18}F]Fluoro-6-thia-heptadecanoic acid as a tracer of free fatty acid uptake and oxidation in myocardium and skeletal muscle

Energy Technology Data Exchange (ETDEWEB)

Takala, Teemu O.; Nuutila, Pirjo [Turku PET Centre, Turku University Central Hospital, PO Box 52, 20521 Turku (Finland); Department of Medicine, University of Turku (Finland); Pulkki, Kari [Department of Clinical Chemistry, University of Turku (Finland); Oikonen, Vesa; Groenroos, Tove; Bergman, Joergen; Forsback, Sarita; Knuuti, Juhani [Turku PET Centre, Turku University Central Hospital, PO Box 52, 20521 Turku (Finland); Savunen, Timo; Vaehaesilta, Tommi [Department of Surgery, University of Turku (Finland); Luotolahti, Matti [Department of Clinical Physiology, University of Turku (Finland); Kallajoki, Markku [Department of Pathology, University of Turku (Finland)

2002-12-01

14(R,S)-[{sup 18}F]Fluoro-6-thia-heptadecanoic acid ([{sup 18}F]FTHA) is a long-chain fatty acid substrate for fatty acid metabolism. [{sup 18}F]FTHA has been used to study fatty acid metabolism in human heart and skeletal muscle. It has been suggested that the rate of radioactivity accumulation in the myocardium reflects the beta-oxidation rate of free fatty acids (FFAs). However, the net accumulation of FFAs in tissue always represents the sum of FFA oxidation and incorporation into triglycerides. The fraction of [{sup 18}F]FTHA entering directly into mitochondria for oxidation has not been previously measured. Eight anaesthetized pigs were studied with [{sup 18}F]FTHA and positron emission tomography (PET). Immediately after each PET experiment, tissue samples from myocardium and skeletal muscle were taken for the isolation of mitochondria and measurements of radioactivity accumulation, and for intracellular [{sup 18}F]FTHA metabolite analysis. Fractional [{sup 18}F]FTHA uptake rates were calculated both by graphical analysis of PET data and by measuring {sup 18}F in the tissue samples. Fractional [{sup 18}F]FTHA uptake rates based on the analysis of tissue samples were 0.56{+-}0.17 ml g{sup -1} min{sup -1} and 0.037{+-}0.007 ml g{sup -1} min{sup -1} for myocardium and skeletal muscle (mean {+-} SD), respectively. The myocardial results obtained from the PET data (0.50{+-}0.11 ml g{sup -1} min{sup -1}) were similar to the values obtained from the tissue samples (r=0.94, P=0.002). We also found that 89%{+-}23% (mean{+-}SD, n=7) of the {sup 18}F entered mitochondria in myocardium, as compared with only 36%{+-}15% (mean{+-}SD, n=7) in skeletal muscle. Intracellular [{sup 18}F]FTHA metabolite analysis showed that a major part of [{sup 18}F]FTHA is metabolized in the mitochondria in the heart. Our data suggest that 89% of [{sup 18}F]FTHA taken up by the heart enters mitochondria. This supports the hypothesis that [{sup 18}F]FTHA traces FFA beta-oxidation in the heart

Determination of Elements in Normal and Leukemic Human Whole Blood by Neutron Activation Analysis

Energy Technology Data Exchange (ETDEWEB)

Brune, D; Frykberg, B; Samsahl, K; Wester, P O

1961-11-15

By means of gamma-spectrometry the following elements were simultaneously determined in normal and leukemic human whole blood: Cu, Mn, Zn, Sr, Na, P, Ca, Rb, Cd, Sb, Au, Cs and Fe. Chemical separations were performed according to a group separation method using ion-exchange technique. No significant difference between the concentrations of the elements in normal- and leukemic blood was observed.

Determination of Elements in Normal and Leukemic Human Whole Blood by Neutron Activation Analysis

International Nuclear Information System (INIS)

Brune, D.; Frykberg, B.; Samsahl, K.; Wester, P.O.

1961-11-01

By means of gamma-spectrometry the following elements were simultaneously determined in normal and leukemic human whole blood: Cu, Mn, Zn, Sr, Na, P, Ca, Rb, Cd, Sb, Au, Cs and Fe. Chemical separations were performed according to a group separation method using ion-exchange technique. No significant difference between the concentrations of the elements in normal- and leukemic blood was observed

Enhanced normal short-term human myelopoiesis in mice engineered to express human-specific myeloid growth factors.

Science.gov (United States)

Miller, Paul H; Cheung, Alice M S; Beer, Philip A; Knapp, David J H F; Dhillon, Kiran; Rabu, Gabrielle; Rostamirad, Shabnam; Humphries, R Keith; Eaves, Connie J

2013-01-31

Better methods to characterize normal human hematopoietic cells with short-term repopulating activity cells (STRCs) are needed to facilitate improving recovery rates in transplanted patients.We now show that 5-fold more human myeloid cells are produced in sublethally irradiated NOD/SCID-IL-2Receptor-γchain-null (NSG) mice engineered to constitutively produce human interleukin-3, granulocyte-macrophage colony-stimulating factor and Steel factor (NSG-3GS mice) than in regular NSG mice 3 weeks after an intravenous injection of CD34 human cord blood cells. Importantly, the NSG-3GS mice also show a concomitant and matched increase in circulating mature human neutrophils. Imaging NSG-3GS recipients of lenti-luciferase-transduced cells showed that human cells being produced 3 weeks posttransplant were heterogeneously distributed, validating the blood as a more representative measure of transplanted STRC activity. Limiting dilution transplants further demonstrated that the early increase in human granulopoiesis in NSG-3GS mice reflects an expanded output of differentiated cells per STRC rather than an increase in STRC detection. NSG-3GS mice support enhanced clonal outputs from human short-term repopulating cells (STRCs) without affecting their engrafting efficiency. Increased human STRC clone sizes enable their more precise and efficient measurement by peripheral blood monitoring.

Human osteoarthritic cartilage is synthetically more active but in culture less vital than normal cartilage

NARCIS (Netherlands)

Lafeber, F. P.; van Roy, H.; Wilbrink, B.; Huber-Bruning, O.; Bijlsma, J. W.

1992-01-01

The proteoglycan turnover of human osteoarthritic (OA) cartilage was compared to that of normal (N) cartilage. The cartilage was obtained postmortem from human femoral knee condyles. Short term cultures were compared to longterm cultures, and proteoglycan synthesis rate, content and release

THE EFFECT OF COMBINED ANTIHYPERTENSIVE THERAPY ON THE BASIC PARAMETERS OF THE LEFT VENTRICLE MYOCARDIUM STRUCTURE AND FUNCTION IN WOMEN WITH METABOLIC SYNDROME AND HYPOTHYROIDISM

Directory of Open Access Journals (Sweden)

V. V. Skibitskiy

2012-01-01

Full Text Available Aim. To study the effect of combined antihypertensive therapy on the basic parameters of the left ventricle (LV myocardium structure and function in women with arterial hypertension (HT, metabolic syndrome (MS and hypothyroidism. Material and methods. Women (n=196 with HT grade 2–3 and MS were included into the study. Standard clinical examination including an assessment of thyroid status, ambulatory blood pressure (BP monitoring and echocardiography was performed at baseline and after 6 months. The patients were split into 3 groups: control (without hypothyroidism with subclinical and manifested (symptomatic hypothyroidism (SH and MH. Depending on baseline heart rate (HR patients of each group received a combination of amlodipine+losartan (A+L in HR <85/min or a combination of amlodipine+moxonidine (A+M in in HR ≥85/min. Results. The significant antihypertensive effect was found in patients of the control group due to both A+L and A+M combination (target BP was reached in 85.7 and 88.2%, respectively. In patients with hypothyroidism significant antihypertensive effects was observed only during A+M therapy (target BP in SH and MH was achieved in 82.8 and 82.4%, respectively. In the control group A+L and A+M combinations increased a number of patients with normal LV geometry (85.7 and 86.7, respectively and diastolic function (78.6 and 80%, respectively. In hypothyroidism A+M therapy resulted in more prominent increase in a number of patients with normal LV geometry (75% in both SH and MH and diastolic function (in SH and MH 83.3 и 85.7%, respectively than these in A+L therapy (р<0.05. Conclusion. The combination of A+M has advantages over A+L combination in antihypertensive efficacy as well as in the effect on the structural and functional state of the LV myocardium in women with HT and MS associated with hypothyroidism.

THE EFFECT OF COMBINED ANTIHYPERTENSIVE THERAPY ON THE BASIC PARAMETERS OF THE LEFT VENTRICLE MYOCARDIUM STRUCTURE AND FUNCTION IN WOMEN WITH METABOLIC SYNDROME AND HYPOTHYROIDISM

Directory of Open Access Journals (Sweden)

V. V. Skibitskiy

2015-12-01

Full Text Available Aim. To study the effect of combined antihypertensive therapy on the basic parameters of the left ventricle (LV myocardium structure and function in women with arterial hypertension (HT, metabolic syndrome (MS and hypothyroidism. Material and methods. Women (n=196 with HT grade 2–3 and MS were included into the study. Standard clinical examination including an assessment of thyroid status, ambulatory blood pressure (BP monitoring and echocardiography was performed at baseline and after 6 months. The patients were split into 3 groups: control (without hypothyroidism with subclinical and manifested (symptomatic hypothyroidism (SH and MH. Depending on baseline heart rate (HR patients of each group received a combination of amlodipine+losartan (A+L in HR <85/min or a combination of amlodipine+moxonidine (A+M in in HR ≥85/min. Results. The significant antihypertensive effect was found in patients of the control group due to both A+L and A+M combination (target BP was reached in 85.7 and 88.2%, respectively. In patients with hypothyroidism significant antihypertensive effects was observed only during A+M therapy (target BP in SH and MH was achieved in 82.8 and 82.4%, respectively. In the control group A+L and A+M combinations increased a number of patients with normal LV geometry (85.7 and 86.7, respectively and diastolic function (78.6 and 80%, respectively. In hypothyroidism A+M therapy resulted in more prominent increase in a number of patients with normal LV geometry (75% in both SH and MH and diastolic function (in SH and MH 83.3 и 85.7%, respectively than these in A+L therapy (р<0.05. Conclusion. The combination of A+M has advantages over A+L combination in antihypertensive efficacy as well as in the effect on the structural and functional state of the LV myocardium in women with HT and MS associated with hypothyroidism.

Normal development and growth of the human neurocranium and cranial base.

Science.gov (United States)

Friede, H

1981-01-01

The literature on normal development and growth of certain areas of the human head is reviewed, starting with the early induction of the desmal neurocranium. the development of the brain capsule with its dural reinforcement bands and their connection with the basicranium is discussed, as is the primordial chondrocranium, including its bone replacement. Growth of the calvaria and the three cranial fossae is also analysed. Special interest is focused on the anterior fossa, as knowledge of the growth in this area is very important for an understanding of pathogenesis and possibilities of treating premature craniosynostosis. Finally it is stressed that close observation of the effects of treatment on this pathology may increase our knowledge of normal growth.

Biomechanics of normal and pathological gait: implications for understanding human locomotor control.

Science.gov (United States)

Winter, D A

1989-12-01

The biomechanical (kinetic) analysis of human gait reveals the integrated and detailed motor patterns that are essential in pinpointing the abnormal patterns in pathological gait. In a similar manner, these motor patterns (moments, powers, and EMGs) can be used to identify synergies and to validate theories of CNS control. Based on kinetic and EMG patterns for a wide range of normal subjects and cadences, evidence is presented that both supports and negates the central pattern generator theory of locomotion. Adaptive motor patterns that are evident in peripheral gait pathologies reinforce a strong peripheral rather than a central control. Finally, a three-component subtask theory of human gait is presented and is supported by reference to the motor patterns seen in a normal gait. The identified subtasks are (a) support (against collapse during stance); (b) dynamic balance of the upper body, also during stance; and (c) feedforward control of the foot trajectory to achieve safe ground clearance and a gentle heel contact.

In vivo H MR spectroscopy of human brain in six normal volunteers

International Nuclear Information System (INIS)

Choe, Bo Young; Suh, Tae Suk; Bahk, Yong Whee; Shinn, Kyung Sub

1993-01-01

In vivo H MR spectroscopic studies were performed on the human brain in six normal volunteers. Some distinct proton metabolites, such as N-acetylaspartate (NAA), creatine/phosphocreatine (Cr), choline/phosphocholine (Cho), myo-inositol (Ins) and lipid (fat) were clearly identified in normal brain tissue. The signal intensity of NAA resonance is strongest. The standard ratios of metabolites from the normal brain tissue in specific regions were obtained for the references of further in vivo H MR spectroscopic studies. Our initial resulting suggest the in vivo H MR spectroscopy may provide more precise diagnosis on the basis of the metabolic information on brain tissues. The unique ability of In vivo H MR spectroscopy to offer noninvasive information about tissue biochemistry in patients will stimulate its impact on clinical research and disease diagnosis

Interaction of metabolic and respiratory acidosis with α and β-adrenoceptor stimulation in rat myocardium.

Science.gov (United States)

Biais, Matthieu; Jouffroy, Romain; Carillion, Aude; Feldman, Sarah; Jobart-Malfait, Aude; Riou, Bruno; Amour, Julien

2012-12-01

The effects of acute respiratory versus metabolic acidosis on the myocardium and their consequences on adrenoceptor stimulation remain poorly described. We compared the effects of metabolic and respiratory acidosis on inotropy and lusitropy in rat myocardium and their effects on the responses to α- and β-adrenoceptor stimulations. The effects of acute respiratory and metabolic acidosis (pH 7.10) and their interactions with α and β-adrenoceptor stimulations were studied in isolated rat left ventricular papillary muscle (n=8 per group). Intracellular pH was measured using confocal microscopy and a pH-sensitive fluorophore in isolated rat cardiomyocytes. Data are mean percentages of baseline±SD. Respiratory acidosis induced more pronounced negative inotropic effects than metabolic acidosis did both in isotonic (45±3 versus 63±6%, Prespiratory or metabolic acidosis. The inotropic response to β-adrenergic stimulation was impaired only in metabolic acidosis (137±12 versus 200±33%, Pacidosis. The lusitropic response to β-adrenergic stimulation was not modified by respiratory or metabolic acidosis. Acute metabolic and respiratory acidosis induce different myocardial effects related to different decreases in intracellular pH. Only metabolic acidosis impairs the positive inotropic effect of β-adrenergic stimulation.

Change of short-term memory effect in acute ischemic ventricular myocardium: a computational study.

Science.gov (United States)

Mei, Xi; Wang, Jing; Zhang, Hong; Liu, Zhi-cheng; Zhang, Zhen-xi

2014-02-01

The ionic mechanism of change in short-term memory (STM) during acute myocardial ischemia has not been well understood. In this paper, an advanced guinea pig ventricular model developed by Luo and Rudy was used to investigate STM property of ischemic ventricular myocardium. STM response was calculated by testing the time to reach steady-state action potential duration (APD) after an abrupt shortening of basic cycling length (BCL) in the pacing protocol. Electrical restitution curves (RCs), which can simultaneously visualize multiple aspects of APD restitution and STM, were obtained from dynamic and local S1S2 restitution portrait (RP), which consist of a longer interval stimulus (S1) and a shorter interval stimulus (S2). The angle between dynamic RC and local S1S2 RC reflects the amount of STM. Our results indicated that compared with control (normal) condition, time constant of STM response in the ischemic condition decreased significantly. Meanwhile the angle which reflects STM amount is less in ischemic model than that in control model. By tracking the effect of ischemia on intracellular ion concentration and membrane currents, we declared that changes in membrane currents caused by ischemia exert subtle influences on STM; it is only the decline of intracellular calcium concentration that give rise to the most decrement of STM. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Early assessment of tissue viability with radioiodinated heptadecanoic acid in reperfused canine myocardium: Comparison with thallium-201

International Nuclear Information System (INIS)

Chappuis, F.; Meier, B.; Belenger, J.; Blaeuenstein, P.L.; Lerch, R.

1990-01-01

Myocardial scintigraphy with heptadecanoic acid labeled with iodine-123 (123I-HDA) may allow early noninvasive delineation of viable myocardium after reperfusion. In this study myocardial uptake of 123I-HDA was compared with that of thallium-201 in six closed-chest dogs after 5 hours of occlusion followed by 1 hour of reperfusion of the left anterior descending coronary artery. Myocardial blood flow was measured with microspheres, and myocardial viability was assessed by means of triphenyltetrazolium chloride staining. In viable areas of the reperfused region, 123I-HDA uptake, thallium-201 uptake, and myocardial blood flow were similar to those measured in the control circumflex region. However, in infarcted areas they were reduced to 48 +/- 2% (mean +/- SEM; p less than 0.001), 59 +/- 3% (p less than 0.001), and 74 +/- 5% (p less than 0.001) of control values, respectively. Results of multiple regression analysis showed that thallium-201 uptake primarily reflected the level of flow during reperfusion, whereas 123I-HDA uptake was dependent on both myocardial blood flow and viability. At each level of flow, 123I-HDA uptake was significantly lower in infarcted than in viable myocardium. By means of discriminant analysis, 123I-HDA uptake was found to be the single most important predictor of viability, whereas thallium-201 was only of limited importance. Myocardial 123I-HDA uptake greater than or equal to 71% or myocardial thallium-201 uptake greater than or equal to 73% best differentiated viable from infarcted myocardium. According to these criteria, 123I-HDA predicted myocardial viability with a sensitivity of 77%, a specificity of 84% and a predictive accuracy of 81%

Temperature dependence of the kinetics of isometric myocardium relaxation

Energy Technology Data Exchange (ETDEWEB)

Izakov, V.Ya.; Bykov, B.L.; Kimmelman, I.Ya.

1981-11-01

The dependence of the exponential decay constant expressing the isometric relaxation of the myocardium on temperature is investigated in animals with various specific contents of myocardial sarcoplasmic reticulum. Experiments were performed on cardiac ventricles and atria isolated from rabbits, frogs and turtles and electrically stimulated to produce maximal contraction at temperatures from 10 to 35 C. Arrhenius plots derived from the data are found to be linear in the myocardia of the rabbit and frog, with a greater activation energy for the relaxation found in the rabbit. The Arrhenius plot for the turtle, which has a sarcoplasmic reticulum content intermediate between those of the frog and rabbit, corresponds to two straight lines with different activation energies. Results thus support the hypothesis of two separate mechanisms of calcium removal, involving the sarcoplasmic reticulum and cellular membrane, in muscle relaxation.

99mTcO(BAT-NI), a novel nitroimidazole tracer: in vivo uptake studies in ischaemic myocardium

International Nuclear Information System (INIS)

Hoffend, J.; Linke, G.; Mohammed, A.; Haberkorn, U.; Tiefenbacher, C.P.; Eisenhut, M.

2003-01-01

Myocardial perfusion single-photon emission tomography (SPET) performed with cationic technetium-99m complexes indicates ischaemic areas as cold lesions. By contrast, nitroimidazole derivatives labelled with fluorine-18 or 99m Tc have recently shown promising results for hot spot imaging of ischaemic myocardium. This study evaluates 99m TcO(BAT-NI), a new 99m Tc complex comprising the nitroimidazole ligand, 2,10-dimercapto-2, 10-dimethyl-4, 8-diaza-6-[4-(2-nitroimidazolyl)butyl]undecane, in a low-flow in vivo model of myocardial ischaemia in thoracotomised rats. To elucidate the influence of the 2-nitroimidazole group on ischaemia-induced uptake, comparisons with ligand derivatives were performed where (a) the 2-nitro group was deleted [ 99m TcO(BAT-I)], (b) the 2-nitroimidazole functionality was replaced by a Br atom [ 99m TcO(BAT-Br)] and (c) the 99m TcO(BAT) moiety was replaced by an iodine-125 iodophenoxybutyl ligand ( 125 IP-NI). The radiolabelled compounds were i.v. injected 15 min after reducing resting myocardial blood flow by 50-60% and the uptake of radioactivity was assessed 90 min post injection. Autoradiography of left ventricular short-axis slices showed median uptake ratios of ischaemic/non-ischaemic myocardium (I/N) of 3.4, 4.5 and 3.4 for 99m TcO(BAT-NI), 99m TcO(BAT-I) and 99m TcO(BAT-Br), respectively. In contrast, 125 IP-NI was not preferentially taken up by ischaemic myocardium. Accumulation of 99m TcO(BAT-NI) in ischaemic heart regions was comparable to that in the liver. Biodistribution studies showed a median uptake of 0.65% ID/g of 99m TcO(BAT-NI) in ischaemic tissue and an I/N of 3.3. On planar images of the thorax and upper abdomen the ischaemic hearts were visualised faintly; the median heart to lung count ratio for 99m TcO(BAT-NI) was 1.7, and the median heart to liver count ratio was 1.0. We conclude that uptake of 99m TcO(BAT-NI) in ischaemic myocardium does not depend on the nitroimidazole moiety but is intrinsic to the BAT complex

Articular cartilage explant culture; an appropriate in vitro system to compare osteoarthritic and normal human cartilage

NARCIS (Netherlands)

Lafeber, F. P.; Vander Kraan, P. M.; van Roy, J. L.; Huber-Bruning, O.; Bijlsma, J. W.

1993-01-01

Proteoglycan metabolism of normal and histologically mild to moderate osteoarthritic cartilage explants were studied. Explants were obtained from the human knee of donors aged over 40 years. Proteoglycan content, synthesis and release were very similar in normal cartilage obtained from donors with

The research on biodistribution of 131I-iodosennoside A in normal mice and to evaluate myocardial activity

International Nuclear Information System (INIS)

Wang Junhu; Yin Zhiqi; Jiang Cuihua; Jiang Xiao; Li Yue; Zhang Jian; Sun Ziping; Ni Yicheng

2013-01-01

Purpose: The objective of this project is to evaluate biodistribution of [ 131 I]-Iodosennoside A in normal mice and explore the feasibility on the diagnosis of myocardial infarction. Methods: Iodogen method was used to radioiodinate sennoside A with 131 I. [ 131 I] Iodosennoside A was intravenously injected into mice. Three groups of mice were killed at 4 h, 24 h and 48 h post injection respectively and the radioactive uptake in major organs were calculated. Rats were subjected to left anterior descending (LAD) coronary artery ligation to induce acute myocardial infarction. Rat models of myocardial infarction were intravenously injected [ 131 I] iodosennoside A. 24 h after injection of [ 131 I] iodosennoside A, the regional distribution of radioiodinated sennoside A was determined by radioactivity counting technique. 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining and autoradiography were per- formed with 2 mm thick sections of hearts for postmortem verifications. Results: The study showed high uptake of [ 131 I] iodosennoside A in kidneys and fast blood clearance. At 24 h post injection, radioactivity concentration in infarcted myocardium was over 11.9 times higher than in normal myocardium. Preferential uptake of the [ 131 I] iodosennoside A in necrotic tissue was confirmed by perfect match of images from TTC staining and autoradiography. Conclusion: The result proved that [ 131 I] iodosennoside A has myocardial necrosis affinity and may serve as a marker on the diagnosis of myocardial infarction. (authors)

The sinusoidal lining cells in "normal" human liver. A scanning electron microscopic investigation

DEFF Research Database (Denmark)

Horn, T; Henriksen, Jens Henrik Sahl; Christoffersen, P

1986-01-01

The scanning electron microscopic was used to study the fenestrations of human liver sinusoids. Thirteen biopsies, where light microscopy and transmission electron microscopy revealed normal sinusoidal architecture, were investigated. The number of fenestrae was calculated in acinar zone 3...

Characterization of the functional and anatomical differences in the atrial and ventricular myocardium from three species of elasmobranch fishes

DEFF Research Database (Denmark)

Larsen, Julie; Bushnell, Peter; Steffensen, John

2017-01-01

We assessed the functional properties in atrial and ventricular myocardium (using isolated cardiac strips) of smooth dogfish (Mustelus canis), clearnose skate (Raja eglanteria), and sandbar shark (Carcharhinus plumbeus) by blocking Ca2+ release from the sarcoplasmic reticulum (SR) with ryanodine...... positive first derivative (i.e., contractility), and increased time to 50 % relaxation in atrial tissue from smooth dogfish at 30 °C. It also increased times to peak force and half relaxation in clearnose skate atrial and ventricular tissue at both temperatures, but only in atrial tissue from sandbar shark...... at 30 °C; indicating that SR involvement in excitation–contraction (EC) coupling is species- and temperature-specific in elasmobranch fishes, as it is in teleost fishes. Atrial and ventricular myocardium from all three species displayed a negative force–frequency relationship, but there was no evidence...

Correlation of hypoxia inducible factor-1α and vascular endothelium growth factor in rat myocardium during aerobic and anaerobic exercise

Directory of Open Access Journals (Sweden)

Rostika Flora

2012-08-01

Full Text Available Background: Exercise increases the need for oxygen to generate ATP through oxidative phosphorylation. If the high energy demand during exercise is not balanced by sufficient oxygen supply, hypoxia occurs in skeletal muscle tissue leading to upregulation of hypoxia inducible factor-1α (HIF-1α. The activity of HIF-1α increases the expression of various genes in order to reduce the metabolic dependence on oxygen and to increase oxygen supply to the tissue, e.g., VEGF which plays a role in angiogenesis. In myocardium, it is unclear whether exercise leads to hypoxia and whether HIF-1α and VEGF play a role in the mechanism of hypoxic adaptation. This study aimed to investigate the correlation of HIF-1α and VEGF in heart muscle tissue of rats during aerobic and anaerobic exercise.Methods: A rat treadmill was used with a specific exercise program for 1, 3, 7 and 10 days. The concentrations of HIF-1α and VEGF were measured the myocardium.Results: Both, HIF-1α protein and VEGF were increased (p < 0.05 in the groups with aerobic and anaerobic exercise. Concentrations of HIF-1α were highest on the first day of activity, being higher in the anaerobic than in the aerobic group (156.8 ± 33.1 vs. 116.03 ± 5.66. Likewise, the highest concentration of VEGF in the group with anaerobic exercise occurred on the first day (36.37 ± 2:35, while in the aerobic group, VEGF concentration was highest on day 3 (40.66 ± 1.73. The correlation between the myocardial tissue consentrations of HIF-1α and VEGF is moderate (r = 0.59 in the aerobic group and strong in the anaerobic group (r = 0.69.Conclusion: Aerobic and anaerobic exercise increase HIF-1α and VEGF concentrations in rat myocardium in specific patterns. The anaerobic condition triggers vascularization stronger and obviously earlier than aerobic exercise. (Med J Indones. 2012;21:133-40Keywords: Exercise, HIF-1α, myocardium, VEGF

Effect of resveratrol and zinc on intracellular zinc status in normal human prostate epithelial cells

Science.gov (United States)

To evaluate the influence of resveratrol on cellular zinc status, normal human prostate epithelial (NHPrE) cells were treated with 6 levels of resveratrol (0, 0.5, 1, 2.5, 5 and 10 microM) and 4 levels of zinc [0, 4, 16, and 32 microM for zinc-deficient (ZD), zinc-normal (ZN), zinc-adequate (ZA), an...

Identification and Characterization of Plasma Cells in Normal Human Bone Marrow by High-Resolution Flow Cytometry

NARCIS (Netherlands)

Terstappen, Leonardus Wendelinus Mathias Marie; Johnsen, Steen; Segers-Nolten, Gezina M.J.; Loken, Michael R.

1990-01-01

The low frequency of plasma cells and the lack of specific cell surface markers has been a major obstacle for a detailed characterization of plasma cells in normal human bone marrow. Multiparameter flow cytometry enabled the identification of plasma cells in normal bone marrow aspirates. The plasma

Multistep process of neoplastic transformation of normal human fibroblasts by 60Co gamma rays and Harvey sarcoma viruses

Energy Technology Data Exchange (ETDEWEB)

Namba, M.; Nishitani, K.; Fukushima, F.; Kimoto, T.; Nose, K.

1986-03-15

As reported previously (Namba et al., 1985), normal human fibroblasts were transformed by 60Co gamma-ray irradiation into immortal cells with abnormal karyotypes. These transformed cells (KMST-6), however, showed a low cloning efficiency in soft agar and no transplantability. However, upon treatment with Harvey murine sarcoma virus (Ha-MSV), the cells acquired elevated clonability in soft agar and transplantability in nude mice. Ha-MSV alone, however, did not convert normal human fibroblasts into either immortal or tumorigenic cells. The Ha-MSV-transformed KMST-6 cells showed an enhanced expression of the ras oncogene, but normal and 60Co gamma-ray-transformed cells did not. Our current data suggest that gamma rays worked against normal human cells as an initiator, giving rise to chromosome aberrations and immortality, and that Ha-MSV, probably through its ras oncogene, played a role in the progression of the malignant cell population to a more malignant one showing enhanced colony formation in soft agar and tumorigenicity in nude mice.

Thallium-201 for myocardial imaging: appearance of the normal heart

International Nuclear Information System (INIS)

Cook, D.J.; Bailey, I.; Strauss, H.W.; Rouleau, J.; Wagner, H.N. Jr.; Pitt, B.

1976-01-01

Thallium-201 myocardial perfusion images were obtained from 13 healthy adults after tracer administration both at rest and at maximal stress. On the rest-injected scan, tracer was seen in left ventricular myocardium, liver, and spleen. In two subjects with resting tachycardia, the right ventricular myocardium was slightly visualized after tracer injection at rest. When tracer was administered at stress, the left ventricular activity was more nearly homogeneous and the left ventricle was better defined on the scan. The left-ventricle-to-lung-background activity ratio increased from 2.4 at rest to 3.4 at stress. The right ventricular myocardium was seen on the stress-injected scan. Phantom studies, performed to define the optimum position for visualization of lesions, showed that small lesions were best defined when seen either en face or in tangent. Scans should be performed at stress whenever possible and multiple views are essential

Effect of hyperbaric oxygenation on carbohydrate metabolism protein synthesis in the myocardium during sustained hypodynamia

Science.gov (United States)

Makarov, G. A.

1980-01-01

Glycolysis and the intensity of protein synthesis were studied in 140 white male rats in subcellular fractions of the myocardium during 45 day hypodynamia and hyperbaric oxygenation. Hypodynamia increased: (1) the amount of lactic acids; (2) the amount of pyruvic acid; (3) the lactate/pyruvate coefficient; and (4) the activities of aldolase and lactate dehydrogenase. Hyperbaric oxygenation was found to have a favorable metabolic effect on the animals with hypodynamia.

Exponential relationship between DMIPP uptake and blood flow in normal and ischemic canine myocardium

Energy Technology Data Exchange (ETDEWEB)

Comans, E.F.I.; Lingen, A. van; Bax, J.J.; Sloof, G.W. [Free Univ. Hospital, Amsterdam (Netherlands). Dept. of Nuclear Medicine; Visser, F.C. [Free Univ. Hospital, Amsterdam (Netherlands). Dept. of Cardiology; Vusse, G.J. van der [Limburg Univ., Maastricht (Netherlands). Cardiovascular Research Inst.; Knapp, F.F. Jun. [Oak Ridge Lab., TN (United States). Nuclear Medicine Group

1998-12-31

In 10 open-chest dogs the left anterior descending coronary artery was cannulated and extracorporally bypass (ECB) perfused at reduced flow. Myocardial blood flow (MBF) was assessed with Scandium-46 labeled microspheres. Forty minutes after i.v. injection of DMIPP, the heart was excised and cut into 120 samples. In each sample MBF (ml/g*min) and DMIPP uptake (percentage of the injected dose per gram: %id/g) were assessed. The relation between normalized MBF and DMIPP uptake was assessed using a linear, with a zero and with a non-zero intercept, and an exponential model function: A[1-e{sup -MBF/Fc}], where A and Fc are the amplitude and flow constant, respectively. The goodness of fit for all models was expressed as the standard error of estimate (SEE). In all individual dogs the relation between DMIPP uptake and MBF was significantly better (p<0.001) represented by an exponential model than a linear model with zero intercept. In 8 of 10 dogs the exponential model showed a better fit than the linear model with a non-zero intercept. The difference was significant (p<0.05) in 5 dogs. For Pooled data, linear regression analysis with a non-zero intercept revealed: DMIPP=0.54+0.44*MBF (SEE: 0.18) and with a zero intercept: DMIPP=0.97*MBF (SEE: 0.27). The goodness of fit of the exponential model: DMIPP=1.07[1-e{sup -MBF/0.35}] (SEE: 0.15) was significantly better (p<0.0001) than the linear models. In the normal to low MBF range, uptake of the dimenthyl branched fatty acid analogue DMIPP shows an exponential relationship, which is more appropriate than a linear relationship from a physiological point of view. (orig./MG) [Deutsch] An 10 Hunden mit eroeffnetem Brustkorb wurde der Ramus interventricularis anterior der linken Koronararterie kanueliert und ueber einen extrakorporalen Bypass (ECB) mit einem reduzierten Fluss perfundiert. Der myokardiale Blutfluss (MBF) wurde ueber Scandium-46-markierte Mikrosphaeren erfasst. Vierzig Minuten nach der iv. Injektion von DMIPP wurde

Gestational trophoblastic neoplasia after spontaneous human chorionic gonadotropin normalization following molar pregnancy evacuation.

Science.gov (United States)

Braga, Antonio; Maestá, Izildinha; Matos, Michelle; Elias, Kevin M; Rizzo, Julianna; Viggiano, Maurício Guilherme Campos

2015-11-01

To evaluate the risk of gestational trophoblastic neoplasia (GTN) after spontaneous human chorionic gonadotropin normalization in postmolar follow-up. Retrospective chart review of 2284 consecutive cases of hydatidiform mole with spontaneous normalization of hCG following uterine evacuation treated at one of five Brazilian reference centers from January 2002 to June 2013. After hCG normalization, GTN occurred in 10/2284 patients (0.4%; 95% CI 0.2%-0.8%). GTN developed in 9/1424 patients (0.6%; 95% CI 0.3%-1.2%) after a complete hydatidiform mole, in 1/849 patients (0.1%; 95% CInormalization was 18months, and no diagnoses were made before six months of postmolar surveillance. Patients who required more than 56days to achieve a normal hCG value had a ten-fold increased risk of developing GTN after hCG normalization (9/1074; 0.8%; 95% CI 0.4%-1.6%) compared to those who reached a normal hCG level in fewer than 56days (1/1210;0.08%; 95% CInormalization following molar pregnancy is exceedingly rare, and the few patients who do develop GTN after achieving a normal hCG value are likely to be diagnosed after completing the commonly recommended six months of postmolar surveillance. Current recommendations for surveillance after hCG normalization should be revisited. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of acidity and chemical composition of sup(99m)Tc-radiopharmaceuticals on sup(99m)Tc accumulation in necrotic tissue of rat myocardium

Energy Technology Data Exchange (ETDEWEB)

Vilcek, S; Machan, V; Kalincak, M [Ustav Radioekologie a Vyuzitia Jadrovej Techniky, Kosice (Czechoslovakia); Nicak, A [Univerzita P.J. Safarika, Kosice (Czechoslovakia). Lekarska Fakulta

1981-04-30

Experiments showed that the cumulation of technetium-99m following the administration of /sup 99m/Tc-Sn-pyrophosphate and s/sup 99m/Tc-Sn-oxytetracycline in the necrotic tissue of rat myocardium damaged by cauterization depended on the end pH value. The maximum /sup 99m/Tc cumulation in the myocardial lesion was noted when the end pH value ranged in 5.5 to 6.0. It appeared that pyrophosphate concentration decrease below the critical limit not only affected the cumulation of /sup 99m/Tc in the particular organs but also in the necrotic tissue of the myocardium.

Effect of acidity and chemical composition of sup(99m)Tc-radiopharmaceuticals on sup(99m)Tc accumulation in necrotic tissue of rat myocardium

International Nuclear Information System (INIS)

Vilcek, S.; Machan, V.; Kalincak, M.; Nicak, A.

1981-01-01

Experiments showed that the cumulation of technetium-99m following the administration of sup(99m)Tc-Sn-pyrophosphate and sup(99m)Tc-Sn-oxytetracycline in the necrotic tissue of rat myocardium damaged by cauterization depended on the end pH value. The maximum sup(99m)Tc cumulation in the myocardial lesion was noted when the end pH value ranged in 5.5 to 6.0. It appeared that pyrophosphate concentration decrease below the critical limit not only affected the cumulation of sup(99m)Tc in the particular organs but also in the necrotic tissue of the myocardium. (author)

Serial change of 123I-BMIPP SPECT imaging during recovery from stunned myocardium after acute myocardial infarction. Correlation with 201Tl and two-dimensional echocardiography

International Nuclear Information System (INIS)

Nakano, Akira; Kondo, Makoto; Tokunaga, Satoshi; Akiyama, Kiyozumi; Mori, Yoshihisa; Nosue, Yasuhiro; Makita, Toshinori; Tanio, Hitoshi; Shimono, Yukio

1995-01-01

Using 123 I-β-methyl iodophenyl pentadecanoic acid ( 123 I-BMIPP), we investigated changes in myocardial fatty acid metabolism at recovery from stunned myocardium after acute myocardial infarction (AMI), correlation with recovery of regional wall motion and thallium-201 ( 201 Tl) distribution in particular. The subjects were 15 patients who underwent successful reperfusion therapy after the first onset of AMI. None of the patients had multi-vessel disease or ischemic episode during their clinical course. Patients underwent 123 I-BMIPP scintigraphy, 201 Tl scintigraphy and two-dimensional echocardiography during the acute and chronic phases. Then, we compared regional wall motion with distribution of 123 I-BMIPP and 201 Tl. Regional wall motion and SPECT were evaluated by the established 16 segment model. In patients, showing serial improvement in regional wall motion, there was 80.0% (8/10) showed normal 201 Tl distribution during the acute phase or normalized during the chronic phase. However, distribution of 123 I-BMIPP normalized only in 10.0% (1/10) of this group. In examination of each segment that showed serial improvement in regional wall motion, 92.3% (24/26) of these segments showed normal distribution of 201 Tl during the acute phase or normalized distribution during chronic phase, despite distribution of 123 I-BMIPP improved in only 3.8% (1/26) of these segments. These indicate that, in the process of recovery from myocardial stunning after AMI, abnormal distribution of 123 I-BMIPP continued longer than abnormal distribution of 201 Tl. (author)

Experimental Model of Gene Transfection in Healthy Canine Myocardium: Perspectives of Gene Therapy for Ischemic Heart Disease

Directory of Open Access Journals (Sweden)

Renato A. K. Kalil

2002-09-01

Full Text Available OBJECTIVE: To assess the transfection of the gene that encodes green fluorescent protein (GFP through direct intramyocardial injection. METHODS: The pREGFP plasmid vector was used. The EGFP gene was inserted downstream from the constitutive promoter of the Rous sarcoma virus. Five male dogs were used (mean weight 13.5 kg, in which 0.5 mL of saline solution (n=1 or 0.5 mL of plasmid solution containing 0.5 µg of pREGFP/dog (n=4 were injected into the myocardium of the left ventricular lateral wall. The dogs were euthanized 1 week later, and cardiac biopsies were obtained. RESULTS: Fluorescence microscopy showed differences between the cells transfected and not transfected with pREGFP plasmid. Mild fluorescence was observed in the cardiac fibers that received saline solution; however, the myocardial cells transfected with pREGFP had overt EGFP expression. CONCLUSION: Transfection with the EGFP gene in healthy canine myocardium was effective. The reproduction of this efficacy using vascular endothelial growth factor (VEGF instead of EGFP aims at developing gene therapy for ischemic heart disease.

Cardiac lymphoscintigraphy following closed-chest catheter injection of radiolabeled colloid into the myocardium of dogs: concise communication

International Nuclear Information System (INIS)

Osbakken, M.D.; Kopiwoda, S.Y.; Swan, A.; Castronovo, F.P.; Strauss, H.W.

1982-01-01

A catheter technique for injection of radiolabeled colloids into the myocardium was developed and tested in a series of 15 dogs. A multipurpose angiographic catheter was modified to permit an inner core of PE-50 polyethylene tubing, tipped with a 23-gage needle, to pass through the lumen for intra-myocardial injection of the femoral artery: for the right ventricle, the femoral vein. The catheter advanced under fluoroscopy until the desired surface for injection is reached. The inner core is then extended to lodge the needle in the endocardium. A mixture of Renogratin (to confirm the endocardial injection site) and radiolabeled colloid was injected in up to 6 hr. In three dogs the procedure was repeated 3 or 4 times. From two to five nodes were visible in all animals, irrespective of whether the right or left ventricular myocardium was injected. In two animals the injection was given intravenously, and no nodes were seen. These data suggest that cardiac lymphatic drainage can be studied with a catheter injection method

The amount of viable and dyssynchronous myocardium is associated with response to cardiac resynchronization therapy: initial clinical results using multiparametric ECG-gated [{sup 18}F]FDG PET

Energy Technology Data Exchange (ETDEWEB)

Lehner, Sebastian; Uebleis, Christopher; Haug, Alexander; Bartenstein, Peter [University of Munich, Department of Nuclear Medicine, Munich (Germany); Schuessler, Franziska; Kaeaeb, Stefan; Estner, Heidi [University of Munich, Medical Department I, Munich (Germany); Van Kriekinge, Serge D.; Germano, Guido [UCLA, Cedars-Sinai Medical Center, Los Angeles and David Geffen School of Medicine, Los Angeles, CA (United States); Hacker, Marcus [Medical University of Vienna, Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Theraphy, Vienna (Austria)

2013-12-15

There is still a significant amount of patients who do not sufficiently respond to cardiac resynchronization therapy (CRT). Previous studies demonstrated that the amount of dyssynchronous myocardium was predictive of response to CRT. Otherwise, non-response is frequently associated with high amounts of scar tissue. The combination of these parameters might yield a more accurate prediction of response. We hypothesized that the probability of a CRT response increases with the presence of high amounts of ''viable and dyssynchronous'' myocardium. A total of 19 patients (17 male, 61 {+-} 10 years) underwent ECG-gated [{sup 18}F]fluorodeoxyglucose (FDG) myocardial positron emission tomography (PET) before CRT device implantation and were followed for 6 months. Response to CRT was defined as clinical improvement of at least one New York Heart Association (NYHA) class in combination with left ventricular (LV) ejection fraction (EF) improvement of >5 %. Twelve responders (71 %) and seven non-responders (29 %) were identified. For each patient bullseye maps of FDG uptake and phase analysis were calculated (QPS/QGS 2012, Cedars-Sinai, Los Angeles, CA, USA) and fused. Amounts of myocardium representing ''viable and synchronous'', ''scar and synchronous'', viable and dyssynchronous or ''scar and dyssynchronous'' myocardium were quantified by planimetric measurements of the fused bullseye maps. Responders by definition showed significant decrease in NYHA class and significant increase of LVEF. Furthermore, a significantly higher amount of viable and dyssynchronous myocardium was found as compared to non-responders (21 {+-} 13 % vs 6 {+-} 5 %; p < 0.05). Combined assessment of myocardial viability and LV dyssynchrony is feasible using multiparametric [{sup 18}F]FDG PET and could improve conventional response prediction criteria for CRT. (orig.)

Effects of hydroxyl radical induced-Injury in atrial versus ventricular myocardium of dog and rabbit

Directory of Open Access Journals (Sweden)

Nitisha Hiranandani

2010-09-01

Full Text Available Aim: Despite the widespread use of ventricular tissue in the investigation involving hydroxyl-radical (OH* injury, one of the most potent mediators in ischemia-reperfusion injury, little is known about the impact on atrial myocardium. In this study we thus compared the OH*-induced injury response between atrial and right ventricular muscles from both rabbits and dogs under identical experimental conditions. Methods: Small, contracting ventricular and atrial rabbit and dog trabeculae were directly exposed to OH*, and contractile properties were examined and quantified. Results: A brief OH* exposure led to transient rigor like contracture with marked elevation of diastolic tension and depression of developed force. Although the injury response showed similarities between atrial and ventricular myocardium, there were significant differences as well. In rabbit atrial muscles, the development of the contracture and its peak was much faster as compared to ventricular muscles. Also, at the peak of contracture, both rabbit and dog atrial muscles show a lesser degree of contractile dysfunction. Conclusion: These results indicate that both atrial and ventricular muscles develop a rigor like contracture after acute OH*-induced injury, and atrial muscles showed a lesser degree of contractile dysfunction. Comparison of dog versus rabbit tissue shows that the response was similar in magnitude, but slower to develop in dog tissue.

Identification of normal and cancerous human colorectal muscularis propria by multiphoton microscopy in different sections

International Nuclear Information System (INIS)

Zhou, Yi; Li, Lianhuang; Zhuo, Shuangmu; Zhu, Xiaoqin; Chen, Jianxin; Chen, Zhifen; Guan, Guoxian; Kang, Deyong

2016-01-01

Multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) as a potential diagnostic tool is attractive. MPM can effectively provide information about morphological and biochemical changes in biological tissues at the molecular level. In this paper, we attempt to identify normal and cancerous human colorectal muscularis propria by multiphoton microscopy in different sections (both in transverse and longitudinal sections). The results show that MPM can display different microstructure changes in the transverse and longitudinal sections of colorectal muscularis propria. MPM also can quantitatively describe the alteration of collagen content between normal and cancerous muscle layers. These are important pathological findings that MPM images can bring more detailed complementary information about tissue architecture and cell morphology through observing the transverse and longitudinal sections of colorectal muscularis propria. This work demonstrates that MPM can be better for identifying the microstructural characteristics of normal and cancerous human colorectal muscularis propria in different sections. (paper)

Identification of normal and cancerous human colorectal muscularis propria by multiphoton microscopy in different sections

Science.gov (United States)

Zhou, Yi; Chen, Zhifen; Kang, Deyong; li, Lianhuang; Zhuo, Shuangmu; Zhu, Xiaoqin; Guan, Guoxian; Chen, Jianxin

2016-01-01

Multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) as a potential diagnostic tool is attractive. MPM can effectively provide information about morphological and biochemical changes in biological tissues at the molecular level. In this paper, we attempt to identify normal and cancerous human colorectal muscularis propria by multiphoton microscopy in different sections (both in transverse and longitudinal sections). The results show that MPM can display different microstructure changes in the transverse and longitudinal sections of colorectal muscularis propria. MPM also can quantitatively describe the alteration of collagen content between normal and cancerous muscle layers. These are important pathological findings that MPM images can bring more detailed complementary information about tissue architecture and cell morphology through observing the transverse and longitudinal sections of colorectal muscularis propria. This work demonstrates that MPM can be better for identifying the microstructural characteristics of normal and cancerous human colorectal muscularis propria in different sections.

Pig models for the human heart failure syndrome

DEFF Research Database (Denmark)

Hunter, Ingrid; Terzic, Dijana; Zois, Nora Elisabeth

2014-01-01

Human heart failure remains a challenging illness despite advances in the diagnosis and treatment of heart failure patients. There is a need for further improvement of our understanding of the failing myocardium and its molecular deterioration. Porcine models provide an important research tool...... in this respect as molecular changes can be examined in detail, which is simply not feasible in human patients. However, the human heart failure syndrome is based on symptoms and signs, where pig models mostly mimic the myocardial damage, but without decisive data on clinical presentation and, therefore, a heart...... to elucidate the human heart failure syndrome....

Effect of ethanol and the catalase inhibitor aminotriazole on lipid peroxidation in the rat myocardium

International Nuclear Information System (INIS)

Panchenko, L.F.; Pirozhkov, S.V.; Popova, S.V.; Antonenkov, V.D.

1987-01-01

The authors study the effect of chronic administration of ethanol and aminotriazole on the level of lipid peroxidation in the ray myocardium. The action of natural and artificial antioxidants on alcohol-induced lipid peroxidation also was studied. To determine the level of chemiluminescence, 1 ml of a sample of nuclear free homogenate or of the total fraction of particles was introduced for radioactivity measurement. After incubation the spontaneous weak luminescence was measured

The Fate of a Normal Human Cell Traversed by a Single Charged Particle

Science.gov (United States)

Fournier, C.; Zahnreich, S.; Kraft, D.; Friedrich, T.; Voss, K.-O.; Durante, M.; Ritter, S.

2012-01-01

The long-term “fate” of normal human cells after single hits of charged particles is one of the oldest unsolved issues in radiation protection and cellular radiobiology. Using a high-precision heavy-ion microbeam we could target normal human fibroblasts with exactly one or five carbon ions and measured the early cytogenetic damage and the late behaviour using single-cell cloning. Around 70% of the first cycle cells presented visible aberrations in mFISH after a single ion traversal, and about 5% of the cells were still able to form colonies. In one third of selected high-proliferative colonies we observed clonal (radiation-induced) aberrations. Terminal differentiation and markers of senescence (PCNA, p16) in the descendants of cells traversed by one carbon ion occurred earlier than in controls, but no evidence of radiation-induced chromosomal instability was found. We conclude that cells surviving single-ion traversal, often carrying clonal chromosome aberrations, undergo accelerated senescence but maintain chromosomal stability. PMID:22966418

Repair replication in cultured normal and transformed human fibroblasts

International Nuclear Information System (INIS)

Smith, C.A.; Hanawalt, P.C.

1976-01-01

Repair replication in response to ultraviolet irradiation has been studied in normal human diploid fibroblast cultures, W138, and an SV40 transformant, VA13. Quantitative comparisons have been made using the combined isotopic and density labelling method for assaying repair replication. No significant difference was found in the amount of repair replication performed, its dose response, or the time course between growing and confluent W138 cells, early passage and senescent cells, or normal W138 cells and the transformed VA13 cells. When [ 3 H]dThd was employed as the isotopic label in the presence of a 30-200 fold excess of unlabelled BrdUrd apparent differences in repair replication were seen between W138 cells shortly after subcultivation and cells which had been allowed to reach confluence. These differences were the same over a wide dose range and regardless of the passage number of the cells, but could be influenced by using different serum lots. The differences were not seen, however, when [ 3 H]BrdUrd provided the isotopic label; thus they reflect either impurities in the [ 3 H]dThd or a slight discrimination by some cellular process

Acute myocardial ischemia: magnetic resonance contrast enhancement with gadolinium-DTPA

International Nuclear Information System (INIS)

McNamara, M.T.; Higgins, C.B.; Ehman, R.L.; Revel, D.; Sievers, R.; Brasch, R.C.

1984-01-01

Gadolinium-DTPA (Gd-DTPA) was used to improve the diagnostic utility of magnetic resonance (MR) in detecting early ischemia, before the onset of infarction. Following one minute of left anterior descending coronary artery occlusion, 9 dogs were intraveneously injected with either 0.5 mM/kg of Gd-DTPA (6 dogs) or normal saline (3 dogs). There was no visible difference in intensity or alterations in magnetic relaxation times between normal and ischemic myocardium in the control (saline-injected) animals. The Gd-DTPA-injected dogs had a well-defined segment of high intensity representing the ischemic myocardium in the anterior wall of the left ventricle. Both T1 and T2 were significantly shortened in the normal myocardium of the Gd-DTPA animals, but relatively greater T2 relaxation rate enhancement resulted in reduced intensity of normal myocardium, thus increasing contrast with ischemic myocardium. It is concluded that Gd-DTPA has the potential to expand the sensitivity and diagnostic utility of MR in the study of occlusive coronary artery disease

Influence of the sarcoplasmic reticulum on the inotropic responses of the rat myocardium resulting from changes in rate and rhythm.

Science.gov (United States)

Mill, J G; Vassallo, D V; Leite, C M; Campagnaro, P

1994-06-01

1. The role of the sarcoplasmic reticulum (SR) in the inotropic responses produced by changes in stimulation rate and rhythm and resting tension was investigated in the rat myocardium. 2. Rat papillary muscles contracting isometrically (basic stimulation rate = 30/min) were superfused in vitro with normal Krebs solution and after addition of ryanodine (1 microM). Post-rest potentiation was obtained after pauses of 5, 10, 15, 30, 60 and 120 s, and the stimulation rate was changed from 6 to 90 bpm. Post-extrasystolic potentiation was induced by interpolating an extra stimulus after an interval of 413 +/- 15 ms. NiCl2 (2 mM) was used to confirm that contractions obtained after SR blockade with ryanodine were activated only by sarcolemmal calcium influx. 3. In the presence of ryanodine, the post-rest potentiation phenomenon disappears and the force-frequency relationship changes from the typical force decrease produced by rate increase to force increase. Under the effect of ryanodine, resting tension increased with the increase in stimulation rate. This behavior was enhanced by reducing extracellular KCl from 5.4 mM to 1 mM. This maneuver decreases Na(+)-K(+)-ATPase and increases intracellular Na+ activity, which reduces Ca2+ extrusion through the Na(+)-Ca2+ exchange mechanism. 4. SR participation in the post-extrasystolic potentiation phenomenon is also suggested because ryanodine treatment reversed the extrasystolic force depression into potentiation. In the presence of ryanodine, blockade of Ca2+ influx with NiCl2 (2 mM) abolished isometric contractions indicating that after SR blockade contractions are mainly dependent on sarcolemmal Ca2+ influx. 5. The results suggest that the SR is involved in the genesis of post-rest potentiation and contributes to the typical force-frequency relationship of the rat myocardium and to the post-extrasystolic potentiation phenomenon. Moreover, SR activity seems to be important for the maintenance of low resting tension in the

Abnormal X : autosome ratio, but normal X chromosome inactivation in human triploid cultures

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Norwood Thomas H

2006-07-01

Full Text Available Abstract Background X chromosome inactivation (XCI is that aspect of mammalian dosage compensation that brings about equivalence of X-linked gene expression between females and males by inactivating one of the two X chromosomes (Xi in normal female cells, leaving them with a single active X (Xa as in male cells. In cells with more than two X's, but a diploid autosomal complement, all X's but one, Xa, are inactivated. This phenomenon is commonly thought to suggest 1 that normal development requires a ratio of one Xa per diploid autosomal set, and 2 that an early event in XCI is the marking of one X to be active, with remaining X's becoming inactivated by default. Results Triploids provide a test of these ideas because the ratio of one Xa per diploid autosomal set cannot be achieved, yet this abnormal ratio should not necessarily affect the one-Xa choice mechanism for XCI. Previous studies of XCI patterns in murine triploids support the single-Xa model, but human triploids mostly have two-Xa cells, whether they are XXX or XXY. The XCI patterns we observe in fibroblast cultures from different XXX human triploids suggest that the two-Xa pattern of XCI is selected for, and may have resulted from rare segregation errors or Xi reactivation. Conclusion The initial X inactivation pattern in human triploids, therefore, is likely to resemble the pattern that predominates in murine triploids, i.e., a single Xa, with the remaining X's inactive. Furthermore, our studies of XIST RNA accumulation and promoter methylation suggest that the basic features of XCI are normal in triploids despite the abnormal X:autosome ratio.

Production of a Marfan cellular phenotype by expressing a mutant human fibrillin allele on a normal human or murine genetic background

Energy Technology Data Exchange (ETDEWEB)

Eldadah, Z.A.; Dietz, H.C. [Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States); Brenn, T. [Stanford Univ. Medical Center, CA (United States)] [and others

1994-09-01

The Marfan Syndrome (MFS) is a heritable disorder of connective tissue caused by defects in fibrillin (FBN1), a 350 kD glycoprotein and principal component of the extracellular microfibril. Previous correlations of mutant transcript level and disease severity suggested a dominant negative model of MFS pathogenesis. To address this hypothesis we assembled an expression construct containing the mutant allele from a patient with severe MFS. This mutation causes skipping of FBN1 exon 2 and a frame shift, leading to a premature termination codon in exon 4. The predicted peptide would thus consist of 55 wild type and 45 missense amino acids. The construct was stably transfected into cultured human and mouse fibroblasts, and several clonal cell populations were established. Human and mouse cells expressing the truncated peptide exhibited markedly diminished fibrillin deposition and disorganized microfibrillar architecture by immunofluorescence. Pulse-chase analysis of these cells demonstrated normal levels of fibrillin synthesis but substantially decreased fibrillin deposition into the extracellular matrix. These data illustrate that expression of a mutant FBN1 allele, on a background of two normal alleles, is sufficient to disrupt normal fibrillin aggregation and reproduce the MFS cellular phenotype. This provides confirmation of a dominant negative model of MFS pathogenesis and may offer mutant allele knockout as a strategy for gene therapy. In addition, these data underscore the importance of the FBN1 amino-terminus in normal multimer formation and suggest that expression of the human extreme 5{prime} FBN1 coding sequence may be sufficient, in isolation, to produce an animal model of MFS. Indeed, transgenic mice harboring this mutant allele have been produced, and phenotype analysis is currently in progress.

Distortion-Product Otoacoustic Emission Measured Below 300 Hz in Normal-Hearing Human Subjects

DEFF Research Database (Denmark)

Christensen, Anders Tornvig; Ordoñez Pizarro, Rodrigo Eduardo; Hammershøi, Dorte

2017-01-01

, a custom-built low-frequency acoustic probe was put to use in 21 normal-hearing human subjects (of 34 recruited). Distortion-product otoacoustic emission (DPOAE) was measured in the enclosed ear canal volume as the response to two simultaneously presented tones with frequencies f1 and f2. The stimulus...

Enhanced reactivation and mutagenesis of UV-irradiated adenovirus in normal human fibroblasts

International Nuclear Information System (INIS)

Bennett, C.B.; Rainbow, A.J.

1988-01-01

UV-enhanced reactivation (UVER) and UV-enhanced mutagenesis (UVEM) for two adenovirus temperature-sensitive mutants were examined following the infection of normal human fibroblasts. UV-irradiation of the virus alone resulted in dose-dependent increase in the UV-induced reversion frequency (RF) of viral progeny and a dose-dependent exponential decrease in progeny survival, when infecting non-irradiated cells. Analysis of the slopes of the UV-induced reversion curves suggested that 2.5 ± 0.3 and 2.4 ± 0.5 'hits' were required to produce a targeted reversion event among the viral progeny of Ad5ts36 and Ad5ts125 respectively. UV-irradiation of cells 24 h prior to infection resulted in a significant increase in progeny survival for UV-irradiated virus (UVER factor = 3.4 ± 0.8) concomitant with a significant increase in RF for UV-irradiated virus (targeted increase = 1.9 ± 0.3). The UV-induced RF per lethal hit to the virus was also significantly greater in UV-irradiated compared with non-irradiated cells. These results are consistent with the existence of a UV-inducible error-prone DNA repair mechanism in normal human cells. (author)

Method for radio imaging the myocardium of mammals using radio-labelled lipophil cations

International Nuclear Information System (INIS)

1984-01-01

The invention relates to a method for the radio imaging of myocardia of mammals by concentrating a radiolabelled cation in myocardial tissue and by producing a radiograph using imaging techniques. According to the invention, it is found that a group of substances shows a preference to myocardial tissues upon intravenous injection in mammals. The characteristic of the invention is that radiolabelled quaternary ammonium, quaternary phosphorous or quaternary arsenic compounds with at least two aryl groups are intravenously injected. These substances provide a sufficiently high radioactivity giving an approved diagnostic image of the myocardium. (G.J.P.)

Nitrate administration increases blood flow in dysfunctional but viable myocardium, leading to improved assessment of myocardial viability : A PET study

NARCIS (Netherlands)

Slart, Riemer H. J. A.; Agool, Ali; van Veldhuisen, Dirk J.; Dierckx, Rudi A.; Bax, Jeroen J.

SPECT with Tc-99m-labeled agents is better able to detect viability after nitrate administration. Nitrates induce vasoclilation and may increase blood flow to severely hypoperfused but viable myocardium, thereby enhancing tracer delivery and improving the detection of viability. Quantitative data on

Investigation of dynamic SPECT measurements of the arterial input function in human subjects using simulation, phantom and human studies

Science.gov (United States)

Winant, Celeste D.; Aparici, Carina Mari; Zelnik, Yuval R.; Reutter, Bryan W.; Sitek, Arkadiusz; Bacharach, Stephen L.; Gullberg, Grant T.

2012-01-01

Computer simulations, a phantom study and a human study were performed to determine whether a slowly rotating single-photon computed emission tomography (SPECT) system could provide accurate arterial input functions for quantification of myocardial perfusion imaging using kinetic models. The errors induced by data inconsistency associated with imaging with slow camera rotation during tracer injection were evaluated with an approach called SPECT/P (dynamic SPECT from positron emission tomography (PET)) and SPECT/D (dynamic SPECT from database of SPECT phantom projections). SPECT/P simulated SPECT-like dynamic projections using reprojections of reconstructed dynamic 94Tc-methoxyisobutylisonitrile (94Tc-MIBI) PET images acquired in three human subjects (1 min infusion). This approach was used to evaluate the accuracy of estimating myocardial wash-in rate parameters K1 for rotation speeds providing 180° of projection data every 27 or 54 s. Blood input and myocardium tissue time-activity curves (TACs) were estimated using spatiotemporal splines. These were fit to a one-compartment perfusion model to obtain wash-in rate parameters K1. For the second method (SPECT/D), an anthropomorphic cardiac torso phantom was used to create real SPECT dynamic projection data of a tracer distribution derived from 94Tc-MIBI PET scans in the blood pool, myocardium, liver and background. This method introduced attenuation, collimation and scatter into the modeling of dynamic SPECT projections. Both approaches were used to evaluate the accuracy of estimating myocardial wash-in parameters for rotation speeds providing 180° of projection data every 27 and 54 s. Dynamic cardiac SPECT was also performed in a human subject at rest using a hybrid SPECT/CT scanner. Dynamic measurements of 99mTc-tetrofosmin in the myocardium were obtained using an infusion time of 2 min. Blood input, myocardium tissue and liver TACs were estimated using the same spatiotemporal splines. The spatiotemporal maximum

Investigation of dynamic SPECT measurements of the arterial input function in human subjects using simulation, phantom and human studies

International Nuclear Information System (INIS)

Winant, Celeste D; Aparici, Carina Mari; Bacharach, Stephen L; Gullberg, Grant T; Zelnik, Yuval R; Reutter, Bryan W; Sitek, Arkadiusz

2012-01-01

Computer simulations, a phantom study and a human study were performed to determine whether a slowly rotating single-photon computed emission tomography (SPECT) system could provide accurate arterial input functions for quantification of myocardial perfusion imaging using kinetic models. The errors induced by data inconsistency associated with imaging with slow camera rotation during tracer injection were evaluated with an approach called SPECT/P (dynamic SPECT from positron emission tomography (PET)) and SPECT/D (dynamic SPECT from database of SPECT phantom projections). SPECT/P simulated SPECT-like dynamic projections using reprojections of reconstructed dynamic 94 Tc-methoxyisobutylisonitrile ( 94 Tc-MIBI) PET images acquired in three human subjects (1 min infusion). This approach was used to evaluate the accuracy of estimating myocardial wash-in rate parameters K 1 for rotation speeds providing 180° of projection data every 27 or 54 s. Blood input and myocardium tissue time-activity curves (TACs) were estimated using spatiotemporal splines. These were fit to a one-compartment perfusion model to obtain wash-in rate parameters K 1 . For the second method (SPECT/D), an anthropomorphic cardiac torso phantom was used to create real SPECT dynamic projection data of a tracer distribution derived from 94 Tc-MIBI PET scans in the blood pool, myocardium, liver and background. This method introduced attenuation, collimation and scatter into the modeling of dynamic SPECT projections. Both approaches were used to evaluate the accuracy of estimating myocardial wash-in parameters for rotation speeds providing 180° of projection data every 27 and 54 s. Dynamic cardiac SPECT was also performed in a human subject at rest using a hybrid SPECT/CT scanner. Dynamic measurements of 99m Tc-tetrofosmin in the myocardium were obtained using an infusion time of 2 min. Blood input, myocardium tissue and liver TACs were estimated using the same spatiotemporal splines. The spatiotemporal

Hyperventilation and circadian rhythm of the electrical stability of rat myocardium

Directory of Open Access Journals (Sweden)

Svorc P

2013-08-01

Full Text Available Pavol Svorc,1,2 Alexander Marossy,1 Pavol Svorc Jr2 1Department of Physiology, Medical Faculty, Safarik University, Kosice, Slovak Republic; 2Department of Physiology, Medical Faculty, Ostrava University, Ostrava, Czech Republic Objective: Respiratory alkalosis is an extremely common and complicated problem affecting virtually every organ system where the etiologies may be related to pulmonary or cardiovascular disorders. However, there are only few works describing daytime experiments or synchronization of animals to the external environmental periodicity. The aim of the study is to describe the circadian rhythm of the electrical stability of the heart under hyperventilatory conditions. Methods: Circadian rhythms of the electrical stability of the heart, measured by ventricular arrhythmia threshold ([VAT] measurement in 3 hour intervals, were followed during normal artificial ventilation (40 breaths/minute, tidal volume = 1 mL/100 g; n = 17 and hyperventilation (80 breaths/minute, tidal volume = 2 mL/100 g; n = 7 in pentobarbital (40 mg/kg administered intraperitoneally anesthetized female Wistar rats, after 4 week adaptation on the light/dark regime of 12 hour light/12 hour dark (40%–60% humidity, room temperature of 24°C in cages, two animals/cage with access to food and water ad libitum, with the dark period from 18.00h to 06.00h for 4 weeks. Results: The 24 hour course of the VAT showed the highest susceptibility of the rat ventricular myocardium to arrhythmias between 12.00h and 15.00h, and highest resistance between 19.20h and 00.28h (acrophase −338° in time at 22.53h with confidence intervals −2,880° to −70°, under normoxic conditions. Mesor was 2.59 ± 0.53 mA and amplitude 0.33 ± 0.11 mA. Hyperventilation increased the VAT at each interval of the measurement, but did not change the character of its circadian rhythm. Acrophase was on −40° (02.40h, mesor was increased (2.91 mA, and amplitude was decreased (0.13 m

Polarization sensitive changes in the human macula associated with normal aging and age-related macular degeneration

Science.gov (United States)

VanNasdale, Dean Allan, Jr.

2011-12-01

The human macula occupies a relatively small, but crucial retinal area, as it is the location responsible for our most acute spatial vision and best color discrimination. Localizing important landmarks in the retina is difficult even in normal eyes where morphological inter-individual variability is high. This becomes even more challenging in the presence of sight-threatening pathology. With respect to the human macula, there remains a significant gap in the understanding of normal structure and function. Even less is known about the pathological mechanisms that occur in sight-threatening diseases including age-related macular degeneration. Because relatively little is known about normal aging changes, it is also difficult to differentiate those changes from changes associated with retinal disease. To better understand normal and pathological changes in the macula, imaging techniques using specific optical signatures are required. Structural features in the macula can be distinguished based on their intrinsic properties using specific light/tissue interactions. Because of the high degree of structural regularity in the macula, polarization sensitive imaging is potentially a useful tool for evaluating the morphology and integrity of the cellular architecture for both normal individuals and those affected by disease. In our investigations, we used polarization sensitive imaging to determining normal landmarks that are important clinically and for research investigations. We found that precision and accuracy in localizing the central macula was greatly improved through the use of polarization sensitive imaging. We also found that specific polarization alterations can be used to demonstrate systematic changes as a function of age, disproportionately affecting the central macular region. When evaluating patients with age-related macular degeneration, we found that precision and accuracy of localizing the central macula was also improved, even when significant pathology

Human papilloma virus DNAs immortalize normal human mammary epithelial cells and reduce their growth factor requirements

International Nuclear Information System (INIS)

Band, V.; Zajchowski, D.; Kulesa, V.; Sager, R.

1990-01-01

Human papilloma virus (HPV) types 16 and 18 are most commonly associated with cervical carcinoma in patients and induce immortalization of human keratinocytes in culture. HPV has not been associated with breast cancer. This report describes the immortalization of normal human mammary epithelial cells (76N) by plasmid pHPV18 or pHPV16, each containing the linearized viral genome. Transfectants were grown continuously for more than 60 passages, whereas 76N cells senesce after 18-20 passages. The transfectants also differ from 76N cells in cloning in a completely defined medium called D2 and growing a minimally supplemented defined medium (D3) containing epidermal growth factor. All transfectant tested contain integrated HPV DNA, express HPV RNA, and produce HPV E7 protein. HPV transfectants do not form tumors in a nude mouse assay. It is concluded that products of the HPV genome induce immortalization of human breast epithelial cells and reduce their growth factor requirements. This result raises the possibility that HPV might be involved in breast cancer. Furthermore, other tissue-specific primary epithelial cells that are presently difficult to grown and investigate may also be immortalized by HPV

Plasma Amino Acid Abnormalities in Chronic Heart Failure. Mechanisms, Potential Risks and Targets in Human Myocardium Metabolism

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Roberto Aquilani

2017-11-01

Full Text Available The goal of this study was to measure arterial amino acid levels in patients with chronic heart failure (CHF, and relate them to left ventricular function and disease severity. Amino acids (AAs play a crucial role for heart protein-energy metabolism. In heart failure, arterial AAs, which are the major determinant of AA uptake by the myocardium, are rarely measured. Forty-one subjects with clinically stable CHF (New York Heart Association (NYHA class II to IV were analyzed. After overnight fasting, blood samples from the radial artery were taken to measure AA concentrations. Calorie (KcalI, protein-, fat-, carbohydrate-intake, resting energy expenditure (REE, total daily energy expenditure (REE × 1.3, and cardiac right catheterization variables were all measured. Eight matched controls were compared for all measurements, with the exception of cardiac catheterization. Compared with controls, CHF patients had reduced arterial AA levels, of which both their number and reduced rates are related to Heart Failure (HF severity. Arterial aspartic acid correlated with stroke volume index (r = 0.6263; p < 0.0001 and cardiac index (r = 0.4243; p = 0.0028. The value of arterial aspartic acid (µmol/L multiplied by the cardiac index was associated with left ventricular ejection fraction (r = 0.3765; p = 0.0076. All NYHA groups had adequate protein intake (≥1.1 g/kg/day and inadequate calorie intake (KcalI < REE × 1.3 was found only in class IV patients. This study showed that CHF patients had reduced arterial AA levels directly related to clinical disease severity and left ventricular dysfunction.

Reconstruction and Visualization of Fiber and Laminar Structure in the Normal Human Heart from Ex Vivo DTMRI Data

International Nuclear Information System (INIS)

Rohmer, Damien; Sitek, Arkadiusz; Gullberg, Grant T.

2006-01-01

Background--The human heart is composed of a helical network of muscle fibers. These fibers are organized to form sheets that are separated by cleavage surfaces. This complex structure of fibers and sheets is responsible for the orthotropic mechanical properties of cardiac muscle. The understanding of the configuration of the 3D fiber and sheet structure is important for modeling the mechanical and electrical properties of the heart and changes in this configuration maybe of significant importance to understand the remodeling after myocardial infarction. Methods--Anisotropic least square filtering followed by fiber and sheet tracking techniques were applied to Diffusion Tensor Magnetic Resonance Imaging (DTMRI) data of the excised human heart. The fiber configuration was visualized by using thin tubes to increase 3-dimensional visual perception of the complex structure. The sheet structures were reconstructed from the DTMRI data, obtaining surfaces that span the wall from the endo- to the epicardium. All visualizations were performed using the high-quality ray-tracing software POV-Ray. Results--The fibers are shown to lie in sheets that have concave or convex transmural structure which correspond to histological studies published in the literature. The fiber angles varied depending on the position between the epi- and endocardium. The sheets had a complex structure that depended on the location within the myocardium. In the apex region the sheets had more curvature. Conclusions--A high-quality visualization algorithm applied to demonstrated high quality DTMRI data is able to elicit the comprehension of the complex 3 dimensional structure of the fibers and sheets in the heart

Proton MR spectroscopic features of the human liver: in-vivo application to the normal condition

International Nuclear Information System (INIS)

Cho, Soon Gu; Kim, Mi Young; Kim, Young Soo; Choi, Won; Shin, Seok Hwan; Ok, Chul Soo; Suh, Chang Hae

1999-01-01

To determine the feasibility of MR spectroscopy in the living human liver, and to evaluate the corresponding proton MR spectroscopic features. In fifteen normal volunteers with neither previous nor present liver disease, the proton MR spectroscopic findings were reviewed. Twelve subjects were male and three were female ; they were aged between 28 and 32 (mean, 30) years. MR spectroscopy involved the use of a 1.5T GE Signa Horizon system with body coil(GE Medical System, Milwaukee, U.S.A). We used STEAM (Stimulated Echo-Acquisition Mode) with 3000/30 msec of TR/TE for signal acquisition, and the prone position without respiratory interruption. Mean and standard deviation of the ratios of glutamate+glutamine/lipids, phosphomonoesters/lipids, and glycogen+glucose/lipids were calculated from the area of their peaks. The proton MR spectroscopic findings of normal human livers showed four distinctive peaks, i.e. lipids, glutamate and glutamine complex, phosphomonoesters, and glycogen and glucose complex. The mean and standard deviation of the ratios of glutamate+glutamine/lipids, phosphomonoesters/lipids, and glycogen+glucose/lipids were 0.02±0.01, 0.01±0.01, and 0.04±0.03, respectively. In living normal human livers, MR spectroscopy can be successfully applied. When applied to a liver whose condition is pathologic, the findings can be used as a standard

Biophysical foundations for the study of the electrical excitability and action potential propagation in myocardium

International Nuclear Information System (INIS)

Suarez Antola, R.

1991-01-01

The electric current flow in the heterogeneous and anysotropic volume conductor of the myocardium is studied. The equations of bidomain theory are derived using an approach framed in the theory of averaged fields, introducing microscopic, mesoscopic and macroscopic spatial scales. However, the procedure, compatible with the histological and the anatomical details of the organ, is different from the multiple scale asymptotic expansions usually applied in homogeneization problems. A probabilistic approach framed in large numbers theorems is used to derive the equation for membrane ionic current from the stochastic activity of the channels at the microscopic level. An operational procedure suitable to define a sharp bidomain boundary from the fuzzy distribution of structural details and physical properties at the histological level is given. The problem of threshold is studied. The sizes and shapes of critical masses of cardiac cells that must be depolarized above threshold in order to produce a propagated action potential are determined by an approximate analytical procedure. The concept of family of threshold patterns for the emergence of action potentials in the heart is introduced. This concept is applied to discuss the conditions of emergence of ectopic focus. Analytical formulae are derived, for the time constant and the rheobase for electrical stimulation of the myocardium. These formulae are in good agreement with known experimental results. New experiments that could be done to confirm or reject them are suggested

Cardiac lymphoscintigraphy following closed-chest catheter injection of radiolabeled colloid into the myocardium of dogs: concise communication

International Nuclear Information System (INIS)

Osbakken, M.D.; Kopiwoda, S.Y.; Swan, A.; Castronovo, F.P.; Strauss, H.W.

1982-01-01

A catheter technique for injection of radiolabeled colloids into the myocardium was developed and tested in a series of 15 dogs. A multipurpose angiographic catheter was modified to permit an inner core of PE-50 polyethylene tubing, tipped with a 23-gage needle, to pass through the lumen for intra-myocardial injection of radiocolloids. For injection of the left ventricle, the catheter is introduced through the femoral artery: for the right ventricle, the femoral vein. The catheter advanced under fluoroscopy until the desired surface for injection is reached. The inner core is then extended to lodge the needle in the endocardium. A mixture of Renografin (to confirm the endocardial injection site) and radiolabeled colloid was injected in 13 animals. Ten minutes after injection, scintigraphy was begun and continued for up to 6 hr. In three dogs the procedure was repeated 3 or 4 times. From two to five nodes were visible in all animals, irrespective of whether the right or left ventricular myocardium was injected. In two animals the injection was given intravenously, and no nodes were seen. These data suggest that cardiac lymphatic drainage can be studied with a catheter injection method

Ultrastructural analysis of the structure and distribution of the adherens junctions in the rats’ ventricular myocardium during postnatal stages of ontogeny after the infl uence of chronic prenatal hypoxia

Directory of Open Access Journals (Sweden)

N. S. Petruk

2013-12-01

Full Text Available Background. Antenatal and prenatal hypoxia causes changes in all the organs of fetuses and newborns and in the heart, particularly. Hypoxic damage of the cardiovascular system occurs in 40-70% of newborns. Currently we observe the increase of meaning of the morphological studies for the prenatal diagnosis of human’s heart diseases. It’s known that in adaptive remodeling of cardiomyocytes in the postnatal cardiogenesis of rat redistribution of diffusely located intercellular junctions from the periphery to the terminal areas of the cell occurs. The formation of a definitive pattern of intercellular junctions is completed at the puberty. But how chronic prenatal hypoxia influences the specialized adherens junctions in the rats’ ventricular myocardium is completely unknown and this requires further study. Objective. To provide complex qualitative and quantitative comparative ultrastructural analysis of the intercellular connection changes in rat ventricular myocardium on the stages of postnatal ontogenesis in the norm and under the chronic fetal hypoxia. Materials and methods. We have conducted ultrastructural analysis and distribution of the adherens junctions in the rats’ ventricles on the 1st, 3rd, 7th, 14th, 30th days during postnatal ontogeny and among mature animals in the normal development and under the chronic fetal hypoxia. Experimental chronic hypoxia was modeled by intraperitoneal injection of 1% aqueous solution of the NaNO2 in a daily dose of 50 mg/kg of body weight in the term from 10th to 21st days of pregnancy. Transmission electron microscopy, morphometric and statistical methods were applied. Pairwise comparisons between means of different groups were performed using a Student t-test where, for each couple of normally distributed populations, the null hypothesis that the means are equal was verified. Results. Pronounced increase (80,6%; p <0,05 of the content of desmosomes in the intercalated disk in the period from 7th

Low-dose dobutamine stress gated SPET for identification of viable myocardium: comparison with stress-rest perfusion SPET and PET

International Nuclear Information System (INIS)

Yoshinaga, Keiichiro; Tamaki, Nagara; Katoh, Chietsugu; Kuge, Yuji; Noriyasu, Kazuyuki; Yamada, Satoshi; Ito, Yoshinori; Kohya, Tetsuro; Kitabatake, Akira; Kawai, Yuko

2002-01-01

The detection of viable myocardium is important for the prediction of functional recovery after revascularisation. However, a fixed perfusion defect often includes viable myocardium, and perfusion imaging then underestimates myocardial viability. We previously reported that low-dose dobutamine stress gated single-photon emission tomography (SPET) provides similar findings to dobutamine stress echocardiography in the assessment of myocardial viability. The present study investigated whether low-dose dobutamine stress gated SPET is of additional value as compared with stress-rest technetium-99m tetrofosmin SPET for the detection of myocardial viability. Standard stress-rest perfusion SPET, low-dose dobutamine stress gated SPET and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) were studied in 23 patients (mean age 67±7.6 years) with previous myocardial infarction. Twenty-one of them were successfully studied with each technique. FDG PET viability (FDG uptake ≥50%) was employed as the gold standard. One-day stress-rest 99m Tc-tetrofosmin myocardial SPET was performed. After the resting study, gated SPET was acquired following infusion of 7.5 μg kg -1 min -1 of dobutamine. Left ventricular wall motion in 16 segments was assessed by cine mode display using a four-point scale. Myocardial viability was considered present when there was improvement by one point. Of a total of 336 segments analysed, 53 had persistent defects on stress-rest perfusion SPET. FDG viability was seen in 16 of 17 dobutamine-responsive segments, but in only 11 of 36 dobutamine non-responsive segments (P<0.01). Thus, in the segments with persistent defects, viability findings on low-dose dobutamine stress gated SPET were concordant with those on FDG PET in 77% of segments (kappa value =0.55). For the detection of FDG-viable myocardium, the combination of stress-rest perfusion SPET and low-dose dobutamine stress gated SPET achieved a better sensitivity than stress

N-isopropyl-p-iodoamphetamine receptors in normal and cancerous tissue of the human lung

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Tanaka, Eiko; Mishima, Michiaki; Kawakami, Kenzo; Sakai, Naoki; Sugiura, Naoharu; Kuno, Kenshi [Kyoto Univ. (Japan). Dept. of Clinical Physiology; Taniguchi, Takashi [Kyoto Pharmaceutical Univ. (Japan). Dept. of Neurobiology

1993-04-01

N-Isopropyl-p-iodoamphetamine (IMP) receptors in normal human lung tissue were characterized using a radioligand binding assay with iodine-125 IMP as the ligand. Saturation binding studies revealed the presence of two binding sites with dissociation constant (K[sub d]) values of 53[+-]2 and 4687[+-]124 nM and maximum binding capacity (Bmax) values of 7[+-]1 and 133[+-]27 pmol/mg protein (n=5) respectively. The IC[sub 50] values of various amines were as follows: IMP, 9x10[sup -5] M; propranolol, 5x10[sup -4] M; haloperidol, 6x10[sup -4] M; ketamine, 9x10[sup -3] M; dopamine, 1x10[sup -2] M. The IMP receptors of cancerous tissue obtained from human lung also had two binding sites with K[sub d] values of 54[+-]2 and 5277[+-]652 nM and Bmax values of 7[+-]1 and 103[+-]21 pmol/mg protein (n=3) respectively. There was no significant difference in binding parameters between normal and cancerous lung tissue. These results demonstrate the existence of IMP receptors and suggest that cancer does not affect the nature of IMP receptors in human lung tissue. (orig.).

The kinetics of {beta}-methyl-substituted labelled fatty acids in ischaemic myocardium: an analysis in man and with a blood-perfused isolated heart model

Energy Technology Data Exchange (ETDEWEB)

Marie, P.Y.; Ayalew, A.; Hassan, N.; Olivier, P.; Karcher, G.; Bertrand, A. [Dept. of Nuclear Medicine, UPRES EA, Nancy (France); Menu, P. [Dept. of Hematology and Physiology, University Henri Poincare, Nancy (France); Angioi, M.; Mertes, P.M.; Danchin, N. [Dept. of Cardiology, UPRES EA, Nancy (France); Fagret, D. [Dept. of Nuclear Medicine, Grenoble (France); Pasqualini, R. [CIS Bio International, Gif-sur-Yvette (France)

1999-05-01

{beta}-Methyl-substituted free fatty acids (FFAs) have been developed for myocardial single-photon emission tomography (SPET) imaging, but little is known about their kinetics in ischaemic conditions. The aim of this study was to determine the changes in the myocardial kinetics of a {beta}-methyl-branched FFA, [{sup 123}I]16-iodo-3-methyl-hexadecanoic acid (MIHA), under ischaemic conditions. The kinetics of MIHA were analysed: (a) using a blood-perfused isolated heart model subjected to moderate ischaemia (50% flow reduction) and (b) in patients who had an exercise thallium-201 SPET defect corresponding to either necrotic (n = 13) or chronically ischaemic and viable (n = 15) myocardium, and who underwent two consecutive SPET studies after MIHA injection. In animals, the myocardial early retention fraction of MIHA, but not its clearance rate, was dependent on coronary flow, the early retention fraction being higher in ischaemic than in normoxic conditions (0.24{+-}0.10 vs 0.14{+-}0.04, P = 0.004). In the patient SPET studies, the uptake of MIHA calculated in ischaemic and viable areas (G1: 74%{+-}9% of maximal left ventricular value) was different from that calculated in necrotic (G2: 59%{+-}7%, P<0.001) or normal (G3: 88{+-}6%, P<0.001) areas. By contrast, MIHA-clearance calculated between the two consecutive SPET studies was not different in G1, G2 and G3. Unlike in the case of other FFAs, the myocardial clearance of MIHA is not decreased by ischaemia. However, the early retention of MIHA is increased in the case of a moderate reduction in coronary flow, a property which might help in the detection of viability in chronically ischaemic myocardium. (orig.) With 5 figs., 3 tabs., 44 refs.

Comparison of exercise and pharmacologic stress in myocardium perfusion imaging for CHD

International Nuclear Information System (INIS)

Li Zebo; Zheng Kangni; Cheng Xiaorui; Liu Hui; Cheng Yihai

1995-01-01

In order to provide a proper stress test, exercise, dipyridamole and ATP stress were compared. Three modalities were compared with respect to the detecting rate, methodology, hemodynamic and side effects. There are no significant differences in their ability of detecting coronary heart disease (CHD) (P>0.05). Exercise stress causes an increase in heart rate, blood pressure and myocardium oxygen consumption. Pharmacologic stress cause a slight increase in heart rate, but a decrease in blood pressure (P<0.01). Exercise stress is a basic method with good image quality, but it needs a special equipment. Pharmacologic stress is an easier, cheaper and safer method, particularly useful for patients unable to perform exercise test

Effects of substrate availability on myocardial C-11 palmitate kinetics by positron emission tomography in normal subjects and patients with ventricular dysfunction

International Nuclear Information System (INIS)

Schelbert, H.R.; Henze, E.; Sochor, H.; Grossman, R.G.; Huang, S.C.; Barrio, J.R.; Schwaiger, M.; Phelps, M.E.

1986-01-01

The possibility of demonstrating noninvasively with C-11 palmitate and positron emission tomography (PET) changes in myocardial substrate metabolism in normal and diseased human myocardium in response to altered substrate availability in blood and disease-related abnormalities was examined in five normal volunteers and 16 patients with ventricular dysfunction. C-11 palmitate injection and serial PET imaging were performed after an overnight fast (control period) and again 2 hours later after oral glucose (50 gm). Myocardial C-11 time-activity curves from serial PET images revealed a biexponential clearance pattern. An early rapid phase, defined by relative size and clearance half-time, reflects C-11 palmitate oxidation and the late slow phase tracer deposition in the endogenous lipid pool. During the control period, the tracer fraction entering the early rapid phase averaged 47 +/- 13% (SD) in normal subjects and 45 +/- 12% in patients. Corresponding clearance half-times were 19 +/- 7 and 20 +/- 5 minutes, respectively. Heart rate and blood pressure remained unchanged after glucose, but plasma glucose levels rose by 72.5% in normal subjects and by 98.9% in patients, while free fatty acid levels fell by 72% and 42% respectively. In normal subjects, the tracer fraction in the early rapid phase fell by 43% (p less than 0.005) and the clearance half-time increased by 46%. In patients, the response of C-11 palmitate tissue kinetics to glucose was variable. In nine patients, it was similar to normal subjects while in the other seven patients, the tracer fraction entering the rapid clearance phase increased after glucose by 30% (p less than 0.05) associated with a 36% (p less than 0.05) decline in clearance half-times. This was unrelated to disease etiology or plasma substrate levels but occurred mostly in left ventricles with more severely depressed function

The role of CD133 in normal human prostate stem cells and malignant cancer-initiating cells.

Science.gov (United States)

Vander Griend, Donald J; Karthaus, Wouter L; Dalrymple, Susan; Meeker, Alan; DeMarzo, Angelo M; Isaacs, John T

2008-12-01

Resolving the specific cell of origin for prostate cancer is critical to define rational targets for therapeutic intervention and requires the isolation and characterization of both normal human prostate stem cells and prostate cancer-initiating cells (CIC). Single epithelial cells from fresh normal human prostate tissue and prostate epithelial cell (PrEC) cultures derived from them were evaluated for the presence of subpopulations expressing stem cell markers and exhibiting stem-like growth characteristics. When epithelial cell suspensions containing cells expressing the stem cell marker CD133+ are inoculated in vivo, regeneration of stratified human prostate glands requires inductive prostate stromal cells. PrEC cultures contain a small subpopulation of CD133+ cells, and fluorescence-activated cell sorting-purified CD133+ PrECs self-renew and regenerate cell populations expressing markers of transit-amplifying cells (DeltaNp63), intermediate cells (prostate stem cell antigen), and neuroendocrine cells (CD56). Using a series of CD133 monoclonal antibodies, attachment and growth of CD133+ PrECs requires surface expression of full-length glycosylated CD133 protein. Within a series of androgen receptor-positive (AR+) human prostate cancer cell lines, CD133+ cells are present at a low frequency, self-renew, express AR, generate phenotypically heterogeneous progeny negative for CD133, and possess an unlimited proliferative capacity, consistent with CD133+ cells being CICs. Unlike normal adult prostate stem cells, prostate CICs are AR+ and do not require functional CD133. This suggests that (a) AR-expressing prostate CICs are derived from a malignantly transformed intermediate cell that acquires "stem-like activity" and not from a malignantly transformed normal stem cell and (b) AR signaling pathways are a therapeutic target for prostate CICs.

[Differential gene expression profile in ischemic myocardium of Wistar rats with acute myocardial infarction: the study on gene construction, identification and function].

Science.gov (United States)

Guo, Chun Yu; Yin, Hui Jun; Jiang, Yue Rong; Xue, Mei; Zhang, Lu; Shi, Da Zhuo

2008-06-18

To construct the differential genes expressed profile in the ischemic myocardium tissue reduced from acute myocardial infarction(AMI), and determine the biological functions of target genes. AMI model was generated by ligation of the left anterior descending coronary artery in Wistar rats. Total RNA was extracted from the normal and the ischemic heart tissues under the ligation point 7 days after the operation. Differential gene expression profiles of the two samples were constructed using Long Serial Analysis of Gene Expression(LongSAGE). Real time fluorescence quantitative PCR was used to verify gene expression profile and to identify the expression of 2 functional genes. The activities of enzymes from functional genes were determined by histochemistry. A total of 15,966 tags were screened from the normal and the ischemic LongSAGE maps. The similarities of the sequences were compared using the BLAST algebra in NCBI and 7,665 novel tags were found. In the ischemic tissue 142 genes were significantly changed compared with those in the normal tissue (Ppathways of oxidation and phosphorylation, ATP synthesis and glycolysis. The partial genes identified by LongSAGE were confirmed using real time fluorescence quantitative PCR. Two genes related to energy metabolism, COX5a and ATP5e, were screened and quantified. Expression of two functional genes down-regulated at their mRNA levels and the activities of correlative functional enzymes decreased compared with those in the normal tissue. AMI causes a series of changes in gene expression, in which the abnormal expression of genes related to energy metabolism could be one of the molecular mechanisms of AMI. The intervention of the expressions of COX5a and ATP5e may be a new target for AMI therapy.

Effects of organophosphorus flame retardant TDCPP on normal human corneal epithelial cells: Implications for human health.

Science.gov (United States)

Xiang, Ping; Liu, Rong-Yan; Li, Chao; Gao, Peng; Cui, Xin-Yi; Ma, Lena Q

2017-11-01

Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is one of the most detected organophosphorus flame retardants (OPFRs) in the environment, especially in indoor dust. Continuous daily exposure to TDCPP-containing dust may adversely impact human cornea. However, its detrimental effects on human corneal epithelium are largely unknown. In this study, we investigated the cell apoptosis in normal human corneal epithelial cells (HCECs) after TDCPP exposure and elucidated the underlying molecular mechanisms. Our data indicated a dose-dependent decrease of cell viability after TDCPP exposure with LC 50 at 202 μg/mL. A concentration-dependent apoptotic sign was observed in HCECs after exposing to ≥2 μg/mL TDCPP. Endoplasmic reticulum stress induction was evidenced by up-regulation of its biomarker genes (ATF-4, CHOP, BiP, and XBP1). Furthermore, alternation of Bcl-2/Bax expression, mitochondrial membrane potential loss, cellular ATP content decrease, and caspase-3 and -9 activity increase were observed after exposing to 2 or 20 μg/mL TDCPP. Taken together, the data implicated the involvement of endoplasmic reticulum stress in TDCPP-induced HCEC apoptosis, probably mediated by mitochondrial apoptotic pathway. Our findings showed TDCPP exposure induced toxicity to human cornea. Due to TDCPP's presence at high levels in indoor dust, further study is warranted to evaluate its health risk on human corneas. Published by Elsevier Ltd.

Application of a New Robust ECG T-Wave Delineation Algorithm for the Evaluation of the Autonomic Innervation of the Myocardium

DEFF Research Database (Denmark)

Cesari, Matteo; Mehlsen, Jesper; Mehlsen, Anne-Birgitte

2016-01-01

T-wave amplitude (TWA) is a well know index of the autonomic innervation of the myocardium. However, until now it has been evaluated only manually or with simple and inefficient algorithms. In this paper, we developed a new robust single-lead electrocardiogram (ECG) T-wave delineation algorithm...

Ketone body metabolism in normal and diabetic human skeletal muscle

International Nuclear Information System (INIS)

Nosadini, R.; Avogaro, A.; Sacca, L.

1985-01-01

Although the liver is considered the major source of ketone bodies (KB) in humans, these compounds may also be formed by nonhepatic tissues. To study this aspect further, 3-[ 14 C]hydroxybutyrate (BOH) or [3- 14 C]acetoacetate (AcAc) were constantly infused after a priming dose and contemporaneous arterial and venous samples were taken at splanchnic, heart, kidney, and leg sites in eight normal subjects (N) undergoing diagnostic catheterization and at the forearm site in five normal and six ketotic diabetic (D) subjects. After 70 min of infusion, tracer and tracee levels of AcAc and BOH reached a steady state in the artery and vein in both normal and diabetic subjects. The venous-arterial (V-A) difference at the forearm step for cold KB was negligible both in normal and diabetic subjects, whereas for labeled KB it was approximately 10-fold higher in diabetic subjects (V-A AcAc, -31 +/- 7 and -270 +/- 34 dpm/ml in N and D, respectively; V-A BOH, -38 +/- 6 and -344 +/- 126 dpm/ml in N and D, respectively). The authors assumed that the V-A difference in tracer concentration was consistent with dilution of the tracer by newly synthesized tracee inside the muscle and calculated that the forearm muscle produces KB at a rate of 16.2 +/- 3.3 mumol/min in D and 0.9 +/- 0.9 mumol/min in N. These findings can be accounted for by the hypothesis that the disappearance flux of KB from circulation was replaced by an equivalent flux of KB entering the vein at the muscle step in D but not in N. Moreover, in N KB were not only produced but also utilized by the splanchnic area (39 +/- 9 mumol/min)

Radionuclide imaging in primary and secondary disorders of the myocardium

International Nuclear Information System (INIS)

Follansbee, W.P.

1987-01-01

The list of all potential causes of myocardial disease or injury is an extensive one: a condensed version is presented. Conceptually these processes can be categorized into those which are, or appear to be, primary to the myocardium and those which secondarily involve it. Nuclear imaging procedures, particularly those used to assess ventricular function, are in a general sense potentially applicable to the clinical evaluation of any of these entities. In certain of these conditions, however, nuclear cardiac procedures have a demonstrated or potential additional and more specific role for the diagnosis and quantification of the entity. A number of these, including coronary artery disease, valvular heart disease, cor pulmonale, and myocardial trauma, are the topics of other chapters and, therefore, are not dealt with further here. The remainder of the myocardial disorders in which nuclear imaging procedures have a recognized or potential specific role are the focus of this discussion

Mucous solids and liquid secretion by airways: studies with normal pig, cystic fibrosis human, and non-cystic fibrosis human bronchi

Science.gov (United States)

Martens, Chelsea J.; Inglis, Sarah K.; Valentine, Vincent G.; Garrison, Jennifer; Conner, Gregory E.

2011-01-01

To better understand how airways produce thick airway mucus, nonvolatile solids were measured in liquid secreted by bronchi from normal pig, cystic fibrosis (CF) human, and non-CF human lungs. Bronchi were exposed to various secretagogues and anion secretion inhibitors to induce a range of liquid volume secretion rates. In all three groups, the relationship of solids concentration (percent nonvolatile solids) to liquid volume secretion rate was curvilinear, with higher solids concentration associated with lower rates of liquid volume secretion. In contrast, the secretion rates of solids mass and water mass as functions of liquid volume secretion rates exhibited positive linear correlations. The y-intercepts of the solids mass-liquid volume secretion relationships for all three groups were positive, thus accounting for the higher solids concentrations in airway liquid at low rates of secretion. Predictive models derived from the solids mass and water mass linear equations fit the experimental percent solids data for the three groups. The ratio of solids mass secretion to liquid volume secretion was 5.2 and 2.4 times higher for CF bronchi than for pig and non-CF bronchi, respectively. These results indicate that normal pig, non-CF human, and CF human bronchi produce a high-percent-solids mucus (>8%) at low rates of liquid volume secretion (≤1.0 μl·cm−2·h−1). However, CF bronchi produce mucus with twice the percent solids (∼8%) of pig or non-CF human bronchi at liquid volume secretion rates ≥4.0 μl·cm−2·h−1. PMID:21622844

A coupled 3D-1D numerical monodomain solver for cardiac electrical activation in the myocardium with detailed Purkinje network

Science.gov (United States)

Vergara, Christian; Lange, Matthias; Palamara, Simone; Lassila, Toni; Frangi, Alejandro F.; Quarteroni, Alfio

2016-03-01

We present a model for the electrophysiology in the heart to handle the electrical propagation through the Purkinje system and in the myocardium, with two-way coupling at the Purkinje-muscle junctions. In both the subproblems the monodomain model is considered, whereas at the junctions a resistor element is included that induces an orthodromic propagation delay from the Purkinje network towards the heart muscle. We prove a sufficient condition for convergence of a fixed-point iterative algorithm to the numerical solution of the coupled problem. Numerical comparison of activation patterns is made with two different combinations of models for the coupled Purkinje network/myocardium system, the eikonal/eikonal and the monodomain/monodomain models. Test cases are investigated for both physiological and pathological activation of a model left ventricle. Finally, we prove the reliability of the monodomain/monodomain coupling on a realistic scenario. Our results underlie the importance of using physiologically realistic Purkinje-trees with propagation solved using the monodomain model for simulating cardiac activation.

Effects of sterilizing radiation dose on the amino acid composition of normal human Ig(G)

International Nuclear Information System (INIS)

Kaupert, N.L.; Mariano, E.E.

1981-01-01

In order to verify gamma radiation effect of 60 Co, samples of Normal human Ig(G) in a) pH 7 solutions with different concentrations, and b) in liophilized state, were irradiated. In both, the quali and quantitative amino acid compositions have been studied. No changes in amino acid composition were observed, for doses up to 10 Mrad delivered to the liophilized samples. Nevertheless, when 5 mg/ml and 10 mg/ml solutions of Ig(G) were irradiated with a 2 Mrad gamma dose, both were affected. The damage appeared in greater proportion in the samples with lower concentration. Cistine was the amino acid most damaged and the loss of methionine, proline histidine, arginine, tirosine and phenilalanine, decreased in this order. The analysis of the experimental data shows that liophilized human Ig(G) can be treated with doses higher than those required to achieve sterilization, without modifying its immunologic and primary proteic structure properties. Therefore, gamma sterilization feasibility has been proved for normal human Ig(G) only in the liophilized state. (author) [es

Ex vivo 2D and 3D HSV-2 infection model using human normal vaginal epithelial cells.

Science.gov (United States)

Zhu, Yaqi; Yang, Yan; Guo, Juanjuan; Dai, Ying; Ye, Lina; Qiu, Jianbin; Zeng, Zhihong; Wu, Xiaoting; Xing, Yanmei; Long, Xiang; Wu, Xufeng; Ye, Lin; Wang, Shubin; Li, Hui

2017-02-28

Herpes simplex virus type 2 (HSV-2) infects human genital mucosa and establishes life-long latent infection. It is unmet need to establish a human cell-based microphysiological system for virus biology and anti-viral drug discovery. One of barriers is lacking of culture system of normal epithelial cells in vitro over decades. In this study, we established human normal vaginal epithelial cell (HNVEC) culture using co-culture system. HNVEC cells were then propagated rapidly and stably in a defined culture condition. HNVEC cells exhibited a normal diploid karyotype and formed the well-defined and polarized spheres in matrigel three-dimension (3D) culture, while malignant cells (HeLa) formed disorganized and nonpolar solid spheres. HNVEC cells had a normal cellular response to DNA damage and had no transforming property using soft agar assays. HNVEC expressed epithelial marker cytokeratin 14 (CK14) and p63, but not cytokeratin 18 (CK18). Next, we reconstructed HNVEC-derived 3D vaginal epithelium using air-liquid interface (ALI) culture. This 3D vaginal epithelium has the basal and apical layers with expression of epithelial markers as its originated human vaginal tissue. Finally, we established an HSV-2 infection model based on the reconstructed 3D vaginal epithelium. After inoculation of HSV-2 (G strain) at apical layer of the reconstructed 3D vaginal epithelium, we observed obvious pathological effects gradually spreading from the apical layer to basal layer with expression of a viral protein. Thus, we established an ex vivo 2D and 3D HSV-2 infection model that can be used for HSV-2 virology and anti-viral drug discovery.

Lethality and the depression on DNA synthesis in UV-irradiated normal human and xeroderma pigmentosum cells

Energy Technology Data Exchange (ETDEWEB)

Shinohara, K. (Kobe Univ. (Japan). School of Medicine)

1983-12-01

Ultraviolet radiation suppresses the semiconservative DNA replication in mammalian cells. The rate of DNA synthesis is initially depressed and later recovers after low doses of UV radiation in human cells. Such a response is more sensitive to UV radiation in cells derived from patients with xeroderma pigmentosum (XP) than that in normal human cells. The relative rate of DNA synthesis is not always correlated with cell survival because, unlike cell survival, the dose-response curve of the relative rate of DNA synthesis shows the biphasic nature of the sensitivity. In the experiments reported herein, the total amount (not the rate) of DNA synthesized during a long interval of incubation which covers the period of inhibition and recovery (but not longer than one generation time) after irradiation with various doses of UV radiation was examined in normal human and XP cells, and was found to be well correlated with cell survival in all the cells tested.

[Effect of medicines for activating blood and reinforcing Qi on angiogenesis in infarcted myocardium edge area of acute myocardial infarction model in rats].

Science.gov (United States)

Zang, Wen-Hua; Yin, Shen-Hua; Tang, De-Cai; Li, Bing-Bing

2014-03-01

To study the effect of medicines for activating blood and reinforcing Qi on the number of new micro-vessels and the protein expressions of VEGF and bFGF in the infarcted myocardium edge area of acute myocardial infarction (AMI) model in rats. The AMI model of rats was established. After the successful model establishment, rats were randomly divided into the sham-operated group, the model group, the Danshen-Huangqi (1 : 2) group, the Danshen-Huangqi (1 : 1) group, the Chuanxiong-Huangqi (1 : 2) group, the Danshen group, the Chuanxiong group, the Chishao group and the Shexiang Baoxin pill group, with five rats in each group. Rats in each medicated group were orally administered with drugs as per 13.5 g x kg(-1) x d(-1) once everyday for three weeks. The immunohistochemical SP method was adopted to detect the expression of vWF in myocardial tissues, and count the number of micro-vessels (MVC). The protein expression of VEGF and bFGF in myocardial tissues were determined by Western blot. The new micro-vessels stained by vWF factor could be found in the infarcted myocardium edge area of the sham-operated group, the model group and all of medicated groups. The sham-operated group show unobvious new micro-vessels in myocardial tissues. A small amount of new micro-vessels could be seen in the infarcted myocardium edge area of the model group. Whereas a larger number of micro-vessels could be seen in the infarcted myocardium edge area of all of medicated groups. The differences between the sham-operated group and the model group had statistical significance (P effect in promoting angiogenesis. Their mechanism for promoting angiogenesis may be related to the improvement of the protein expressions of VEGF and bFGF, so as to increase the contents of VEGF and bFGF and promote the angiogenesis of new vessels.

Effects of telmisartan on the expression of NADPH oxidase subunits in the myocardium of type 2 diabetic rats

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Jia-wei LI

2011-10-01

Full Text Available Objective To explore the effect of telmisartan on the expression of NADPH oxidase subunits p22phox and NOX4 in the myocardiam of type 2 diabetic rats.Methods Thirty-six male Wistar rats were randomly divided into two groups: normal control group(group A,n=10,diabetic model group(n=26.Type 2 diabetic model was established by high-fat and high-sugar diet followed by intraperitoneal injection of a low dose of streptozotocin(STZ.After the model was reproduced successfully,20 diabetic rats were randomly divided into diabetic subgroup(group B,n=10 and telmisartan-treated subgroup(group C,n=10.Rats in group C were orally administered telmisartan(5mg/kg/d,and rats in group A and B were given equivalent volume of normal saline.All rats were sacrificed 12 weeks after treatment.The mRNA expressions of myocardial p22phox and NOX4 were detected by real-time fluorescence quantitative PCR,and the protein expressions of myocardial connective tissue growth factor(CTGF and copper-zinc-superoxide dismutase(Cu-Zn-SOD were detected by immunohistochemical staining.Results Compared with group A,the ratio of heart/body weight,the mRNA expression of myocardial p22phox and NOX4,and the protein expression of myocardial CTGF increased significantly in group B,and the protein expression of myocardial Cu-Zn-SOD decreased significantly(P 0.05.Conclusions Telmisartan can down-regulate the over-expression of myocardial NOX4 and p22phox mRNA in type 2 diabetic rats,lessen the myocardial damage induced by oxidative stress,thus plays a protective role in the myocardium of diabetic rats.

Combined evaluation of rest-redistribution thallium-201 tomography and low-dose dobutamine echocardiography enhances the identification of viable myocardium in patients with chronic coronary artery disease

International Nuclear Information System (INIS)

Pace, L.; Cuocolo, A.; Salvatore, M.; Perrone-Filardi, P.; Prastaro, M.; Vezzuto, P.; Crisci, T.; Dellegrottaglie, S.; Piscione, F.; Chiariello, M.; Mainenti, P.P.; Varrone, A.

1998-01-01

The purpose of this study was to evaluate whether combined evaluation by discriminant analysis of rest-redistribution thallium-201 tomography and low-dose dobutamine echocardiography enhances the accuracy in identifying viable myocardium in patients with chronic coronary artery disease. Rest-redistribution 201 Tl has high sensitivity but low specificity in identifying viable myocardium, while the opposite is true for low-dose dobutamine echocardiography. Forty-six patients underwent low-dose dobutamine echocardiography and rest-redistribution 201 Tl tomography on the same day. Rest echocardiography was repeated at least 30 days (mean 40±20) after myocardial revascularization. Discriminant analysis was applied to the results of 201 Tl tomography and dobutamine echocardiography to classify a/dyskinetic segments as viable or non-viable. In 92 a/dyskinetic segments that were revascularized, rest-redistribution 201 Tl tomography yielded an accuracy of 75%, while the accuracy of dobutamine echocardiography was 70% (P 201 Tl imaging are useful and complementary techniques for identifying viable myocardium in patients with chronic coronary artery disease. Combined evaluation by discriminant analysis significantly improves accuracy, although the cost-effectiveness of such an approach remains to be determined. (orig.)

Reproducible pattern of microRNA in normal human skin

DEFF Research Database (Denmark)

Holst, Line; Kaczkowski, Bogumil; Gniadecki, Robert

2010-01-01

RNA expression pattern in normal human skin. Here we investigated miRNA expression profiles from skin biopsies of 8 healthy volunteers taken from sun protected and mildly photo damaged skin using the modified protocol for miRNA extraction. We were able to show a constant pattern of miRNA expression between......MicroRNAs (miRNAs) regulate cell growth, differentiation and apoptosis via specific targeting of messenger RNA (mRNA). Aberrant mRNA expression contributes to pathological processes such as carcinogenesis. To take advantage of miRNA profiling in skin disease it is essential to investigate mi...... different individuals. We did not find any significant differences in miRNA expression between sun protected and mildly photodamaged skin. These results may be valuable for future design of studies on miRNA expression in skin disease....

Impedance planimetric description of normal rectoanal motility in humans

DEFF Research Database (Denmark)

Andersen, Inge S; Michelsen, Hanne B; Krogh, Klaus

2007-01-01

PURPOSE: Manometry and pressure-volume measurements are commonly used to study anorectal physiology. However, the methods are limited by several sources of error. Recently, a new impedance planimetric system has been introduced in a porcine model. It allows simultaneous determination of anorectal...... pressures and multiple rectal luminal cross-sectional areas. This study was designed to study normal human rectoanal motility by means of impedance planimetry with multiple rectal cross-sectional areas and rectal and anal pressure. METHODS: Twelve healthy volunteers (10 females), aged 24 to 53 years, were...... the experiment, the cross-sectional area at all channels showed strong cyclic contractile activity and the anal pressure increased by approximately 100 percent. CONCLUSIONS: The new rectal impedance planimetry system allows highly detailed description of rectoanal motility patterns. It has promise as a new...

Reproducible pattern of microRNA in normal human skin

DEFF Research Database (Denmark)

Holst, Line; Kaczkowski, Bogumil; Gniadecki, Robert

2010-01-01

RNA expression pattern in normal human skin. Here we investigated miRNA expression profiles from skin biopsies of 8 healthy volunteers taken from sun protected and mildly photo damaged skin using the modified protocol for miRNA extraction. We were able to show a constant pattern of miRNA expression between...... different individuals. We did not find any significant differences in miRNA expression between sun protected and mildly photodamaged skin. These results may be valuable for future design of studies on miRNA expression in skin disease.......MicroRNAs (miRNAs) regulate cell growth, differentiation and apoptosis via specific targeting of messenger RNA (mRNA). Aberrant mRNA expression contributes to pathological processes such as carcinogenesis. To take advantage of miRNA profiling in skin disease it is essential to investigate mi...

Ginsenoside Rg3 induces DNA damage in human osteosarcoma cells and reduces MNNG-induced DNA damage and apoptosis in normal human cells.

Science.gov (United States)

Zhang, Yue-Hui; Li, Hai-Dong; Li, Bo; Jiang, Sheng-Dan; Jiang, Lei-Sheng

2014-02-01

Panax ginseng is a Chinese medicinal herb. Ginsenosides are the main bioactive components of P. ginseng, and ginsenoside Rg3 is the primary ginsenoside. Ginsenosides can potently kill various types of cancer cells. The present study was designed to evaluate the potential genotoxicity of ginsenoside Rg3 in human osteosarcoma cells and the protective effect of ginsenoside Rg3 with respect to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced DNA damage and apoptosis in a normal human cell line (human fibroblasts). Four human osteosarcoma cell lines (MG-63, OS732, U-2OS and HOS cells) and a normal human cell line (human fibroblasts) were employed to investigate the cytotoxicity of ginsenosides Rg3 by MTT assay. Alkaline comet assay and γH2AX focus staining were used to detect the DNA damage in MG-63 and U-2OS cells. The extent of cell apoptosis was determined by flow cytometry and a DNA ladder assay. Our results demonstrated that the cytotoxicity of ginsenoside Rg3 was dose-dependent in the human osteosarcoma cell lines, and MG-63 and U-2OS cells were the most sensitive to ginsenoside Rg3. As expected, compared to the negative control, ginsenoside Rg3 significantly increased DNA damage in a concentration-dependent manner. In agreement with the comet assay data, the percentage of γH2AX-positive MG-63 and U-2OS cells indicated that ginsenoside Rg3 induced DNA double-strand breaks in a concentration-dependent manner. The results also suggest that ginsenoside Rg3 reduces the extent of MNNG-induced DNA damage and apoptosis in human fibroblasts.

Regulation of pigmentation by substrate elasticity in normal human melanocytes and melanotic MNT1 human melanoma cells.

Science.gov (United States)

Choi, Hyunjung; Kim, Mina; Ahn, Song Ih; Cho, Eun-Gyung; Lee, Tae Ryong; Shin, Jennifer H

2014-03-01

The elasticity of the cellular microenvironment is a key regulator of cellular physiology in many cell types. To investigate the effects of substrate stiffness on the pigmentation process, we cultured normal human melanocytes (NHM) and MNT1 melanoma cells on laminin-coated polydimethylsiloxane (PDMS) substrates of different stiffness. The dendricity of NHM and MNT1 cells was reduced as the substrate stiffness decreased, and the degree of melanosome transfer from NHM or MNT1 cells to normal human keratinocytes was decreased on softer substrates with the reduced dendricity. Gene and protein expressions of MITF, tyrosinase, TRP2, and gp100/PMEL17 exhibited a consistent decreasing trend with the decreasing stiffness. Because the stiffness sensing is mediated by focal adhesion complex through integrin receptors, we checked laminin specific integrin alpha 6 and p-FAK for MNT1 cells to observe that the substrate adhesion was weakened as the substrate stiffness decreased. Weaker adhesion on a softer substrate was accompanied by dynamic shape changes in MNT1 cells with higher speed and larger scattering. Dendritic MNT1 cells cultured on a stiffer substrate exhibited lower migration with smaller root mean squared displacement. These results demonstrate the possibility that skin pigmentation can be influenced by mechanical properties of the cellular microenvironment and can increase when the skin becomes stiff. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Multistep carcinogenesis of normal human fibroblasts. Human fibroblasts immortalized by repeated treatment with Co-60 gamma rays were transformed into tumorigenic cells with Ha-ras oncogenes.

Science.gov (United States)

Namba, M; Nishitani, K; Fukushima, F; Kimoto, T

1988-01-01

Two normal mortal human fibroblast cell strains were transformed into immortal cell lines, SUSM-1 and KMST-6, by treatment with 4-nitroquinoline 1-oxide (4NQO) and Co-60 gamma rays, respectively. These immortalized cell lines showed morphological changes of cells and remarkable chromosome aberrations, but neither of them grew in soft agar or formed tumors in nude mice. The immortal cell line, KMST-6, was then converted into neoplastic cells by treatment with Harvey murine sarcoma virus (Ha-MSV) or the c-Ha-ras oncogene derived from a human lung carcinoma. These neoplastically transformed cells acquired anchorage-independent growth potential and developed tumors when transplanted into nude mice. All the tumors grew progressively without regression until the animals died of tumors. In addition, the tumors were transplantable into other nude mice. Normal human fibroblasts, on the other hand, were not transformed into either immortal or tumorigenic cells by treatment with Ha-MSV or c-Ha-ras alone. Our present data indicate that (1) the chemical carcinogen, 4NQO, or gamma rays worked as an initiator of carcinogenesis in normal human cells, giving rise to immortality, and (2) the ras gene played a role in the progression of the immortally transformed cells to more malignant cells showing anchorage-independent growth and tumorigenicity. In other words, the immortalization process of human cells seems to be a pivotal or rate-limiting step in the carcinogenesis of human cells.

Effect of dioxin on normal and leukemic human hematopoietic cells

Energy Technology Data Exchange (ETDEWEB)

Lambertenghi-Deliliers, G.; Soligo, D. [Univ. degli Studi, Milan (Italy). Dipt. die Ematologia, Ospedale Maggiore Policlinico IRCCS; Fracchiolla, N.S. [Ospedale Maggiore Policlinico IRCCS, Milan (Italy). Dipt. di Ematologia; Servida, F. [Fondazione Matarelli, Milan (Italy); Bertazzi, P.A. [Istituti Clinici di Perfezionamento, Milan (Italy). Dipt. di Medicina del Lavoro

2004-09-15

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) arises from chlorination of phenolic substrates or from partial combustion of organic materials in the presence of chlorine sources. TCDD has a large number of biological effects such as long-lasting skin disease, cardiovascular disease, diabete and cancer. TCDD is the prototypical agonist of the aryl hydrocarbon receptor (AhR), a member of the erb-A family that also includes the receptors for steroids, thyroid hormones, peroxisome proliferators and retinoids. When bound to dioxin, the AhR can bind to DNA and alter the expression of some genes including cytokines and growth factors. In this study, we analyzed the effect of escalating doses of TCDD on human CD34{sup +} progenitor cells from the leukapheresis of normal donors stimulated with G-CSF as well as the human myeloid leukemic cell lines HL60 (promyelocytic leukemia) and K562 (chronic myelogenous leukemia). The possible specific modulation of gene expression induced by the TCDD exposure was then tested by means of microarray analyses.

Revisiting vocal perception in non-human animals: a review of vowel discrimination, speaker voice recognition, and speaker normalization

Directory of Open Access Journals (Sweden)

Buddhamas eKriengwatana

2015-01-01

Full Text Available The extent to which human speech perception evolved by taking advantage of predispositions and pre-existing features of vertebrate auditory and cognitive systems remains a central question in the evolution of speech. This paper reviews asymmetries in vowel perception, speaker voice recognition, and speaker normalization in non-human animals – topics that have not been thoroughly discussed in relation to the abilities of non-human animals, but are nonetheless important aspects of vocal perception. Throughout this paper we demonstrate that addressing these issues in non-human animals is relevant and worthwhile because many non-human animals must deal with similar issues in their natural environment. That is, they must also discriminate between similar-sounding vocalizations, determine signaler identity from vocalizations, and resolve signaler-dependent variation in vocalizations from conspecifics. Overall, we find that, although plausible, the current evidence is insufficiently strong to conclude that directional asymmetries in vowel perception are specific to humans, or that non-human animals can use voice characteristics to recognize human individuals. However, we do find some indication that non-human animals can normalize speaker differences. Accordingly, we identify avenues for future research that would greatly improve and advance our understanding of these topics.

Characterization of ultraviolet light-induced diphtheria toxin-resistant mutations in normal and Xeroderma pigmentosum human fibroblasts

International Nuclear Information System (INIS)

Glover, T.W.

1979-01-01

Quantitative mutagenesis studies in human cells have been severely limited by the lack of reliable genetic markers. Experiments were therefore performed to develop and characterize a better quantitative mutation assay for human cells. The uv-induction of diphtheria toxin resistant (DT/sup r/) mutations in normal and excision repair defective xeroderma pigmentosum (XP) fibroblasts has been quantitatively characterized. A concentration of diphtheria toxin to use in the selection of resistant mutants was determined whereby DT/sup r/ cells are cross-resistant to Pseudomonas aeurginosa exotoxin A, indicating mutants have altered elongation factor-2 (EF-2) which is not susceptible to ADP-ribosylation by either toxin. Results of this study indicate that XP fibroblasts have higher uv-induced mutation frequencies per unit uv-dose but similar frequencies per unit survival compared to normal cells as measured using a new genetic marker for quantitative mutagenesis. Furthermore, these results support a prediction of the mutation theory of cancer, namely, that cells from individuals with certain human syndromes that predispose the individual to cancer will have higher induced mutation frequencies than cells from non-susceptible individuals. This newly characterized genetic marker should be useful in quantitative mutagenesis studies in human cells

Mechanical properties of the normal human cartilage-bone complex in relation to age

DEFF Research Database (Denmark)

Ding, Ming; Dalstra, M; Linde, F

1998-01-01

OBJECTIVE: This study investigates the age-related variations in the mechanical properties of the normal human tibial cartilage-bone complex and the relationships between cartilage and bone. DESIGN: A novel technique was applied to assess the mechanical properties of the cartilage and bone by mea...... that are of importance for the understanding of the etiology and pathogenesis of degenerative joint diseases, such as arthrosis....

Reflectance spectrometry of normal and bruised human skins: experiments and modeling

International Nuclear Information System (INIS)

Kim, Oleg; Alber, Mark; McMurdy, John; Lines, Collin; Crawford, Gregory; Duffy, Susan

2012-01-01

A stochastic photon transport model in multilayer skin tissue combined with reflectance spectroscopy measurements is used to study normal and bruised skins. The model is shown to provide a very good approximation to both normal and bruised real skin tissues by comparing experimental and simulated reflectance spectra. The sensitivity analysis of the skin reflectance spectrum to variations of skin layer thicknesses, blood oxygenation parameter and concentrations of main chromophores is performed to optimize model parameters. The reflectance spectrum of a developed bruise in a healthy adult is simulated, and the concentrations of bilirubin, blood volume fraction and blood oxygenation parameter are determined for different times as the bruise progresses. It is shown that bilirubin and blood volume fraction reach their peak values at 80 and 55 h after contusion, respectively, and the oxygenation parameter is lower than its normal value during 80 h after contusion occurred. The obtained time correlations of chromophore concentrations in developing contusions are shown to be consistent with previous studies. The developed model uses a detailed seven-layer skin approximation for contusion and allows one to obtain more biologically relevant results than those obtained with previous models using one- to three-layer skin approximations. A combination of modeling with spectroscopy measurements provides a new tool for detailed biomedical studies of human skin tissue and for age determination of contusions. (paper)

Magnetic resonance imaging in patients with unstable angina: comparison with acute myocardial infarction and normals

International Nuclear Information System (INIS)

Ahmad, M.; Johnson, R.F. Jr.; Fawcett, H.D.; Schreiber, M.H.

1988-01-01

The role of magnetic resonance imaging in characterizing normal, ischemic and infarcted segments of myocardium was examined in 8 patients with unstable angina, 11 patients with acute myocardial infarction, and 7 patients with stable angina. Eleven normal volunteers were imaged for comparison. Myocardial segments in short axis magnetic resonance images were classified as normal or abnormal on the basis of perfusion changes observed in thallium-201 images in 22 patients and according to the electrocariographic localization of infarction in 4 patients. T2 relaxation time was measured in 57 myocardial segments with abnormal perfusion (24 with reversible and 33 with irreversible perfusion changes) and in 25 normally perfused segments. T2 measurements in normally perfused segments of patients with acute myocardial infarction, unstable angina and stable angina were within normal range derived from T2 measurements in 48 myocardial segments of 11 normal volunteers (42 +/- 10 ms). T2 in abnormal myocardial segments of patients with stable angina also was not significantly different from normal. T2 of abnormal segments in patients with unstable angina (64 +/- 14 in reversibly ischemic and 67 +/- 21 in the irreversibly ischemic segments) was prolonged when compared to normal (p less than 0.0001) and was not significantly different from T2 in abnormal segments of patients with acute myocardial infarction (62 +/- 18 for reversibly and 66 +/- 11 for irreversibly ischemic segments). The data indicate that T2 prolongation is not specific for acute myocardial infarction and may be observed in abnormally perfused segments of patients with unstable angina

Effects of hyperthermia and ionizing radiation in normal and ataxia telangiectasia human fibroblast lines

International Nuclear Information System (INIS)

Mitchel, R.E.J.; Chan, A.; Smith, B.P.; Child, S.D.; Paterson, M.C.

1984-01-01

The effects of 45 0 C hyperthermia and γ radiation have been studied in three normal human fibroblast lines (GM38, GM730, WI38) and compared to the effects in two lines derived from patients with the hereditary disease ataxia telangiectasia (AR3BI, AT5BI). All lines, both normal and γ-sensitive AT, showed a similar resistance to killing by heat alone, suggesting that the defect responsible for the increased radiation sensitivity in AT lines does not confer increased heat sensitivity. Shouldered survival curves were obtained in each case indicating the ability to accumulate sublethal heat damage. All normal and AT cell lines exhibited increased resistance to the lethal effects of heat in response to a thermal stress, indicating that the defect that causes radiosensitivity in AT cell lines does not prevent the induction of thermotolerance. It was hypothesized that in normal cells, this heat treatment inactivates the process which is already defective in AT lines, and that this process may be required for the proper rejoining of double-strand breaks produced during the repair of other radiation-induced lesions

Finite element based nonlinear normalization of human lumbar intervertebral disc stiffness to account for its morphology.

Science.gov (United States)

Maquer, Ghislain; Laurent, Marc; Brandejsky, Vaclav; Pretterklieber, Michael L; Zysset, Philippe K

2014-06-01

Disc degeneration, usually associated with low back pain and changes of intervertebral stiffness, represents a major health issue. As the intervertebral disc (IVD) morphology influences its stiffness, the link between mechanical properties and degenerative grade is partially lost without an efficient normalization of the stiffness with respect to the morphology. Moreover, although the behavior of soft tissues is highly nonlinear, only linear normalization protocols have been defined so far for the disc stiffness. Thus, the aim of this work is to propose a nonlinear normalization based on finite elements (FE) simulations and evaluate its impact on the stiffness of human anatomical specimens of lumbar IVD. First, a parameter study involving simulations of biomechanical tests (compression, flexion/extension, bilateral torsion and bending) on 20 FE models of IVDs with various dimensions was carried out to evaluate the effect of the disc's geometry on its compliance and establish stiffness/morphology relations necessary to the nonlinear normalization. The computed stiffness was then normalized by height (H), cross-sectional area (CSA), polar moment of inertia (J) or moments of inertia (Ixx, Iyy) to quantify the effect of both linear and nonlinear normalizations. In the second part of the study, T1-weighted MRI images were acquired to determine H, CSA, J, Ixx and Iyy of 14 human lumbar IVDs. Based on the measured morphology and pre-established relation with stiffness, linear and nonlinear normalization routines were then applied to the compliance of the specimens for each quasi-static biomechanical test. The variability of the stiffness prior to and after normalization was assessed via coefficient of variation (CV). The FE study confirmed that larger and thinner IVDs were stiffer while the normalization strongly attenuated the effect of the disc geometry on its stiffness. Yet, notwithstanding the results of the FE study, the experimental stiffness showed consistently

Quantitative analysis of normal thallium-201 tomographic studies

International Nuclear Information System (INIS)

Eisner, R.L.; Gober, A.; Cerqueira, M.

1985-01-01

To determine the normal (nl) distribution of Tl-201 uptake post exercise (EX) and at redistribution (RD) and nl washout, Tl-201 rotational tomographic (tomo) studies were performed in 40 subjects: 16 angiographic (angio) nls and 24 nl volunteers (12 from Emory and 12 from Yale). Oblique angle short axis slices were subjected to maximal count circumferential profile analysis. Data were displayed as a ''bullseye'' functional map with the apex at the center and base at the periphery. The bullseye was not uniform in all regions because of the variable effects of attenuation and resolution at different view angles. In all studies, the septum: lateral wall ratio was 1.0 in males and approximately equal to 1.0 in females. This occurred predominantly because of anterior defects due to breast soft tissue attenuation. EX and RD bullseyes were similar. Using a bi-exponential model for Tl kinetics, 4 hour normalized washout ranged 49-54% in each group and showed minimal variation between walls throughout the bullseye. Thus, there are well defined variations in Tl-201 uptake in the nl myocardium which must be taken into consideration when analyzing pt data. Because of these defects and the lack of adequate methods for attenuation correction, quantitative analysis of Tl-201 studies must include direct comparison with gender-matched nl data sets

Modulation of ephrinB2 leads to increased angiogenesis in ischemic myocardium and endothelial cell proliferation

International Nuclear Information System (INIS)

Mansson-Broberg, Agneta; Siddiqui, Anwar J.; Genander, Maria; Grinnemo, Karl-Henrik; Hao Xiaojin; Andersson, Agneta B.; Waerdell, Eva; Sylven, Christer; Corbascio, Matthias

2008-01-01

Eph/ephrin signaling is pivotal in prenatal angiogenesis while its potential role in postnatal angiogenesis largely remains to be explored. Therefore its putative angiogenic and therapeutic effects were explored in endothelium and in myocardial ischemia. In culture of human aortic endothelial cells the fusion protein ephrinB2-Fc induced cell proliferation (p < 0.0005) and in the murine aortic ring model ephrinB2-Fc induced increased sprouting (p < 0.05). Myocardial infarction was induced by ligation of the left anterior descending artery in mouse. During the following 2 weeks mRNA of the receptor/ligand pair EphB4/ephrinB2 was expressed dichotomously (p < 0.05) and other Eph/ephrin pairs were expressed to a lesser degree. Twenty-four hours after intraperitoneal administration of ephrinB2-Fc it was detected in abundance throughout the myocardium along capillaries, showing signs of increased mitosis. After 4 weeks the capillary density was increased 28% in the periinfarcted area (p < 0.05) to a level not different from healthy regions of the heart where no change was observed. These results implicate that EphB4/ephrinB2 is an important signaling pathway in ischemic heart disease and its modulation may induce therapeutic angiogenesis

Human Pluripotent Stem Cell Differentiation into Functional Epicardial Progenitor Cells

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Juan Antonio Guadix

2017-12-01

Full Text Available Summary: Human pluripotent stem cells (hPSCs are widely used to study cardiovascular cell differentiation and function. Here, we induced differentiation of hPSCs (both embryonic and induced to proepicardial/epicardial progenitor cells that cover the heart during development. Addition of retinoic acid (RA and bone morphogenetic protein 4 (BMP4 promoted expression of the mesodermal marker PDGFRα, upregulated characteristic (proepicardial progenitor cell genes, and downregulated transcription of myocardial genes. We confirmed the (proepicardial-like properties of these cells using in vitro co-culture assays and in ovo grafting of hPSC-epicardial cells into chick embryos. Our data show that RA + BMP4-treated hPSCs differentiate into (proepicardial-like cells displaying functional properties (adhesion and spreading over the myocardium of their in vivo counterpart. The results extend evidence that hPSCs are an excellent model to study (proepicardial differentiation into cardiovascular cells in human development and evaluate their potential for cardiac regeneration. : The authors have shown that hPSCs can be instructed in vitro to differentiate into a specific cardiac embryonic progenitor cell population called the proepicardium. Proepicardial cells are required for normal formation of the heart during development and might contribute to the development of cell-based therapies for heart repair. Keywords: human pluripotent stem cells, proepicardium, progenitor cells, cardiovascular, differentiation

First-trimester maternal serum human thyroid-stimulating hormone in chromosomally normal and Down syndrome pregnancies

NARCIS (Netherlands)

Pratt, JJ; de Wolf, BTHM; Mantingh, A

Maternal serum human thyroid-stimulating hormone (TSH) levels were investigated in chromosomally normal and Down syndrome pregnancies to determine whether TSH can be used as a marker for Down syndrome in the first trimester. Measurements were conducted on stored serum samples collected from 23 Down

Necroscopic study of a Chagas' disease chronic case with normal electrocardiograms

International Nuclear Information System (INIS)

Lopes, E.R.; Rocha, A.; Adad, S.J.; Fernandes, E.L.; Chapadeiro, E.

1988-01-01

The morphological changes in the postmortem study of a man probably with the indeterminate form of Chagas' disease are described. The heart exhibited lesions of the epicardium, myocardium and endocardium, as well as of the conduction system, primarily small inflammatory foci. There was mild fibrosis of the myocardium, atrioventricular node, and left bundle branch (at its origin). These alterations, although mild, were similar, in quality, to those described in the other chronic forms of Chagas' disease, and suggest active lesions, with a potential for further development. In the esophagus, among other features, a striking reduction of the number of neurons was observed. (author)

Role of Insulin-like growth factors in initiation of follicle growth in normal and polycystic human ovaries.

Science.gov (United States)

Stubbs, Sharron A; Webber, Lisa J; Stark, Jaroslav; Rice, Suman; Margara, Raul; Lavery, Stuart; Trew, Geoffrey H; Hardy, Kate; Franks, Stephen

2013-08-01

Polycystic ovary syndrome (PCOS), the commonest cause of anovulatory infertility, is characterized by disordered follicle development including increased activation and accelerated growth of preantral follicles. Data from experimental animals and preliminary results from studies of human ovarian tissue suggest that IGFs affect preantral follicle development. Our objectives were to investigate the expression of the type-1 IGF receptor (IGFR-1) in the human ovary and to determine whether IGFs are involved in stimulating the transition of follicles from primordial to primary stage in normal and polycystic ovaries. We used archived ovarian tissue for protein expression studies and small cortical biopsies for follicle isolation and for tissue culture. This was a laboratory-based study, using clinical tissue samples. A total of 54 women, 33 with normal ovaries and 21 with polycystic ovaries, were classified by reference to menstrual cycle history and ultrasonography. We evaluated expression of IGFR-1 mRNA in isolated preantral follicles and of IGFR-1 protein in archived ovarian tissue samples from normal and polycystic ovaries and effects of exogenous IGF-1 on preantral follicle development and survival in cultured fragments of normal and polycystic ovaries. IGFR-1 mRNA and protein was expressed in preantral follicles at all stages of development and enhanced expression was noted in PCOS follicles during early preantral development. IGF-1 stimulated initiation of follicle growth in normal tissue but had little effect on preantral follicle growth in polycystic ovaries in which, characteristically, there was a higher proportion of follicles that had entered the growing phase even before culture. IGFs are plausible candidates in regulation of initiation of human follicle growth, and accelerated preantral follicle growth in PCOS may be due to increased activity of endogenous IGFs.

TOTAL NUMBER, DISTRIBUTION, AND PHENOTYPE OF CELLS EXPRESSING CHONDROITIN SULPHATE PROTEOGLYCANS IN THE NORMAL HUMAN AMYGDALA

Science.gov (United States)

Pantazopoulos, Harry; Murray, Elisabeth A.; Berretta, Sabina

2009-01-01

Chondroitin sulphate proteoglycans (CSPGs) are a key structural component of the brain extracellular matrix. They are involved in critical neurodevelopmental functions and are one of the main components of pericellular aggregates known as perineuronal nets. As a step toward investigating their functional and pathophysiological roles in the human amygdala, we assessed the pattern of CSPG expression in the normal human amygdala using wisteria floribunda agglutinin (WFA) lectin-histochemistry. Total numbers of WFA-labeled elements were measured in the lateral (LN), basal (BN), accessory basal (ABN) and cortical (CO) nuclei of the amygdala from 15 normal adult human subjects. For interspecies qualitative comparison, we also investigated the pattern of WFA labeling in the amygdala of naïve rats (n=32) and rhesus monkeys (Macaca mulatta; n=6). In human amygdala, WFA lectin-histochemistry resulted in labeling of perineuronal nets and cells with clear glial morphology, while neurons did not show WFA-labeling. Total numbers of WFA-labeled glial cells showed high interindividual variability. These cells aggregated in clusters with a consistent between-subjects spatial distribution. In a subset of human subjects (n=5), dual color fluorescence using an antibody raised against glial fibrillary acidic protein (GFAP) and WFA showed that the majority (93.7%) of WFA-labeled glial cells correspond to astrocytes. In rat and monkey amygdala, WFA histochemistry labeled perineuronal nets, but not glial cells. These results suggest that astrocytes are the main cell type expressing CSPGs in the adult human amygdala. Their highly segregated distribution pattern suggests that these cells serve specialized functions within human amygdalar nuclei. PMID:18374308

Dynamic knee alignment and collateral knee laxity and its variations in normal humans

Directory of Open Access Journals (Sweden)

Kamal eDeep

2015-11-01

Full Text Available Alignment of normal, arthritic and replaced human knees is a much debated subject as is the collateral ligamentous laxity. Traditional quantitative values have been challenged. Methods used to measure these are also not without flaws. Authors review the recent literature and a novel method of measurement of these values has been included. This method includes use of computer navigation technique in clinic setting for assessment of the normal or affected knee before the surgery. Computer navigation has been known for achievement of alignment accuracy during knee surgery. Now its use in clinic setting has added to the inventory of measurement methods. Authors dispel the common myth of straight mechanical axis in normal knees and also look at quantification of amount of collateral knee laxity. Based on the scientific studies it has been shown that the mean alignment is in varus in normal knees. It changes from lying non weight bearing position to standing weight bearing position in both coronal and the sagittal planes. It also varies with gender and race. The collateral laxity is also different for males and females. Further studies are needed to define the ideal alignment and collateral laxity which the surgeon should aim for individual knees.

Human BLCAP transcript: new editing events in normal and cancerous tissues.

Science.gov (United States)

Galeano, Federica; Leroy, Anne; Rossetti, Claudia; Gromova, Irina; Gautier, Philippe; Keegan, Liam P; Massimi, Luca; Di Rocco, Concezio; O'Connell, Mary A; Gallo, Angela

2010-07-01

Bladder cancer-associated protein (BLCAP) is a highly conserved protein among species, and it is considered a novel candidate tumor suppressor gene originally identified from human bladder carcinoma. However, little is known about the regulation or the function of this protein. Here, we show that the human BLCAP transcript undergoes multiple A-to-I editing events. Some of the new editing events alter the highly conserved amino terminus of the protein creating alternative protein isoforms by changing the genetically coded amino acids. We found that both ADAR1 and ADAR2-editing enzymes cooperate to edit this transcript and that different tissues displayed distinctive ratios of edited and unedited BLCAP transcripts. Moreover, we observed a general decrease in BLCAP-editing level in astrocytomas, bladder cancer and colorectal cancer when compared with the related normal tissues. The newly identified editing events, found to be downregulated in cancers, could be useful for future studies as a diagnostic tool to distinguish malignancies or epigenetic changes in different tumors.

Cell survival of human tumor cells compared with normal fibroblasts following 60Co gamma irradiation

International Nuclear Information System (INIS)

Lloyd, E.L.; Henning, C.B.; Reynolds, S.D.; Holmblad, G.L.; Trier, J.E.

1982-01-01

Three tumor cell lines, two of which were shown to be HeLa cells, were irradiated with 60 Co gamma irradiation, together with two cell cultures of normal human diploid fibroblasts. Cell survival was studied in three different experiments over a dose range of 2 to 14 gray. All the tumor cell lines showed a very wide shoulder in the dose response curves in contrast to the extremely narrow shoulder of the normal fibroblasts. In addition, the D/sub o/ values for the tumor cell lines were somewhat greater. These two characteristics of the dose response curves resulted in up to 2 orders of magnitude less sensitivity for cell inactivation of HeLa cells when compared with normal cells at high doses (10 gray). Because of these large differences, the extrapolation of results from the irradiation of HeLa cells concerning the mechanisms of normal cell killing should be interpreted with great caution

Adaptation of the cardiovascular system to postinfarction cardiosclerosis in rats with congenital adrenoreactivity of the myocardium.

Science.gov (United States)

Usacheva, M A; Popkova, E V; Smirnova, E A; Saltykova, V A; Belkina, L M

2007-12-01

Three months after myocardial infarction the severity of heart failure and size of postinfarction scars in August rats with inherently reduced adrenoreactivity of the myocardium were similar to those in Wistar rats. The mortality rate in August rats was 2.5-fold lower than in Wistar rats. During the postinfarction period, myocardial adrenoreactivity in August rats remained lower, while the efficiency of cardiac function was 62% higher than in Wistar rats. The incidence of epinephrine-induced arrhythmias in August rats was much lower than in Wistar rats.

Comparison of cerebral metabolism of glucose in normal human and cancer patients

International Nuclear Information System (INIS)

Si, M.

2007-01-01

Full text: Objective: To determine whether the cerebral metabolism in various regions of the normal human brain differs from those of cancer patients in aging by using 18F-FDG PET instrument and SPM software. Materials and Methods We reviewed clinical information of 295 healthy normal samples so called 'normal group' (ranging 21 to 88; mean age+/-SD: 50+/-14) and 290 cancer patients called 'cancer group' (ranging 21 to 85; mean age+/-SD: 54+/-14) who were examined by a whole body GE Discovery LS PET-CT instrument in our center from Aug. 2004 to Dec. 2005.They were selected with: (i) absence of clear focal brain lesions (epilepsy, cerebrovascular diseases etc.); (ii) absence of metabolic diseases, such as hyperthyroidism, hypothyroidism and diabetes; (iii) absence of psychiatric disorders and abuse of drugs and alcohol;( iiii) cancer patients were diagnosed definitely of variable cancers except brain cancer or brain metastasis. Both groups were sub grouped into six with the interval of 10 years old starting from 21, and the gender, educational background and serum glucose are matched. All 12 subgroups were compared to the subgroup of normal 31-40 years old called 'control subgroup' (84 samples; mean age+/-SD: 37.15+/- 2.63). All samples were injected with 18F-FDG (5.55MBq/kg), 45-60 minutes later; their brains were scanned for 10 minutes. Pixel-by-pixel t-statistic analysis was applied to all brain images using the Statistical parametric mapping (SPM2). The hypometabolic areas (p < 0. 01 or p<0.001, uncorrected) were identified in the Stereotaxic coordinate human brain atlas and three dimensional localized by MNI Space utility (MSU) software. Results:1.With increasing of age interval, similar hypometabolic brain areas are detected in both 'normal group' and 'cancer group', they are mainly in the cortical structures such as bilateral prefrontal cortex (BA9), superior temporal gyrus (BA22), parietal cortex (inferior parietal lobule and precuneus(BA40), insula (BA13

Do indices of coronary conductance after reperfusion reflect the extent of salvaged myocardium?

Science.gov (United States)

Shibata, Takahiro; Watanabe, Hisashi; Tsurusaki, Tetsushi; Minai, Kousuke; Ogawa, Takayuki; Iwano, Keiji; Tamura, Tetsutarou; Yoshida, Satoshi; Mutou, Makoto; Imai, Kamon; Horie, Toshinobu; Mochizuki, Seibu

2004-05-01

Existing indices of coronary conductance (hyperemic flow-versus-pressure slope index, FPSI, and zero flow pressure, Pzf) have been developed as measures of microcoronary resistance. These indices, however, refer to cases of normal hearts, and there are no reports studying these indices following acute myocardial infarction. In this study, we investigated whether FPSI and Pzf truly measure the extent of myocardial salvage after successful reperfusion therapy. We also developed a new index of zero pressure flow, Fzp. Nineteen patients who underwent successful reperfusion therapy to the proximal portion of the left anterior descending artery (LAD) were studied. After successful reperfusion therapy, a Doppler wire was placed into the LAD. Aortic pressure was recorded in real time. Results from the aortic pressure and flow meter were combined to produce FPSI, Pzf, and Fzp. All cases underwent a resting thallium (Tl) and BMIPP scintigram within five days of successful reperfusion therapy. Infarcted myocardium was estimated using a severity score calculated from the Tl scintigraphy (TlSS), and the BMIPP (BMIPPSS) was estimated using a severity score. Patients with a TlSS/BMIPPSS ratio of less than 0.4 were assigned to the successful salvage group (group S), while the others were assigned to the failed salvage group (group F). FPSI of group F was 1.91 +/- 0.26 m/sec and of group S was 0.92 +/- 0.43 m/sec (P < 0.01). Pzf of group F was 51 +/- 3 mmHg and of group S was 51 +/- 5 mmHg (NS). Fzp of group F was -98 +/- 16 cm/sec and of group S was -46 +/- 4 cm/sec (P < 0.05). FPSI and the new index of Fzp were useful in estimating the extent of myocardial salvage. Our results suggest that the Pzf index could not differentiate between the two groups.

Transfection of normal human bronchial epithelial cells with the bcl-2 oncogene

Energy Technology Data Exchange (ETDEWEB)

Kennedy, C.H.; Kenyon, K.D.; Tesfaigzi, J. [and others

1995-12-01

In vitro, studies examining the transformation of virus-immortalized human bronchial epithelial (HBE) cells after exposure to chemical and physical carcinogens have contributed to our understanding of the mechanisms that underlie the development of lung cancer. Virus-immortalized HBE cells have been used because of both the limited life span of normal human bronchial epithelial (NHBE) cells in culture (approximately 30-35 population doublins) and their resistance to in vitro malignant transformation. For example, human papillomavirus (HPV)-immortalized HBE cells have been used to study the genetic changes that occur after exposure to {alpha}-particles in vitro. Although this model may prove to be useful for studying the 18% or less of bronchogenic carcinomas found to contain HPV sequences, it is not an appropriate model for studying the majority of lung epithelial malignancies in which HPV DNA is not detected. This view is supported by the fact that HPV-immortalized cell lines commonly exhibit aneuploidy. This results of this study suggest that: (1) NHBE cells can be transiently transfected with the pCMV{Beta} vector; and (2) the antibiotic hygromycin-resistant transfected cells.

Transfection of normal human bronchial epithelial cells with the bcl-2 oncogene

International Nuclear Information System (INIS)

Kennedy, C.H.; Kenyon, K.D.; Tesfaigzi, J.

1995-01-01

In vitro, studies examining the transformation of virus-immortalized human bronchial epithelial (HBE) cells after exposure to chemical and physical carcinogens have contributed to our understanding of the mechanisms that underlie the development of lung cancer. Virus-immortalized HBE cells have been used because of both the limited life span of normal human bronchial epithelial (NHBE) cells in culture (approximately 30-35 population doublins) and their resistance to in vitro malignant transformation. For example, human papillomavirus (HPV)-immortalized HBE cells have been used to study the genetic changes that occur after exposure to α-particles in vitro. Although this model may prove to be useful for studying the 18% or less of bronchogenic carcinomas found to contain HPV sequences, it is not an appropriate model for studying the majority of lung epithelial malignancies in which HPV DNA is not detected. This view is supported by the fact that HPV-immortalized cell lines commonly exhibit aneuploidy. This results of this study suggest that: (1) NHBE cells can be transiently transfected with the pCMVΒ vector; and (2) the antibiotic hygromycin-resistant transfected cells

Fractional flow reserve guided percutaneous coronary intervention results in reduced ischemic myocardium and improved outcomes.

Science.gov (United States)

Sawant, Abhishek C; Bhardwaj, Aishwarya; Banerjee, Kinjal; Jobanputra, Yash; Kumar, Arnav; Parikh, Parth; Kandregula, Krishna C; Poddar, Kanhaiya; Ellis, Stephen G; Nair, Ravi; Corbelli, John; Kapadia, Samir

2018-02-06

To determine if fractional flow reserve guided percutaneous coronary intervention (FFR-guided PCI) is associated with reduced ischemic myocardium compared with angiography-guided PCI. Although FFR-guided PCI has been shown to improve outcomes, it remains unclear if it reduces the extent of ischemic myocardium at risk compared with angiography-guided PCI. We evaluated 380 patients (190 FFR-guided PCI cases and 190 propensity-matched controls) who underwent PCI from 2009 to 2014. Clinical, laboratory, angiographic, stress testing, and major adverse cardiac events [MACE] (all-cause mortality, recurrence of MI requiring PCI, stroke) data were collected. Mean age was 63 ± 11 years; the majority of patients were males (76%) and Caucasian (77%). Median duration of follow up was 3.4 [Range: 1.9, 5.0] years. Procedural complications including coronary dissection (2% vs. 0%, P = .12) and perforation (0% vs. 0%, P = 1.00) were similar between FFR-guided and angiography-guided PCI patients. FFR-guided PCI patients had lower unadjusted (14.7% vs. 23.2%, P = .04) and adjusted [OR = 0.58 (95% CI: 0.34-0.98)] risk of repeat revascularization at one year. FFR-guided PCI patients were less likely (23% vs. 32%, P = .02) to have ischemia and had lower (5.9% vs. 21.1%, P guided PCI, FFR-guided PCI results in less repeat revascularization and a lower incidence of post PCI ischemia translating into improved survival, without an increase in complications. © 2018 Wiley Periodicals, Inc.

A simulation study of the reaction of human heart to biphasic electrical shocks

Directory of Open Access Journals (Sweden)

Seemann Gunnar

2004-06-01

Full Text Available Abstract Background This article presents a study, which examines the effects of biphasic electrical shocks on human ventricular tissue. The effects of this type of shock are not yet fully understood. Animal experiments showed the superiority of biphasic shocks over monophasic ones in defibrillation. A mathematical computer simulation can increase the knowledge of human heart behavior. Methods The research presented in this article was done with different models representing a three-dimensional wedge of ventricular myocardium. The electrophysiology was described with Priebe-Beuckelmann model. The realistic fiber twist, which is specific to human myocardium was included. Planar electrodes were placed at the ends of the longest side of the virtual cardiac wedge, in a bath medium. They were sources of electrical shocks, which varied in magnitude from 0.1 to 5 V. In a second arrangement ring electrodes were placed directly on myocardium for getting a better view on secondary electrical sources. The electrical reaction of the tissue was generated with a bidomain model. Results The reaction of the tissue to the electrical shock was specific to the initial imposed characteristics. Depolarization appeared in the first 5 ms in different locations. A further study of the cardiac tissue behavior revealed, which features influence the response of the considered muscle. It was shown that the time needed by the tissue to be totally depolarized is much shorter when a biphasic shock is applied. Each simulation ended only after complete repolarization was achieved. This created the possibility of gathering information from all states corresponding to one cycle of the cardiac rhythm. Conclusions The differences between the reaction of the homogeneous tissue and a tissue, which contains cleavage planes, reveals important aspects of superiority of biphasic pulses. ...

Reconstruction and Visualization of Fiber and Laminar Structure inthe Normal Human Heart from Ex Vivo DTMRI Data

Energy Technology Data Exchange (ETDEWEB)

Rohmer, Damien; Sitek, Arkadiusz; Gullberg, Grant T.

2006-12-18

Background - The human heart is composed of a helicalnetwork of muscle fibers. These fibers are organized to form sheets thatare separated by cleavage surfaces. This complex structure of fibers andsheets is responsible for the orthotropic mechanical properties ofcardiac muscle. The understanding of the configuration of the 3D fiberand sheet structure is important for modeling the mechanical andelectrical properties of the heart and changes in this configuration maybe of significant importance to understand the remodeling aftermyocardial infarction.Methods - Anisotropic least square filteringfollowed by fiber and sheet tracking techniques were applied to DiffusionTensor Magnetic Resonance Imaging (DTMRI) data of the excised humanheart. The fiber configuration was visualized by using thin tubes toincrease 3-dimensional visual perception of the complex structure. Thesheet structures were reconstructed from the DTMRI data, obtainingsurfaces that span the wall from the endo- to the epicardium. Allvisualizations were performed using the high-quality ray-tracing softwarePOV-Ray. Results - The fibers are shown to lie in sheets that haveconcave or convex transmural structure which correspond to histologicalstudies published in the literature. The fiber angles varied depending onthe position between the epi- and endocardium. The sheets had a complexstructure that depended on the location within the myocardium. In theapex region the sheets had more curvature. Conclusions - A high-qualityvisualization algorithm applied to demonstrated high quality DTMRI datais able to elicit the comprehension of the complex 3 dimensionalstructure of the fibers and sheets in the heart.

Intramuscular injection of human umbilical cord-derived mesenchymal stem cells improves cardiac function in dilated cardiomyopathy rats.

Science.gov (United States)

Mao, Chenggang; Hou, Xu; Wang, Benzhen; Chi, Jingwei; Jiang, Yanjie; Zhang, Caining; Li, Zipu

2017-01-28

Stem cells provide a promising candidate for the treatment of the fatal pediatric dilated cardiomyopathy (DCM). This study aimed to investigate the effects of intramuscular injection of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) on the cardiac function of a DCM rat model. A DCM model was established by intraperitoneal injections of doxorubicin in Sprague-Dawley rats. hUCMSCs at different concentrations or cultured medium were injected via limb skeletal muscles, with blank medium injected as the control. The rats were monitored for 4 weeks, meanwhile BNP, cTNI, VEGF, HGF, GM-CSF, and LIF in the peripheral blood were examined by ELISA, and cardiac function was monitored by echocardiography (Echo-CG). Finally, the expression of IGF-1, HGF, and VEGF in the myocardium was examined by histoimmunochemistry and real-time PCR, and the ultrastructure of the myocardium was examined by electron microscopy. Injection of hUCMSCs markedly improved cardiac function in the DCM rats by significantly elevating left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS). The BNP and cTNI levels in the peripheral blood were reduced by hUCMSCs, while HGF, LIF, GM-CSF, and VEGF were increased by hUCMSCs. Expression of IGF-1, HGF, and VEGF in the myocardium from the DCM rats was significantly increased by hUCMSC injection. Furthermore, hUCMSCs protected the ultrastructure of cardiomyocytes by attenuating mitochondrial swelling and maintaining sarcolemma integrity. Intramuscular injection of UCMSCs can improve DCM-induced cardiac function impairment and protect the myocardium. These effects may be mediated by regulation of relevant cytokines in serum and the myocardium.

Occurrence of FSH, inhibin and other hypothalamic-pituitary-intestinal hormones in normal fertility, subfertility, and tumors of human testes.

Science.gov (United States)

Mehta, M K; Garde, S V; Sheth, A R

1995-01-01

To compare the distribution of peptide hormones in presumably normal human testicular tissues and specimens exhibiting any of five pathologies. Biopsies from patients having testicular malfunctions were prepared as sections and specifically immunohistochemically stained for inhibin, FSH, serotonin, AUP, and oxytocin. Immunocytochemical studies revealed the presence of various hypophysial-pituitary-intestinal hormones, viz., FSH, inhibin, arginine vasopressin (AVP), calcitonin, serotonin, oxytocin, adrenocorticotropin (ACTH), gastrin, secretin, and somatostatin in human testicular biopsies exhibiting normal spermatogenesis, Sertoli-cell-only syndrome, spermatogenic arrest, Leydig cell hyperplasia, Leydig cell tumor, and seminoma. Intensity of immunostaining for all peptides except FSH was stronger in cases of subfertile as compared to normal testis. Intensity of immunostaining with inhibin was maximum in Leydig cell tumor. These regulatory peptides may be involved in the pathophysiology of the testes.

Peculiarities of cardiac hemodynamics and functional state of left ventricular myocardium in teenagers with connective heart tissue dysplasia

Directory of Open Access Journals (Sweden)

Makhmudova F.M.

2011-03-01

Full Text Available The aim of investigation is to study heart hemodynamics in teenagers with connective tissue dysplasia of heart (CTDH. 35 patients ages 12 to 15 years with CTDH have been observed: Group I (n=14 are the patients with mitral valve prolapse (MVP without mitral regurgitation (MR and myxomatous degeneration(MD or isolated minor heart abnormalities (MHA, Group II (n=11are patients with MVP and MR in combination with 1 or2 MHA, and Group III (n=10 are patients with MVP and mixoid degeneration (MD in combination with 2 or more MHA. The control group consisted of 15 patients of the same age without MHA. All the children passed Doppler and echocardiography. According to the results significant changes of cardiohemodynamic indices in patients of Group I were not observed. The changes of size and volume indices of the left ventricle (LV, increase in wall thickness and diastolic dysfunction of the LV were observed in Group II. The significant changes of systolic function of left ventricular myocardium were observed in Group III. The study comes to the conclusion that teenagers with CTDH have definite changes of heart hemodynamics and functional state of left ventricular myocardium. These changes depend on mitral regurgitation, myxomatous degeneration and MHA combination

An Intron 9 CYP19 Gene Variant (IVS9+5G>A), Present in an Aromatase-Deficient Girl, Affects Normal Splicing and Is Also Present in Normal Human Steroidogenic Tissues.

Science.gov (United States)

Saraco, Nora; Nesi-Franca, Suzana; Sainz, Romina; Marino, Roxana; Marques-Pereira, Rosana; La Pastina, Julia; Perez Garrido, Natalia; Sandrini, Romolo; Rivarola, Marco Aurelio; de Lacerda, Luiz; Belgorosky, Alicia

2015-01-01

Splicing CYP19 gene variants causing aromatase deficiency in 46,XX disorder of sexual development (DSD) patients have been reported in a few cases. A misbalance between normal and aberrant splicing variants was proposed to explain spontaneous pubertal breast development but an incomplete sex maturation progress. The aim of this study was to functionally characterize a novel CYP19A1 intronic homozygote mutation (IVS9+5G>A) in a 46,XX DSD girl presenting spontaneous breast development and primary amenorrhea, and to evaluate similar splicing variant expression in normal steroidogenic tissues. Genomic DNA analysis, splicing prediction programs, splicing assays, and in vitro protein expression and enzyme activity analyses were carried out. CYP19A1 mRNA expression in human steroidogenic tissues was also studied. A novel IVS9+5G>A homozygote mutation was found. In silico analysis predicts the disappearance of the splicing donor site in intron 9, confirmed by patient peripheral leukocyte cP450arom and in vitro studies. Protein analysis showed a shorter and inactive protein. The intron 9 transcript variant was also found in human steroidogenic tissues. The mutation IVS9+5G>A generates a splicing variant that includes intron 9 which is also present in normal human steroidogenic tissues, suggesting that a misbalance between normal and aberrant splicing variants might occur in target tissues, explaining the clinical phenotype in the affected patient. © 2015 S. Karger AG, Basel.

Evaluation of the transforming growth factor-beta activity in normal and dry eye human tears by CCL-185 cell bioassay.

Science.gov (United States)

Zheng, Xiaofen; De Paiva, Cintia S; Rao, Kavita; Li, De-Quan; Farley, William J; Stern, Michael; Pflugfelder, Stephen C

2010-09-01

To develop a new bioassay method using human lung epithelial cells (CCL-185) to assess activity of transforming growth factor beta (TGF-beta) in human tear fluid from normal subjects and patients with dry eye. Two epithelial cell lines, mink lung cells (CCL-64) and human lung cells (CCL-185), were compared to detect the active form of TGF-beta by BrdU incorporation (quantitation of cell DNA synthesis) and WST assay (metabolic activity of viable cells). The effect of TGF-beta on the growth of CCL-185 cells was observed microscopically. Human tears from normal control subjects and patients with dry eye (DE) with and without Sjögren syndrome were evaluated for TGF-beta concentration by Luminex microbead assay, and TGF-beta activity by the CCL-185 cell growth inhibition bioassay. The metabolic activity of viable CCL-185 cells, measured by WST, was shown to be proportional to the TGF-beta1 concentration (R = 0.919) and confirmed by BrdU assay (R = 0.969). Compared with CCL-185, metabolic activity of viable cells and DNA synthesis, measured by WST and BrdU incorporation assays, were shown to be less proportional to the TGF-beta1 concentration in the CCL-64 line (R = 0.42 and 0.17, respectively). Coincubation with human anti-TGF-beta1 antibody (MAB-240) yielded a dose-dependent inhibition of TGF-beta1 (0.3 ng/mL) activity. CCL-185 cell growth observed microscopically was noted to decrease in response to increasing TGF-beta1 concentrations. Levels of immuodetectable TGF-beta1 and TGF-beta2 were similar in normal and DE tears. TGF-beta bioactivity in DE human tears measured by the CCL-185 cells assay was found to be higher (9777.5 +/- 10481.9 pg/mL) than those in normal controls (4129.3 +/- 1342.9 pg/mL) (P tears and 37.6% TGF-beta in normal tears were found to be biologically active. The CCL-185 cell assay was found to be a suitable tool for assessing TGF-beta activity in human tears. Tear TGF-beta bioactivity increases in DE, particularly in Sjögren syndrome, where

Myocardial pre-synaptic sympathetic function correlates with glucose uptake in the failing human heart

Energy Technology Data Exchange (ETDEWEB)

Mongillo, Marco; Leccisotti, Lucia [Hammersmith Hospital, Medical Research Council Clinical Sciences Centre, Imperial College Faculty of Medicine, London (United Kingdom); John, Anna S. [Hammersmith Hospital, National Heart and Lung Institute, Imperial College, London (United Kingdom); Pennell, Dudley J. [Royal Brompton Hospital, National Heart and Lung Institute, Imperial College, London (United Kingdom); Camici, Paolo G. [Hammersmith Hospital, Medical Research Council Clinical Sciences Centre, Imperial College Faculty of Medicine, London (United Kingdom); Hammersmith Hospital, National Heart and Lung Institute, Imperial College, London (United Kingdom)

2007-08-15

We have previously shown that the myocardium of patients with heart failure (HF) is insulin resistant. Chronic {beta}-adrenergic stimulation has been implicated in insulin resistance in cultured cardiomyocytes in vitro, where sustained noradrenaline stimulation inhibited insulin-modulated glucose uptake. As the failing heart is characterized by increased sympathetic drive, we hypothesized that there is a correlation between pre-synaptic sympathetic function and insulin sensitivity in the myocardium of patients with HF. Eight patients (aged 67 {+-} 7 years) with coronary artery disease and left ventricular dysfunction (ejection fraction 44 {+-} 10%) underwent function and viability assessment with cardiovascular magnetic resonance. Myocardial glucose utilization (MGU) was measured using positron emission tomography (PET) with {sup 18}F-fluorodeoxyglucose (FDG). Pre-synaptic noradrenaline re-uptake was measured by calculating [{sup 11}C]meta-hydroxy-ephedrine (HED) volume of distribution (V{sub d}) with PET. Two groups of healthy volunteers served as controls for the FDG (n = 8, aged 52 {+-} 4 years, p < 0.01 vs patients) and HED (n = 8, aged 40 {+-} 6 years, p < 0.01 vs patients) data. MGU in patients was reduced in both normal remote (0.44 {+-} 0.14 {mu}mol.min{sup -1}.g{sup -1}) and dysfunctional (0.49 {+-} 0.14 {mu}mol.min{sup -1}.g{sup -1}) segments compared with controls (0.61 {+-} 0.7 {mu}mol.min{sup -1}.g{sup -1}; p < 0.001 vs both). HED V{sub d} was reduced in dysfunctional segments of patients (38.9 {+-} 21.2 ml.g{sup -1}) compared with normal segments (52.2 {+-} 19.6 ml.g{sup -1}) and compared with controls (62.7 {+-} 11.3 ml.g{sup -1}). In patients, regional MGU was correlated with HED V{sub d}. The results of this study provide novel evidence of a correlation between cardiac sympathetic function and insulin sensitivity, which may represent one of the mechanisms contributing to insulin resistance in failing human hearts. (orig.)

Simple noninvasive quantification method for measuring myocardial glucose utilization in humans employing positron emission tomography and fluorine-18 deoxyglucose

International Nuclear Information System (INIS)

Gambhir, S.S.; Schwaiger, M.; Huang, S.C.; Krivokapich, J.; Schelbert, H.R.; Nienaber, C.A.; Phelps, M.E.

1989-01-01

To estimate regional myocardial glucose utilization (rMGU) with positron emission tomography (PET) and 2-[ 18 F]fluoro-2-deoxy-D-glucose (FDG) in humans, we studied a method which simplifies the experimental procedure and is computationally efficient. This imaging approach uses a blood time-activity curve derived from a region of interest (ROI) drawn over dynamic PET images of the left ventricle (LV), and a Patlak graphic analysis. The spillover of radioactivity from the cardiac chambers to the myocardium is automatically removed by this analysis. Estimates of rMGU were obtained from FDG PET cardiac studies of six normal human subjects. Results from this study indicate that the FDG time-activity curve obtained from the LV ROI matched well with the arterial plasma curve. The rMGU obtained by Patlak graphic analysis was in good agreement with direct curve fitting results (r = 0.90). The average standard error of the estimate of the Patlak rMGU was low (3%). These results demonstrate the practical usefulness of a simplified method for the estimation of rMGU in humans by PET. This approach is noninvasive, computationally fast, and highly suited for developing parametric images of myocardial glucose utilization rate

Prognostic Significance of Remote Myocardium Alterations Assessed by Quantitative Noncontrast T1 Mapping in ST-Segment Elevation Myocardial Infarction.

Science.gov (United States)

Reinstadler, Sebastian J; Stiermaier, Thomas; Liebetrau, Johanna; Fuernau, Georg; Eitel, Charlotte; de Waha, Suzanne; Desch, Steffen; Reil, Jan-Christian; Pöss, Janine; Metzler, Bernhard; Lücke, Christian; Gutberlet, Matthias; Schuler, Gerhard; Thiele, Holger; Eitel, Ingo

2018-03-01

This study assessed the prognostic significance of remote zone native T1 alterations for the prediction of clinical events in a population with ST-segment elevation myocardial infarction (STEMI) who were treated by primary percutaneous coronary intervention (PPCI) and compared it with conventional markers of infarct severity. The exact role and incremental prognostic relevance of remote myocardium native T1 mapping alterations assessed by cardiac magnetic resonance (CMR) after STEMI remains unclear. We included 255 consecutive patients with STEMI who were reperfused within 12 h after symptom onset. CMR core laboratory analysis was performed to assess left ventricular (LV) function, standard infarct characteristics, and native T1 values of the remote, noninfarcted myocardium. The primary endpoint was a composite of death, reinfarction, and new congestive heart failure within 6 months (major adverse cardiac events [MACE]). Patients with increased remote zone native T1 values (>1,129 ms) had significantly larger infarcts (p = 0.012), less myocardial salvage (p = 0.002), and more pronounced LV dysfunction (p = 0.011). In multivariable analysis, remote zone native T1 was independently associated with MACE after adjusting for clinical risk factors (p = 0.001) or other CMR variables (p = 0.007). In C-statistics, native T1 of remote myocardium provided incremental prognostic information beyond clinical risk factors, LV ejection fraction, and other markers of infarct severity (all p remote zone native T1 to a model of prognostic CMR parameters (ejection fraction, infarct size, and myocardial salvage index) led to net reclassification improvement of 0.82 (95% confidence interval: 0.46 to 1.17; p remote zone alterations by quantitative noncontrast T1 mapping provided independent and incremental prognostic information in addition to clinical risk factors and traditional CMR outcome markers. Remote zone alterations may thus represent a novel therapeutic target and a

Repair of human DNA: radiation and chemical damage in normal and xeroderma pigmentosum cells

International Nuclear Information System (INIS)

Regan, J.D.; Setlow, R.B.

1976-01-01

We present the experimental evidence we have gathered, using a particular assay for DNA repair in human cells, the photolysis of bromodeoxyuridine (BrdUrd) incorporated during repair. This assay characterizes the sequence of repair events that occur in human cells after radiation, both ultraviolet and ionizing, and permits an estimation of the size of the average repaired region after these physical insults to DNA. We will discuss chemical insults to DNA and attempt to liken the repair processes after chemical damages of various kinds to those repair processes that occur in human DNA after damage from physical agents. We will also show results indicating that, under certain conditions, repair events resembling those seen after uv-irradiation can be observed in normal human cells after ionizing radiation. Furthermore the XP cells, defective in the repair of uv-induced DNA damage, show defective repair of these uv-like DNA lesions induced by ionizing radiation

Nicotine promotes proliferation and collagen synthesis of chondrocytes isolated from normal human and osteoarthritis patients.

Science.gov (United States)

Ying, Xiaozhou; Cheng, Shaowen; Shen, Yue; Cheng, Xiaojie; An Rompis, Ferdinand; Wang, Wei; Lin, Zhongqin; Chen, Qingyu; Zhang, Wei; Kou, Dongquan; Peng, Lei; Tian, Xin Qiao; Lu, Chuan Zhu

2012-01-01

The aims of the study were to show the direct effect of nicotine with different concentrations (0, 25, 50, and 100 ng/ml) on chondrocytes isolated from normal human and osteoarthritis patients, respectively. Microscopic observation was performed during the culture with an inverted microscope. Methyl thiazolyl tetrazolium (MTT) assay method was adopted to observe the influence of nicotine on the proliferation of chondrocytes, and real-time PCR and ELISA were used to assay the mRNA and protein expression of type II collagen and aggrecan, respectively. We discovered that the OA chondrocytes were similar to fibroblasts in shape and grow slower than normal chondrocytes. The proliferation of the two kinds of chondrocytes was increased in a concentration-dependent manner and in a time-dependent manner (P<0.05). Also, we found that the mRNA level of type II collagen were upregulated under 25-100 ng/ml nicotine doses both in the two kinds of chondrocytes compared with control. The expression of protein levels of type II collagen were synthesized in line with the increase in mRNA. No effect was observed on aggrecan synthesis with any nicotine dose. We concluded that nicotine has the same effect on both chondrocytes, obtained either from osteoarthritis patients or from normal human, and the positive effect of smoking in OA may relate to the alteration in metabolism of chondrocytes.

HSP10 selective preference for myeloid and megakaryocytic precursors in normal human bone marrow

Directory of Open Access Journals (Sweden)

F Cappello

2009-06-01

Full Text Available Heat shock proteins (HSPs constitute a heterogeneous family of proteins involved in cell homeostasis. During cell life they are involved in harmful insults, as well as in immune and inflammatory reactions. It is known that they regulate gene expression, and cell proliferation, differentiation and death. HSP60 is a mitochondrial chaperonin, highly preserved during evolution, responsible of protein folding. Its function is strictly dependent on HSP10 in both prokaryotic and eukaryotic elements. We investigated the presence and the expression of HSP60 and HSP10 in a series of 20 normal human bone marrow specimens (NHBM by the means of immunohistochemistry. NHBM showed no expression of HSP60, probably due to its being below the detectable threshold, as already demonstrated in other normal human tissues. By contrast, HSP10 showed a selective positivity for myeloid and megakaryocytic lineages. The positivity was restricted to precursor cells, while mature elements were constantly negative.We postulate that HSP10 plays a role in bone marrow cell differentiation other than being a mitochondrial co-chaperonin. The present data emphasize the role of HSP10 during cellular homeostasis and encourage further investigations in this field.

[The effect of prolonged treatment of hypertensive rats with antihypertensive drugs of various actions on the arterial tension and noradrenaline level in the myocardium, brain and aortal].

Science.gov (United States)

Kiriakov, A; Khlebarova, M; Staneva-stoicheva, D; Panova, I

1975-01-01

The authors examined the changes in arterial blood pressure and the content of Noradrenaline in the myocardium, brain and aorta of rats with hypertension due to nephrectomy and treatment with desoxycorticosterone and NaCl, and after a chronic 6-month treatment of hypertension with various antihypertensive means. The most significant reduction of noradrenaline in the three of the examined tissues was found in rats, which received dic. sulfyram (100 mg/kg per os). Clondine (10 mkg/kg, per os) manifested the strongest hypotensive effect and lowered the level of noradrenaline in the myocardium, while it was raised in the aorta. Reserpine (10 mkg/kg, s. c) induced a clear reduction of Noradrenaline content in the brain, but an increase in the other two tissues. Insignificant hypotensive effect was observed in animals, treated with guanetidine (0.5 mg/kg, per os), which did not affect substantially noradrenaline in the examined organs. The increase of noradrenaline level was established in the three of the organs of animals, treated with alpha-methyl-DOFA (25 mg/kg, per os). Furosemide (1 mg/kg, s.c.) induced a statistically significant elevation of noradrenaline in the aorta, but was noneffective to noradrenaline in the myocardium and brain.

Membrane-bound and cytosolic forms of heterotrimeric G proteins in young and adult rat myocardium: influence of neonatal hypo- and hyperthyroidism

Czech Academy of Sciences Publication Activity Database

Novotný, Jiří; Bouřová, Lenka; Kolář, František; Svoboda, Petr

2001-01-01

Roč. 82, č. 2 (2001), s. 215-224 ISSN 0730-2312 R&D Projects: GA ČR GA305/00/1660; GA MŠk VS97099 Institutional research plan: CEZ:AV0Z5011922 Keywords : development * G proteins * young and adult rat myocardium Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.536, year: 2001

Optical redox imaging indices discriminate human breast cancer from normal tissues

Science.gov (United States)

Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

2016-01-01

Abstract. Our long-term goal was to investigate the potential of incorporating redox imaging technique as a breast cancer (BC) diagnosis component to increase the positive predictive value of suspicious imaging finding and to reduce unnecessary biopsies and overdiagnosis. We previously found that precancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. We also revealed abnormal mitochondrial redox state in cancerous specimens from three BC patients. Here, we extend our study to include biopsies of 16 patients. Tissue aliquots were collected from both apparently normal and cancerous tissues from the affected cancer-bearing breasts shortly after surgical resection. All specimens were snap-frozen and scanned with the Chance redox scanner, i.e., the three-dimensional cryogenic NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins) fluorescence imager. We found both Fp and NADH in the cancerous tissues roughly tripled that in the normal tissues (predox ratio Fp/(NADH + Fp) was ∼27% higher in the cancerous tissues (predox ratio alone could predict cancer with reasonable sensitivity and specificity. Our findings suggest that the optical redox imaging technique can provide parameters independent of clinical factors for discriminating cancer from noncancer breast tissues in human patients. PMID:27896360

Establishment of human induced pluripotent stem cell lines from normal fibroblast TIG-1.

Science.gov (United States)

Kumazaki, Tsutomu; Kurata, Sayaka; Matsuo, Taira; Mitsui, Youji; Takahashi, Tomoko

2011-06-01

Normal human cells have a replicative life span and therefore senesce. Usually, normal human cell strains are differentiated cells and reach a terminally differentiated state after a number of cell divisions. At present, definitive differences are not known between replicative senescence and terminal differentiation. TIG-1 is a human fibroblast strain established from fetal lung and has been used extensively in studies of cellular senescence, and numerous data were accumulated at the molecular level. Recently, a method for generating induced pluripotent stem cells (iPSCs) was developed. Using the method, we introduced four reprogramming genes to TIG-1 fibroblasts and succeeded in isolating colonies that had embryonic stem cell (ESC)-like morphologies. They showed alkaline phosphatase activity and expressed ESC markers, as shown by immunostaining of OCT4, SOX2, SSEA4, and TRA-1-81 as well as reverse-transcription polymerase chain reaction (RT-PCR) for OCT4 and NANOG transcripts. Thus, we succeeded in establishing iPSC clones from TIG-1. The iPSC clones could differentiate to cells originated from all three germ-cell layers, as shown by RT-PCR, for messenger RNA (mRNA) expression of α-fetoprotein (endoderm), MSX1 (mesoderm) and microtubule-associated protein 2 (ectoderm), and by immunostaining for α-fetoprotein (endoderm), α-smooth muscle actin (mesoderm), and β-III-tubulin (ectoderm). The iPSCs formed teratoma containing the structures developed from all three germ-cell layers in severe combined immune-deficiency mice. Thus, by comparing the aging process of parental TIG-1 cells and the differentiation process of iPSC-derived fibrocytes to fibroblasts, we can reveal the exact differences in processes between senescence and terminal differentiation.

Retention and clearance of C-11 palmitic acid in ischemic and reperfused canine myocardium

International Nuclear Information System (INIS)

Schwaiger, M.; Schelbert, H.R.; Keen, R.; Vinten-Johansen, J.; Hansen, H.; Selin, C.; Barrio, J.; Huang, S.C.; Phelps, M.E.

1985-01-01

Free fatty acids are the major energy source for cardiac muscle. Oxidation of fatty acid decreases or even ceases during ischemia. Its recovery after transient ischemia remains largely unexplored. Using intracoronary carbon-11 palmitic acid as a tracer of myocardial fatty acid metabolism in an open chest dog model, retention and clearance of tracer in myocardium were evaluated at control, during ischemia and after reperfusion following a 20 minute occlusion of the left anterior descending coronary artery. Myocardial C-11 time-activity curves were analyzed with biexponential curve-fitting routines yielding fractional distribution and clearance half-times of C-11 palmitic acid in myocardial tissue. In animals with permanent occlusion and intracoronary injection of C-11 palmitic acid distal to the occlusion site, the relative size and half-time of the early clearance curve component differed markedly from control values and did not change with ongoing ischemia. Conversely, in animals with only 20 minutes of coronary occlusion, the relative size of the early C-11 clearance phase was still significantly depressed at 20 and 90 minutes of reperfusion but returned to control level at 180 minutes. Tissue C-11 clearance half-times remained significantly prolonged throughout the reperfusion period. Regional function in reperfused myocardium monitored with ultrasonic crystals recovered slowly and was still less than control after 3 hours of reperfusion. The data indicate that after transient ischemia, myocardial fatty acid metabolism fails to recover immediately. Because the metabolic recovery occurs in parallel with recovery of regional function, C-11 palmitic acid in conjunction with positron tomography may be useful for studying regional fatty acid metabolism noninvasively after an ischemic injury, and may be helpful in identifying reversible tissue injury

Constitutive activation of Nrf2 induces a stable reductive state in the mouse myocardium

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Gobinath Shanmugam

2017-08-01

Full Text Available Redox homeostasis regulates key cellular signaling pathways in both physiology and pathology. The cell's antioxidant response provides a defense against oxidative stress and establishes a redox tone permissive for cell signaling. The molecular regulation of the well-known Keap1/Nrf2 system acts as sensor responding to changes in redox homeostasis and is poorly studied in the heart. Importantly, it is not yet known whether Nrf2 alone can serve as a master regulator of cellular redox homeostasis without compensation of the transcriptional regulation of antioxidant response element (ARE genes through alternate mechanisms. Here, we addressed this question using cardiac-specific transgenic expression at two different levels of constitutively active nuclear erythroid related factor 2 (caNrf2 functioning independently of Keap1. The caNrf2 mice showed augmentation of glutathione (GSH, the key regulator of the cellular thiol redox state. The Trans-AM assay for Nrf2-binding to the antioxidant response element (ARE showed a dose-dependent increase associated with upregulation of several major antioxidant genes and proteins. This was accompanied by a significant decrease in dihydroethidium staining and malondialdehyde (MDA in the caNrf2-TG mice myocardium. Interestingly, caNrf2 gene-dosage dependent redox changes were noted resulting in generation of a multi-stage model of pro-reductive and reductive conditions in the myocardium of TG-low and TG-high mice, respectively. These data clearly show that Nrf2 levels alone are capable of serving as the master regulator of the ARE. These models provide an important platform to investigate the impact of the Nrf2 system independent of the need to regulate the activity of Keap1 and the consequent exposure to pro-oxidants or electrophiles, which have numerous off-target effects.

Quantitative proteome profiling of normal human circulating microparticles

DEFF Research Database (Denmark)

Østergaard, Ole; Nielsen, Christoffer T; Iversen, Line V

2012-01-01

Circulating microparticles (MPs) are produced as part of normal physiology. Their numbers, origin, and composition change in pathology. Despite this, the normal MP proteome has not yet been characterized with standardized high-resolution methods. We here quantitatively profile the normal MP...... proteome using nano-LC-MS/MS on an LTQ-Orbitrap with optimized sample collection, preparation, and analysis of 12 different normal samples. Analytical and procedural variation were estimated in triply processed samples analyzed in triplicate from two different donors. Label-free quantitation was validated...... by the correlation of cytoskeletal protein intensities with MP numbers obtained by flow cytometry. Finally, the validity of using pooled samples was evaluated using overlap protein identification numbers and multivariate data analysis. Using conservative parameters, 536 different unique proteins were quantitated...

Transcription factors GATA-4 and GATA-6 in normal and neoplastic human gastrointestinal mucosa

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Mäki Markku

2008-04-01

Full Text Available Abstract Background Human gastrointestinal mucosa regenerates vigorously throughout life, but the factors controlling cell fate in mature mucosa are poorly understood. GATA transcription factors direct cell proliferation and differentiation in many organs, and are implicated in tumorigenesis. GATA-4 and GATA-6 are considered crucial for the formation of murine gastrointestinal mucosa, but their role in human gastrointestinal tract remains unexplored. We studied in detail the expression patterns of these two GATA factors and a GATA-6 down-stream target, Indian hedgehog (Ihh, in normal human gastrointestinal mucosa. Since these factors are considered important for proliferation and differentiation, we also explored the possible alterations in their expression in gastrointestinal neoplasias. The expression of the carcinogenesis-related protein Indian hedgehog was also investigated in comparison to GATA factors. Methods Samples of normal and neoplastic gastrointestinal tract from children and adults were subjected to RNA in situ hybridization with 33P labelled probes and immunohistochemistry, using an avidin-biotin immunoperoxidase system. The pathological tissues examined included samples of chronic and atrophic gastritis as well as adenomas and adenocarcinomas of the colon and rectum. Results GATA-4 was abundant in the differentiated epithelial cells of the proximal parts of the gastrointestinal tract but was absent from the distal parts. In contrast, GATA-6 was expressed throughout the gastrointestinal epithelium, and in the distal gut its expression was most intense at the bottom of the crypts, i.e. cells with proliferative capacity. Both factors were also present in Barrett's esophagus and metaplasia of the stomach. GATA-6 expression was reduced in colon carcinoma. Ihh expression overlapped with that of GATA-6 especially in benign gastrointestinal neoplasias. Conclusion The results suggest differential but overlapping functions for GATA-4 and

Concentrations of AMH and inhibin-B in relation to follicular diameter in normal human small antral follicles

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Andersen, Claus Yding; Schmidt, Kirsten Tryde; Kristensen, Stine Gry

2010-01-01

The aim of the present study was to determine the intrafollicular concentrations of anti-Müllerian hormone (AMH), inhibin-B and steroids in normal human small antral follicles and to relate them to follicular size....

Three-dimensional counting of morphologically normal human red blood cells via digital holographic microscopy

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Yi, Faliu; Moon, Inkyu; Lee, Yeon H.

2015-01-01

Counting morphologically normal cells in human red blood cells (RBCs) is extremely beneficial in the health care field. We propose a three-dimensional (3-D) classification method of automatically determining the morphologically normal RBCs in the phase image of multiple human RBCs that are obtained by off-axis digital holographic microscopy (DHM). The RBC holograms are first recorded by DHM, and then the phase images of multiple RBCs are reconstructed by a computational numerical algorithm. To design the classifier, the three typical RBC shapes, which are stomatocyte, discocyte, and echinocyte, are used for training and testing. Nonmain or abnormal RBC shapes different from the three normal shapes are defined as the fourth category. Ten features, including projected surface area, average phase value, mean corpuscular hemoglobin, perimeter, mean corpuscular hemoglobin surface density, circularity, mean phase of center part, sphericity coefficient, elongation, and pallor, are extracted from each RBC after segmenting the reconstructed phase images by using a watershed transform algorithm. Moreover, four additional properties, such as projected surface area, perimeter, average phase value, and elongation, are measured from the inner part of each cell, which can give significant information beyond the previous 10 features for the separation of the RBC groups; these are verified in the experiment by the statistical method of Hotelling's T-square test. We also apply the principal component analysis algorithm to reduce the dimension number of variables and establish the Gaussian mixture densities using the projected data with the first eight principal components. Consequently, the Gaussian mixtures are used to design the discriminant functions based on Bayesian decision theory. To improve the performance of the Bayes classifier and the accuracy of estimation of its error rate, the leaving-one-out technique is applied. Experimental results show that the proposed method can

Expression of Bcl-2 family proteins and spontaneous apoptosis in normal human testis.

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Oldereid, N B; Angelis, P D; Wiger, R; Clausen, O P

2001-05-01

We investigated the frequency of spontaneous apoptosis and expression of the Bcl-2 family of proteins during normal spermatogenesis in man. Testicular tissue with both normal morphology and DNA content was obtained from necro-donors and fixed in Bouin's solution. A TdT-mediated dUTP end-labelling method (TUNEL) was used for the detection of apoptotic cells. Expression of apoptosis regulatory Bcl-2 family proteins and of p53 and p21(Waf1) was assessed by immunohistochemistry. Germ cell apoptosis was detected in all testes and was mainly seen in primary spermatocytes and spermatids and in a few spermatogonia. Bcl-2 and Bak were preferentially expressed in the compartments of spermatocytes and differentiating spermatids, while Bcl-x was preferentially expressed in spermatogonia. Bax showed a preferential expression in nuclei of round spermatids, whereas Bad was only seen in the acrosome region of various stages of spermatids. Mcl-1 staining was weak without a particular pattern, whereas expression of Bcl-w, p53 and p21(Waf1) proteins was not detected by immunohistochemistry. The results show that spontaneous apoptosis occurs in all male germ cell compartments in humans. Bcl-2 family proteins are distributed preferentially within distinct germ cell compartments suggesting a specific role for these proteins in the processes of differentiation and maturation during human spermatogenesis.

Multivariate prediction of spontaneous repetitive responses in ventricular myocardium exposed in vitro to simulated ischemic conditions.

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Schiariti, M; Puddu, P E; Rouet, R

1994-06-01

Guinea-pig ventricular myocardium was partly exposed to normal Tyrode's superfusion and partly to altered conditions (using modified Tyrode's solution) set to simulate acute myocardial ischemia (PO2 80 +/- 10 mmHg; no glucose; pH 7.00 +/- 0.05; K+ 12 mM). Using a double-chamber tissue bath and standard microelectrode technique, the occurrence of spontaneous repetitive responses was investigated during simulated ischemia (occlusion) and after reperfusing the previously ischemic superfused tissue with normal Tyrode's solution (reperfusion). In 62 experiments (42 animals) the effects of: (1) duration of simulated ischemia (1321 +/- 435 s), (2) stimulation rate (1002 +/- 549 ms) and (3) number of successive simulated ischemic periods (occlusions) (1.58 +/- 0.92) on: (1) resting membrane potential, (2) action potential amplitude, (3) duration of 50 and 90% action potentials and (4) maximal upstroke velocity of action potential were studied. All variables were considered as gradients (delta) between normal and ischemic tissue. Both during occlusion and upon reperfusion, spontaneous repetitive responses were coded as single, couplets, salvos (three to nine and > 10) or total spontaneous repetitive responses (coded present when at least one of the above-mentioned types was seen). The incidence of total spontaneous repetitive responses was 31% (19/62) on occlusion and 85% (53/62) upon reperfusion. Cox's models (forced and stepwise) were used to predict multivariately the occurrence of arrhythmic events considered as both total spontaneous repetitive responses and as separate entities. These models were applicable since continuous monitoring of the experiments enabled exact timing of spontaneous repetitive response onset during both occlusion and reperfusion. In predicting reperfusion spontaneous repetitive responses, total spontaneous repetitive responses and blocks observed during the occlusion period were also considered. Total occlusion spontaneous repetitive responses

Human respiratory syncytial virus load normalized by cell quantification as predictor of acute respiratory tract infection.

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Gómez-Novo, Miriam; Boga, José A; Álvarez-Argüelles, Marta E; Rojo-Alba, Susana; Fernández, Ana; Menéndez, María J; de Oña, María; Melón, Santiago

2018-05-01

Human respiratory syncytial virus (HRSV) is a common cause of respiratory infections. The main objective is to analyze the prediction ability of viral load of HRSV normalized by cell number in respiratory symptoms. A prospective, descriptive, and analytical study was performed. From 7307 respiratory samples processed between December 2014 to April 2016, 1019 HRSV-positive samples, were included in this study. Low respiratory tract infection was present in 729 patients (71.54%). Normalized HRSV load was calculated by quantification of HRSV genome and human β-globin gene and expressed as log10 copies/1000 cells. HRSV mean loads were 4.09 ± 2.08 and 4.82 ± 2.09 log10 copies/1000 cells in the 549 pharyngeal and 470 nasopharyngeal samples, respectively (P respiratory tract infection and 4.22 ± 2.28 log10 copies/1000 cells with upper respiratory tract infection or febrile syndrome (P < 0.05). A possible cut off value to predict LRTI evolution was tentatively established. Normalization of viral load by cell number in the samples is essential to ensure an optimal virological molecular diagnosis avoiding that the quality of samples affects the results. A high viral load can be a useful marker to predict disease progression. © 2018 Wiley Periodicals, Inc.

Consideration of Normal Variation of Perfusion Measurements in the Quantitative Analysis of Myocardial Perfusion SPECT: Usefulness in Assessment of Viable Myocardium

International Nuclear Information System (INIS)

Paeng, Jin Chul; Lim, Il Han; Kim, Ki Bong; Lee, Dong Soo

2008-01-01

Although automatic quantification software of myocardial perfusion SPECT provides highly objective and reproducible quantitative measurements, there is still some limitation in the direct use of quantitative measurements. In this study we derived parameters using normal variation of perfusion measurements, and tried to test the usefulness of these parameters. In order to calculate normal variation of perfusion measurements on myocardial perfusion SPECT, 55 patients (M:F=28:27) of low-likelihood for coronary artery disease were enrolled and 201 Tl rest / 99m Tc-MIBI stress SPECT studies were performed. Using 20-segment model, mean (m) and standard deviation (SD) of perfusion were calculated in each segment. As a myocardial viability assessment group, another 48 patients with known coronary artery disease, who underwent coronary artery bypass graft surgery (CABG) were enrolled. 201 Tl rest / 99m Tc-MIBI stress / 201 Tl 24-hr delayed SPECT was performed before CABG and SPECT was followed up 3 months after CABG. From the preoperative 24-hr delayed SPECT, Q delay (perfusion measurement), Δ delay (Q delay .m) and Z delay ((Q delay .m)/SD) were defined and diagnostic performances of them for myocardial viability were evaluated using area under curve (AUC) on receiver operating characteristic (ROC) curve analysis. Segmental perfusion measurements showed considerable normal variations among segments. In men, the lowest segmental perfusion measurement was 51.8±6.5 and the highest segmental perfusion was 87.0±5.9, and they are 58.7±8.1 and 87.3±6.0, respectively in women. In the viability assessment, Q delay showed AUC of 0.633, while those for Δ delay and Z delay were 0.735 and 0.716, respectively. The AUCs of Δ delay and Z delay were significantly higher than that of Q delay (p=0.001 and 0.018, respectively). The diagnostic performance of Δ delay , which showed highest AUC, was 85% of sensitivity and 53% of specificity at the optimal cutoff of -24.7. On automatic

Characterization of the Structural and Functional Changes in the Myocardium Following Focal Ischemia-Reperfusion Injury

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Ojha, Navdeep; Roy, Sashwati; Radtke, Jared; Simonetti, Orlando; Gnyawali, Surya; Zweier, Jay L.; Kuppusamy, Periannan; Sen, Chandan K.

2015-01-01

High resolution (11.7T) cardiac magnetic resonance imaging (MRI) and histological approaches have been employed in tandem to characterize the secondary damage suffered by the murine myocardium following the initial insult caused by ischemia-reperfusion (IR). IR induced changes in the myocardium were examined in five separate groups at the following time-points after IR: 1h, 1d, 3d, 7d and 14 d. Infarct volume increased from 1h to 1d post-IR. Over time, loss of myocardial function was observed to be associated with increased infarct volume and worsened regional wall motion. In the infarct region, IR caused a decrease in end-systolic thickness coupled with small changes in end-diastolic thickness, leading to massive wall thickening abnormalities. In addition, compromised wall thickening was also observed in left ventricular regions adjacent to the infarct region. A tight correlation (r2 = 0.86) between measured MRI and triphenyltetrazolium chloride (TTC) infarct volumes was noted. Our observation that until day 3 post-IR, the infarct size as measured by TTC staining and MRI were much larger than the myocyte-silent regions in trichrome or H&E stained sections is consistent with the literature and leads to the conclusion that at such early phase the infarct site contains structurally intact myocytes that are functionally compromised. Over time, such affected myocytes were noted to structurally disappear resulting in consistent infarct sizes obtained from MRI, TTC as well as trichrome and hematoxylin/eosin analyses on day 7 following IR. Myocardial remodeling following IR includes secondary myocyte death followed by loss of cardiac function over time. PMID:18375718

Immunohistochemical Study of Expression of Sohlh1 and Sohlh2 in Normal Adult Human Tissues.

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Xiaoli Zhang

Full Text Available The expression pattern of Sohlh1 (spermatogenesis and oogenesis specific basic helix-loop-helix 1 and Sohlh2 in mice has been reported in previous studies. Sohlh1 and Sohlh2 are specifically expressed in spermatogonia, prespermatogonia in male mice and oocytes of primordial and primary follicles in female mice. In this report, we studied the expression pattern of Sohlh1 and Sohlh2 in human adult tissues. Immunohistochemical staining of Sohlh1 and Sohlh2 was performed in 5 samples of normal ovaries and testes, respectively. The results revealed that Sohlh genes are not only expressed in oocytes and spermatogonia, but also in granular cells, theca cells, Sertoli cells and Leydig cells, and in smooth muscles of blood vessel walls. To further investigate the expression of Sohlh genes in other adult human tissues, we collected representative normal adult tissues developed from three embryonic germ layers. Compared with the expression in mice, Sohlhs exhibited a much more extensive expression pattern in human tissues. Sohlhs were detected in testis, ovary and epithelia developed from embryonic endoderm, ectoderm and tissues developed from embryonic mesoderm. Sohlh signals were found in spermatogonia, Sertoli cells and also Leydig cells in testis, while in ovary, the expression was mainly in oocytes of primordial and primary follicles, granular cells and theca cells of secondary follicles. Compared with Sohlh2, the expression of Sohlh1 was stronger and more extensive. Our study explored the expression of Sohlh genes in human tissues and might provide insights for functional studies of Sohlh genes.

Potential genotoxic and cytotoxicity of emamectin benzoate in human normal liver cells.

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Zhang, Zhijie; Zhao, Xinyu; Qin, Xiaosong

2017-10-10

Pesticide residue inducing cancer-related health problems draw people more attention recently. Emamectin benzoate (EMB) has been widely used in agriculture around the world based on its specificity targets. Although potential risk and the molecular mechanism of EMB toxicity to human liver has not been well-characterized. Unlike well-reported toxicity upon central nervous system, potential genotoxic and cytotoxicity of EMB in human liver cell was ignored and very limited. In this study, we identify genotoxicity and cytotoxicity of EMB to human normal liver cells (QSG7701 cell line) in vitro . We demonstrate that EMB inhibited the viability of QSG7701 cells and induced the DNA damage. Established assays of cytotoxicity were performed to characterize the mechanism of EMB toxicity on QSG7701 cells. Typical chromatin condensation and DNA fragmentation indicated the apoptosis of QSG7701 cells induced by EMB. And the intracellular biochemical results demonstrated that EMB-enhanced apoptosis of QSG7701 cells concurrent with generated ROS, a loss of mitochondrial membrane potential, the cytochrome-c release, up regulate the Bax/Bcl-2 and the activation of caspase-9/-3. Our results of EMB induces the death of QSG7701 cells maybe via mitochondrial-mediated intrinsic apoptotic pathways would contribute to promote the awareness of EMB as an extensive used pesticide to human being effects and reveal the underlying mechanisms of potential genotoxic.

Quantitative shear wave imaging optical coherence tomography for noncontact mechanical characterization of myocardium

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Wang, Shang; Lopez, Andrew L.; Morikawa, Yuka; Tao, Ge; Li, Jiasong; Larina, Irina V.; Martin, James F.; Larin, Kirill V.

2015-03-01

Optical coherence elastography (OCE) is an emerging low-coherence imaging technique that provides noninvasive assessment of tissue biomechanics with high spatial resolution. Among various OCE methods, the capability of quantitative measurement of tissue elasticity is of great importance for tissue characterization and pathology detection across different samples. Here we report a quantitative OCE technique, termed quantitative shear wave imaging optical coherence tomography (Q-SWI-OCT), which enables noncontact measurement of tissue Young's modulus based on the ultra-fast imaging of the shear wave propagation inside the sample. A focused air-puff device is used to interrogate the tissue with a low-pressure short-duration air stream that stimulates a localized displacement with the scale at micron level. The propagation of this tissue deformation in the form of shear wave is captured by a phase-sensitive OCT system running with the scan of the M-mode imaging over the path of the wave propagation. The temporal characteristics of the shear wave is quantified based on the cross-correlation of the tissue deformation profiles at all the measurement locations, and linear regression is utilized to fit the data plotted in the domain of time delay versus wave propagation distance. The wave group velocity is thus calculated, which results in the quantitative measurement of the Young's modulus. As the feasibility demonstration, experiments are performed on tissuemimicking phantoms with different agar concentrations and the quantified elasticity values with Q-SWI-OCT agree well with the uniaxial compression tests. For functional characterization of myocardium with this OCE technique, we perform our pilot experiments on ex vivo mouse cardiac muscle tissues with two studies, including 1) elasticity difference of cardiac muscle under relaxation and contract conditions and 2) mechanical heterogeneity of the heart introduced by the muscle fiber orientation. Our results suggest the

Normative values of 99mTc-MIBI distribution in myocardium in males and females, as a basis for quantitative planar scintigraphic method for detection of coronary artery disease in patients of both sexes

International Nuclear Information System (INIS)

Kusmierek, J.; Plachcinska, A.

2001-01-01

Radionuclide perfusion studies of myocardium are being performed using planar and tomographic (SPECT) procedures. The latter method enables better detection as well as assessment of localisation and severity of scintigraphically visualised perfusion defects. On the other hand, lower cost of planar procedures using 99m Tc-MIBI as the tracer and their much wider availability in countries of Central and Eastern Europe could significantly increase the diagnostic potential of nuclear cardiology in this region.The aim of the study was an assessment of normal distribution of 99m Tc-MIBI in the myocardium and generation of normative basis for quantitative planar scintigraphic procedure, aiming at detection of CAD in patients of both sexes.The study was based on 250 patients. The reference (control) group consisted of 53 individuals (29 men, 24 women) with the low ( 0 and LAO 70 0 ). These mean curves differed significantly between both sexes. In LAO 45 0 projection the differences affected mostly the region of the septum and postero-lateral wall of the left ventricle (LV). In LAO 70 0 projection differences were most pronounced in the antero-septal wall of the LV. Sensitivity, specificity and accuracy of CAD detection using the elaborated method, taking into account inter-sex differences, amounted to 86, 87 and 86% respectively in males, and correspondingly 81, 84 and 83% in females. The differences between corresponding indices for two sexes were statistically insignificant. For the whole group of patients the sensitivity, specificity and accuracy was 85, 86 and 85%, respectively. (author)

Genetic determination of human facial morphology: links between cleft-lips and normal variation.

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Boehringer, Stefan; van der Lijn, Fedde; Liu, Fan; Günther, Manuel; Sinigerova, Stella; Nowak, Stefanie; Ludwig, Kerstin U; Herberz, Ruth; Klein, Stefan; Hofman, Albert; Uitterlinden, Andre G; Niessen, Wiro J; Breteler, Monique M B; van der Lugt, Aad; Würtz, Rolf P; Nöthen, Markus M; Horsthemke, Bernhard; Wieczorek, Dagmar; Mangold, Elisabeth; Kayser, Manfred

2011-11-01

Recent genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with non-syndromic cleft lip with or without cleft palate (NSCL/P), and other previous studies showed distinctly differing facial distance measurements when comparing unaffected relatives of NSCL/P patients with normal controls. Here, we test the hypothesis that genetic loci involved in NSCL/P also influence normal variation in facial morphology. We tested 11 SNPs from 10 genomic regions previously showing replicated evidence of association with NSCL/P for association with normal variation of nose width and bizygomatic distance in two cohorts from Germany (N=529) and the Netherlands (N=2497). The two most significant associations found were between nose width and SNP rs1258763 near the GREM1 gene in the German cohort (P=6 × 10(-4)), and between bizygomatic distance and SNP rs987525 at 8q24.21 near the CCDC26 gene (P=0.017) in the Dutch sample. A genetic prediction model explained 2% of phenotype variation in nose width in the German and 0.5% of bizygomatic distance variation in the Dutch cohort. Although preliminary, our data provide a first link between genetic loci involved in a pathological facial trait such as NSCL/P and variation of normal facial morphology. Moreover, we present a first approach for understanding the genetic basis of human facial appearance, a highly intriguing trait with implications on clinical practice, clinical genetics, forensic intelligence, social interactions and personal identity.

Effects of Using Tricaine Methanesulfonate and Metomidate before Euthanasia on the Contractile Properties of Rainbow Trout (Oncorhynchus mykiss) Myocardium.

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Roberts, Jordan C; Syme, Douglas A

2016-01-01

Because many anesthetics work through depressing cell excitability, unanesthetized euthanasia has become common for research involving excitable tissues (for example muscle and nerve) to avoid these depressive effects. However, anesthetic use during euthanasia may be indicated for studies involving isolated tissues if the potential depressive effects of brief anesthetic exposure dissipate after subsequent tissue isolation, washout, and saline perfusion. We explore this here by measuring whether, when applied prior to euthanasia, standard immersion doses of 2 fish anesthetics, tricaine methanesulfonate (TMS; 100 mg/L, n = 6) and methyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate (metomidate, 10 mg/L, n = 6), have residual effects on the contractile properties (force and work output) of isolated and saline-perfused ventricular compact myocardium from rainbow trout (Oncorhynchus mykiss). Results suggest that direct exposure of muscle to immersion doses of TMS-but not metomidate-impairs muscle contractile performance. However, brief exposure (2 to 3 min) to either anesthetic during euthanasia only-providing that the agent is washed out prior to tissue experimentation-does not have an effect on the contractile properties of the myocardium. Therefore, the use of TMS, metomidate, and perhaps other anesthetics that depress cell excitability during euthanasia may be indicated when conducting research on isolated and rinsed tissues.

Incorporation of 14C-linoleic acid in lipids of normal and psoriatic human skin

International Nuclear Information System (INIS)

Ruestow, B.; Metz, D.; Kunze, D.; Meffert, H.

1980-01-01

The 14 C-linoleic acid incorporation in lipids of surviving epidermis and corium of normal and psoriatic human skin was investigated. Changes of lipid metabolism were found in both epidermis and corium. Particularly the turnover of phospholipids was increased in the uninvolved psoriatic epidermis in relation to the involved psoriatic epidermis or to healthy controls. Possible reasons of these phenomena and the significance of structural lipids in psoriasis are discussed. (author)

Effects of Human Mesenchymal Stem Cells Coculture on Calcium-Induced Differentiation of Normal Human Keratinocytes.

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Sah, Shyam Kishor; Kim, Hae Young; Lee, Ji Hae; Lee, Seong-Wook; Kim, Hyung-Sik; Kim, Yeon-Soo; Kang, Kyung-Sun; Kim, Tae-Yoon

2017-06-01

The influence of mesenchymal stem cells (MSCs) on keratinocytes in altered microenvironments is poorly understood. Here, we cocultured umbilical cord blood-derived MSCs with normal human epidermal keratinocytes to evaluate their paracrine effect in the presence of high extracellular calcium (Ca 2+ ) concentration. High Ca 2+ environment to keratinocytes can disrupt normal skin barrier function due to abnormal/premature differentiation of keratinocytes. Surprisingly, we found that MSCs suppress both proliferation and differentiation of keratinocytes under a high Ca 2+ environment in transforming growth factors β1 (TGFβ1)-dependent manner. Furthermore, we determined that MSCs can regulate the mitogen-activated protein kinases, phosphatidylinositol 3-kinase/protein kinase B, and protein kinase C pathways in Ca 2+ -induced differentiated keratinocytes. Knockdown of TGFβ1 from MSCs results in decreased suppression of differentiation with significantly increased proliferation of keratinocytes compared with control MSCs. MSCs-derived TGFβ1 further induced growth inhibition of keratinocyte in high extracellular Ca 2+ environment as analyzed by a decrease in DNA synthesis, accumulation of phosphorylated retinoblastoma protein, cdc2, and increased mRNA level of p21, and independent of TGFβ1/SMAD pathway. Taken together, we found that MSCs-derived TGFβ1 is a critical regulator of keratinocyte function, and involves multiple proximal signaling cascades. Stem Cells 2017;35:1592-1602. © 2017 AlphaMed Press.

Detection of homing-in of stem cells labeled with technetium-99m hexamethylpropyleneamine oxime in infarcted myocardium after intracoronary injection

International Nuclear Information System (INIS)

Patel, Chetan D; Agarwal, Snehlata; Seth, Sandeep; Mohanty, Sujata; Aggarwal, Himesh; Gupta, Namit

2014-01-01

Bone marrow stem cells having myogenic potential are promising candidates for various cell-based therapies for myocardial disease. We present here images showing homing of technetium-99m (Tc-99m) hexamethylpropyleneamine oxime (HMPAO) labeled stem cells in the infarcted myocardium from a pilot study conducted to radio-label part of the stem cells in patients enrolled in a stem cell clinical trial for recent myocardial infarction

Effects of allocryptopine on outward potassium current and slow delayed rectifier potassium current in rabbit myocardium.

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Fu, Yi-Cheng; Zhang, Yu; Tian, Liu-Yang; Li, Nan; Chen, Xi; Cai, Zhong-Qi; Zhu, Chao; Li, Yang

2016-05-01

Allocryptopine (ALL) is an effective alkaloid of Corydalis decumbens (Thunb.) Pers. Papaveraceae and has proved to be anti-arrhythmic. The purpose of our study is to investigate the effects of ALL on transmural repolarizing ionic ingredients of outward potassium current (I to) and slow delayed rectifier potassium current (I Ks). The monophasic action potential (MAP) technique was used to record the MAP duration of the epicardium (Epi), myocardium (M) and endocardium (Endo) of the rabbit heart and the whole cell patch clamp was used to record I to and I Ks in cardiomyocytes of Epi, M and Endo layers that were isolated from rabbit ventricles. The effects of ALL on MAP of Epi, M and Endo layers were disequilibrium. ALL could effectively reduce the transmural dispersion of repolarization (TDR) in rabbit transmural ventricular wall. ALL decreased the current densities of I to and I Ks in a voltage and concentration dependent way and narrowed the repolarizing differences among three layers. The analysis of gating kinetics showed ALL accelerated the channel activation of I to in M layers and partly inhibit the channel openings of I to in Epi, M and Endo cells. On the other hand, ALL mainly slowed channel deactivation of I Ks channel in Epi and Endo layers without affecting its activation. Our study gives partially explanation about the mechanisms of transmural inhibition of I to and I Ks channels by ALL in rabbit myocardium. These findings provide novel perspective regarding the anti-arrhythmogenesis application of ALL in clinical settings.

Gene Expression Networks in the Murine Pulmonary Myocardium Provide Insight into the Pathobiology of Atrial Fibrillation

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Jordan K. Boutilier

2017-09-01

Full Text Available The pulmonary myocardium is a muscular coat surrounding the pulmonary and caval veins. Although its definitive physiological function is unknown, it may have a pathological role as the source of ectopic beats initiating atrial fibrillation. How the pulmonary myocardium gains pacemaker function is not clearly defined, although recent evidence indicates that changed transcriptional gene expression networks are at fault. The gene expression profile of this distinct cell type in situ was examined to investigate underlying molecular events that might contribute to atrial fibrillation. Via systems genetics, a whole-lung transcriptome data set from the BXD recombinant inbred mouse resource was analyzed, uncovering a pulmonary cardiomyocyte gene network of 24 transcripts, coordinately regulated by chromosome 1 and 2 loci. Promoter enrichment analysis and interrogation of publicly available ChIP-seq data suggested that transcription of this gene network may be regulated by the concerted activity of NKX2-5, serum response factor, myocyte enhancer factor 2, and also, at a post-transcriptional level, by RNA binding protein motif 20. Gene ontology terms indicate that this gene network overlaps with molecular markers of the stressed heart. Therefore, we propose that perturbed regulation of this gene network might lead to altered calcium handling, myocyte growth, and contractile force contributing to the aberrant electrophysiological properties observed in atrial fibrillation. We reveal novel molecular interactions and pathways representing possible therapeutic targets for atrial fibrillation. In addition, we highlight the utility of recombinant inbred mouse resources in detecting and characterizing gene expression networks of relatively small populations of cells that have a pathological significance.

Effect of amiodarone on the conversion of thyroxine to triiodotironine in rat myocardium in vivo and in vitro

International Nuclear Information System (INIS)

Ceppi, J.A.; Gonzalez, M.R.; Zaninovich, A.A.

1988-01-01

It was studied the effect of the antiarrhythmic drug amiodarone, on the conversion of T 4 to T 3 by rat myocardium and liver. Wistar rats were injected with amiodarone (AM) or iopanoic acid (IOP), afterwards the liver and the heart were homogenized in krebs-ringer phosphate. Aliquots of 400μl of the homogenized were separated and DTT 8mM and 10 -2 μCi 125 I-T 4 or 125 I-T 3 were added (either the conversion of T 4 to T 3 or degradation of T 3 are measured). In vitro: were added AM 0,1 mM or IOP 10mM. Incubation proceeded for 2 hours at 37 deg C and aliquots were chromatographied. The conversion of T 4 to T 3 in the myocardium and liver in vivo decreased, but in vitro did not have any deiodination of T 4 and the IOP reduced the production of T 3 by heart. Neither drug altered the deiodination of T 3 by heart or liver homogenates. Serum TSH and T 3 were decreased by AM and serum T 4 increased. IOP caused similar variations in T 4 and T 3 , but serum TSH was increased. It is concluded that blocking the T 3 miocardial production by AM may not be the cause of the antiarrhythmic effect of the drug. (M.E.L.) [es

Pulse wave imaging in normal, hypertensive and aneurysmal human aortas in vivo: a feasibility study

International Nuclear Information System (INIS)

Li, Ronny X; Luo, Jianwen; Shahmirzadi, Danial; Konofagou, Elisa E; Balaram, Sandhya K; Chaudhry, Farooq A

2013-01-01

Arterial stiffness is a well-established biomarker for cardiovascular risk, especially in the case of hypertension. The progressive stages of an abdominal aortic aneurysm (AAA) have also been associated with varying arterial stiffness. Pulse wave imaging (PWI) is a noninvasive, ultrasound imaging-based technique that uses the pulse wave-induced arterial wall motion to map the propagation of the pulse wave and measure the regional pulse wave velocity (PWV) as an index of arterial stiffness. In this study, the clinical feasibility of PWI was evaluated in normal, hypertensive, and aneurysmal human aortas. Radiofrequency-based speckle tracking was used to estimate the pulse wave-induced displacements in the abdominal aortic walls of normal (N = 15, mean age 32.5 ± 10.2 years), hypertensive (N = 13, mean age 60.8 ± 15.8 years), and aneurysmal (N = 5, mean age 71.6 ± 11.8 years) human subjects. Linear regression of the spatio-temporal variation of the displacement waveform in the anterior aortic wall over a single cardiac cycle yielded the slope as the PWV and the coefficient of determination r 2 as an approximate measure of the pulse wave propagation uniformity. The aortic PWV measurements in all normal, hypertensive, and AAA subjects were 6.03 ± 1.68, 6.69 ± 2.80, and 10.54 ± 6.52 m s −1 , respectively. There was no significant difference (p = 0.15) between the PWVs of the normal and hypertensive subjects while the PWVs of the AAA subjects were significantly higher (p 2 in the AAA subjects was significantly lower (p 2 ) obtained using PWI, in addition to the PWI images and spatio-temporal maps that provide qualitative visualization of the pulse wave, may potentially provide valuable information for the clinical characterization of aneurysms and other vascular pathologies that regionally alter the arterial wall mechanics. (paper)

Cloning and characterization of the complementary DNA for the B chain of normal human serum C1q.

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Reid, K B; Bentley, D R; Wood, K J

1984-09-06

Normal human C1q is a serum glycoprotein of 460 kDa containing 18 polypeptide chains (6A, 6B, 6C) each 226 amino acids long and each containing an N-terminal collagen-like domain and a C-terminal globular domain. Two unusual forms of C1q have been described: a genetically defective form, which has a molecular mass of approximately 160 kDa and is found in the sera of homozygotes for the defect who show a marked susceptibility to immune complex related disease; a fibroblast form, shown to be synthesized and secreted, in vitro, with a molecular mass of about 800 kDa and with chains approximately 16 kDa greater than those of normal C1q. A higher than normal molecular mass form of C1q has also been described in human colostrum and a form of C1q has been claimed to represent one of the types of Fc receptor on guinea-pig macrophages. To initiate studies, at the genomic level, on these various forms of C1q, and to investigate the possible relation between the C1q genes and the procollagen genes, the complementary DNA corresponding to the B chain of normal C1q has been cloned and characterized.

On the variability of the salting-out curves of proteins of normal human plasma and serum

NARCIS (Netherlands)

Steyn-Parvé, Elizabeth P.; Hout, A.J. van den

1953-01-01

Salting-out curves of proteins of normal human plasma reflect the influence of a number of other factors besides the protein composition: the manner of obtaining the blood, the nature of the anti-coagulant used, the non-protein components of the plasma. Diagrams of serum and plasma obtained from

Binding of digitoxin and digoxin to normal human β-lipoproteins

International Nuclear Information System (INIS)

Brock, A.

1976-01-01

The binding of digitoxin and digoxin to purified β-lipoprotein, obtained from pooled normal human serum, was studied under equilibrium conditions. Even with as high concentrations of unbound digitoxin or digoxin as 4 μmol/l, the preparations of β-lipoproteins, containing cholesterol 1.98-3.95 mmol/l, showed no signs of saturation. The binding affinity of digitoxin was about ten times as high as that of digoxin. Gel filtration chromatography, performed on native serum after addition of 3 H-digitoxin or 3 H-digoxin, showed a minor fraction of the cardiac glycosides to be associated with te protein fraction of highest molecular weight. This phenomenon disappeared after precipitation of the β-lipoproteins. In clinical relations the contribution of protein-bound digitoxin caused by the lipoprotein interaction is immaterial compared to that caused by the albumin interaction. (author)

Myocardial pre-synaptic sympathetic function correlates with glucose uptake in the failing human heart

International Nuclear Information System (INIS)

Mongillo, Marco; Leccisotti, Lucia; John, Anna S.; Pennell, Dudley J.; Camici, Paolo G.

2007-01-01

We have previously shown that the myocardium of patients with heart failure (HF) is insulin resistant. Chronic β-adrenergic stimulation has been implicated in insulin resistance in cultured cardiomyocytes in vitro, where sustained noradrenaline stimulation inhibited insulin-modulated glucose uptake. As the failing heart is characterized by increased sympathetic drive, we hypothesized that there is a correlation between pre-synaptic sympathetic function and insulin sensitivity in the myocardium of patients with HF. Eight patients (aged 67 ± 7 years) with coronary artery disease and left ventricular dysfunction (ejection fraction 44 ± 10%) underwent function and viability assessment with cardiovascular magnetic resonance. Myocardial glucose utilization (MGU) was measured using positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG). Pre-synaptic noradrenaline re-uptake was measured by calculating [ 11 C]meta-hydroxy-ephedrine (HED) volume of distribution (V d ) with PET. Two groups of healthy volunteers served as controls for the FDG (n = 8, aged 52 ± 4 years, p -1 .g -1 ) and dysfunctional (0.49 ± 0.14 μmol.min -1 .g -1 ) segments compared with controls (0.61 ± 0.7 μmol.min -1 .g -1 ; p d was reduced in dysfunctional segments of patients (38.9 ± 21.2 ml.g -1 ) compared with normal segments (52.2 ± 19.6 ml.g -1 ) and compared with controls (62.7 ± 11.3 ml.g -1 ). In patients, regional MGU was correlated with HED V d . The results of this study provide novel evidence of a correlation between cardiac sympathetic function and insulin sensitivity, which may represent one of the mechanisms contributing to insulin resistance in failing human hearts. (orig.)

Origin of nuclear buds and micronuclei in normal and folate-deprived human lymphocytes

International Nuclear Information System (INIS)

Lindberg, Hanna K.; Wang Xu; Jaerventaus, Hilkka; Falck, Ghita C.-M.; Norppa, Hannu; Fenech, Michael

2007-01-01

Micronuclei are formed from chromosomes and chromosomal fragments that lag behind in anaphase and are left outside daughter nuclei in telophase. They may also be derived from broken anaphase bridges. Nuclear buds, micronucleus-like bodies attached to the nucleus by a thin nucleoplasmic connection, have been proposed to be generated similarly to micronuclei during nuclear division or in S-phase as a stage in the extrusion of extra DNA, possibly giving rise to micronuclei. To better understand these phenomena, we have characterized the contents of 894 nuclear buds and 1392 micronuclei in normal and folate-deprived 9-day cultures of human lymphocytes using fluorescence in situ hybridization with pancentromeric and pantelomeric DNA probes. Such information has not earlier been available for human primary cells. Surprisingly, there appears to be no previous data on the occurrence of telomeres in micronuclei (or buds) of normal human cells in general. Our results suggest that nuclear buds and micronuclei have partly different mechanistic origin. Interstitial DNA without centromere or telomere label was clearly more prevalent in nuclear buds (43%) than in micronuclei (13%). DNA with only telomere label or with both centromere and telomere label was more frequent in micronuclei (62% and 22%, respectively) than in nuclear buds (44% and 10%, respectively). Folate deprivation especially increased the frequency of nuclear buds and micronuclei harboring telomeric DNA and nuclear buds harboring interstitial DNA but also buds and micronuclei with both centromeric and telomeric DNA. According to the model we propose, that micronuclei in binucleate lymphocytes primarily derive from lagging chromosomes and terminal acentric fragments during mitosis. Most nuclear buds, however, are suggested to originate from interstitial or terminal acentric fragments, possibly representing nuclear membrane entrapment of DNA that has been left in cytoplasm after nuclear division or excess DNA that

Nanotized PPARα Overexpression Targeted to Hypertrophied Myocardium Improves Cardiac Function by Attenuating the p53-GSK3β-Mediated Mitochondrial Death Pathway.

Science.gov (United States)

Rana, Santanu; Datta, Ritwik; Chaudhuri, Ratul Datta; Chatterjee, Emeli; Chawla-Sarkar, Mamta; Sarkar, Sagartirtha

2018-05-09

Metabolic remodeling of cardiac muscles during pathological hypertrophy is characterized by downregulation of fatty acid oxidation (FAO) regulator, peroxisome proliferator-activated receptor alpha (PPARα). Thereby, we hypothesized that a cardiac-specific induction of PPARα might restore the FAO-related protein expression and resultant energy deficit. In the present study, consequences of PPARα augmentation were evaluated for amelioration of chronic oxidative stress, myocyte apoptosis, and cardiac function during pathological cardiac hypertrophy. Nanotized PPARα overexpression targeted to myocardium was done by a stearic acid-modified carboxymethyl-chitosan (CMC) conjugated to a 20-mer myocyte-targeted peptide (CMCP). Overexpression of PPARα ameliorated pathological hypertrophy and improved cardiac function. Augmented PPARα in hypertrophied myocytes revealed downregulated p53 acetylation (lys 382), leading to reduced apoptosis. Such cells showed increased binding of PPARα with p53 that in turn reduced interaction of p53 with glycogen synthase kinase-3β (GSK3β), which upregulated inactive phospho-GSK3β (serine [Ser]9) expression within mitochondrial protein fraction. Altogether, the altered molecular milieu in PPARα-overexpressed hypertrophy groups restored mitochondrial structure and function both in vitro and in vivo. Cardiomyocyte-targeted overexpression of a protein of interest (PPARα) by nanotized plasmid has been described for the first time in this study. Our data provide a novel insight towards regression of pathological hypertrophy by ameliorating mitochondrial oxidative stress in targeted PPARα-overexpressed myocardium. PPARα-overexpression during pathological hypertrophy showed substantial betterment of mitochondrial structure and function, along with downregulated apoptosis. Myocardium-targeted overexpression of PPARα during pathological cardiac hypertrophy led to an overall improvement of cardiac energy deficit and subsequent cardiac

T1 mapping of the myocardium: Intra-individual assessment of the effect of field strength, cardiac cycle and variation by myocardial region

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Kawel Nadine

2012-05-01

Full Text Available Abstract Background Myocardial T1 relaxation time (T1 time and extracellular volume fraction (ECV are altered in the presence of myocardial fibrosis. The purpose of this study was to evaluate acquisition factors that may result in variation of measured T1 time and ECV including magnetic field strength, cardiac phase and myocardial region. Methods 31 study subjects were enrolled and underwent one cardiovascular MR exam at 1.5 T and two exams at 3 T, each on separate days. A Modified Look-Locker Inversion Recovery (MOLLI sequence was acquired before and 5, 10, 12, 20, 25 and 30 min after administration of 0.15 mmol/kg gadopentetate dimeglumine (Gd-DTPA; Magnevist at 1.5 T (exam 1. For exam 2, MOLLI sequences were acquired at 3 T both during diastole and systole, before and after administration of Gd-DTPA (0.15 mmol/kg Magnevist.Exam 3 was identical to exam 2 except gadobenate dimeglumine was administered (Gd-BOPTA; 0.1 mmol/kg Multihance. T1 times were measured in myocardium and blood. ECV was calculated by (ΔR1myocardium/ΔR1blood*(1-hematocrit. Results Before gadolinium, T1 times of myocardium and blood were significantly greater at 3 T versus 1.5 T (28% and 31% greater, respectively, p  Conclusion ECV is similar at field strengths of 1.5 T and 3 T. Due to minor variations in T1 time and ECV during the cardiac cycle and in different myocardial regions, T1 measurements should be obtained at the same cardiac phase and myocardial region in order to obtain consistent results.

Comparison of multiple assays for detecting human antibodies directed against antigens on normal and malignant tissue culture cells

International Nuclear Information System (INIS)

Rosenberg, S.A.; Schwarz, S.; Anding, H.; Hyatt, C.; Williams, G.M.; Johns Hopkins Univ., Baltimore, Md.

1977-01-01

Four separate assays of human antibody reactivity to four separate normal and malignant human tissue culture cells lines from two patients have been evaluated using a single highly-reactive allogeneic serum. The visual end-point cytolysis assay and the chromium-51 release assay were equally sensitive in measuring complement mediated antibody cytotoxicity and both were far more sensitive than a trypan blue dye exclusion assay. The assay of antibody reactivity by hemadsorption technique was about 10 times more sensitive than any of the cytotoxicity assays. This latter assay measures only IgG antibody however. These assays showed that cell lines from different patients may differ greatly in 'reactivity' to an allogeneic serum and emphasized the importance of utilizing tumor and normal cells from the same patient when using tissue culture cells to search for tumor specific reactivity. These observations emphasize the importance of utilizing multiple assays against paired normal and malignant cells from the same patient to be certain of the specificity and magnitude of the measured antibody

Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential.

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Francesca Oltolina

Full Text Available A major obstacle to an effective myocardium stem cell therapy has always been the delivery and survival of implanted stem cells in the heart. Better engraftment can be achieved if cells are administered as cell aggregates, which maintain their extra-cellular matrix (ECM. We have generated spheroid aggregates in less than 24 h by seeding human cardiac progenitor cells (hCPCs onto methylcellulose hydrogel-coated microwells. Cells within spheroids maintained the expression of stemness/mesenchymal and ECM markers, growth factors and their cognate receptors, cardiac commitment factors, and metalloproteases, as detected by immunofluorescence, q-RT-PCR and immunoarray, and expressed a higher, but regulated, telomerase activity. Compared to cells in monolayers, 3D spheroids secreted also bFGF and showed MMP2 activity. When spheroids were seeded on culture plates, the cells quickly migrated, displaying an increased wound healing ability with or without pharmacological modulation, and reached confluence at a higher rate than cells from conventional monolayers. When spheroids were injected in the heart wall of healthy mice, some cells migrated from the spheroids, engrafted, and remained detectable for at least 1 week after transplantation, while, when the same amount of cells was injected as suspension, no cells were detectable three days after injection. Cells from spheroids displayed the same engraftment capability when they were injected in cardiotoxin-injured myocardium. Our study shows that spherical in vivo ready-to-implant scaffold-less aggregates of hCPCs able to engraft also in the hostile environment of an injured myocardium can be produced with an economic, easy and fast protocol.

Effects of recombinant human interleukin-8 (rhIL-8) on the bone marrow cells of normal BALB/c mice

International Nuclear Information System (INIS)

Liu Yulong; Zhou Jianying; Wang Guoquan; Dai Hong; Duan Yingying; Guo Xiaokui

2001-01-01

Objective: To observe the colony formation ability of recombinant human interleukin-8 (rhIL-8) on bone marrow cells (BMCs) of normal mice in vivo. Methods: By means of cells culture and flow cytometry (FCM), the colony-stimulating activity of rhIL-8 on BMCs of normal mice was studied. Results: The experimental studies in vivo demonstrated that rhIL-8 could not changed the counts of CFU-GM and distribution of cell cycle in BMCs. Conclusion: rhIL-8 has no colony-stimulating activity to BMCs of normal mice

Chronic microelectrode investigations of normal human brain physiology using a hybrid depth electrode.

Science.gov (United States)

Howard, M A; Volkov, I O; Noh, M D; Granner, M A; Mirsky, R; Garell, P C

1997-01-01

Neurosurgeons have unique access to in vivo human brain tissue, and in the course of clinical treatment important scientific advances have been made that further our understanding of normal brain physiology. In the modern era, microelectrode recordings have been used to systematically investigate the cellular properties of lateral temporal cerebral cortex. The current report describes a hybrid depth electrode (HDE) recording technique that was developed to enable neurosurgeons to simultaneously investigate normal cellular physiology during chronic intracranial EEG recordings. The HDE combines microelectrode and EEG recordings sites on a single shaft. Multiple microelectrode recordings are obtained from MRI defined brain sites and single-unit activity is discriminated from these data. To date, over 60 HDEs have been placed in 20 epilepsy surgery patients. Unique physiologic data have been gathered from neurons in numerous brain regions, including amygdala, hippocampus, frontal lobe, insula and Heschl's gyrus. Functional activation studies were carried out without risking patient safety or comfort.

6-[Fluorine-18]Fluorodopamine pharmacokinetics and dosimetry in humans

International Nuclear Information System (INIS)

Goldstein, D.S.; Coronado, L.; Kopin, I.J.

1994-01-01

PET scanning after injection of 6-[ 18 F]fluorodopamine visualizes tissue sympathetic innervation. Organ dosimetric estimates for 6-[ 18 F]fluorodopamine have relied on studies of rats and dogs and on literature about the fate of other radiolabeled catecholamines. This report uses empirical clinical findings in healthy volunteers to refine and extend these estimates. Thoracic PET scanning was conducted and arterial blood and urine samples were obtained after intravenous injection of 6-[ 18 F]fluorodopamine into 10 normal volunteers. The main target organs for 6-[ 18 F]fluorodopamine-derived radioactivity were the wall of the urinary bladder (3.3 rem for a 4-mCi dose and 3.31-hr voiding interval) and the kidneys (2.9 rem for a 4-mCi dose) due to urinary excretion of radioactive metabolites of [ 18 F]-6F-DA. The estimates were about one-fourth those predicted from studies of laboratory animals. At administered doses required to visualize the left ventricular myocardium in humans, a 6-[ 18 F]fluorodopamine injection produces acceptable absorbed radiation doses, with the highest doses to the urinary collecting system. 22 refs., 2 figs., 5 tabs

Zinc in human prostate gland. Normal, hyperplastic and cancerous

International Nuclear Information System (INIS)

Zaichick, V.Ye.; Sviridova, T.V.; Zaichick, S.V.

1997-01-01

Zinc concentration in a prostate gland is much higher than that in other human tissues. Data about zinc changes for different prostate diseases are limited and greatly contradictory. Zinc content was determined for biopsy and resected materials of transrectal puncture tissues from benign prostate hyperplasia (BPH) and prostate cancer. There were 109 patients (50 BPH and 59 cancer) available for the present study. Control group consisted of 37 intact glands of men died an unexpected death (accident, murder, acute cardiac insufficiency, etc.). All materials studied were divided into two parts. One of them was morphologically examined, while another one was subjected to zinc analysis by INAA. Zinc contents (M ± SE) of normal, benign hyperplastic and cancerous prostate glands were found to be 1018 ± 124, 1142 ± 77, and 146 ± 10 μg/g dry tissue, respectively. It was shown that zinc assessments in the materials of transrectal puncture biopsy of indurated prostate sites can be used as an additional test for differential diagnostics of BPH and cancer. Accuracy, sensitivity and specificity of the test are 98 ± 2%. (author)

Raman Spectroscopy of DNA Packaging in Individual Human Sperm Cells distinguishes Normal from Abnormal Cells

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Huser, T; Orme, C; Hollars, C; Corzett, M; Balhorn, R

2009-03-09

Healthy human males produce sperm cells of which about 25-40% have abnormal head shapes. Increases in the percentage of sperm exhibiting aberrant sperm head morphologies have been correlated with male infertility, and biochemical studies of pooled sperm have suggested that sperm with abnormal shape may contain DNA that has not been properly repackaged by protamine during spermatid development. We have used micro-Raman spectroscopy to obtain Raman spectra from individual human sperm cells and examined how differences in the Raman spectra of sperm chromatin correlate with cell shape. We show that Raman spectra of individual sperm cells contain vibrational marker modes that can be used to assess the efficiency of DNA-packaging for each cell. Raman spectra obtained from sperm cells with normal shape provide evidence that DNA in these sperm is very efficiently packaged. We find, however, that the relative protein content per cell and DNA packaging efficiencies are distributed over a relatively wide range for sperm cells with both normal and abnormal shape. These findings indicate that single cell Raman spectroscopy should be a valuable tool in assessing the quality of sperm cells for in-vitro fertilization.

Assessment of area at risk and efficacy of treatment in patients with acute coronary syndrome using 99Tc tetrofosmin imaging in humans

International Nuclear Information System (INIS)

Matsuo, Hitoshi; Watanabe, Sachiro; Nishida, Yoshio

1993-01-01

The determination of the myocardium at risk before intervention and the change in that region after intervention constitute a promising measurement tool for the assessment of acute therapy. A new 99m Tc labeled myocardial blood flow tracer, 99m Tc tetrofosmin, is expected to enable the evaluation of myocardium at risk because of the absence of redistribution. This preliminary study was performed in 9 patients with acute coronary syndrome (4 unstable angina and 5 acute myocardial infarction) to investigate whether recovery of perfusion by tetrofosmin imaging parallels mechanical improvement. Tetrofosmin imaging was performed acutely and 3-30 days later. Visual analysis of defect severity was assessed in both studies. Segments with improvement in perfusion were accompanied by significant wall motion recovery compared with normal and unimproved segments (ΔWMI: normal segments 0.40±0.67, improved segments 1.79±0.68, unimproved segments -0.15±0.16, p 99m Tc tetrofosmin imaging is a useful method for the assessment of the myocardial area at risk and the efficacy of acute therapy in acute myocardial infarction and unstable angina. (author)

Autonomous parvoviruses neither stimulate nor are inhibited by the type I interferon response in human normal or cancer cells.

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Paglino, Justin C; Andres, Wells; van den Pol, Anthony N

2014-05-01

Members of the genus Parvovirus are small, nonenveloped single-stranded DNA viruses that are nonpathogenic in humans but have potential utility as cancer therapeutics. Because the innate immune response to parvoviruses has received relatively little attention, we compared the response to parvoviruses to that of several other types of viruses in human cells. In normal human glia, fibroblasts, or melanocytes, vesicular stomatitis virus evoked robust beta interferon (IFN-β) responses. Cytomegalovirus, pseudorabies virus, and Sindbis virus all evoked a 2-log-unit or greater upregulation of IFN-β in glia; in contrast, LuIII and MVMp parvoviruses did not evoke a detectable IFN-β or interferon-stimulated gene (ISG; MX1, oligoadenylate synthetase [OAS], IFIT-1) response in the same cell types. The lack of response raised the question of whether parvoviral infection can be attenuated by IFN; interestingly, we found that IFN did not decrease parvovirus (MVMp, LuIII, and H-1) infectivity in normal human glia, fibroblasts, or melanocytes. The same was true in human cancers, including glioma, sarcoma, and melanoma. Similarly, IFN failed to attenuate transduction by the dependovirus vector adeno-associated virus type 2. Progeny production of parvoviruses was also unimpaired by IFN in both glioma and melanoma, whereas vesicular stomatitis virus replication was blocked. Sarcoma cells with upregulated IFN signaling that show high levels of resistance to other viruses showed strong infection by LuIII. Unlike many other oncolytic viruses, we found no evidence that impairment of innate immunity in cancer cells plays a role in the oncoselectivity of parvoviruses in human cells. Parvoviral resistance to the effects of IFN in cancer cells may constitute an advantage in the virotherapy of some tumors. Understanding the interactions between oncolytic viruses and the innate immune system will facilitate employing these viruses as therapeutic agents in cancer patients. The cancer

Age-dependent changes of the normal human spine during adulthood.

Science.gov (United States)

Rühli, F J; Müntener, M; Henneberg, M

2005-01-01

The impact of aging on the morphology of the osseous spine is still debated. Clinical studies usually record combined aging effects, as well as age-related degenerative changes. The aim of this study was to determine the impact of (degeneration-independent) aging on the morphology of the osseous human spine during adulthood. Various osseous dimensions of human spinal landmarks at all major vertebral levels have been assessed in macroscopically normal Swiss skeletons (N = 71), with historically known sex and age at death, as well as in larger Central European skeletal samples (N = 277) with anthropologically determined individual age and sex. All measurements were correlated with individual age (or age group) by linear regression and analyzed separately for each sex. Only few osseous spinal dimensions, and only in men, correlate significantly with individual age. Generally, the significant dimensions show an increase in size during adulthood. Similar tendencies, but with significant alterations of spinal measurements in women as well, can be found in the larger samples with anthropologically determined sex and age group. Increase of certain spinal dimensions found in this study may be a reflection of an increase in the robustness of individuals with age. Because of the absence of a significant secular alteration of stature within the well-recorded sample, we exclude secular change in body dimensions as a major bias. Copyright 2005 Wiley Periodicals, Inc

Nystagmus responses in a group of normal humans during earth-horizontal axis rotation

Science.gov (United States)

Wall, Conrad, III; Furman, Joseph M. R.

1989-01-01

Horizontal eye movement responses to earth-horizontal yaw axis rotation were evaluated in 50 normal human subjects who were uniformly distributed in age (20-69 years) and each age group was then divided by gender. Subjects were rotated with eyes open in the dark, using clockwise and counter-clockwise 60 deg velocity trapezoids. The nystagmus slow component velocity is analyzed. It is shown that, despite large intersubject variability, parameters which describe earth-horizontal yaw axis responses are loosely interrelated, and some of them vary significantly with gender and age.

Shape-dependent regulation of proliferation in normal and malignant human cells and its alteration by interferon

International Nuclear Information System (INIS)

Kulesh, D.A.; Greene, J.J.

1986-01-01

The relationship between cell morphology, proliferation, and contact inhibition was studied in normal and malignant human cells which varied in their sensitivity to contact inhibition. Their ability to proliferate was examined under conditions where the cells were constrained into different shapes by plating onto plastic surfaces coated with poly(2-hydroxyethyl methacrylate). Poly(2-hydroxyethyl methacrylate) can precisely vary the shape of cells without toxicity. Cell proliferation was quantitated by cell counts and labeling indices were determined by autoradiography. The normal JHU-1 foreskin fibroblasts and IMR-90 lung fibroblasts exhibited contact-inhibited growth with a saturation density of 2.9 X 10(5) and 2.0 X 10(5) cells/cm2, respectively. These cells also exhibited stringent dependency on cell shape with a mitotic index of less than 3% at poly(2-hydroxyethyl methacrylate) concentrations at which the cells were rounded versus a labeling index of 75-90% when the cells were flat. The malignant bladder carcinoma line RT-4 exhibited partial contact-inhibited growth. Its dependency on cell shape was less stringent than that of normal cells with a mitotic index of 37-40% when rounded and 79% when flat. The malignant fibrosarcoma line, HT1080, was not contact inhibited and was entirely shape independent with a mitotic index of 70-90% regardless of cell shape. Treatment of HT1080 cells with low concentration of human fibroblast interferon (less than 40 units/ml) restored shape-dependent proliferation while having little effect on normal cells. Subantiproliferative doses of interferon were also shown to restore contact-inhibited proliferation control to malignant cells previously lacking it

Comparative study of 201Tl reinjection tomography and combined use of 13N-ammonia and 18F-fluorodeoxyglucose positron emission tomography for detection of viable myocardium

International Nuclear Information System (INIS)

Wang Lijuan; Qi Guoxian; Hu Jian

2001-01-01

Objective: To compare the clinical value of 201 Tl reinjection tomography and combined use of 13 N-ammonia (NH 3 ) regional myocardial perfusion and 18 F-fluorodeoxyglucose (FDG) positron emission tomography transfer function and for the myocardium. Methods: The authors performed exercise 201 Tl SPECT (Tl SPECT) on 20 patients with myocardial infarction and obtained standard 201 Tl exercise-redistribution images. 201 Tl was reinjected immediately after redistribution study, and the images were then acquired as also. The 20 patients also underwent PET imaging with 13 N-NH 3 and 18 F-FDG (NH 3 -FDG PET) within one week of the above study. Vertical and horizontal long axis cuts were divided into nine segments, and uptakes of radioisotope were evaluated into four classes visually (Defect score, DS) (0:normal uptake, 3:severely reduced). Quantitative evaluation was performed on the vertical and horizontal long axis cuts of 201 Tl redistribution, reinjection and FDG PET images using regions of interest. The relative myocardial 201 Tl uptake and 18 F-FDG uptake (% ID) were expressed as the percentage of this reference region accounted for of the maximal counts. Results: In 48 segments identified as viable by the NH 3 -FDG PET images, 45 (93.8%) segments were also identified as viable by the 201 Tl redistribution imaging. Of 24 segments with severe irreversible defects on the 201 Tl redistribution imaging, 87.5% of the segments were concordantly confirmed by 201 Tl reinjection and NH 3 -FDG PET images with 37.5% identified as viable and 50% identified as scar. There was no significant difference in the average % ID, furthermore, regression analysis revealed a high positive correlation in the segmental % ID between 201 Tl reinjection and FDG PET images in the 61 segments with myocardial infarction (r = 0.722). Conclusions: The results show that 201 Tl reinjection tomography is of similar accuracy with NH 3 -FDG PET for detection of viable myocardium and possess important

Kinetics of different 123-I and 14-C fatty acids in normal and diabetic rat myocardium in vivo

International Nuclear Information System (INIS)

Beckurts, T.E.; Shreeve, W.W.; Machulla, H.-J.; Feinendegen, L.E.

1984-01-01

For measuring myocardial metabolism by single photon scintigraphy various iodinated substrate analogues have been proposed. The present study compares in normal and diabetic rats the metabolic pathways of 14-C-palmitic acid (PA), 123-I-para-phenylpentadecanoic acid (I-pPPDA), 123-I-ortho-phenylpentadecanoic acid (I-oPPDA), 14-C-stearic acid (SA) and 123-I-w-heptadecanoic acid (I-ωHDA). In normal and diabetic rats free fatty acids showed a rapid tracer accumulation and an initial rapid, then a slow rate component of release. PA and I-pPPDA were preferentially esterified into triglycerides, whereas SA and I-ωHDA equally distributed between triglycerides and phospholipids. I-oPPDA nearly exclusively labelled the free fatty acid pool. - Turnover of SA and I-ωHDA was similar in triglycerides and phospholipids; yet PA and I-pPPDA continued to increase in triglycerides for 3-5 minutes after injection but decreased in phospholipids. - Following induction of diabetes by Streptocotocin, the primary effect was an inhibition of incorporation of all substrates tested into triglycerides and phospholipids with an initial rapid turnover in the total lipid fraction. - Of the total myocardial activities a considerable fraction was water soluble and another bound to solid tissue residue, with an early maximum and subsequent decline; the values for 14-C-labelled substrates remained below those of radioiodine. Thus different labelled fatty acids behave metabolically differently and promise to be useful for differentiating various intracellular metabolic pathways. External analysis of myocardial fatty acids metabolism requires correction for labelled catabolites. (Author)

Selective Retrograde Venous Revascularization of the Myocardium when PCI or CABG Is Impossible: Investigation in a Porcine Model

DEFF Research Database (Denmark)

Møller, Christian H; Nørgaard, Martin A; Gøtze, Jens P

2008-01-01

We investigated the possibility of nourishing the myocardium through selective retrograde coronary venous bypass grafting (CVBG) with an off-pump technique and evaluated various methods of monitoring the physiological effects of this procedure. In a porcine model, the left internal mammary artery...... tension decreased, but with time some recovery was seen. Cardiac troponin T was elevated. Histological analysis showed ischemic changes. In control pigs, microdialysis was performed for 1.5 hours up to LAD artery ligation, after which all pigs died in ventricular fibrillation arrest. No increase...

DNA crosslinking and cytotoxicity in normal and transformed human cells treated with antitumor nitrosoureas.

OpenAIRE

Erickson, L C; Bradley, M O; Ducore, J M; Ewig, R A; Kohn, K W

1980-01-01

Normal (IMR-90) and simian virus 40-transformed (VA-13) human embryo cells were treated with antitumor nitrosoureas, and the effects on cell viability and cell DNA were compared. All six nitrosoureas tested were more toxic to VA-13 cells than to IMR-90 cells as measured by decrease in cell proliferation or in colony formation. The nitrosoureas capable of generating alkylisocyanates produced a smaller difference between the cell types than did derivatives lacking this capacity. DNA damage was ...

Study of cerebral metabolism of glucose in normal human brain correlated with age

International Nuclear Information System (INIS)

Si, M.

2007-01-01

Full text: The objective was to determine whether cerebral metabolism in various regions of the brain differs with advancing age by using 18F-FDG PET instrument and SPM software. Materials and Methods We reviewed clinical information of 295 healthy normal samples who were examined by a whole body GE Discovery LS PET-CT instrument in our center from Aug. 2004 to Dec. 2005.They (with the age ranging from 21 to 88; mean age+/-SD: 49.77+/-13.51) were selected with: (i)absence of clear focal brain lesions (epilepsy.cerebrovascular diseases etc);(ii) absence of metabolic diseases, such as hyperthyroidism, hypothyroidism and diabetes;(iii) absence of psychiatric disorders and abuse of drugs and alcohol. They were sub grouped into six groups with the interval of 10 years old starting from 21, and the gender, educational background and serum glucose were matched. All subgroups were compared to the control group of 31-40 years old (84 samples; mean age+/-SD: 37.15+/-2.63). All samples were injected with 18F-FDG (5.55MBq/kg), 45-60 minutes later, their brains were scanned for 10min. Pixel-by-pixel t-statistic analysis was applied to all brain images using the Statistical parametric mapping (SPM2) .The hypometabolic areas (p < 0. 01 or p<0.001, uncorrected) were identified in the Stereotaxic coordinate human brain atlas and three-dimensional localized by MNI Space utility (MSU) software. Results:Relative hypometabolic brain areas detected are mainly in the cortical structures such as bilateral prefrontal cortex, superior temporal gyrus(BA22), parietal cortex (inferior parietal lobule and precuneus(BA40, insula(BA13)), parahippocampal gyrus and amygdala (p<0.01).It is especially apparent in the prefrontal cortex (BA9)and sensory-motor cortex(BA5, 7) (p<0.001), while basal ganglia and cerebellum remained metabolically unchanged with advancing age. Conclusions Regional cerebral metabolism of glucose shows a descent tendency with aging, especially in the prefrontal cortex (BA9)and

Digital music exposure reliably induces temporary threshold shift in normal-hearing human subjects.

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Le Prell, Colleen G; Dell, Shawna; Hensley, Brittany; Hall, James W; Campbell, Kathleen C M; Antonelli, Patrick J; Green, Glenn E; Miller, James M; Guire, Kenneth

2012-01-01

One of the challenges for evaluating new otoprotective agents for potential benefit in human populations is the availability of an established clinical paradigm with real-world relevance. These studies were explicitly designed to develop a real-world digital music exposure that reliably induces temporary threshold shift (TTS) in normal-hearing human subjects. Thirty-three subjects participated in studies that measured effects of digital music player use on hearing. Subjects selected either rock or pop music, which was then presented at 93 to 95 (n = 10), 98 to 100 (n = 11), or 100 to 102 (n = 12) dBA in-ear exposure level for a period of 4 hr. Audiograms and distortion product otoacoustic emissions (DPOAEs) were measured before and after music exposure. Postmusic tests were initiated 15 min, 1 hr 15 min, 2 hr 15 min, and 3 hr 15 min after the exposure ended. Additional tests were conducted the following day and 1 week later. Changes in thresholds after the lowest-level exposure were difficult to distinguish from test-retest variability; however, TTS was reliably detected after higher levels of sound exposure. Changes in audiometric thresholds had a "notch" configuration, with the largest changes observed at 4 kHz (mean = 6.3 ± 3.9 dB; range = 0-14 dB). Recovery was largely complete within the first 4 hr postexposure, and all subjects showed complete recovery of both thresholds and DPOAE measures when tested 1 week postexposure. These data provide insight into the variability of TTS induced by music-player use in a healthy, normal-hearing, young adult population, with music playlist, level, and duration carefully controlled. These data confirm the likelihood of temporary changes in auditory function after digital music-player use. Such data are essential for the development of a human clinical trial protocol that provides a highly powered design for evaluating novel therapeutics in human clinical trials. Care must be taken to fully inform potential subjects in

Procalcitonin NH2-terminal cleavage peptide has no mitogenic effect on normal human osteoblast-like cells

International Nuclear Information System (INIS)

Hassager, C.; Bonde, S.K.; Anderson, M.A.; Rink, H.; Spelsberg, T.C.; Riggs, B.L.

1991-01-01

The NH2-terminal cleavage peptide of procalcitonin (N-proCT) recently was reported to be a bone cell mitogen. The authors have investigated the effect of N-proCT on the proliferation of normal human cells that have the phenotype of mature osteoblasts (hOB cells). N-proCT treatment for 24, 48, or 96 h in concentrations from 1 nM to 1 microM did not significantly increase [3H]thymidine uptake (means ranged from -19% to 38% of control, no significant differences) in hOB cells (6-10 cell strains per experiment) plated at four different densities. However, the hOB cells responded significantly to treatment with transforming growth factor β (3 ng/ml), bovine insulin (300 micrograms/ml), or 30% fetal calf serum, which were included in all experiments as positive controls. The [3H]thymidine uptake data were confirmed in a direct cell count experiment tested at 96 h. Thus they data do not support the hypothesis that N-proCT is a potent mitogen for normal human osteoblasts

Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury.

Science.gov (United States)

Godar, Rebecca J; Ma, Xiucui; Liu, Haiyan; Murphy, John T; Weinheimer, Carla J; Kovacs, Attila; Crosby, Seth D; Saftig, Paul; Diwan, Abhinav

2015-01-01

Autophagy, a lysosomal degradative pathway, is potently stimulated in the myocardium by fasting and is essential for maintaining cardiac function during prolonged starvation. We tested the hypothesis that intermittent fasting protects against myocardial ischemia-reperfusion injury via transcriptional stimulation of the autophagy-lysosome machinery. Adult C57BL/6 mice subjected to 24-h periods of fasting, every other day, for 6 wk were protected from in-vivo ischemia-reperfusion injury on a fed day, with marked reduction in infarct size in both sexes as compared with nonfasted controls. This protection was lost in mice heterozygous null for Lamp2 (coding for lysosomal-associated membrane protein 2), which demonstrate impaired autophagy in response to fasting with accumulation of autophagosomes and SQSTM1, an autophagy substrate, in the heart. In lamp2 null mice, intermittent fasting provoked progressive left ventricular dilation, systolic dysfunction and hypertrophy; worsening cardiomyocyte autophagosome accumulation and lack of protection to ischemia-reperfusion injury, suggesting that intact autophagy-lysosome machinery is essential for myocardial homeostasis during intermittent fasting and consequent ischemic cardioprotection. Fasting and refeeding cycles resulted in transcriptional induction followed by downregulation of autophagy-lysosome genes in the myocardium. This was coupled with fasting-induced nuclear translocation of TFEB (transcription factor EB), a master regulator of autophagy-lysosome machinery; followed by rapid decline in nuclear TFEB levels with refeeding. Endogenous TFEB was essential for attenuation of hypoxia-reoxygenation-induced cell death by repetitive starvation, in neonatal rat cardiomyocytes, in-vitro. Taken together, these data suggest that TFEB-mediated transcriptional priming of the autophagy-lysosome machinery mediates the beneficial effects of fasting-induced autophagy in myocardial ischemia-reperfusion injury.

Repetitive stimulation of autophagy-lysosome machinery by intermittent fasting preconditions the myocardium to ischemia-reperfusion injury

Science.gov (United States)

Godar, Rebecca J; Ma, Xiucui; Liu, Haiyan; Murphy, John T; Weinheimer, Carla J; Kovacs, Attila; Crosby, Seth D; Saftig, Paul; Diwan, Abhinav

2015-01-01

Autophagy, a lysosomal degradative pathway, is potently stimulated in the myocardium by fasting and is essential for maintaining cardiac function during prolonged starvation. We tested the hypothesis that intermittent fasting protects against myocardial ischemia-reperfusion injury via transcriptional stimulation of the autophagy-lysosome machinery. Adult C57BL/6 mice subjected to 24-h periods of fasting, every other day, for 6 wk were protected from in-vivo ischemia-reperfusion injury on a fed day, with marked reduction in infarct size in both sexes as compared with nonfasted controls. This protection was lost in mice heterozygous null for Lamp2 (coding for lysosomal-associated membrane protein 2), which demonstrate impaired autophagy in response to fasting with accumulation of autophagosomes and SQSTM1, an autophagy substrate, in the heart. In lamp2 null mice, intermittent fasting provoked progressive left ventricular dilation, systolic dysfunction and hypertrophy; worsening cardiomyocyte autophagosome accumulation and lack of protection to ischemia-reperfusion injury, suggesting that intact autophagy-lysosome machinery is essential for myocardial homeostasis during intermittent fasting and consequent ischemic cardioprotection. Fasting and refeeding cycles resulted in transcriptional induction followed by downregulation of autophagy-lysosome genes in the myocardium. This was coupled with fasting-induced nuclear translocation of TFEB (transcription factor EB), a master regulator of autophagy-lysosome machinery; followed by rapid decline in nuclear TFEB levels with refeeding. Endogenous TFEB was essential for attenuation of hypoxia-reoxygenation-induced cell death by repetitive starvation, in neonatal rat cardiomyocytes, in-vitro. Taken together, these data suggest that TFEB-mediated transcriptional priming of the autophagy-lysosome machinery mediates the beneficial effects of fasting-induced autophagy in myocardial ischemia-reperfusion injury. PMID:26103523

Myocardial perfusion assessment at rest and after dipyridamole: MR signal intensity characteristics of reversible and persistent hypoperfusion

International Nuclear Information System (INIS)

Wintersperger, B.J.; Penzkofer, H.V.; Huber, A.; Meininger, M.; Scheidler, J.; Reiser, M.; Knez, A.; Haberl, R.; Kerner, M.; Knesewitsch, P.

2000-01-01

Methods: Sixteen patients with CAD underwent MR myocardial perfusion assessment at rest and after dipyridamole-induced hyperemia. Qualitative parameters (SI increase, SI upslope) of the SI time-curves were evaluated and characteristics of normal, reversible and persistent hypoperfused myocardium as assessed by 99m TC-SestaMIBI SPECT were compared. Results: Compared with the rest values, normal myocardium showed a significant increase of the SI upslope during hyperemia (P [de

Thallium 201 scintigraphy of the myocardium. A bibliographical survey for image optimisation

International Nuclear Information System (INIS)

Chatelier, Luc.

1979-01-01

At the request of a Nuclear Medicine Service we compiled a review of the literature on thallium 201 myocardium scintigraphy in order to define the optimum parameters for image acquisition; included also are the bibliograhical references of studies on the sensitivities, specificities and accuracies of this technique as compared with electrocardiography in the diagnosis and evaluation of ischemic heart diseases. This examination seems to have a part to play at all stages in the evaluation of ischemic heart diseases, whether for the detection (ischemia) emergency handling (thrombosis) or post-surgical checking (permeability of an aorto-coronary transplant) of these diseases, the great frequency and gravity of which have no longer to be proved. This study covers the whole period since thallium scintigraphy began (1970) until June 1978. Thallium seems to have a great future in cardiology and may be even in other fields since its use is quoted (in only a few publications as yet) for brain, kidney and pancreas scintigraphy [fr

Wearable Multi-Channel Microelectrode Membranes for Elucidating Electrophysiological Phenotypes of Injured Myocardium

Science.gov (United States)

Cao, Hung; Yu, Fei; Zhao, Yu; Zhang, Xiaoxiao; Tai, Joyce; Lee, Juhyun; Darehzereshki, Ali; Bersohn, Malcolm; Lien, Ching-Ling; Chi, Neil C.; Tai, Yu-Chong; Hsiai, Tzung K.

2014-01-01

Understanding the regenerative capacity of small vertebrate models has provided new insights into the plasticity of injured myocardium. Here, we demonstrated the application of flexible microelectrode arrays (MEAs) in elucidating electrophysiological phenotypes of zebrafish and neonatal mouse models of heart regeneration. The 4-electrode MEA membranes were designed to detect electrical signals in the aquatic environment. They were micro-fabricated to adhere to the non-planar body surface of zebrafish and neonatal mice. The acquired signals were processed to display electrocardiogram (ECG) with high signal-to-noise-ratios, and were validated via the use of conventional micro-needle electrodes. The 4-channel MEA provided signal stability and spatial resolution, revealing the site-specific electrical injury currents such as ST-depression in response to ventricular cryo-injury. Thus, our polymer-based and wearable MEA membranes provided electrophysiological insights in long-term conduction phenotypes for small vertebral models of heart injury and regeneration with a translational implication for monitoring cardiac patients. PMID:24945366

Transmural Variation and Anisotropy of Microvascular Flow Conductivity in the Rat Myocardium

KAUST Repository

Smith, Amy F.

2014-05-28

Transmural variations in the relationship between structural and fluid transport properties of myocardial capillary networks are determined via continuum modeling approaches using recent three-dimensional (3D) data on the microvascular structure. Specifically, the permeability tensor, which quantifies the inverse of the blood flow resistivity of the capillary network, is computed by volume-averaging flow solutions in synthetic networks with geometrical and topological properties derived from an anatomically-detailed microvascular data set extracted from the rat myocardium. Results show that the permeability is approximately ten times higher in the principal direction of capillary alignment (the "longitudinal" direction) than perpendicular to this direction, reflecting the strong anisotropy of the microvascular network. Additionally, a 30% increase in capillary diameter from subepicardium to subendocardium is shown to translate to a 130% transmural rise in permeability in the longitudinal capillary direction. This result supports the hypothesis that perfusion is preferentially facilitated during diastole in the subendocardial microvasculature to compensate for the severely-reduced systolic perfusion in the subendocardium.

The small Rho GTPase Rac1 controls normal human dermal fibroblasts proliferation with phosphorylation of the oncoprotein c-myc

International Nuclear Information System (INIS)

Nikolova, Ekaterina; Mitev, Vanio; Zhelev, Nikolai; Deroanne, Christophe F.; Poumay, Yves

2007-01-01

Proliferation of dermal fibroblasts is crucial for the maintenance of skin. The small Rho GTPase, Rac1, has been identified as a key transducer of proliferative signals in various cell types, but in normal human dermal fibroblasts its significance to cell growth control has not been studied. In this study, we applied the method of RNA interference to suppress endogenous Rac1 expression and examined the consequences on human skin fibroblasts. Rac1 knock-down resulted in inhibition of DNA synthesis. This effect was not mediated by inhibition of the central transducer of proliferative stimuli, ERK1/2 or by activation of the pro-apoptotic p38. Rather, as a consequence of the suppressed Rac1 expression we observed a significant decrease in phosphorylation of c-myc, revealing for the first time that in human fibroblasts Rac1 exerts control on proliferation through c-myc phosphorylation. Thus Rac1 activates proliferation of normal fibroblasts through stimulation of c-myc phosphorylation without affecting ERK1/2 activity

Differential Effects of Tea Extracts on Growth and Cytokine Production by Normal and Leukemic Human Leukocytes

Directory of Open Access Journals (Sweden)

Diana Bayer

2012-04-01

Full Text Available Background: Tea is one of the world’s most highly consumed beverages, second only to water. It is affordable and abundant and thus has great potential for improving health of those in both developed and developing areas. Green, oolong, and black teas differ in the extent of fermentation and types of bioactive polyphenols produced. Green tea and its major polyphenol decrease growth of some cancer cells and effect production of immune system cytokines. This study compares the effects of different types of tea extracts on viability and cytokine production by normal and leukemic human T lymphocytes. Generation of the toxic reactive oxygen species H2O2 by extracts was also examined.Methods: The Jurkat T lymphoblastic leukemia cells and mitogen-stimulated normal human peripheral blood mononuclear cells were used in this study. Cell viability was determined by (3-4,5-dimethylthiamizol-2-yl-diphenyltetrazolium bromide assay and production of interleukin-2 by Enzyme-Linked ImmunoSorbent Assay. Levels of H2O2 generated by tea extracts were determined using the xylenol-orange method.Results: We found that green, oolong, and black tea extracts differentially effect the growth and viability of T lymphoblastic leukemia cells and normal peripheral blood mononuclear cells, substantially decreasing both growth and viability of leukemic T lymphocytes and having much lesser effects on their normal counterparts. Tea extracts also had differential effects on the production of the T lymphocyte growth factor interleukin-2, significantly decreasing production by leukemic cells while having only minor effects on normal cells. All three extracts induced H2O2 generation, with green and oolong tea extracts having the greatest effect. Leukemic cells were much more susceptible to growth inhibition and killing by H2O2 than normal lymphocytes.Functional Foods in Health and Disease 2012, 2(4:72-85 Conclusions: The three tea extracts studied altered leukemic T lymphocyte

Enhanced expression of IL-8 in normal human keratinocytes and human keratinocyte cell line HaCaT in vitro after stimulation with contact sensitizers, tolerogens and irritants.

Science.gov (United States)

Mohamadzadeh, M; Müller, M; Hultsch, T; Enk, A; Saloga, J; Knop, J

1994-12-01

To investigate the interleukin-8 production of keratinocytes after stimulation in vitro we have used various agents: (i) contact sensitizer (2,4-dinitrofluorobenzene, 3-n-pentadecylcatechol); (ii) tolerogen (5-methyl-3-n-pentadecylcatechol); (iii) irritant (sodium lauryl sulfate). Interleukin-8 gene expression was assessed by northern blot hybridization of the total cytoplasmic RNA extracted from subconfluent normal human keratinocyte cultures and the keratinocyte cell line HaCaT using a radiolabeled DNA probe specific for human interleukin-8. Interleukin-8 gene expression was markedly increased upon in vitro stimulation after 1-6 h with contact sensitizers, tolerogen and the irritant. In contrast, interleukin-8 production was not detectable in unstimulated normal human keratinocytes or the HaCaT keratinocyte cell line. These results suggest that the induction and production of interleukin-8 is a response to nonspecific stimuli and may play a critical role in the early response to immunogenic or inflammatory signals in man.

Culture of normal human blood cells in a diffusion chamber system II. Lymphocyte and plasma cell kinetics

International Nuclear Information System (INIS)

Chikkappa, G.; Carsten, A.L.; Chanana, A.D.; Cronkite, E.P.

1979-01-01

Normal human blood leukocytes were cultured in Millipore diffusion chambers implanted into the peritoneal cavities of irradiated mice. The evaluation of survival and proliferation kinetics of cells in lymphyocytic series suggested that the lymphoid cells are formed from transition of small and/or large lymphocytes, and the lymphoblasts from the lymphoid cells. There was also evidence indicating that some of the cells in these two compartments are formed by proliferation. The evaluation of plasmacytic series suggested that the plasma cells are formed from plasmacytoid-lymphocytes by transition, and the latter from the transition of lymphocytes. In addition, relatively a small fraction of cells in these two compartments are formed by proliferation. mature plasma cells do not and immature plasma cells do proliferate. Estimation of magnitude of plasma cells formed in the cultures at day 18 indicated that at least one plasma cell is formed for every 6 normal human blood lymphocytes introduced into the culture

Angiographically demonstrated coronary collaterals predict residual viable myocardium in patients with chronic myocardial infarction. A regional metabolic study

International Nuclear Information System (INIS)

Fukai, Masumi; Ii, Masaaki; Nakakoji, Takahiro

2000-01-01

Angiographical demonstration of coronary collateral circulation may suggest the presence of residual viable myocardium. The development of coronary collaterals was judged according to Rentrop's classification in 37 patients with old anteroseptal myocardial infarction and 13 control patients with chest pain syndrome. The subjects with myocardial infarction were divided into 2 groups: 17 patients with the main branch of the left coronary artery clearly identified by collateral blood flow from the contralateral coronary artery [Coll (+) group, male/female 10/7, mean age 56.6 years] and 20 patients with obscure coronary trunk [Coll (-) group, male/female 16/4, mean age 54.9 years]. Thallium-201 myocardial scintigraphy and examination of local myocardial metabolism were carried out by measuring the flux of lactic acid under dipyridamole infusion load. Coronary stenosis of 99% or total occlusion was found in only 5 of 20 patients (25%) in the Coll (-) group but in 16 of 17 patients (94%) in the Coll (+) group (p<0.001). Redistribution of myocardial scintigraphy was found in 11 of 15 patients (73%) in the Coll (+) group, but only 3 of 18 patients (17%) in the Coll (-) group (p<0.01). The myocardial lactic acid extraction rate was -13.2±17.0% in the Coll (+) group, but 9.1±13.2% in the Coll (-) group (p<0.001). These results suggest that coronary collateral may contribute to minimizing the infarct area and to prediction of the presence of viable myocardium. (author)

Establishment of ultra long-lived cell lines by transfection of TERT into normal human fibroblast TIG-1 and their characterization.

Science.gov (United States)

Kamada, Mizuna; Kumazaki, Tsutomu; Matsuo, Taira; Mitsui, Youji; Takahashi, Tomoko

2012-06-01

To establish useful human normal cell lines, TERT (telomerase reverse transcriptase) cDNA was transfected into normal female lung fibroblast, TIG-1. After long-term-sub-cultivation of 74 individual clones selected for resistance to G418, we obtained 55 cultures with normal range of life span [75 PDL (population doubling level)], 16 cultures with extended life span (75-140 PDL). In addition, 3 immortal cell strains and unexpectedly, one ultra long-lived cell line (ULT-1) with life span of 166 PDL were established. IMT-1, one of the immortal cell strains was confirmed to maintain long telomere length, high telomerase activity and an extremely low level of p16INK4A. They also showed moderate p53 and p21CIP1 expression, keeping vigorous growth rate even at 450 PDL. High level of fibronectin and collagen 1α expression confirmed IMT-1 as normal fibroblasts, although one X chromosome had been lost. ULT-1, however, kept a near normal karyotypes and had shortening of telomere length, high expression of p16INK4A, moderate levels of senescence associated-β-galactosidase positive cells and decreased growth rate only after 150 PDs (population doublings), and finally reached senescence at 166 PDL with morphology of normal senescent fibroblasts. As resources of standard normal human cell, abundant vials of early and middle passages of ULT-1 have been stocked. The use of the cell line is discussed, focusing on isograft of artificial skin and screening of anti-aging or safe chemical agents.

The value of magnetic resonance spectroscopy in diagnosing myocardial infarction

International Nuclear Information System (INIS)

Gao Fabao; Huang Zhilan; Fang Hong; Zhao Haitao; Suo Liping; Gao Yuangui; Mao Songshou

1999-01-01

Objective: To determine the amount of high-energy phosphates and internal ratios various phosphate metabolites in myocardium of normal subjects and patients with myocardial infarction using 31 P MR spectroscopy ( 31 P MRS), and to assess the clinical value of 31 P MRS in patients with myocardial infarction (MI). Method: Fifteen patients (all men, aged 31-66 years, mean 53.8 years) of MI (acute 5, chronic 10) with ejection fraction of less than 46% and 8 healthy volunteers (normal controls) were studied using a 1.5-T Siemens Magneton 63 SP MR imager. The 10-cm diameter surface coil ( 1 H and 31 P double-tuned surface coil) was employed. To minimize motion artifacts, the subjects were examined in prone position with chest wall lying just above the surface coil. 31 P MRS study was further conducted in 7 of 15 patients after PTCA and coronary thrombolytic therapy. Results: In the control group, the myocardium PCr/β-ATP and Pi/PCr ratio were 1.58 +- 0.19 and 0.36 +- 0.17, respectively, while in patients with MI, these parameters were 0.98 +- 0.31 and 1.22 +- 0.66 (P 31 P MRS in MI in Chinese population was first reported. The contents of high-energy metabolites and their ratios in myocardium in both normal control and those with MI were studied. Myocardial high energy phosphates were not depleted in human MI. 31 P MRS possesses a great potential in evaluating myocardial viability, effects of reperfusion, and the recovery of myocardial physiologic function after reestablishment of coronary blood flow

Human paraoxonase and HDL-cholesterol in pakistan patients with acute myocardial infarction and normal healthy adults

International Nuclear Information System (INIS)

Iqbal, I.P.; Khan, A.H.; Mehboobali, N.

2007-01-01

Human serum paraoxonase is a high density lipoprotein (HDL)-bound enzyme exhibiting antiatherogenic properties. The aim of this study was to investigate any relationship between serum paraoxonase activity and serum levels of HDL-cholesterol in Pakistani patients with acute myocardial infarction (AMI) compared to normal healthy subjects and to examine possible association between serum paraoxonase activity and AMI in Pakistani population. In a case-control study, serum paraoxonase activity and serum levels of HDL-cholesterol and LDL-cholesterol were monitored in 164 Pakistani patients with AMI and 106 normal healthy adults matched for gender, BMI and age within 10 years. Mean serum concentration of HDL-cholesterol and mean serum paraoxonase activity in AMI patients were not significantly different from the corresponding values in normal healthy subjects. Mean serum paraoxonase activity value was significantly lower in normal healthy subjects with low HDL-cholesterol (serum levels < 40mg/dl) compared to the value in those with normal levels of HDL-cholesterol (P=0.04). In AMI patients, paraoxonase activity was lower in subjects with low HDL-cholesterol compared to those with normal levels of HDL-cholesterol, however, the decrease was not statistically significant. Correlation analyses of the data revealed a moderate association of paraoxonase activity with HDL-cholesterol (Pearson's r= 0.225, P<0.01 for AMI patients and r=0.281, P<0.01 for normal healthy controls). Seventy three percent of normal healthy subjects and 65% of AMI patients in this study had low HDL-cholesterol. Low serum paraoxonase activity and high prevalence of low HDL-cholesterol in Pakistani population could be contributing to the high rates of coronary heart disease in this population. (author)

Characterization of the functional and anatomical differences in the atrial and ventricular myocardium from three species of elasmobranch fishes: smooth dogfish (Mustelus canis), sandbar shark (Carcharhinus plumbeus), and clearnose skate (Raja eglanteria).

Science.gov (United States)

Larsen, Julie; Bushnell, Peter; Steffensen, John; Pedersen, Morten; Qvortrup, Klaus; Brill, Richard

2017-02-01

We assessed the functional properties in atrial and ventricular myocardium (using isolated cardiac strips) of smooth dogfish (Mustelus canis), clearnose skate (Raja eglanteria), and sandbar shark (Carcharhinus plumbeus) by blocking Ca 2+ release from the sarcoplasmic reticulum (SR) with ryanodine and thapsigargin and measuring the resultant changes in contraction-relaxation parameters and the force-frequency relationship at 20 °C and 30 °C. We also examined ultrastructural differences with electron microscopy. In tissues from smooth dogfish, net force (per cross-sectional area) and measures of the speeds of contraction and relaxation were all higher in atrial than ventricular myocardium at both temperatures. Atrial-ventricular differences were evident in the other two species primarily in measures of the rates of contraction and relaxation. Ryanodine-thapsigargin treatment reduced net force and its maximum positive first derivative (i.e., contractility), and increased time to 50 % relaxation in atrial tissue from smooth dogfish at 30 °C. It also increased times to peak force and half relaxation in clearnose skate atrial and ventricular tissue at both temperatures, but only in atrial tissue from sandbar shark at 30 °C; indicating that SR involvement in excitation-contraction (EC) coupling is species- and temperature-specific in elasmobranch fishes, as it is in teleost fishes. Atrial and ventricular myocardium from all three species displayed a negative force-frequency relationship, but there was no evidence that SR involvement in EC coupling was influenced by heart rate. SR was evident in electron micrographs, generally located in proximity to mitochondria and intercalated discs, and to a lesser extent between the myofibrils; with mitochondria being more numerous in ventricular than atrial myocardium in all three species.

Repetitive in vivo treatment with human recombinant interleukin-1 beta modifies beta-cell function in normal rats

DEFF Research Database (Denmark)

Wogensen, L D; Reimers, J; Nerup, J

1992-01-01

It is unknown whether interleukin-1 exerts a bimodal effect on Beta-cell function in vivo, and whether interleukin-1 has a diabetogenic action in normal animals. We therefore studied: (a) acute effects 2 h after an intraperitoneal bolus injection of 4 micrograms of recombinant human interleukin-1...

Gonadotropin-releasing hormone radioimmunoassay and its measurement in normal human plasma, secondary amenorrhea, and postmenopausal syndrome

International Nuclear Information System (INIS)

Rosenblum, N.G.; Schlaff, S.

1976-01-01

A sensitive and specific double antibody radioimmunoassay for gonadotropin-releasing hormone (GnRH) has been developed for measurement in ethanol extracts of human plasma. Iodinated hormone was prepared with the use of the chloramine-T method, and antibodies were developed in rabbits over a six-month period with a GnRH synthetic copolymer immunogen. A Scatchard plot revealed at least three species of antibody. The assay can measure conservatively at the 5 pg. per milliliter level and shows no cross-reactivity with other available hypothalamic and pituitary hormones. The releasing hormone was quantitatively recovered from human plasma with immunologic identity to native hormone. Unextracted plasma could not be used because of nonspecific displacement. The measurement of GnRH in individuals receiving 100 μg of intravenous bolus infusions of the synthetic decapeptide show extremely elevated values with two half-lives: one of two to four minutes and another of 35 to 40 minutes. In our experiments, we have found measurable GnRH in patients with secondary amenorrhea and at the midcycle in normal women. In the normal cycling woman during the follicular and luteal phases, GnRH was undetectable. In postmenopausal women with extreme hypoestrogenism and markedly elevated luteinizing hormone values, GnRH was also undetectable. No bursts of GnRH could be detected in normal men when sampled every ten minutes over a two-hour period and every two hours throughout the day

DNA strand breaking and rejoining in response to ultraviolet light in normal human and xeroderma pigmentosum cells

International Nuclear Information System (INIS)

Dingman, C.W.; Kakunaga, T.

1976-01-01

A description is given of a reproducible technique for measuring DNA strand breaking and rejoining in cells after treatment with U.V.-light. Results obtained with normal human cells, xeroderma pigmentosum cells (XP, complementation group A) and XP variant cells suggested that all three of these cell-types can carry out single-strand incision with equal rapidity. However, the breaks so induced appeared to be only slowly rejoined in the XP variant cells and rejoined not at all in XP complementation group A cells. Furthermore, parental strand rejoining was inhibited by caffeine in XP variant cells but not in normal cells. (author)

A patient with type I CD36 deficiency whose myocardium accumulated 123I-BMIPP after 4 years.

Science.gov (United States)

Ito, K; Sugihara, H; Tanabe, T; Zen, K; Hikosaka, T; Adachi, Y; Katoh, S; Azuma, A; Nakagawa, M

2001-06-01

A 73-year-old man with aortic regurgitation was examined by 123I-alpha-methyl-p-iodophenylpentadecanoic acid (BMIPP) myocardial single photon emission computed tomography (SPECT) in 1995. Myocardial accumulation was not evident on either the early or the delayed image obtained 15 minutes and 3 hours, respectively, after injecting 123I-BMIPP. Flow cytometric analysis of CD36 expression in monocytes and platelets identified a type I CD36 deficiency. The patient was hospitalized for severe heart failure in 1999. Upon admission, the cardiothoracic ratio on chest X-rays was 73%, and the left ventricular end-diastolic diameter on echocardiograms was enlarged to 77 mm. On the second day, we performed 123I-BMIPP myocardial SPECT. Myocardial accumulation was evident in the delayed, but not in the early image. We repeated 123I-BMIPP myocardial SPECT on the 10th day after admission. Myocardial accumulation was evident on both early and delayed images. 99mTc-tetrofosmin myocardial SPECT was immediately performed after 123I-BMIPP myocardial SPECT to distinguish myocardial from pooling images in the left ventricle, but, because the images from both 99Tc-tetrofosmin and 123I-BMIPP myocardial SPECT were idential, we considered that the 123I-BMIPP myocardial SPECT images reflected the actual myocardial condition. The CD36 molecule transports long-chain fatty acid (LCFA) on the myocardial membrane, but 123I-BMIPP scintigraphy does not show any myocardial accumulation in patients with type I CD36 deficiency, indicating that myocardial LCFA uptake occurs through CD36 on the human myocardial membrane. Even though our patient had type I CD36 deficiency, BMIPP was uptaken by the myocardium during heart failure, suggesting a variant pathway on the human myocardial membrane for LCFA uptake.