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Sample records for complex major abdominal

  1. Closed incision prophylactic negative pressure wound therapy in patients undergoing major complex abdominal wall repair

    NARCIS (Netherlands)

    de Vries, F. E. E.; Atema, J. J.; Lapid, O.; Obdeijn, M. C.; Boermeester, M. A.

    2017-01-01

    Purpose To evaluate if incisional prophylactic negative pressure wound therapy (pNPWT) reduces wound infections and other wound complications in high-risk patients undergoing major complex ventral abdominal wall repair. Methods Retrospective before-after comparison nested in a consecutive series of

  2. Effect of Dex medetomidine on Neuromuscular Blockade in Patients Undergoing Complex Major Abdominal or Pelvic Surgery

    International Nuclear Information System (INIS)

    El-Awady, G.A.; Abdelhalim, J.M.K.; Azer, M.S.

    2003-01-01

    Dex medetomidine is a highly selective α2 agonist with anesthetic, analgesic and sympatholytic properties. Its neuromuscular effects in humans are unknown. This study evaluates the effect of dex medetomidine on neuromuscular block and hemodynamics during thiopental/ isoflurane anesthesia for patients with complex abdominal or pelvic surgery. Patients and methods: During thiopental/isoflurane anesthesia, the rocuronium infusion rate was adjusted in 20 complex surgery patients to maintain a stable first response (T1) in the train of four sequence of 50% ± 3 of the pre-rocuronium value. Dex medetomidine was then administered by infusion pump, targeting a plasma dex medetomidine concentration of 0.6 ng/dL for 45 min. The evoked mechanical responses of the adductor pollicis responses (T1 response and T4/T1 ratio), systolic blood pressure, diastolic blood pressure and heart rate (HR) were measured during the dex medetomidine infusion using repeated measures analysis of variance. Plasma levels ranged from 0.73 to 1.38 ng/mL. Results: T1 values decreased during the infusion from 55(ρ2 to 38±9 ((ρ< 0.05). T4/Tl values did not change during the infusion. Dex medetomidine increased SBP (ρ< 0.001) and decreased HR ((ρ< 0.05) (10 min median values) during the infusion compared with values before the infusion. This study demonstrated that dex medetomidine decreased T1, increased SBP and decreased HR during thiopental/isoflurane anesthesia. Conclusion: We conclude that dex medetomidine induced direct vasoconstriction may alter pharmacokinetics of rocuronium, therefore increasing plasma rocuronium concentration. Although these effects were statistically significant, further studies should be held for understanding and characterizing the peripheral vasoconstrictive effects of a2 agonists that allow better management and determination of drug dosing regimens

  3. Expression of triggering receptor on myeloid cell 1 and histocompatibility complex molecules in sepsis and major abdominal surgery.

    Science.gov (United States)

    González-Roldán, Nestor; Ferat-Osorio, Eduardo; Aduna-Vicente, Rosalía; Wong-Baeza, Isabel; Esquivel-Callejas, Noemí; Astudillo-de la Vega, Horacio; Sánchez-Fernández, Patricio; Arriaga-Pizano, Lourdes; Villasís-Keever, Miguel Angel; López-Macías, Constantino; Isibasi, Armando

    2005-12-21

    To evaluate the surface expression of triggering receptor on myeloid cell 1 (TREM-1), class II major histocompatibility complex molecules (HLA-DR), and the expression of the splicing variant (svTREM-1) of TREM-1 in septic patients and those subjected to major abdominal surgery. Using flow cytometry, we examined the surface expression of TREM-1 and HLA-DR in peripheral blood monocytes from 11 septic patients, 7 elective gastrointestinal surgical patients, and 10 healthy volunteers. svTREM-1 levels were analyzed by RT-PCR. Basal expression of TREM-1 and HLA-DR in healthy volunteers was 35.91+/-14.75 MFI and 75.8+/-18.3%, respectively. In septic patients, TREM-1 expression was 59.9+/-23.9 MFI and HLA-DR expression was 44.39+/-20.25%, with a significant difference between healthy and septic groups (PSIRS, CARS, and sepsis.

  4. Perioperative Factors Predicting Prolonged Postoperative Ileus After Major Abdominal Surgery.

    Science.gov (United States)

    Sugawara, Kotaro; Kawaguchi, Yoshikuni; Nomura, Yukihiro; Suka, Yusuke; Kawasaki, Keishi; Uemura, Yukari; Koike, Daisuke; Nagai, Motoki; Furuya, Takatoshi; Tanaka, Nobutaka

    2017-11-08

    Prolonged postoperative ileus (PPOI) is among the common complications adversely affecting postoperative outcomes. Predictors of PPOI after major abdominal surgery remain unclear, although various PPOI predictors have been reported in patients undergoing colorectal surgery. This study aimed to devise a model for stratifying the probability of PPOI in patients undergoing abdominal surgery. Between 2012 and 2013, 841 patients underwent major abdominal surgery after excluding patients who underwent less-invasive abdominal surgery, ileus-associated surgery, and emergency surgery. Postoperative managements were generally based on enhanced recovery after surgery (ERAS) program. The definition of PPOI was based on nausea, no oral diet, flatus absence, abdominal distension, and radiographic findings. A nomogram was devised by evaluating predictive factors for PPOI. Of the 841 patients, 73 (8.8%) developed PPOI. Multivariable logistic regression analysis revealed smoking history (P = 0.025), colorectal surgery (P = 0.004), and an open surgical approach (P = 0.002) to all be independent predictive factors for PPOI. A nomogram was devised by employing these three significant predictive factors. The prediction model showed relatively good discrimination performance, the concordance index of which was 0.71 (95%CI 0.66-0.77). The probability of PPOI in patients with a smoking history who underwent open colorectal surgery was calculated to be 19.6%. Colorectal surgery, open abdominal surgery, and smoking history were found to be independent predictive factors for PPOI in patients who underwent major abdominal surgery. A nomogram based on these factors was shown to be useful for identifying patients with a high probability of developing PPOI.

  5. Criteria for definition of a complex abdominal wall hernia.

    Science.gov (United States)

    Slater, N J; Montgomery, A; Berrevoet, F; Carbonell, A M; Chang, A; Franklin, M; Kercher, K W; Lammers, B J; Parra-Davilla, E; Roll, S; Towfigh, S; van Geffen, E; Conze, J; van Goor, H

    2014-02-01

    A clear definition of "complex (abdominal wall) hernia" is missing, though the term is often used. Practically all "complex hernia" literature is retrospective and lacks proper description of the population. There is need for clarification and classification to improve patient care and allow comparison of different surgical approaches. The aim of this study was to reach consensus on criteria used to define a patient with "complex" hernia. Three consensus meetings were convened by surgeons with expertise in complex abdominal wall hernias, aimed at laying down criteria that can be used to define "complex hernia" patients, and to divide patients in severity classes. To aid discussion, literature review was performed to identify hernia classification systems, and to find evidence for patient and hernia variables that influence treatment and/or prognosis. Consensus was reached on 22 patient and hernia variables for "complex" hernia criteria inclusion which were grouped under four categories: "Size and location", "Contamination/soft tissue condition", "Patient history/risk factors", and "Clinical scenario". These variables were further divided in three patient severity classes ('Minor', 'Moderate', and 'Major') to provide guidance for peri-operative planning and measures, the risk of a complicated post-operative course, and the extent of financial costs associated with treatment of these hernia patients. Common criteria that can be used in defining and describing "complex" (abdominal wall) hernia patients have been identified and divided under four categories and three severity classes. Next step would be to create and validate treatment algorithms to guide the choice of surgical technique including mesh type for the various complex hernias.

  6. Meta-analysis of immunonutrition in major abdominal surgery.

    Science.gov (United States)

    Probst, P; Ohmann, S; Klaiber, U; Hüttner, F J; Billeter, A T; Ulrich, A; Büchler, M W; Diener, M K

    2017-11-01

    The objective of this study was to evaluate the potential benefits of immunonutrition in major abdominal surgery with special regard to subgroups and influence of bias. A systematic literature search from January 1985 to July 2015 was performed in MEDLINE, Embase and CENTRAL. Only RCTs investigating immunonutrition in major abdominal surgery were included. Outcomes evaluated were mortality, overall complications, infectious complications and length of hospital stay. The influence of different domains of bias was evaluated in sensitivity analyses. Evidence was rated according to the GRADE Working Group grading of evidence. A total of 83 RCTs with 7116 patients were included. Mortality was not altered by immunonutrition. Taking all trials into account, immunonutrition reduced overall complications (odds ratio (OR) 0·79, 95 per cent c.i. 0·66 to 0·94; P = 0·01), infectious complications (OR 0·58, 0·51 to 0·66; P high and unclear risk of bias. Publication bias seemed to be present for infectious complications (P = 0·002). Non-industry-funded trials reported no positive effects for overall complications (OR 1·13, 0·88 to 1·46; P = 0·34), whereas those funded by industry reported large effects (OR 0·66, 0·48 to 0·91; P = 0·01). Immunonutrition after major abdominal surgery did not seem to alter mortality (GRADE: high quality of evidence). Immunonutrition reduced overall complications, infectious complications and shortened hospital stay (GRADE: low to moderate). The existence of bias lowers confidence in the evidence (GRADE approach). © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

  7. Postoperative interleukin-6 level and early detection of complications after elective major abdominal surgery

    NARCIS (Netherlands)

    Rettig, Thijs C. D.; Verwijmeren, Lisa; Dijkstra, Ineke M.; Boerma, Djamila; Van De Garde, Ewoudt M. W.|info:eu-repo/dai/nl/304841528; Noordzij, Peter G.

    2016-01-01

    Objective: To assess the association of systemic inflammation and outcome after major abdominal surgery. Background: Major abdominal surgery carries a high postoperative morbidity and mortality rate. Studies suggest that inflammation is associated with unfavorable outcome. Methods: Levels of

  8. Abdominal wall closure in bladder exstrophy complex repair by ...

    African Journals Online (AJOL)

    Background and Objectives: The Exstrophy Complex (EC) is a serious malformation of midline abdominal wall. Wide pubis prevents approximating the lateralized rectus muscle and leads to dehiscence and fi stula formation. Our aim was to recommend an easier method for abdominal wall closure in the Bladder Exstrophy ...

  9. Dehydration and fluid volume kinetics before major open abdominal surgery.

    Science.gov (United States)

    Hahn, R G; Bahlmann, H; Nilsson, L

    2014-11-01

    Assessment of dehydration in the preoperative setting is of potential clinical value. The present study uses urine analysis and plasma volume kinetics, which have both been validated against induced changes in body water in volunteers, to study the incidence and severity of dehydration before open abdominal surgery begins. Thirty patients (mean age 64 years) had their urine analysed before major elective open abdominal surgery for colour, specific weight, osmolality and creatinine. The results were scored and the mean taken to represent a 'dehydration index'. Thereafter, the patients received an infusion of 5 ml/kg of Ringer's acetate intravenously for over 15 min. Blood was sampled for 70 min and the blood haemoglobin concentration used to estimate the plasma volume kinetics. Distribution of fluid occurred more slowly (P dehydrated as compared with euhydrated patients. The dehydration index indicated that the fluid deficit in these patients corresponded to 2.5% of the body weight, whereas the deficit in the others was 1%. In contrast, the 11 patients who later developed postoperative nausea and vomiting had a very short elimination half-life, only 9 min (median, P dehydration before major surgery was modest as evidenced both by urine sampling and volume kinetic analysis. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  10. Circadian distribution of sleep phases after major abdominal surgery

    DEFF Research Database (Denmark)

    Gogenur, I.; Wildschiotz, G.; Rosenberg, J.

    2008-01-01

    Background. It is believed that the severely disturbed night-time sleep architecture after surgery is associated with increased cardiovascular morbidity with rebound of rapid eye movement (REM). The daytime sleep pattern of patients after major general surgery has not been investigated before. We...... decided to study the circadian distribution of sleep phases before and after surgery. Methods. Eleven patients undergoing elective major abdominal surgery were included in the study. Continuous ambulatory polysomnographic monitoring was made 24 h before surgery and 36 h after surgery, thus including two...... time awake (P=0.016) in the postoperative daytime period compared with the preoperative daytime period. Five patients had REM sleep during the daytime after surgery. Three of these patients did not have REM sleep during the preceding postoperative night. There was significantly reduced night-time REM...

  11. Abdominal binders may reduce pain and improve physical function after major abdominal surgery - a systematic review

    DEFF Research Database (Denmark)

    Rothman, Josephine Philip; Gunnarsson, Ulf; Bisgaard, Thue

    2014-01-01

    with the use of abdominal binders. Reduction of pulmonary function during use of abdominal binders has not been revealed. CONCLUSION: Abdominal binders reduce post-operative psychological distress, but their effect on post-operative pain after laparotomy and seroma formation after ventral hernia repair remains......INTRODUCTION: Evidence for the effect of post-operative abdominal binders on post-operative pain, seroma formation, physical function, pulmonary function and increased intra-abdominal pressure among patients after surgery remains largely un-investigated. METHODS: A systematic review was conducted....... The PubMed, EMBASE and Cochrane databases were searched for studies on the use of abdominal binders after abdominal surgery or abdominoplasty. All types of clinical studies were included. Two independent assessors evaluated the scientific quality of the studies. The primary outcomes were pain, seroma...

  12. Complement activation and interleukin response in major abdominal surgery.

    Science.gov (United States)

    Kvarnström, A L; Sarbinowski, R T; Bengtson, J-P; Jacobsson, L M; Bengtsson, A L

    2012-05-01

    The objective of this study was to evaluate whether major abdominal surgery leads to complement activation and interleukin response and whether the kind of anaesthesia influence complement activation and the release of inflammatory interleukins. The study design was prospective and randomised. Fifty patients undergoing open major colorectal surgery due to cancer disease or inflammatory bowel disease were studied. Twenty-five patients were given total intravenous anaesthesia (TIVA) with propofol and remifentanil, and 25 patients were given inhalational anaesthesia with sevoflurane and fentanyl. To determine complement activation (C3a and SC5b-9) and the release of pro- and anti-inflammatory interleukins (tumour necrosis factor-a (TNF-a)), interleukin-1b (IL-1b), IL-6, IL-8, IL-4 and IL-10), blood samples were drawn preoperatively, 60 minutes after start of surgery, 30 minutes after end of surgery and 24 hours postoperatively. Complement was activated and pro-inflammatory interleukins (IL-6 and IL-8) and anti-inflammatory interleukins (IL-10) were released during major colorectal surgery. There was no significant difference between TIVA and inhalational anaesthesia regarding complement activation and cytokine release. Major colorectal surgery leads to activation of the complement cascade and the release of both pro-inflammatory and anti-inflammatory cytokines. There are no significant differences between total intravenous anaesthesia (TIVA) with propofol and remifentanil and inhalational anaesthesia with sevoflurane and fentanyl regarding complement activation and the release of pro- and anti-inflammatory interleukins. © 2012 The Authors. Scandinavian Journal of Immunology © 2012 Blackwell Publishing Ltd. Scandinavian Journal of Immunology.

  13. Criteria for definition of a complex abdominal wall hernia

    NARCIS (Netherlands)

    Slater, N.J.; Montgomery, A.; Berrevoet, F.; Carbonell, A.M.; Chang, A.; Franklin, M.; Kercher, K.W.; Lammers, B.J.; Parra-Davilla, E.; Roll, S.; Towfigh, S.; Geffen, E. van; Conze, J.; Goor, H. van

    2014-01-01

    PURPOSE: A clear definition of "complex (abdominal wall) hernia" is missing, though the term is often used. Practically all "complex hernia" literature is retrospective and lacks proper description of the population. There is need for clarification and classification to improve patient care and

  14. Abdominal binders may reduce pain and improve physical function after major abdominal surgery - a systematic review

    DEFF Research Database (Denmark)

    Rothman, Josephine Philip; Gunnarsson, Ulf; Bisgaard, Thue

    2014-01-01

    INTRODUCTION: Evidence for the effect of post-operative abdominal binders on post-operative pain, seroma formation, physical function, pulmonary function and increased intra-abdominal pressure among patients after surgery remains largely un-investigated. METHODS: A systematic review was conducted....... The PubMed, EMBASE and Cochrane databases were searched for studies on the use of abdominal binders after abdominal surgery or abdominoplasty. All types of clinical studies were included. Two independent assessors evaluated the scientific quality of the studies. The primary outcomes were pain, seroma...... to reduce seroma formation after laparoscopic ventral herniotomy and a non-significant reduction in pain. Physical function was improved, whereas evidence supports a beneficial effect on psychological distress after open abdominal surgery. Evidence also supports that intra-abdominal pressure increases...

  15. Oxygen uptake after major abdominal surgery: effect of clonidine.

    Science.gov (United States)

    Quintin, L; Viale, J P; Annat, G; Hoen, J P; Butin, E; Cottet-Emard, J M; Levron, J C; Bussery, D; Motin, J

    1991-02-01

    To examine the effect of an alpha-2 agonist, clonidine, on oxygen uptake and on the incidence of postoperative shivering, 28 patients presenting for major abdominal surgery were randomly assigned in a double-blind manner to one of two groups. Intraoperatively, 14 patients received 5 micrograms.kg-1 clonidine infused over 3 h (clonidine group), and 14 patients received placebo (placebo group). Oxygen uptake was measured continuously over the first 3 postoperative hours with a mass spectrometer system. Circulatory variables, esophageal temperature, and skin temperature were measured over the first 6 postoperative hours. Heart rate, mean arterial pressure, rate pressure product, and norepinephrine concentration were decreased in the clonidine group (P less than 2 x 10(-4)). There were no differences among groups in the incidence of shivering and in the rate of increase of esophageal temperature. By contrast, oxygen uptake was lower in the clonidine group (P = 4 x 10(-4)). This contrasting pattern may be secondary to a reduction in the intensity of mean muscular tremor in the clonidine group.

  16. Urethral obstruction malformation complex: a cause of abdominal muscle deficiency and the "prune belly".

    Science.gov (United States)

    Pagon, R A; Smith, D W; Shepard, T H

    1979-06-01

    Abdominal muscle deficiency with a "prune belly" abdomen as been a major feature of the so-called prune belly syndrome, which has been regarded as a specific entity, although the etiology and developmental pathology are not understood. We present evidence that abdominal muscle deficiency is an etiologically nonspecific anatomic defect which is secondary to fetal abdominal distention of various causes. One of the more common causes is urethral obstruction with consequent early bladder distention, causing abdominal distention and other anomalies, a constellation of findings which we have termed the urethral obstruction malformation complex. This interpretation of the etiology of most cases of prune belly syndrome accounts for the male predominance, the observed variability in severity, and the lack of a defined mode of inheritance. Recurrence risk figures need to be redefined for each specific obstructing lesion of the urethra. The possibility of early prenatal diagnosis and management of fetuses with urethral obstruction needs further study.

  17. Heterotopic intra-abdominal ossification in a complex ventral hernia defect.

    Science.gov (United States)

    Obeid, A; Sarhane, Ka; Berjaoui, T; Abiad, F

    2014-02-01

    Heterotopic ossification, an entity common in orthopaedic practice frequently involving the hip, knee or other joints, is rarely encountered in abdominal wounds and mesentery. This unusual condition, referred to as mesenteric ossification, is typically associated with intra-abdominal catastrophes. Surgical repair following such catastrophes has always been a challenge as the abdominal wall architecture is frequently distorted by the multiple laparotomies previously performed. In addition, the presence of several enterocutaneous fistulae further compounds the reconstruction approach, especially when mesh material is planned for use. We report a case of intra-abdominal heterotopic ossification with mesenteric involvement after a penetrating injury to the abdomen, followed by multiple laparotomies that ended in a complex abdominal wall hernia with major loss of domain, and multiple enterocutaneous fistulae. The patient was treated with resection of the bony deposits from the abdominal wound and cavity, along with excision of the fistula sites. This was followed by a component separation technique and the use of a biologic mesh graft to reconstruct the abdominal wall.

  18. Predicting mortality in damage control surgery for major abdominal ...

    African Journals Online (AJOL)

    0.001), low base excess (p=0.002), pH (p<0.001), core temperature (p=0.002), and high blood transfusion requirement over 24 hours (p=0.002). Conclusion. The overall survival of patients after damage control procedures for abdominal trauma ...

  19. Laparoscopy in major abdominal emergency surgery seems to be a safe procedure

    DEFF Research Database (Denmark)

    Nielsen, Liv Bjerre Juul; Tengberg, Line Toft; Bay-Nielsen, Morten

    2017-01-01

    INTRODUCTION: Laparoscopy is well established in the majority of elective procedures in abdominal surgery. In contrast, it is primarily used in minor surgery such as appendectomy or cholecystectomy in the emergent setting. This study aimed to analyze the safety and effectiveness of a laparoscopic...... approach in a large cohort of major abdominal emergencies. METHODS: A population-based cohort from the Region of Copenhagen, Denmark, including n = 1,139 patients undergoing major abdominal emergency surgery in 2012. RESULTS: A total of 313 patients were operated with an initial laparoscopic approach; 37...... days in the laparoscopic group, 12 days in the converted group and 11 days in the group of open operations. CONCLUSIONS: In a large, unselected group of major abdominal emergencies, we report a low rate of complications for operations conducted by an initial laparoscopic approach, and a high rate...

  20. Post-operative analgesia for major abdominal surgery and its effectiveness in a tertiary care hospital

    OpenAIRE

    Ahmed, Aliya; Latif, Naveed; Khan, Robyna

    2013-01-01

    Background: Post-operative pain is often inadequately treated. Optimal utilization of the available resources is essential for improving pain management. Aims: The aim of our study was to determine pain management strategies employed after major abdominal surgeries at our institute and their efficacy and safety. Settings and Design: Prospective observational study conducted at a tertiary care hospital. Materials and Methods: Patients undergoing elective major abdominal surgeries w...

  1. Pulmonary complications after major abdominal surgery: National Surgical Quality Improvement Program analysis.

    Science.gov (United States)

    Yang, Chun Kevin; Teng, Annabelle; Lee, David Y; Rose, Keith

    2015-10-01

    Postoperative pulmonary complications (PPCs) after major abdominal surgery are common and associated with significant morbidity and high cost of care. The objective of this study was to identify the risk factors for PPCs after major abdominal surgery. The American College of Surgeons' National Surgical Quality Improvement Program database from 2005-2012 was queried for patients who underwent major abdominal surgery (esophagectomy, gastrectomy, pacnreatectomy, enterectomy, hepatectomy, colectomy, and proctectomy). Predictors of PPCs were identified using multivariate logistic regression. Of 165,196 patients who underwent major abdominal surgery 9595 (5.8%) suffered PPCs (pneumonia 3.2%, prolonged ventilator support ≥48 h 3.0%, and unplanned intubation 2.8%). On multivariate analysis, significant predictors of overall and individual PPCs include esophagectomy, advanced American Society of Anesthesiology Classification System, dependent functional status, prolonged operative time, age ≥80 y, severe chronic obstructive pulmonary disease, preoperative shock, ascites, and smoking. Obesity was not a risk factor. Female gender was overall protective for PPCs. PPCs after abdominal procedures are associated with a number of clinical variables. Esophageal operations and American Society of Anesthesiology Classification System were the strongest predictors. These results provide a framework for identifying patients at risk for developing pulmonary complications after major abdominal surgery. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Predicting mortality in damage control surgery for major abdominal ...

    African Journals Online (AJOL)

    has increased the survival rate after major trauma to over. 50%.1-6. The term ... Package for the Social Sciences (SPSS) for Windows, ver- sion 12.0 (SAS .... J Surg 2004; 91: 1095-1101. 8. American College of Surgeon's Committee on Trauma. Advanced Trauma. Life Support Manual. Chicago: ACS, 1997: 11-242. Table Iv.

  3. Exposure to environmental microbiota explains persistent abdominal pain and irritable bowel syndrome after a major flood.

    Science.gov (United States)

    Yusof, NurFadhilah; Hamid, Nurhazwani; Ma, Zheng Feei; Lawenko, Rona Marie; Wan Mohammad, Wan Mohd Zahiruddin; Collins, Deirdre A; Liong, Min Tze; Odamaki, Toshitaka; Xiao, Jinzhong; Lee, Yeong Yeh

    2017-01-01

    After an environmental disaster, the affected community is at increased risk for persistent abdominal pain but mechanisms are unclear. Therefore, our study aimed to determine association between abdominal pain and poor water, sanitation and hygiene (WaSH) practices, and if small intestinal bacterial overgrowth (SIBO) and/or gut dysbiosis explain IBS, impaired quality of life (QOL), anxiety and/or depression after a major flood. New onset abdominal pain, IBS based on the Rome III criteria, WaSH practices, QOL, anxiety and/or depression, SIBO (hydrogen breath testing) and stools for metagenomic sequencing were assessed in flood victims. Of 211 participants, 37.9% ( n  = 80) had abdominal pain and 17% ( n  = 36) with IBS subtyped diarrhea and/or mixed type ( n  = 27 or 12.8%) being the most common. Poor WaSH practices and impaired quality of life during flood were significantly associated with IBS. Using linear discriminant analysis effect size method, gut dysbiosis was observed in those with anxiety (Bacteroidetes and Proteobacteria, effect size 4.8), abdominal pain (Fusobacteria , Staphylococcus, Megamonas and Plesiomonas , effect size 4.0) and IBS ( Plesiomonas and Trabulsiella , effect size 3.0). Disturbed gut microbiota because of environmentally-derived organisms may explain persistent abdominal pain and IBS after a major environmental disaster in the presence of poor WaSH practices.

  4. Imaging of small bowel-related complications following major abdominal surgery

    Energy Technology Data Exchange (ETDEWEB)

    Sandrasegaran, Kumaresan [Department of Radiology, Indiana University Medical Center, UH 0279, 550 N. University Boulevard, Indianapolis, IN 46202 (United States); Maglinte, Dean D.T. [Department of Radiology, Indiana University Medical Center, UH 0279, 550 N. University Boulevard, Indianapolis, IN 46202 (United States)]. E-mail: dmaglint@iupui.edu

    2005-03-01

    To recognize and document the small bowel reactions following major abdominal surgery is an important key for a correct diagnosis. Usually, plain abdominal radiography is the initial imaging examination requested in the immediate postoperative period, whereas gastrointestinal contrast studies are used to look for specific complications. In some countries, especially in Europe, sonography is widely employed to evaluate any acute affection of the abdomen. CT is commonly used to assess postoperative abdominal complications; in our institution also CT enteroclysis is often performed, to provide additional important informations. Radiologist should be able to diagnose less common types of obstruction, such as afferent loop, closed loop, strangulating obstruction as well as internal hernia. This knowledge may assume a critical importance for surgeons to decide on therapy. In this article, we focus our attention on the imaging (particularly CT) in small bowel complications following abdominal surgery.

  5. Perioperative growth hormone treatment and functional outcome after major abdominal surgery

    DEFF Research Database (Denmark)

    Kissmeyer-Nielsen, Peter; Jensen, Martin Bach; Laurberg, Søren

    1999-01-01

    OBJECTIVE: To evaluate short- and long-term effects of perioperative human growth hormone (hGH) treatment on physical performance and fatigue in younger patients undergoing a major abdominal operation in a normal postoperative regimen with oral nutrition. SUMMARY BACKGROUND DATA: Muscle wasting...... and functional impairment follow major abdominal surgery. METHODS: Twenty-four patients with ulcerative colitis undergoing ileoanal J-pouch surgery were randomized to hGH (12 IU/day) or placebo treatment from 2 days before to 7 days after surgery. Measurements were performed 2 days before and 10, 30, and 90 days...

  6. Interventional treatment experience in multiple injury with major abdominal or pelvic injuries: 160 cases analysis

    Directory of Open Access Journals (Sweden)

    Tian-Xi Zhang

    2018-02-01

    Conclusion: The emergent intervention for embolization and haemorrhage control of multiple trauma patients with a major abdominal or pelvic injury and visceral organ haemorrhage has the advantages of less trauma, shorter operation time, shorter hospital stay, less blood transfusion in comparison to the traditional emergency surgeries.

  7. Lack of circadian variation in the activity of the autonomic nervous system after major abdominal operations

    DEFF Research Database (Denmark)

    Gögenur, Ismail; Rosenberg-Adamsen, Susan; Lie, Claus

    2002-01-01

    patients who had had major abdominal operations. INTERVENTIONS: Patients were monitored with 24-hour Holter ECG on the second postoperative day-evening-night. We calculated heart rate variability from the standard deviation of all normal R-R intervals (excluding ectopics-NN intervals) around the mean NN...

  8. Management of Complex Abdominal Wall Defects Associated with Penetrating Abdominal Trauma

    Science.gov (United States)

    2014-05-09

    soiling at the time of injury; they all had loss of abdominal wall skin, muscle and fascia. The grading system of abdominal wall injury described by...were made to close the abdomen; bowel func- tion was slow to improve due to the systemic sepsis. It was only Box 1 Some of the principles of management...amount of tension using pulley sutures through the surrounding muscle and fascia, and an on-lay polygalactin mesh placed over this. Dermal-holding

  9. Preoperative enoxaparin versus postoperative semuloparin thromboprophylaxis in major abdominal surgery: a randomized controlled trial.

    Science.gov (United States)

    Kakkar, Ajay K; Agnelli, Giancarlo; Fisher, William; George, Daniel; Lassen, Michael R; Mismetti, Patrick; Mouret, Patrick; Murphy, Judith; Lawson, Francesca; Turpie, Alexander G G

    2014-06-01

    To compare efficacy and safety of thromboprophylaxis with semuloparin started postoperatively versus enoxaparin started preoperatively in major abdominal surgery. Venous thromboembolism is an important complication following major abdominal surgery. Semuloparin is a novel ultra-low-molecular-weight heparin with high antifactor Xa and minimal antifactor IIa activity. In this double-blind noninferiority trial, adult patients undergoing major abdominal or pelvic operation under general anesthesia lasting more than 45 minutes were assigned to either daily enoxaparin 40 mg commenced preoperatively or daily semuloparin 20 mg commenced postoperatively, for 7 to 10 days. Patients underwent bilateral leg venography between 7 and 11 days postsurgery. The primary efficacy end point was the composite of any deep vein thrombosis, nonfatal pulmonary embolism, or all-cause death. The primary safety outcome was bleeding. Both were independently adjudicated. In total, 4413 patients were randomized; 3030 (1499 in the enoxaparin and 1531 in the semuloparin groups) were evaluable for the primary efficacy end point, which occurred in 97 patients (6.3%) in the semuloparin group and 82 patients (5.5%) in the enoxaparin group [odds ratio (OR) = 1.16, 95% confidence interval (CI): 0.84-1.59]. On the basis of a noninferiority margin of 1.25, postoperative semuloparin did not demonstrate noninferiority to preoperative enoxaparin. Major bleeding occurred in 63 of 2175 patients (2.9%) in the semuloparin group and 98 of 2177 patients (4.5%) in the enoxaparin group (OR = 0.63, 95% CI: 0.46-0.87). Semuloparin commenced postoperatively did not demonstrate noninferiority to enoxaparin initiated preoperatively for thromboprophylaxis after major abdominal surgery. Study registered with clinicaltrials.gov: NCT00679588.

  10. Major abdominal surgery in octogenarians: should high age affect surgical decision-making?

    Science.gov (United States)

    Straatman, Jennifer; Van der Wielen, Nicole; Cuesta, Miguel A; de Lange-de Klerk, Elly S M; van der Peet, Donald L

    2016-11-01

    Over the last decades longevity has increased significantly, with more octogenarians undergoing surgery. Here, we assess surgical outcomes after major abdominal surgery in octogenarians. Observational cohort of 874 patients undergoing major abdominal elective surgery between January 2009 and March 2014. Seventy-six octogenarians were propensity matched to 76 younger patients, corrected for sex, body mass index, American Society of Anesthesiologists classification, comorbidity, indication, and type of surgery. Minor complications were more prevalent in octogenarians (P = .01) and consisted mainly of respiratory complications; progressing to respiratory insufficiency requiring intubation in 28.6%. Preoperative weight loss (odds ratio 3 [1.1 to 8.3]) and upper gastrointestinal surgery (odds ratio 11 [2 to 60]) were associated with minor complications. Octogenarians are at increased risk of minor complications after major abdominal surgery. Major complication rates were similar, indicating the importance of preoperative assessment and standardized surgical techniques. Taking into account preoperative morbidities and type of surgery and techniques. Implementation of quality control algorithms may further improve outcomes in octogenarians. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Electrical impedance tomography during major open upper abdominal surgery: a pilot-study.

    Science.gov (United States)

    Schaefer, Maximilian S; Wania, Viktoria; Bastin, Bea; Schmalz, Ursula; Kienbaum, Peter; Beiderlinden, Martin; Treschan, Tanja A

    2014-01-01

    Electrical impedance tomography (EIT) of the lungs facilitates visualization of ventilation distribution during mechanical ventilation. Its intraoperative use could provide the basis for individual optimization of ventilator settings, especially in patients at risk for ventilation-perfusion mismatch and impaired gas exchange, such as patients undergoing major open upper abdominal surgery. EIT throughout major open upper abdominal surgery could encounter difficulties in belt positioning and signal quality. Thus, we conducted a pilot-study and tested whether EIT is feasible in patients undergoing major open upper abdominal surgery. Following institutional review board's approval and written informed consent, we included patients scheduled for major open upper abdominal surgery of at least 3 hours duration. EIT measurements were conducted prior to intubation, at the time of skin incision, then hourly during surgery until shortly prior to extubation and after extubation. Number of successful intraoperative EIT measurements and reasons for failures were documented. From the valid measurements, a functional EIT image of changes in tidal impedance was generated for every time point. Regions of interest were defined as horizontal halves of the picture. Monitoring of ventilation distribution was assessed using the center of ventilation index, and also using the total and dorsal ventilated lung area. All parameter values prior to and post intubation as well as extubation were compared. A p abdominal surgery lasting 4-13 hours were planned in 14 patients. The electrode belt was attached between the 2(nd) and 4(th) intercostal space. Consecutive valid measurements could be acquired in 13 patients (93%). 111 intraoperative measurements could be retrieved as planned (93%). Main obstacle was the contact of skin electrodes. Despite the high belt position, distribution of tidal volume showed a significant shift of ventilation towards ventral lung regions after intubation. This

  12. Post-operative analgesia for major abdominal surgery and its effectiveness in a tertiary care hospital

    Directory of Open Access Journals (Sweden)

    Aliya Ahmed

    2013-01-01

    Conclusion: Epidural, PCIA and opioid infusions are used for pain relief after major abdominal surgeries at our hospital. Although there is limited drug availability, regular assessments and appropriate dose adjustments by acute pain management service (APMS and use of multimodal analgesia led to a high level of patient satisfaction. We recommend that feedback to the primary anesthesiologists by APMS is of utmost importance to enable improvement in practice.

  13. Infectious Complications after Major Abdominal Cancer Surgery: In Search of Improvable Risk Factors.

    Science.gov (United States)

    Smit, Linda C; Bruins, Marjan J; Patijn, Gijs A; Ruijs, Gijs J H M

    2016-12-01

    Major resections for esophageal, gastric, hepatic, pancreatic, and colorectal cancer continue to be associated with a high peri-operative morbidity of up to 30%-40%. To a large extent, this morbidity is caused by infectious complications that add up to a considerable burden to patients and hospital costs. The objective of this large retrospective cross-sectional study was to determine independent patient and operation-related risk factors for infectious complications after major abdominal cancer operations to elucidate how infection rates can be reduced and improve health-care quality. In 1,389 cancer patients who underwent a major resection procedure between 2009 and 2013, infectious complications and their independent determinants were analyzed by multivariable logistic regression (p abdominal drainage (OR 1.41; p = 0.024) and a duration of surgery of ≥180 min (OR 1.85; p = 0.001) were risk factors for surgical site infections. Total parenteral nutrition was significantly associated with intravascular catheter-induced infections (OR 18.09; p abdominal cancer operations were identified, providing opportunities for further reducing peri-operative infections. General awareness and focus on preventing infectious complications may have a significant impact on health-care outcomes and costs.

  14. Intravenous fluid restriction after major abdominal surgery: a randomized blinded clinical trial

    Directory of Open Access Journals (Sweden)

    Legemate Dink A

    2009-07-01

    Full Text Available Abstract Background Intravenous (IV fluid administration is an essential part of postoperative care. Some studies suggest that a restricted post-operative fluid regime reduces complications and postoperative hospital stay after surgery. We investigated the effects of postoperative fluid restriction in surgical patients undergoing major abdominal surgery. Methods In a blinded randomized trial, 62 patients (ASA I-III undergoing elective major abdominal surgical procedures in a university hospital were allocated either to a restricted (1.5 L/24 h or a standard postoperative IV fluid regime (2.5 L/24 h. Primary endpoint was length of postoperative hospital stay (PHS. Secondary endpoints included postoperative complications and time to restore gastric functions. Results After a 1-year inclusion period, an unplanned interim analysis was made because of many protocol violations due to patient deterioration. In the group with the restricted regime we found a significantly increased PHS (12.3 vs. 8.3 days; p = 0.049 and significantly more major complications: 12 in 30 (40% vs. 5 in 32 (16% patients (Absolute Risk Increase: 0.24 [95%CI: 0.03 to 0.46], i.e. a number needed to harm of 4 [95%CI: 2–33]. Therefore, the trial was stopped prematurely. Intention to treat analysis showed no differences in time to restore gastric functions between the groups. Conclusion Restricted postoperative IV fluid management, as performed in this trial, in patients undergoing major abdominal surgery appears harmful as it is accompanied by an increased risk of major postoperative complications and a prolonged postoperative hospital stay. Trial registration Current Controlled Trials ISRCTN16719551

  15. Efficacy of postoperative continuous wound infiltration with local anesthetic after major abdominal surgery.

    Science.gov (United States)

    Abadir, Adel R; Nicolas, Fred; Gharabawy, Ramiz; Shah, Trusha; Michael, Rafik

    2009-01-01

    The aim of this study was to evaluate the analgesic efficacy, safety, opioid sparing effects and improvement of respiratory function when using 0.2% ropivacaine continuous wound infiltration after major intra-abdominal surgery. Forty patients undergoing major intra-abdominal surgery requiring a midline incision of > or = 20 cm were enrolled into this IRB-approved, randomized, prospective controlled study. Group 1: 20 patients, parenteral analgesia (control group). Group II: 20 patients, with local anesthetic wound infiltration (pain pump group). At the end of the procedure, in the pain pump group of patients, a multi hole, 20-gauge catheter was inserted percutaneously, above the fascia. An initial dose of 10 ml of 0.2% ropivacaine was injected in the wound through the catheter. A device provided continuous delivery of 0.2% ropivacaine; the infusion was initiated at 6 ml/h for the following two days. The total "rescue" morphine and oxycodone/acetaminophen tablets administered were significantly lower in the pain pump group. At all time intervals, resting pain scores were significantly lower in the pain pump group when compared with the control group. However, at the 4-48 and 12-48 hours pain scores generated after leg raise and coughing, respectively, were significantly lower in group II. The patient vital capacities were insignificantly higher in group II. We conclude that after major abdominal surgery, infiltration and continuous wound instillation with 0.2% ropivacaine decreases postoperative pain, opioid requirements and oral analgesia. Early patient rehabilitation, hastening convalescence, and preventing respiratory complications are expected outcomes of this approach.

  16. Post-operative analgesia for major abdominal surgery and its effectiveness in a tertiary care hospital

    Science.gov (United States)

    Ahmed, Aliya; Latif, Naveed; Khan, Robyna

    2013-01-01

    Background: Post-operative pain is often inadequately treated. Optimal utilization of the available resources is essential for improving pain management. Aims: The aim of our study was to determine pain management strategies employed after major abdominal surgeries at our institute and their efficacy and safety. Settings and Design: Prospective observational study conducted at a tertiary care hospital. Materials and Methods: Patients undergoing elective major abdominal surgeries were included. Post-operative analgesic strategy, co-analgesics used, pain and sedation scores, motor block, nausea and vomiting were recorded and patient satisfaction was determined. Results: Data was collected on 100 patients. Epidural analgesia was used in 61, patient controlled intravenous analgesia (PCIA) in 25 and opioid infusion in 14 patients. Multimodal analgesia was employed in 98 patients. The level of epidural was between L1-L3 in 31, T10-L1 in 20 and T8-T10 in 10 patients. Pethidine was used in 80% of patients receiving PCIA. Patients with epidurals at T8-T10 had lower pain scores. Fifteen patients had motor block, 73% of which were with epidural at L1-L3. Fourteen patients complained of nausea. Ninety nine out of 100 patients were satisfied with their analgesia. Conclusion: Epidural, PCIA and opioid infusions are used for pain relief after major abdominal surgeries at our hospital. Although there is limited drug availability, regular assessments and appropriate dose adjustments by acute pain management service (APMS) and use of multimodal analgesia led to a high level of patient satisfaction. We recommend that feedback to the primary anesthesiologists by APMS is of utmost importance to enable improvement in practice. PMID:24249983

  17. The Use of Autologous Peritoneum for Complete Caval Replacement Following Resection of Major Intra-abdominal Malignancies.

    Science.gov (United States)

    Coubeau, Laurent; Rico Juri, Juan-Manuel; Ciccarelli, Olga; Jabbour, Nicolas; Lerut, Jan

    2017-04-01

    Assessment of a simple layer peritoneal tube used as an autogenous inferior vena cava replacement. Extensive en-bloc multivisceral resection including major vessels is effective in selected abdominal malignancies, but the need for vascular reconstruction represents a surgical challenge. We describe the use of autologous peritoneum for caval replacement. Autogenous parietal peritoneum without fascial backing was harvested and tubularized to replace the inferior vena cava (IVC) in four patients with complex abdominal tumors. Surgical morbidity was evaluated using the Clavien-Dindo classification, and graft patency was systematically evaluated with ultrasound. All four patients had multiorgan resections for malignancies involving the retro-hepatic IVC, and they all required the replacement of infrarenal and suprarenal IVC segments. Additionally, all four required a right nephrectomy, two had a combined major hepatectomy, and one patient needed a veno-venous bypass. All had an R0 resection. A clinical follow-up took place between 5 and 11 months after surgery for each patient. Four-month graft patency was confirmed by ultra-sound and TDM with no sign of disease recurrence. Autologous peritoneum without fascial backing is a good and safe option for circumferential replacement of IVC after extensive en-bloc tumor resection with IVC involvement.

  18. Differential Effects of Intraoperative Positive End-expiratory Pressure (PEEP) on Respiratory Outcome in Major Abdominal Surgery Versus Craniotomy

    DEFF Research Database (Denmark)

    de Jong, Myrthe A C; Ladha, Karim S; Melo, Marcos F Vidal

    2015-01-01

    abdominal surgery patients and 5063 craniotomy patients. Analysis was performed using multivariable logistic regression. The primary outcome was a composite of major postoperative respiratory complications (respiratory failure, reintubation, pulmonary edema, and pneumonia) within 3 days of surgery. RESULTS...

  19. The association of pre-operative physical fitness and physical activity with outcome after scheduled major abdominal surgery

    NARCIS (Netherlands)

    Dronkers, J.J.; Chorus, A.M.J.; Meeteren, N.L.U. van; Hopman-Rock, M.

    2013-01-01

    We studied whether reported physical activity and measurements of fitness (hand, leg and inspiration) were associated with postoperative in-hospital mortality, length of stay and discharge destination in 169 patients after major oncological abdominal surgery. In multivariate analysis, adequate

  20. Postoperative analgesia after major abdominal surgery: Fentanyl–bupivacaine patient controlled epidural analgesia versus fentanyl patient controlled intravenous analgesia

    Directory of Open Access Journals (Sweden)

    Hazem El Sayed Moawad

    2014-10-01

    Conclusion: This study concluded that both PCEA and PCIA were effective in pain relief after major abdominal surgery but PCEA was much better in pain relief, less sedating effect and overall patient satisfaction.

  1. A prospective cohort study comparing early opioid requirement between Chinese from Hong Kong and Caucasian Australians after major abdominal surgery

    DEFF Research Database (Denmark)

    Konstantatos, A H; Imberger, G; Angliss, M

    2012-01-01

    The relationship between ethnicity and early opioid consumption is not well understood. Our prospective cohort study tested whether Chinese patients in Hong Kong require less opioid after major abdominal surgery compared with Caucasian patients in Australia.......The relationship between ethnicity and early opioid consumption is not well understood. Our prospective cohort study tested whether Chinese patients in Hong Kong require less opioid after major abdominal surgery compared with Caucasian patients in Australia....

  2. The Impact of Two Different Transfusion Strategies on Patient Immune Response during Major Abdominal Surgery: A Preliminary Report

    OpenAIRE

    Theodoraki, Kassiani; Markatou, Maria; Rizos, Demetrios; Fassoulaki, Argyro

    2014-01-01

    Blood transfusion is associated with well-known risks. We investigated the difference between a restrictive versus a liberal transfusion strategy on the immune response, as expressed by the production of inflammatory mediators, in patients subjected to major abdominal surgery procedures. Fifty-eight patients undergoing major abdominal surgery were randomized preoperatively to either a restrictive transfusion protocol or a liberal transfusion protocol (with transfusion if hemoglobin dropped be...

  3. Preoperative abdominal muscle elongation with botulinum toxin A for complex incisional ventral hernia repair.

    Science.gov (United States)

    Farooque, Faisal; Jacombs, Anita S W; Roussos, Emmanouel; Read, John W; Dardano, Anthony N; Edye, Michael; Ibrahim, Nabeel

    2016-01-01

    Surgical repair of recurrent abdominal incisional hernia(s) can be challenging due to complex operative conditions, intense post-operative pain, potential respiratory compromise and lateral muscle traction predisposing to early recurrence. We report our preliminary results with botulinum toxin A (BTA) injection causing flaccid paralysis (relaxation) of the lateral abdominal wall muscles prior to surgery. A prospective pilot study measured the effect of preoperative BTA prior to elective repair of recurrent abdominal hernias. Under ultrasound control, 2 weeks prior to surgery, 50 units of BTA was injected into the external oblique, internal oblique and transversus abdominis muscles at three sites on each side of the lateral abdominal wall (total dose 300 units). Pre- and post-BTA abdominal computed tomography measured changes in abdominal wall muscle thickness and length. All hernias were repaired with laparoscopic or laparoscopic-assisted mesh techniques in a single or two-staged procedure. Eight patients received BTA injections which were tolerated with no complications. Post-BTA preoperative computed tomography showed a significant increase in mean length of lateral abdominal wall from 18.5 cm pre-BTA to 21.3 cm post-BTA (P = 0.017) with a mean unstretched length gain of 2.8 cm per side (range 0.8-6.0 cm). All hernias were surgically reduced with mesh with no early recurrence. Preoperative BTA injection prior to complex abdominal hernia repair is a safe procedure that causes flaccid relaxation, elongation and thinning of the lateral abdominal muscles and decrease in hernia defect. Although further evaluation is required, BTA injections may be a useful adjunct to surgical repair of complex incisional hernias. © 2015 Royal Australasian College of Surgeons.

  4. The Major Histocompatibility Complex in Transplantation

    Directory of Open Access Journals (Sweden)

    Marco Antonio Ayala García

    2012-01-01

    Full Text Available The transplant of organs is one of the greatest therapeutic achievements of the twentieth century. In organ transplantation, the adaptive immunity is considered the main response exerted to the transplanted tissue, since the principal target of the immune response is the MHC (major histocompatibility complex molecules expressed on the surface of donor cells. However, we should not forget that the innate and adaptive immunities are closely interrelated and should be viewed as complementary and cooperating. When a human transplant is performed, HLA (human leukocyte antigens molecules from a donor are recognized by the recipient's immune system triggering an alloimmune response Matching of donor and recipient for MHC antigens has been shown to have a significant positive effect on graft acceptance. This paper will present MHC, the innate and adaptive immunities, and clinical HLA testing.

  5. The Major Histocompatibility Complex in Transplantation

    Science.gov (United States)

    Ayala García, Marco Antonio; González Yebra, Beatriz; López Flores, Andrea Liliana; Guaní Guerra, Eduardo

    2012-01-01

    The transplant of organs is one of the greatest therapeutic achievements of the twentieth century. In organ transplantation, the adaptive immunity is considered the main response exerted to the transplanted tissue, since the principal target of the immune response is the MHC (major histocompatibility complex) molecules expressed on the surface of donor cells. However, we should not forget that the innate and adaptive immunities are closely interrelated and should be viewed as complementary and cooperating. When a human transplant is performed, HLA (human leukocyte antigens) molecules from a donor are recognized by the recipient's immune system triggering an alloimmune response Matching of donor and recipient for MHC antigens has been shown to have a significant positive effect on graft acceptance. This paper will present MHC, the innate and adaptive immunities, and clinical HLA testing. PMID:22778908

  6. Preoperative exercise therapy for elective major abdominal surgery: a systematic review.

    Science.gov (United States)

    Pouwels, Sjaak; Stokmans, Rutger A; Willigendael, Edith M; Nienhuijs, Simon W; Rosman, Camiel; van Ramshorst, Bert; Teijink, Joep A W

    2014-01-01

    The impact of postoperative complications after Major Abdominal Surgery (MAS) is substantial, especially when socio-economical aspects are taken into account. This systematic review focuses on the effects of preoperative exercise therapy (PEXT) on physical fitness prior to MAS, length of hospital admission and postoperative complications in patients eligible for MAS, and on what is known about the most effective kind of exercise regime. A systematic search identified randomised controlled trials on exercise therapy and pulmonary physiotherapy prior to MAS. The methodological quality of the included studies was rated using the 'Delphi List For Quality Assessment of Randomised Clinical Trials'. The level of agreement between the two reviewers was estimated with Cohen's kappa. A total of 6 studies were included, whose methodological quality ranged from moderate to good. Cohen's kappa was 0.90. Three studies reported on improving physical fitness prior to MAS with the aid of PEXT. Two studies reported on the effect of training on postoperative complications, showing contradictory results. Three studies focused on the effect of preoperative chest physiotherapy on postoperative lung function parameters after MAS. While the effects seem positive, the optimal training regime is still unclear. Preoperative exercise therapy might be effective in improving the physical fitness of patients prior to major abdominal surgery, and preoperative chest physiotherapy seems effective in reducing pulmonary complications. However consensus on training method is lacking. Future research should focus on the method and effect of PEXT before high-risk surgical procedures. Copyright © 2013 Surgical Associates Ltd. All rights reserved.

  7. NUTRITIONAL ASSESSMENT IN PATIENTS PREDICTED TO MAJOR ABDOMINAL SURGERY AT THE GENERAL HOSPITAL CELJE

    Directory of Open Access Journals (Sweden)

    Ernest Novak

    2001-12-01

    Full Text Available Background. Malnutrition has serious implications for recovery after surgery. Early detection of malnutrition with nutritional support minimizes postoperative complications. Nutritional assessment tools need to be simple and suitable for use in everyday practice. In our study we wanted to determine, how many patients might benefit from nutritional support.Methods. From April to August 1999 fifty consecutively admitted patients predicted to major abdominal surgery have been examined. We used Mini nutritional assessment (MNA, Buzby’s nutrition risk index (NRI, blood albumin level and weight loss in the last 3 months period prior to the examination, to assess nutritional status.Results. We examined 50 patients (27 males and 23 females, age 76.5 ± 16.5 and confirmed malnutrition in 40% of patients with MNA and serum albumin level. The increased risk for nutrition-associated complications was confirmed by NRI and weight loss in 44%.Conclusions. A confident diagnosis of malnutrition and increased risk for nutrition-associated complications can be established by using a combination of simple methods like MNA, NRI, weight loss and serum albumin level. Almost half of the patients admitted for major abdominal surgery in General hospital Celje suffer from malnutrition and they may benefit with early nutritional intervention.

  8. Major Depression as a Complex Dynamic System.

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    Angélique O J Cramer

    Full Text Available In this paper, we characterize major depression (MD as a complex dynamic system in which symptoms (e.g., insomnia and fatigue are directly connected to one another in a network structure. We hypothesize that individuals can be characterized by their own network with unique architecture and resulting dynamics. With respect to architecture, we show that individuals vulnerable to developing MD are those with strong connections between symptoms: e.g., only one night of poor sleep suffices to make a particular person feel tired. Such vulnerable networks, when pushed by forces external to the system such as stress, are more likely to end up in a depressed state; whereas networks with weaker connections tend to remain in or return to a non-depressed state. We show this with a simulation in which we model the probability of a symptom becoming 'active' as a logistic function of the activity of its neighboring symptoms. Additionally, we show that this model potentially explains some well-known empirical phenomena such as spontaneous recovery as well as accommodates existing theories about the various subtypes of MD. To our knowledge, we offer the first intra-individual, symptom-based, process model with the potential to explain the pathogenesis and maintenance of major depression.

  9. Intraperitoneal And Incisional Bupivacaine Analgesia For Major Abdominal/Gynecologic Surgery: A Placebocontrolled

    Directory of Open Access Journals (Sweden)

    R. Azarfarin

    2006-05-01

    Full Text Available Background:Postoperative pain is an important surgical problem. Recent studies in pain pathophysiology have led to the hypothesis that with perioperative administration of analgesics (pre-emptive analgesia it may be possible to prevent or reduce postoperative pain. This study was planned to investigate the efficacy of pre-emptive analgesia on postoperative pain after major gynecologic abdominal surgeries. Methods: In this prospective, double-blinded, randomized, and placebocontrolled trial, 60 ASA physical status I and II patients undergoing major abdominal gynecologic surgeries were randomized to receive 45 mL of bupivacaine 0.375% or 45mL of normal saline; 30 mL and 15 mL of the treatment solution was administered into the peritoneal cavity and incision, respectively, before wound closure. The pain score of the patients was evaluated by the visual analogue scale (VAS on awakening, and at 6, 12, and 24h after surgery. Time to first analgesia request and total analgesic requirements in the first 24h were recorded. Results: Pain scores were significantly higher in the placebo group than in the bupivacaine group on awakening (5.98±1.01 v.s 1.05±1.05; p<0.001, and at 6h after surgery (5.37±0.85 vs. 2.51±1.02; p<0.001. First request to analgesia was significantly longer in the bupivacaine patients than in the placebo group (5.87±3.04 h vs.1.35±0.36; p<0.001.Meperidine consumption over 24h was 96.00 ±17.53 mg in the placebo group compared with 23.28 ±14.89 mg in the bupivacaine patients (p<0.001.Conclusion:A combination of intraperitoneal and incisional bupivacaine infiltration at the end of abdominal gynecologic surgeries reduces postoperative pain on awakening and for 6 hours after surgery, and provides significant opioidsparing analgesia for 24 h after gynecologic abdominal surgeries.

  10. Differential Effects of Intraoperative Positive End-expiratory Pressure (PEEP) on Respiratory Outcome in Major Abdominal Surgery Versus Craniotomy

    Science.gov (United States)

    Vidal Melo, Marcos F.; Staehr-Rye, Anne Kathrine; Bittner, Edward A.; Kurth, Tobias; Eikermann, Matthias

    2016-01-01

    Objectives In this study, we examined whether (1) positive end-expiratory pressure (PEEP) has a protective effect on the risk of major postoperative respiratory complications in a cohort of patients undergoing major abdominal surgeries and craniotomies, and (2) the effect of PEEP is differed by surgery type. Background Protective mechanical ventilation with lower tidal volumes and PEEP reduces compounded postoperative complications after abdominal surgery. However, data regarding the use of intraoperative PEEP is conflicting. Methods In this observational study, we included 5915 major abdominal surgery patients and 5063 craniotomy patients. Analysis was performed using multivariable logistic regression. The primary outcome was a composite of major postoperative respiratory complications (respiratory failure, reintubation, pulmonary edema, and pneumonia) within 3 days of surgery. Results Within the entire study population (major abdominal surgeries and craniotomies), we found an association between application of PEEP ≥5cmH2O and a decreased risk of postoperative respiratory complications compared with PEEP 5cmH2O was associated with a significant lower odds of respiratory complications in patients undergoing major abdominal surgery (odds ratio 0.53, 95% confidence interval 0.39 – 0.72), effects that translated to deceased hospital length of stay [median hospital length of stay : 6 days (4–9 days), incidence rate ratios for each additional day: 0.91 (0.84 - 0.98)], whereas PEEP >5cmH2O was not significantly associated with reduced odds of respiratory complications or hospital length of stay in patients undergoing craniotomy. Conclusions The protective effects of PEEP are procedure specific with meaningful effects observed in patients undergoing major abdominal surgery. Our data suggest that default mechanical ventilator settings should include PEEP of 5–10cmH2O during major abdominal surgery. PMID:26496082

  11. Entropy vs. Majorization: What Determines Complexity?

    Directory of Open Access Journals (Sweden)

    William Seitz

    2014-07-01

    Full Text Available The evolution of a microcanonical statistical ensemble of states of isolated systems from order to disorder as determined by increasing entropy, is compared to an alternative evolution that is determined by mixing character. The fact that the partitions of an integer N are in one-to-one correspondence with macrostates for N distinguishable objects is noted. Orders for integer partitions are given, including the original order by Young and the Boltzmann order by entropy. Mixing character (represented by Young diagrams is seen to be a partially ordered quality rather than a quantity (See Ruch, 1975. The majorization partial order is reviewed as is its Hasse diagram representation known as the Young Diagram Lattice (YDL.Two lattices that show allowed transitions between macrostates are obtained from the YDL: we term these the mixing lattice and the diversity lattice. We study the dynamics (time evolution on the two lattices, namely the sequence of steps on the lattices (i.e., the path or trajectory that leads from low entropy, less mixed states to high entropy, highly mixed states. These paths are sequences of macrostates with monotonically increasing entropy. The distributions of path lengths on the two lattices are obtained via Monte Carlo methods, and surprisingly both distributions appear Gaussian. However, the width of the path length distribution for diversity is the square root of the mixing case, suggesting a qualitative difference in their temporal evolution. Another surprising result is that some macrostates occur in many paths while others do not. The evolution at low entropy and at high entropy is quite simple, but at intermediate entropies, the number of possible evolutionary paths is extremely large (due to the extensive branching of the lattices. A quantitative complexity measure associated with incomparability of macrostates in the mixing partial order is proposed, complementing Kolmogorov complexity and Shannon entropy.

  12. Postoperative acute kidney injury in high-risk patients undergoing major abdominal surgery.

    Science.gov (United States)

    Romagnoli, Stefano; Zagli, Giovanni; Tuccinardi, Germana; Tofani, Lorenzo; Chelazzi, Cosimo; Villa, Gianluca; Cianchi, Fabio; Coratti, Andrea; De Gaudio, Angelo Raffaele; Ricci, Zaccaria

    2016-10-01

    Acute kidney injury (AKI) is a frequent complication in high-risk patients undergoing major surgery and is associated with longer hospital stay, increased risk for nosocomial infection and significantly higher costs. A prospective observational study exploring the incidence of AKI (AKIN classification at any stage) in high-risk patients within 48 hours after major abdominal surgery was conducted. Patients' preoperative characteristics, intraoperative management, and outcome were evaluated for associations with AKI using a logistic regression model. Data from 258 patients were analyzed. Thirty-one patients (12%) developed AKI, reaching the AKIN stage 1. No patient reached an AKIN stage higher than 1. AKI patients were older (75.2 vs 70.2 years; P = 0.0113) and had a higher body mass index (26.5 vs 25.1 kg/m(2)). In addition, AKI patients had a significantly longer ICU length of stay (3.4 vs 2.4 days; P= .0017). Creatinine levels of AKI patients increased significantly compared to the preoperative levels at 24 (P= .0486), 48 (P= .0011) and 72 hours (P= .0055), while after 72 hours it showed a downwards trend. At ICU discharge, 28 out of 31 patients (90.3%) recovered preoperative levels. Multivariate analysis identified age (OR 1.088; P= .002) and BMI (OR 1.124; P= .022) as risk factors for AKI development. Moreover, AKI development was an independent risk factor for ICU stays longer than 48 hours (OR 2.561; P= .019). Mild AKI is a not rare complication in high-risk patients undergoing major abdominal surgery. Although in almost the totality of cases, the indicators of renal function recovered to preoperative levels, post-operative AKI represents a primary risk factor for a prolonged ICU stay. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Major histocompatibility complex genomics and human disease.

    Science.gov (United States)

    Trowsdale, John; Knight, Julian C

    2013-01-01

    Over several decades, various forms of genomic analysis of the human major histocompatibility complex (MHC) have been extremely successful in picking up many disease associations. This is to be expected, as the MHC region is one of the most gene-dense and polymorphic stretches of human DNA. It also encodes proteins critical to immunity, including several controlling antigen processing and presentation. Single-nucleotide polymorphism genotyping and human leukocyte antigen (HLA) imputation now permit the screening of large sample sets, a technique further facilitated by high-throughput sequencing. These methods promise to yield more precise contributions of MHC variants to disease. However, interpretation of MHC-disease associations in terms of the functions of variants has been problematic. Most studies confirm the paramount importance of class I and class II molecules, which are key to resistance to infection. Infection is likely driving the extreme variation of these genes across the human population, but this has been difficult to demonstrate. In contrast, many associations with autoimmune conditions have been shown to be specific to certain class I and class II alleles. Interestingly, conditions other than infections and autoimmunity are also associated with the MHC, including some cancers and neuropathies. These associations could be indirect, owing, for example, to the infectious history of a particular individual and selective pressures operating at the population level.

  14. Feasibility of real-time location systems in monitoring recovery after major abdominal surgery.

    Science.gov (United States)

    Dorrell, Robert D; Vermillion, Sarah A; Clark, Clancy J

    2017-12-01

    Early mobilization after major abdominal surgery decreases postoperative complications and length of stay, and has become a key component of enhanced recovery pathways. However, objective measures of patient movement after surgery are limited. Real-time location systems (RTLS), typically used for asset tracking, provide a novel approach to monitoring in-hospital patient activity. The current study investigates the feasibility of using RTLS to objectively track postoperative patient mobilization. The real-time location system employs a meshed network of infrared and RFID sensors and detectors that sample device locations every 3 s resulting in over 1 million data points per day. RTLS tracking was evaluated systematically in three phases: (1) sensitivity and specificity of the tracking device using simulated patient scenarios, (2) retrospective passive movement analysis of patient-linked equipment, and (3) prospective observational analysis of a patient-attached tracking device. RTLS tracking detected a simulated movement out of a room with sensitivity of 91% and specificity 100%. Specificity decreased to 75% if time out of room was less than 3 min. All RTLS-tagged patient-linked equipment was identified for 18 patients, but measurable patient movement associated with equipment was detected for only 2 patients (11%) with 1-8 out-of-room walks per day. Ten patients were prospectively monitored using RTLS badges following major abdominal surgery. Patient movement was recorded using patient diaries, direct observation, and an accelerometer. Sensitivity and specificity of RTLS patient tracking were both 100% in detecting out-of-room ambulation and correlated well with direct observation and patient-reported ambulation. Real-time location systems are a novel technology capable of objectively and accurately monitoring patient movement and provide an innovative approach to promoting early mobilization after surgery.

  15. The major histocompatibility complex in the chicken

    DEFF Research Database (Denmark)

    Guillemot, F; Kaufman, J F; Skjoedt, K

    1989-01-01

    The chicken B complex is the first non-mammalian MHC characterized at the molecular level. It differs from the human HLA and murine H-2 complexes in the small size of the class I (B-F) and class II (B-L) genes and their close proximity. This proximity accounts for the absence of recombination......-induced tumors associated with some B complex haplotypes. Udgivelsesdato: 1989-Sep...

  16. Sclerotic bone lesions at abdominal magnetic resonance imaging in children with tuberous sclerosis complex

    International Nuclear Information System (INIS)

    Boronat, Susana; Barber, Ignasi; Pargaonkar, Vivek; Chang, Joshua; Thiele, Elizabeth A.

    2016-01-01

    Sclerotic bone lesions are often seen on chest CT in adults with tuberous sclerosis complex. To characterize bone lesions at abdominal MRI in children with tuberous sclerosis complex. This retrospective review included 70 children with tuberous sclerosis complex who had undergone abdominal MRI for renal imaging. An additional longitudinal study was performed in 50 children who had had two or more MRI scans. Abdominal CT (eight children) and radiographs (three children) were reviewed and compared with MRI. A total of 173 sclerotic bone lesions were detected in 51/70 children (73%; 95% confidence interval: 0.61-0.82) chiefly affecting vertebral pedicles. New lesions appeared in 20 children and growth of previous sclerotic bone lesions was documented in 14 children. Sclerotic bone lesions were more frequent in girls and in children with more extensive renal involvement. Sclerotic bone lesions are commonly detected by abdominal MRI in children with tuberous sclerosis complex. They usually affect posterior vertebral elements and their number and size increase with age. As current recommendations for tuberous sclerosis complex surveillance include renal MR performed in childhood, recognition of these lesions is useful. (orig.)

  17. Sclerotic bone lesions at abdominal magnetic resonance imaging in children with tuberous sclerosis complex

    Energy Technology Data Exchange (ETDEWEB)

    Boronat, Susana [Massachusetts General Hospital, Department of Neurology, Boston, MA (United States); Universitat Autonoma de Barcelona, Department of Pediatric Neurology, Vall d' Hebron Hospital, Barcelona (Spain); Barber, Ignasi [Universitat Autonoma de Barcelona, Department of Pediatric Radiology, Vall d' Hebron Hospital, Barcelona (Spain); Pargaonkar, Vivek [Massachusetts General Hospital, Department of Radiology, Boston, MA (United States); Chang, Joshua; Thiele, Elizabeth A. [Massachusetts General Hospital, Department of Neurology, Boston, MA (United States)

    2016-05-15

    Sclerotic bone lesions are often seen on chest CT in adults with tuberous sclerosis complex. To characterize bone lesions at abdominal MRI in children with tuberous sclerosis complex. This retrospective review included 70 children with tuberous sclerosis complex who had undergone abdominal MRI for renal imaging. An additional longitudinal study was performed in 50 children who had had two or more MRI scans. Abdominal CT (eight children) and radiographs (three children) were reviewed and compared with MRI. A total of 173 sclerotic bone lesions were detected in 51/70 children (73%; 95% confidence interval: 0.61-0.82) chiefly affecting vertebral pedicles. New lesions appeared in 20 children and growth of previous sclerotic bone lesions was documented in 14 children. Sclerotic bone lesions were more frequent in girls and in children with more extensive renal involvement. Sclerotic bone lesions are commonly detected by abdominal MRI in children with tuberous sclerosis complex. They usually affect posterior vertebral elements and their number and size increase with age. As current recommendations for tuberous sclerosis complex surveillance include renal MR performed in childhood, recognition of these lesions is useful. (orig.)

  18. Association of Health Literacy With Postoperative Outcomes in Patients Undergoing Major Abdominal Surgery.

    Science.gov (United States)

    Wright, Jesse P; Edwards, Gretchen C; Goggins, Kathryn; Tiwari, Vikram; Maiga, Amelia; Moses, Kelvin; Kripalani, Sunil; Idrees, Kamran

    2018-02-01

    Low health literacy is known to adversely affect health outcomes in patients with chronic medical conditions. To our knowledge, the association of health literacy with postoperative outcomes has not been studied in-depth in a surgical patient population. To evaluate the association of health literacy with postoperative outcomes in patients undergoing major abdominal surgery. From November 2010 to December 2013, 1239 patients who were undergoing elective gastric, colorectal, hepatic, and pancreatic resections for both benign and malignant disease at a single academic institution were retrospectively reviewed. Patient demographics, education, insurance status, procedure type, American Society of Anesthesiologists status, Charlson comorbidity index, and postoperative outcomes, including length of stay, emergency department visits, and hospital readmissions, were reviewed from electronic medical records. Health literacy levels were assessed using the Brief Health Literacy Screen, a validated tool that was administered by nursing staff members on hospital admission. Multivariate analysis was used to determine the association of health literacy levels on postoperative outcomes, controlling for patient demographics and clinical characteristics. The association of health literacy with postoperative 30-day emergency department visits, 90-day hospital readmissions, and index hospitalization length of stay. Of the 1239 patients who participated in this study, 624 (50.4%) were women, 1083 (87.4%) where white, 96 (7.7%) were black, and 60 (4.8%) were of other race/ethnicity. The mean (SD) Brief Health Literacy Screen score was 12.9 (SD, 2.75; range, 3-15) and the median educational attainment was 13.0 years. Patients with lower health literacy levels had a longer length of stay in unadjusted (95% CI, 0.95-0.99; P = .004) and adjusted (95% CI, 0.03-0.26; P = .02) analyses. However, lower health literacy was not significantly associated with increased rates of 30-day

  19. Recruitment Maneuver in Elderly Patients with Different Peripheral Chemoreflex Sensitivity during Major Abdominal Surgery

    Directory of Open Access Journals (Sweden)

    Nikita Trembach

    2016-01-01

    Full Text Available The goal of the study was to evaluate the effect of a recruitment maneuver on respiratory biomechanics, oxygenation, and hemodynamics in patients suffering from chronic heart failure with different peripheral chemoreflex sensitivity. The study was conducted in 115 elderly patients which underwent major abdominal surgery under general/epidural surgery. Peripheral chemoreflex sensitivity (PCS was evaluated with breath-holding duration (BHD during breath-holding test. All patients were divided into two groups: group H had a high PCS (BHD = 38 seconds or less, n=49; Group M had a middle PCS (BHD more than 38 seconds, n=66. Recruitment maneuver improved oxygenation and respiratory biomechanics in all cases. However, cardiac output decreased by an average of 18%–31% in group H compared to 18%–28% in group M. SVR either remained unchanged or decreased by up to 14% of the initial value in group H, while, in group M, it had a tendency to increase, which was 24% of the initial value. So, recruitment maneuver is an effective method to improve oxygenation and biomechanical properties of the respiratory system but in patients with increased peripheral chemoreflex sensitivity it associates with the risk of hemodynamic disturbances.

  20. Recruitment Maneuver in Elderly Patients with Different Peripheral Chemoreflex Sensitivity during Major Abdominal Surgery.

    Science.gov (United States)

    Trembach, Nikita; Zabolotskikh, Igor

    2016-01-01

    The goal of the study was to evaluate the effect of a recruitment maneuver on respiratory biomechanics, oxygenation, and hemodynamics in patients suffering from chronic heart failure with different peripheral chemoreflex sensitivity. The study was conducted in 115 elderly patients which underwent major abdominal surgery under general/epidural surgery. Peripheral chemoreflex sensitivity (PCS) was evaluated with breath-holding duration (BHD) during breath-holding test. All patients were divided into two groups: group H had a high PCS (BHD = 38 seconds or less, n = 49); Group M had a middle PCS (BHD more than 38 seconds, n = 66). Recruitment maneuver improved oxygenation and respiratory biomechanics in all cases. However, cardiac output decreased by an average of 18%-31% in group H compared to 18%-28% in group M. SVR either remained unchanged or decreased by up to 14% of the initial value in group H, while, in group M, it had a tendency to increase, which was 24% of the initial value. So, recruitment maneuver is an effective method to improve oxygenation and biomechanical properties of the respiratory system but in patients with increased peripheral chemoreflex sensitivity it associates with the risk of hemodynamic disturbances.

  1. Intra-operative remifentanil might influence pain levels in the immediate postoperative period after major abdominal surgery

    DEFF Research Database (Denmark)

    Hansen, EG; Duedahl, Tina H; Rømsing, Janne

    2005-01-01

    Remifentanil, a widely used analgesic agent in anaesthesia, has a rapid onset and short duration of action. In clinical settings, this requires an appropriate pain strategy to prevent unacceptable pain in the post-operative period. The aim of this study was to investigate whether remifentanil had...... any impact on post-operative pain and opioid consumption after major abdominal surgery....

  2. Distinction by radioisotope technique of a subgroup with increased thrombophilic potential among patients submitted to major abdominal surgery

    DEFF Research Database (Denmark)

    Rasmussen, A; Toftdahl, D; Lindholt, J

    1986-01-01

    Deep vein thrombosis (DVT) detectable by the 99mTechnetium-labeled plasmin test developed in 13 (37%) of 35 sequentially studied patients, all above 40 years, undergoing elective major abdominal surgery. Ten of the 13 patients with DVT had an abnormal pulmonary perfusion scintigram, suggesting pu...

  3. Intra-operative remifentanil might influence pain levels in the immediate post-operative period after major abdominal surgery

    DEFF Research Database (Denmark)

    Hansen, E G; Duedahl, T H; Rømsing, J

    2005-01-01

    Remifentanil, a widely used analgesic agent in anaesthesia, has a rapid onset and short duration of action. In clinical settings, this requires an appropriate pain strategy to prevent unacceptable pain in the post-operative period. The aim of this study was to investigate whether remifentanil had...... any impact on post-operative pain and opioid consumption after major abdominal surgery....

  4. Qureshi-5 Catheter for Complex Supra- and Abdominal-Aortic Catheterization.

    Science.gov (United States)

    Qureshi, Adnan I; Xiao, WeiGang; Liu, HongLiang

    2015-10-01

    The use of previously described catheter technique was expanded to complex supra- and abdominal- aortic catheterizations. A new (Qureshi 5) catheter with curved shape at the distal end that has two lumens was used. One of lumens can accommodate a 0.035-inch guide wire and the second lumen can accommodate a 0.018-inch guide wire and terminates at the beginning of the distal curve of the first lumen. The manipulation and engagement of the curved distal end catheter was facilitated by rotation and movement of the J-shaped 0.018-inch guide wire extended coaxial and beyond the distal end of catheter. Subsequently, either contrast was injected or a 0.035-inch guide wire advanced into the target artery. The catheters were used in one patient to perform diagnostic cerebral and abdominal angiography through a 6F introducer sheath placed in the right common femoral artery. The catheterization was complex because of severe tortuosity of arch and descending aorta secondary to kyphosis. The left and right internal carotid arteries and left and right vertebral arteries, left renal artery, and superior mesenteric artery were catheterized in patient (fluoroscopy time 19:46 min). No complications were observed in the patient. The Qureshi-5 catheter was successful in complex supra- and abdominal-aortic catheterizations.

  5. Reconstruction of complex thoraco-abdominal defects with extended anterolateral thigh flap

    Directory of Open Access Journals (Sweden)

    Yadav Prabha

    2010-01-01

    Full Text Available Background: The reconstruction of complex thoraco-abdominal defects following tumour ablative procedures has evolved over the years from the use of pedicle flaps to free flaps. The free extended anterolateral thigh flap is a good choice to cover large defects in one stage. Materials and Methods: From 2004 to 2009, five patients with complex defects of the thoracic and abdominal wall following tumour ablation were reconstructed in one stage and were studied. The commonest tumour was chondrosarcoma. The skeletal component was reconstructed with methylmethacrylate bone cement and polypropylene mesh and the soft tissue with free extended anterolateral thigh flap. The flaps were anastomosed with internal mammary vessels. The donor sites of the flaps were covered with split-skin graft. Result: All the flaps survived well. One flap required re-exploration for venous congestion and was successfully salvaged. Two flaps had post operative wound infection and were managed conservatively. All flap donor sites developed hyper-pigmentation, contour deformity and cobble stone appearance. Conclusion: Single-stage reconstruction of the complex defects of the thoraco-abdominal region is feasible with extended anterolateral thigh flap and can be adopted as the first procedure of choice.

  6. OEIS complex with major cardiac malformation: a case report.

    Science.gov (United States)

    Batra, Prerna; Saha, Abhijeet; Vilhekar, K Y; Gupta, Anshu

    2007-04-01

    OEIS Complex is a rare congenital multisystem defect that consists of omphalocele, exstrophy, imperforate anus and spinal defects. We report a case of such complex with additional major cardiac and other multisystem anomalies which are rarely described in literature. The authors give a review of literature on this infrequent complex along with a discussion on its pathogenesis, differential diagnosis and prenatal diagnosis.

  7. Personalised Prehabilitation in High-risk Patients Undergoing Elective Major Abdominal Surgery: A Randomized Blinded Controlled Trial.

    Science.gov (United States)

    Barberan-Garcia, Anael; Ubré, Marta; Roca, Josep; Lacy, Antonio M; Burgos, Felip; Risco, Raquel; Momblán, Dulce; Balust, Jaume; Blanco, Isabel; Martínez-Pallí, Graciela

    2018-01-01

    The aim of this study was to assess the impact of personalized prehabilitation on postoperative complications in high-risk patients undergoing elective major abdominal surgery. Prehabilitation, including endurance exercise training and promotion of physical activity, in patients undergoing major abdominal surgery has been postulated as an effective preventive intervention to reduce postoperative complications. However, the existing studies provide controversial results and show a clear bias toward low-risk patients. This was a randomized blinded controlled trial. Eligible candidates accepting to participate were blindly randomized (1:1 ratio) to control (standard care) or intervention (standard care + prehabilitation) groups. Inclusion criteria were: i) age >70 years; and/or, ii) American Society of Anesthesiologists score III/IV. Prehabilitation covered 3 actions: i) motivational interview; ii) high-intensity endurance training; and promotion of physical activity. The main study outcome was the proportion of patients suffering postoperative complications. Secondary outcomes included the endurance time (ET) during cycle-ergometer exercise. We randomized 71 patients to the control arm and 73 to intervention. After excluding 19 patients because of changes in the surgical plan, 63 controls and 62 intervention patients were included in the intention-to-treat analysis. The intervention group enhanced aerobic capacity [ΔET 135 (218) %; P high-risk candidates for elective major abdominal surgery, which can be explained by the increased aerobic capacity.

  8. High-sensitive cardiac troponin T measurements in prediction of non-cardiac complications after major abdominal surgery.

    Science.gov (United States)

    Noordzij, P G; van Geffen, O; Dijkstra, I M; Boerma, D; Meinders, A J; Rettig, T C D; Eefting, F D; van Loon, D; van de Garde, E M W; van Dongen, E P A

    2015-06-01

    Postoperative non-cardiac complication rates are as high as 11-28% after high-risk abdominal procedures. Emerging evidence indicates that postoperative cardiac troponin T elevations are associated with adverse outcome in non-cardiac surgery. The aim of this study was to determine the relationship between postoperative high-sensitive cardiac troponin T elevations and non-cardiac complications in patients after major abdominal surgery. This prospective observational single-centre cohort study included patients at risk for coronary artery disease undergoing elective major abdominal surgery. Cardiac troponin was measured before surgery and at day 1, 3, and 7. Multivariable logistic regression analysis was performed to examine the adjusted association for different cut-off concentrations of postoperative myocardial injury and non-cardiac outcome. In 203 patients, 690 high-sensitive cardiac troponin T measurements were performed. Fifty-three patients (26%) had a non-cardiac complication within 30 days after surgery. Hospital mortality was 4% (8/203). An increase in cardiac troponin T concentration ≥100% compared with baseline was a superior independent predictor of non-cardiac postoperative clinical complications (adjusted odds ratio 4.3, 95% confidence interval 1.8-10.1, Phigh-sensitive cardiac troponin T increase ≥100% is a strong predictor of non-cardiac 30 day complications, increased hospital stay and hospital mortality in patients undergoing major abdominal surgery. NCT02150486. © The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Reliability of trans-abdominal ultrasonography in determining exact location of placenta in patients of placenta previa major

    International Nuclear Information System (INIS)

    Zafar, M.; Hayat, N; Gul, U.

    2017-01-01

    Objective: To determine the reliability of trans-abdominal ultrasonographical localization of placenta in cases of placenta previa major, by taking peroperative finding as gold standard. Study Design: Validation study. Place and Duration of Study: Maternity ward, Obstetrics and Gynecology department, Military Hospital Rawalpindi from 2007 to 2008. Patients and Methods: A total of 100 patients fulfilling the inclusion and exclusion criteria were recruited for the study. These patients were admitted to the maternity ward, where trans-abdominal ultrasound was performed, site of the placenta and its relation to the internal os was documented. These patients under went elective cesarean section, during which the site and relation of the placenta to the internal os was confirmed. Results: The mean age of patients was 34.23 +- 6.76 years. Transabdominal ultrasound had a sensitivity of 93.4 percent in localizing major placenta previa while the specificity was 83 percent. Positive predictive value was 94.7 percent, negative predictive value was 80 percent and accuracy 91 percent. Conclusion: Trans-abdominal ultrasound was found highly effective in diagnosing and localizing placenta previa. (author)

  10. Latissimus dorsi free flap reconstruction of major abdominal defect in treatment of giant Marjolin's ulcer

    DEFF Research Database (Denmark)

    Steffensen, Signe Muus; Thomassen, Anders; Jensen, Jesper Poul Naested

    2014-01-01

    We present a case of a 56-year-old man with a giant carcinoma in the abdominal wall. Based on positron emission tomography/computed tomography (PET/CT) scan there were FDG-avid lymph nodes in the ipsilateral axillary and groin, suspicious for metastases. At contrast-enhanced CT the parietal...... peritoneum seemed free of tumor invasion, which was essential to radical surgery planning. The tumor was completely removed with clear margins of resection and no metastasis in the resected lymph nodes. The PET/CT scan was repeated after 4 months, showing no signs of recurrence....

  11. An efficient unsupervised fetal QRS complex detection from abdominal maternal ECG.

    Science.gov (United States)

    Varanini, M; Tartarisco, G; Billeci, L; Macerata, A; Pioggia, G; Balocchi, R

    2014-08-01

    Non-invasive fetal heart rate is of great relevance in clinical practice to monitor fetal health state during pregnancy. To date, however, despite significant advances in the field of electrocardiography, the analysis of abdominal fetal ECG is considered a challenging problem for biomedical and signal processing communities. This is mainly due to the low signal-to-noise ratio of fetal ECG and difficulties in cancellation of maternal QRS complexes, motion and electromyographic artefacts. In this paper we present an efficient unsupervised algorithm for fetal QRS complex detection from abdominal multichannel signal recordings combining ICA and maternal ECG cancelling, which outperforms each single method. The signal is first pre-processed to remove impulsive artefacts, baseline wandering and power line interference. The following steps are then applied: maternal ECG extraction through independent component analysis (ICA); maternal QRS detection; maternal ECG cancelling through weighted singular value decomposition; enhancing of fetal ECG through ICA and fetal QRS detection. We participated in the Physionet/Computing in Cardiology Challenge 2013, obtaining the top official scores of the challenge (among 53 teams of participants) of event 1 and event 2 concerning fetal heart rate and fetal interbeat intervals estimation section. The developed algorithms are released as open-source on the Physionet website.

  12. Outcome of intraoperative goal-directed therapy using Vigileo/FloTrac in high-risk patients scheduled for major abdominal surgeries: A prospective randomized trial

    Directory of Open Access Journals (Sweden)

    Mohammed A. Elgendy

    2017-07-01

    Conclusion: The applied protocol for intraoperative GDT provided significant reduction of PO morbidities, ICU and hospital LOS but couldn‘t significantly reduce mortality rates in high risk patients scheduled for major abdominal surgeries.

  13. Dopexamine has no additional benefit in high-risk patients receiving goal-directed fluid therapy undergoing major abdominal surgery.

    Science.gov (United States)

    Davies, Simon J; Yates, David; Wilson, R Jonathan T

    2011-01-01

    Dopexamine has been shown to reduce both mortality and morbidity in major surgery when it is used as part of a protocol to increase oxygen delivery in the perioperative period. A European multicenter study has examined the use of dopexamine in patients undergoing major abdominal surgery, showing a trend toward improved survival and reduced complications in high-risk patients when receiving low-dose dopexamine (0.5 μg · kg(-1) · min(-1)). A reduced oxygen uptake at the anaerobic threshold (AT) has been shown to confer a significant risk of mortality in patients undergoing major abdominal surgery and allows objective identification of a high-risk operative group. In this study, we assessed the effects of low-dose dopexamine on morbidity after major abdominal surgery in patients who were at increased risk by virtue of a reduced AT. Patients undergoing elective major colorectal or urological surgery who had an AT of surgery, a radial arterial cannula was placed and attached to an Edwards Lifesciences FloTrac/Vigileo system for measuring cardiac output. Patients were given a 250-mL bolus of Voluven (6% hydroxyethyl starch 130/0.4 in 0.9% sodium chloride) until the stroke volume no longer increased by 10%, then received either dopexamine (0.5 μg · kg(-1) · min(-1)) or saline 0.9% for 24 hours. During surgery, fluid boluses of Voluven were given if the stroke volume variation was >10%. No crystalloid was given during surgery. A standardized postoperative fluid regime with Hartmann solution was prescribed at 1.5 mL · kg(-1) · h(-1) for 24 hours. The primary outcome measure was postoperative morbidity measured by the Postoperative Morbidity Survey. One hundred twenty-four patients were recruited over a 23-month period. The incidence of morbidity as measured by the Postoperative Morbidity Survey on day 5 was 55% in the control group versus 47% in the dopexamine group (P = 0.14). There was no significant reduction in morbidity on any measured postoperative day

  14. Rives-Stoppa incisional hernia repair combined with laparoscopic separation of abdominal wall components: a novel approach to complex abdominal wall closure.

    Science.gov (United States)

    Cox, T C; Pearl, J P; Ritter, E M

    2010-12-01

    The Rives-Stoppa incisional hernia repair is the gold standard for mesh repair of complex incisional hernias. The risk of infection can be reduced if fascia is closed over the prosthetic mesh. Fascial closure in large defects may require extensive dissection and can result in devascularization of the overlying skin and denervation of the abdominal wall musculature. Laparoscopic components separation minimizes these risks while facilitating anterior fascial closure. The combined technique of Rives-Stoppa repair augmented by laparoscopic separation of abdominal wall components has not previously been reported. We retrospectively reviewed our initial experience with this combined technique for incisional hernia repair. A Rives-Stoppa incisional hernia repair is performed with mesh placed in the retromuscular position. If the anterior fascia cannot be closed, a laparoscopic separation of abdominal wall components is performed to facilitate fascial closure without creation of skin flaps. Six patients were identified. Three patients developed hernias following laparotomy from severe injuries sustained during combat. The other patients included hernia after esophagectomy, retroperitoneal liposarcoma resection, and complicated diverticulitis. Average defect size was 270 cm(2). Complete primary fascial closure anterior to the mesh was achieved in 66% of the patients. No mortalities occurred and at short term follow-up no incisional hernia recurrences have developed. Early post operative complications included a superficial skin infection not involving mesh and a recurrent enterocutaneous fistula. The authors conclude that Rives-Stoppa repair augmented by laparoscopic components separation is an innovative method for reconstruction of complex abdominal wall defects. Laparoscopic components separation allows fascial closure to be achieved anterior to the mesh in large incisional hernias, which may reduce wound infection rates.

  15. Phage display of peptide / major histocompatibility class I complexes

    DEFF Research Database (Denmark)

    Vest Hansen, N; Ostergaard Pedersen, L; Stryhn, A

    2001-01-01

    Major histocompatibility complex class I (MHC-I) molecules sample peptides from the intracellular environment and present them to cytotoxic T cells (CTL). To establish a selection system, and, thereby, enable a library approach to identify the specificities involved (that of the MHC-I for peptides...... and subsequently that ot the T cell receptor for peptide-MHC-I complex), we have fused a single chain peptide-MHC-I complex to the phage minor coat protein, gpIII, and displayed it on filamentous phage. Expression of peptide-MHC-I complexes was shown with relevant conformation-specific monoclonal antibodies and......, more importantly, with a unique "T cell receptor-like" (i. e. peptide-specific, MHC-I-restricted) antibody. Thus, properly assembled and folded peptide-MHC-I complexes can be displayed on filamentous phage. Despite the successful display, interaction with T cells could not be demonstrated....

  16. Among 1,706 cases of abdominal wall reconstruction, what factors influence the occurrence of major operative complications?

    Science.gov (United States)

    Fischer, John P; Wink, Jason D; Nelson, Jonas A; Kovach, Stephen J

    2014-02-01

    Abdominal wall reconstruction (AWR) poses a substantial operative challenge, often in the setting of multiple failed attempts at repair in high-risk patients. Our aim was to assess risk factors for major operative morbidity after AWR using the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) patient database. A review of the ACS-NSQIP database of outcomes from 2005 to 2010 was performed to identify patients undergoing AWR utilizing Current Procedural Terminology codes for ventral hernia repair and a concomitant component separation. Independent variables included patient demographics, medical comorbidities, and operative considerations. Major operative complication (deep wound infection, graft or prosthetic loss, or unplanned return to the operating room within 30 days) was used as our dependent variable. Stepwise, multivariate logistic regression was performed to evaluate patient risk factors influencing the occurrence of major operative complications. We identified 1,706 patients with an average age of 55.9 ± 12.8 years with 30.1% undergoing concurrent intra-abdominal procedures and 57.1% undergoing mesh repair. Notable medical comorbidities included obesity (63.4%), smoking (24.9%), hypertension (53.1%), diabetes (19.9%), and anemia (22.6%). Average operative time was 211.7 ± 105.0 minutes. Regression analysis determined that prolonged operative time (odds ratio [OR], 2.7; P 2 (OR, 1.8; P = .009) were positively associated, whereas advanced age (OR, 0.5; P = .005) was negatively associated with the occurrence of major operative complications. Greater operative times and overall patient health are important prognostic factors for individuals undergoing AWR. The increased physiologic stress of a greater operative duration on patients who often have multiple comorbidities seems to play a significant role in predicting negative outcomes after AWR. Copyright © 2014 Mosby, Inc. All rights reserved.

  17. Human major histocompatibility complex contains genes for the major heat shock protein HSP70

    International Nuclear Information System (INIS)

    Sargent, C.A.; Dunham, I.; Campbell, R.D.; Trowsdale, J.

    1989-01-01

    Little is known as to why a large number of human diseases are influenced by the major histocompatibility complex. In some cases, a direct involvement of the products of the polymorphic class I and class II, as well as the less variable products of the class III, genes has been proposed. During characterization of the class III region for the presence of additional loci, the authors have located a duplicated locus encoding the major heat shock protein HSP70 between the complement and tumor necrosis factor genes. The HSP70 loci are 12 kilobases apart and lie 92 kilobases telomeric of the C2 gene. As HSP70 proteins have been linked with a protective role during and after cellular stress, and HSP70 analogues are often presented as antigens in bacterial and protozoal infections, this finding may have major implications with regard to the major histocompatibility complex and associated diseases

  18. Human major histocompatibility complex contains genes for the major heat shock protein HSP70

    Energy Technology Data Exchange (ETDEWEB)

    Sargent, C.A.; Dunham, I.; Campbell, R.D. (Medical Research Council Immunochemistry Unit , Oxford (England)); Trowsdale, J. (Imperial Cancer Research Fund, London (England))

    1989-03-01

    Little is known as to why a large number of human diseases are influenced by the major histocompatibility complex. In some cases, a direct involvement of the products of the polymorphic class I and class II, as well as the less variable products of the class III, genes has been proposed. During characterization of the class III region for the presence of additional loci, the authors have located a duplicated locus encoding the major heat shock protein HSP70 between the complement and tumor necrosis factor genes. The HSP70 loci are 12 kilobases apart and lie 92 kilobases telomeric of the C2 gene. As HSP70 proteins have been linked with a protective role during and after cellular stress, and HSP70 analogues are often presented as antigens in bacterial and protozoal infections, this finding may have major implications with regard to the major histocompatibility complex and associated diseases.

  19. Major Histocompatibility complex-DMB allelic diversity in old and ...

    African Journals Online (AJOL)

    Finally, a cluster grouping human and gorilla DMB cDNA sequences is obtained using a dendrogram (for the MHC genes, i.e.: C4d trees); this is in contrast to others' results that obtain a human/chimpanzee cluster using different DNA sequences. Keywords: MHC (Major Histocompatibility Complex), MHC-DMB, HLA-DMB, ...

  20. Aesthetic aspects of abdominal wall and external genital reconstructive surgery in bladder exstrophy-epispadias complex.

    Science.gov (United States)

    VanderBrink, Brian A; Stock, Jeffrey A; Hanna, Moneer K

    2006-03-01

    Long-term follow-up of patients born with classical bladder exstrophy-epispadias complex (EEC) reveals that many of them suffer from poor self-image, and the aesthetic aspects of the genitalia and lower abdomen acquire greater significance with age. In this article, we review the aesthetic outcomes in performing puboplasty, umbilicoplasty, and genitoplasty in patients born with EEC. Retrospective review of the cosmetic and functional outcomes in 116 patients born with EEC treated by puboplasty, umbilicoplasty, or genitoplasty was performed. Satisfaction with the cosmetic and functional outcomes of these three reconstructive surgeries was high following initial reconstructive efforts (> 90%). Attention to cosmesis during abdominal wall and genital reconstruction for EEC helps to improve a patient's perception of body image and self-esteem. Our experience with these procedures over the past 25 years demonstrated that the efforts directed toward aesthetics have been well worthwhile.

  1. MOLECULAR GENETICS OF THE SWINE MAJOR HISTOCOMPATIBILITY COMPLEX, THE SLA COMPLEX

    Science.gov (United States)

    The swine major histocompatibility complex (MHC) or swine leukocyte antigen (SLA) complex is one of the most gene-dense regions in the swine genome. It consists of three major gene clusters, the SLA class I, class III and class II regions, that span ~1.1, 0.7 and 0.5 Mb, respectively, making the swi...

  2. Robotic Transversus Abdominis Release (TAR: is it possible to offer minimally invasive surgery for abdominal wall complex defects?

    Directory of Open Access Journals (Sweden)

    MARIA VITÓRIA FRANÇA DO AMARAL

    Full Text Available ABSTRACT We describe the preliminary national experience and the early results of the use of robotic surgery to perform the posterior separation of abdominal wall components by the Transversus Abdominis Release (TAR technique for the correction of complex defects of the abdominal wall. We performed the procedures between 04/2/2015 and 06/15/2015 and the follow-up time was up to six months, with a minimum of two months. The mean surgical time was five hours and 40 minutes. Two patients required laparoscopic re-intervention, since one developed hernia by peritoneal migration of the mesh and one had mesh extrusion. The procedure proved to be technically feasible, with a still long surgical time. Considering the potential advantages of robotic surgery and those related to TAR and the results obtained when these two techniques are associated, we conclude that they seem to be a good option for the correction of complex abdominal wall defects.

  3. The Impact of Two Different Transfusion Strategies on Patient Immune Response during Major Abdominal Surgery: A Preliminary Report

    Directory of Open Access Journals (Sweden)

    Kassiani Theodoraki

    2014-01-01

    Full Text Available Blood transfusion is associated with well-known risks. We investigated the difference between a restrictive versus a liberal transfusion strategy on the immune response, as expressed by the production of inflammatory mediators, in patients subjected to major abdominal surgery procedures. Fifty-eight patients undergoing major abdominal surgery were randomized preoperatively to either a restrictive transfusion protocol or a liberal transfusion protocol (with transfusion if hemoglobin dropped below 7.7 g dL−1 or 9.9 g dL−1, respectively. In a subgroup of 20 patients randomly selected from the original allocation groups, blood was sampled for measurement of IL-6, IL-10, and TNFα. Postoperative levels of IL-10 were higher in the liberal transfusion group on the first postoperative day (49.82±29.07 vs. 15.83±13.22 pg mL−1, P<0.05. Peak postoperative IL-10 levels correlated with the units of blood transfused as well as the mean duration of storage and the storage time of the oldest unit transfused (r2=0.38, P=0.032, r2=0.52, P=0.007, and r2=0.68, P<0.001, respectively. IL-10 levels were elevated in patients with a more liberal red blood cell transfusion strategy. The strength of the association between anti-inflammatory IL-10 and transfusion variables indicates that IL-10 may be an important factor in transfusion-associated immunomodulation. This trial is registered under ClinicalTrials.gov Identifier: NCT02020525.

  4. Restrictive versus liberal fluid therapy in major abdominal surgery (RELIEF): rationale and design for a multicentre randomised trial.

    Science.gov (United States)

    Myles, Paul; Bellomo, Rinaldo; Corcoran, Tomas; Forbes, Andrew; Wallace, Sophie; Peyton, Philip; Christophi, Chris; Story, David; Leslie, Kate; Serpell, Jonathan; McGuinness, Shay; Parke, Rachel

    2017-03-03

    The optimal intravenous fluid regimen for patients undergoing major abdominal surgery is unclear. However, results from many small studies suggest a restrictive regimen may lead to better outcomes. A large, definitive clinical trial evaluating perioperative fluid replacement in major abdominal surgery, therefore, is required. We designed a pragmatic, multicentre, randomised, controlled trial (the RELIEF trial). A total of 3000 patients were enrolled in this study and randomly allocated to a restrictive or liberal fluid regimen in a 1:1 ratio, stratified by centre and planned critical care admission. The expected fluid volumes in the first 24 hour from the start of surgery in restrictive and liberal groups were ≤3.0 L and ≥5.4 L, respectively. Patient enrolment is complete, and follow-up for the primary end point is ongoing. The primary outcome is disability-free survival at 1 year after surgery, with disability defined as a persistent (at least 6 months) reduction in functional status using the 12-item version of the World Health Organisation Disability Assessment Schedule. The RELIEF trial has been approved by the responsible ethics committees of all participating sites. Participant recruitment began in March 2013 and was completed in August 2016, and 1-year follow-up will conclude in August 2017. Publication of the results of the RELIEF trial is anticipated in early 2018. ClinicalTrials.gov identifier NCT01424150. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  5. Attitudes of patients and care providers to enhanced recovery after surgery programs after major abdominal surgery.

    Science.gov (United States)

    Hughes, Michael; Coolsen, Marielle M E; Aahlin, Eirik K; Harrison, Ewen M; McNally, Stephen J; Dejong, C H C; Lassen, Kristoffer; Wigmore, Stephen J

    2015-01-01

    Enhanced recovery after surgery (ERAS) is a well-established pathway of perioperative care in surgery in an increasing number of specialties. To implement protocols and maintain high levels of compliance, continued support from care providers and patients is vital. This survey aimed to assess the perceptions of care providers and patients of the relevance and importance of the ERAS targets and strategies. Pre- and post-operative surveys were completed by patients who underwent major hepatic, colorectal, or oesophagogastric surgery in three major centers in Scotland, Norway, and The Netherlands. Anonymous web-based and article surveys were also sent to surgeons, anesthetists, and nurses experienced in delivering enhanced recovery protocols. Each questionnaire asked the responder to rate a selection of enhanced recovery targets and strategies in terms of perceived importance. One hundred nine patients and 57 care providers completed the preoperative survey. Overall, both patients and care providers rated the majority of items as important and supported ERAS principles. Freedom from nausea (median, 10; interquartile range [IQR], 8-10) and pain at rest (median, 10; IQR, 8-10) were the care components rated the highest by both patients and care providers. Early return of bowel function (median, 7; IQR, 5-8) and avoiding preanesthetic sedation (median, 6; IQR, 3.75-8) were scored the lowest by care providers. ERAS principles are supported by both patients and care providers. This is important when attempting to implement and maintain an ERAS program. Controversies still remain regarding the relative importance of individual ERAS components. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Epidemiology and Impact of Abdominal Oblique Injuries in Major and Minor League Baseball.

    Science.gov (United States)

    Camp, Christopher L; Conte, Stan; Cohen, Steven B; Thompson, Matthew; D' Angelo, John; Nguyen, Joseph T; Dines, Joshua S

    2017-03-01

    Oblique injuries are known to be a common cause of time out of play for professional baseball players, and prior work has suggested that injury rates may be on the rise in Major League Baseball (MLB). To better understand the current incidence of oblique injuries, determine their impact based on time out of play, and to identify common injury patterns that may guide future injury prevention programs. Descriptive epidemiological study. Using the MLB Health and Injury Tracking System, all oblique injuries that resulted in time out of play in MLB and Minor League Baseball (MiLB) during the 2011 to 2015 seasons were identified. Player demographics such as age, position/role, and handedness were included. Injury-specific factors analyzed included the following: date of injury, timing during season, days missed, mechanism, side, treatment, and reinjury status. A total of 996 oblique injuries occurred in 259 (26%) MLB and 737 (74%) MiLB players. Although the injury rate was steady in MiLB, the MLB injury rate declined ( P = .037). A total of 22,064 days were missed at a mean rate of 4413 days per season and 22.2 days per injury. The majority of these occurred during batting (n = 455, 46%) or pitching (n = 348, 35%), with pitchers losing 5 days more per injury than batters ( P time out of play in professional baseball. The vast majority of injuries occur on the lead side, and these injuries result in the greatest amount time out of play. The benefit of injections for the treatment of oblique injuries remains unknown.

  7. Diagnostic value of C-reactive protein to rule out infectious complications after major abdominal surgery: a systematic review and meta-analysis

    NARCIS (Netherlands)

    Gans, Sarah L.; Atema, Jasper J.; van Dieren, Susan; Groot Koerkamp, Bas; Boermeester, Marja A.

    2015-01-01

    Infectious complications occur frequently after major abdominal surgery and have a major influence on patient outcome and hospital costs. A marker that can rule out postoperative infectious complications (PICs) could aid patient selection for safe and early hospital discharge. C-reactive protein

  8. Human major histocompatibility complex contains genes for the major heat shock protein HSP70.

    OpenAIRE

    Sargent, C A; Dunham, I; Trowsdale, J; Campbell, R D

    1989-01-01

    Little is known as to why a large number of human diseases are influenced by the major histocompatibility complex. In some cases, a direct involvement of the products of the polymorphic class I and class II, aas well as the less variable products of the class III, genes has been proposed. During characterization of the class III region for the presence of additional loci, we have located a duplicated locus encoding the major heat shock protein HSP70 between the complement and tumor necrosis f...

  9. Risk Stratification for Major Postoperative Complications in Patients Undergoing Intra-abdominal General Surgery Using Latent Class Analysis.

    Science.gov (United States)

    Kim, Minjae; Wall, Melanie M; Li, Guohua

    2018-03-01

    Preoperative risk stratification is a critical element in assessing the risks and benefits of surgery. Prior work has demonstrated that intra-abdominal general surgery patients can be classified based on their comorbidities and risk factors using latent class analysis (LCA), a model-based clustering technique designed to find groups of patients that are similar with respect to characteristics entered into the model. Moreover, the latent risk classes were predictive of 30-day mortality. We evaluated the use of latent risk classes to predict the risk of major postoperative complications. An observational, retrospective cohort of patients undergoing intra-abdominal general surgery in the 2005 to 2010 American College of Surgeons National Surgical Quality Improvement Program was obtained. Known preoperative comorbidity and risk factor data were entered into LCA models to identify the latent risk classes. Complications were defined as: acute kidney injury, acute respiratory failure, cardiac arrest, deep vein thrombosis, myocardial infarction, organ space infection, pneumonia, postoperative bleeding, pulmonary embolism, sepsis/septic shock, stroke, unplanned reintubation, and/or wound dehiscence. Relative risk regression determined the associations between the latent classes and the 30-day complication risks, with adjustments for the surgical procedure. The area under the curve (AUC) of the receiver operator characteristic curve assessed model performance. LCA fit a 9-class model on 466,177 observations. The composite complication risk was 18.4% but varied from 7.7% in the lowest risk class to 56.7% in the highest risk class. After adjusting for procedure, the latent risk classes were significantly associated with complications, with risk ratios (95% confidence intervals) (compared to the class with the average risk) varying from 0.56 (0.54-0.58) in the lowest risk class to 2.15 (2.11-2.20) in the highest risk class, a 4-fold difference. In models incorporating surgical

  10. Use of insulin sensitizers for the treatment of major depressive disorder: a pilot study of pioglitazone for major depression accompanied by abdominal obesity.

    Science.gov (United States)

    Kemp, David E; Ismail-Beigi, Faramarz; Ganocy, Stephen J; Conroy, Carla; Gao, Keming; Obral, Sarah; Fein, Elizabeth; Findling, Robert L; Calabrese, Joseph R

    2012-02-01

    This study was conducted to examine the safety and efficacy of pioglitazone, a thiazolidinedione insulin sensitizer, in adult outpatients with major depressive disorder. In a 12-week, open-label, flexible-dose study, 23 patients with major depressive disorder received pioglitazone monotherapy or adjunctive therapy initiated at 15 mg daily. Subjects were required to meet criteria for abdominal obesity (waist circumference>35 in. in women and >40 in. in men) or metabolic syndrome. The primary efficacy measure was the change from baseline to Week 12 on the Inventory of Depressive Symptomatology (IDS) total score. Partial responders (≥25% decrease in IDS total score) were eligible to participate in an optional extension phase for an additional three months. Pioglitazone decreased depression symptom severity from a total IDS score of 40.3±1.8 to 19.2±1.8 at Week 12 (pdepressive symptoms was maintained during an additional 3-month extension phase (total duration=24 weeks) according to IDS total scores (pdepression severity and improve several markers of cardiometabolic risk, including insulin resistance and inflammation. Larger, placebo-controlled studies are indicated. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Birdsong signals individual diversity at the major histocompatibility complex.

    Science.gov (United States)

    Slade, J W G; Watson, M J; MacDougall-Shackleton, E A

    2017-11-01

    The major histocompatibility complex (MHC) plays a key role in vertebrate immunity, and pathogen-mediated selection often favours certain allelic combinations. Assessing potential mates' MHC profiles may provide receivers with genetic benefits (identifying MHC-compatible mates and producing optimally diverse offspring) and/or material benefits (identifying optimally diverse mates capable of high parental investment). Oscine songbirds learn songs during early life, such that song repertoire content can reflect population of origin while song complexity can reflect early life condition. Thus birdsong may advertise the singer's genetic dissimilarity to others in the population (and, presumably, compatibility with potential mates), or individual genetic diversity (and thus condition-dependent material benefits). We tested whether song repertoire content and/or complexity signal MHC class IIβ dissimilarity and/or diversity in male song sparrows ( Melospiza melodia ). Pairwise dissimilarity in repertoire content did not predict MHC dissimilarity between males, suggesting that locally rare songs do not signal rare MHC profiles. Thus, geographical variation in song may not facilitate MHC-mediated inbreeding or outbreeding. Larger repertoires were associated with intermediate MHC diversity, suggesting intermediate rather than maximal MHC diversity is optimal. This could reflect trade-offs between resisting infection and autoimmune disorders. Song complexity may advertise optimal MHC diversity, a trait affecting disease resistance and capacity for parental care. © 2017 The Author(s).

  12. Continuous monitoring of cerebral oxygen saturation in elderly patients undergoing major abdominal surgery minimizes brain exposure to potential hypoxia.

    Science.gov (United States)

    Casati, Andrea; Fanelli, Guido; Pietropaoli, Paolo; Proietti, Rodolfo; Tufano, Rosalba; Danelli, Giorgio; Fierro, Giuseppe; Fierro, Giovanni; De Cosmo, Germano; Servillo, Giovanni

    2005-09-01

    Elderly patients are more prone than younger patients to develop cerebral desaturation because of the reduced physiologic reserve that accompanies aging. To evaluate whether monitoring cerebral oxygen saturation (rSO(2)) minimizes intraoperative cerebral desaturation, we prospectively monitored rSO(2) in 122 elderly patients undergoing major abdominal surgery with general anesthesia. Patients were randomly allocated to an intervention group (the monitor was visible and rSO(2) was maintained at > or =75% of preinduction values; n = 56) or a control group (the monitor was blinded and anesthesia was managed routinely; n = 66). Cerebral desaturation (rSO(2) reduction <75% of baseline) was observed in 11 patients of the treatment group (20%) and 15 patients of the control group (23%) (P = 0.82). Mean (95% confidence intervals) values of mean rSO(2) were higher (66% [64%-68%]) and the area under the curve below 75% of baseline (AUCrSO2(2)< 75% of baseline) was lower (0.4 min% [0.1-0.8 min%]) in patients of the treatment group than in patients of the control group (61% [59%-63%] and 80 min% [2-144 min%], respectively; P = 0.002 and P = 0.017). When considering only patients developing intraoperative cerebral desaturation, a lower Mini Mental State Elimination (MMSE) score was observed at the seventh postoperative day in the control group (26 [25-30]) than in the treatment group (28 [26-30]) (P = 0.02), with a significant correlation between the AUCrSO(2) < 75% of baseline and postoperative decrease in MMSE score from preoperative values (r(2)= 0.25, P = 0.01). Patients of the control group with intraoperative cerebral desaturation also experienced a longer time to postanesthesia care unit (PACU) discharge (47 min [13-56 min]) and longer hospital stay (24 days [7-53] days) compared with patients of the treatment group (25 min [15-35 min] and 10 days [7-23 days], respectively; P = 0.01 and P = 0.007). Using rSO(2) monitoring to manage anesthesia in elderly patients

  13. The Major Histocompatibility Complex in Bovines: A Review

    Science.gov (United States)

    Behl, Jyotsna Dhingra; Verma, N. K.; Tyagi, Neha; Mishra, Priyanka; Behl, Rahul; Joshi, B. K.

    2012-01-01

    Productivity in dairy cattle and buffaloes depends on the genetic factors governing the production of milk and milk constituents as well as genetic factors controlling disease resistance or susceptibility. The immune system is the adaptive defense system that has evolved in vertebrates to protect them from invading pathogens and also carcinomas. It is remarkable in the sense that it is able to generate an enormous variety of cells and biomolecules which interact with each other in numerous ways to form a complex network that helps to recognize, counteract, and eliminate the apparently limitless number of foreign invading pathogens/molecules. The major histocompatibility complex which is found to occur in all mammalian species plays a central role in the development of the immune system. It is an important candidate gene involved in susceptibility/resistance to various diseases. It is associated with intercellular recognition and with self/nonself discrimination. It plays major role in determining whether transplanted tissue will be accepted as self or rejected as foreign. PMID:23738132

  14. Core muscle size assessed by perioperative abdominal CT scan is related to mortality, postoperative complications, and hospitalization after major abdominal surgery

    DEFF Research Database (Denmark)

    Hasselager, Rune; Gögenur, Ismail

    2014-01-01

    of these found significantly longer length of stay related to low core muscle area. Seven studies investigated 1-year and long-term mortality after surgery, whereof only one did not find significantly increased mortality related to low core muscle area. Furthermore, one study found increased short-term (... abdominal surgery. RESULTS: Eight studies were found. Four studies investigated postoperative complications related to core muscle area. Three of these studies found significantly increased risk of complications related to low core muscle area. Three studies investigated length of hospitalization, and two...

  15. Association of Major Dietary Patterns with General and Abdominal Obesity in Iranian Patients with Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Ghane Basiri, Marjan; Sotoudeh, Gity; Djalali, Mahmood; Reza Eshraghian, Mohammad; Noorshahi, Neda; Rafiee, Masoumeh; Nikbazm, Ronak; Karimi, Zeinab; Koohdani, Fariba

    2015-01-01

    The aim of this study was to identify dietary patterns associated with general and abdominal obesity in type 2 diabetic patients. We included 728 patients (35 - 65 years) with type 2 diabetes mellitus in this cross-sectional study. The usual dietary intake of individuals over 1 year was collected using a validated semi-quantitative food frequency questionnaire. Weight, height, and waist circumference were measured according to standard protocol. The two major dietary patterns identified by factor analysis were healthy and unhealthy dietary patterns. After adjustment for potential confounders, subjects in the highest quintile of the healthy dietary pattern scores had a lower odds ratio for the general obesity when compared to the lowest quintile (OR = 0.45, 95 % CI = 0.26 - 0.79, P for trend = 0.02), while patients in the highest quintile of the unhealthy dietary pattern scores had greater odds for the general obesity (OR = 3.2, 95 % CI = 1.8 - 5.9, P for trend obesity, even after adjusting for confounding factors. This study shows that in patients with type 2 diabetes mellitus, a healthy dietary pattern is inversely associated and an unhealthy dietary pattern is directly associated with general obesity.

  16. The association of pre-operative physical fitness and physical activity with outcome after scheduled major abdominal surgery.

    Science.gov (United States)

    Dronkers, J J; Chorus, A M J; van Meeteren, N L U; Hopman-Rock, M

    2013-01-01

    We studied whether reported physical activity and measurements of fitness (hand, leg and inspiration) were associated with postoperative in-hospital mortality, length of stay and discharge destination in 169 patients after major oncological abdominal surgery. In multivariate analysis, adequate activity level (OR 5.5, 95% CI 1.4-21.9) and inspiratory muscle endurance (OR 5.2, 95% CI 1.4-19.1) were independently associated with short-term mortality, whereas conventional factors, such as age and heart disease, were not. Adequate activity level (OR 6.7, 95% CI 1.4-3.0) was also independently associated with discharge destination. The factors that were independently associated with a shorter length of hospital stay were as follows: absence of chronic obstructive pulmonary disease (HR 0.6, 95% CI 0.3-1.1); adequate activity level (HR 0.6, 95% CI 0.4-0.8); and inspiratory muscle strength (HR 0.6, 95% CI 0.5-0.9). For all postoperative outcomes physical activity and fitness significantly improved the predictive value compared with known risk factors, such as age and comorbidities. We conclude that pre-operative questionnaires of physical activity and measurements of fitness contribute to the prediction of postoperative outcomes. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

  17. Genetic analysis of atherosclerosis identifies a major susceptibility locus in the major histocompatibility complex of mice.

    Science.gov (United States)

    Grainger, Andrew T; Jones, Michael B; Li, Jing; Chen, Mei-Hua; Manichaikul, Ani; Shi, Weibin

    2016-11-01

    Recent genome-wide association studies (GWAS) have identified over 50 significant loci containing common variants associated with coronary artery disease. However, these variants explain only 26% of the genetic heritability of the disease, suggesting that many more variants remain to be discovered. Here, we examined the genetic basis underlying the marked difference between SM/J-Apoe -/- and BALB/cJ-Apoe -/- mice in atherosclerotic lesion formation. 206 female F 2 mice generated from an intercross between the two Apoe -/- strains were fed 12 weeks of western diet. Atherosclerotic lesion sizes in the aortic root were measured and 149 genetic markers genotyped across the entire genome. A significant locus, named Ath49 (LOD score: 4.18), for atherosclerosis was mapped to the H2 complex [mouse major histocompatibility complex (MHC)] on chromosome 17. Bioinformatic analysis identified 12 probable candidate genes, including Tnfrsf21, Adgrf1, Adgrf5, Mep1a, and Pla2g7. Corresponding human genomic regions of Ath49 showed significant association with coronary heart disease. Five suggestive loci on chromosomes 1, 4, 5, and 8 for atherosclerosis were also identified. Atherosclerotic lesion sizes were significantly correlated with HDL but not with non-HDL cholesterol, triglyceride or glucose levels in the F 2 cohort. We have identified the MHC as a major genetic determinant of atherosclerosis, highlighting the importance of inflammation in atherogenesis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Differential analgesic effects of low-dose epidural morphine and morphine-bupivacaine at rest and during mobilization after major abdominal surgery

    DEFF Research Database (Denmark)

    Dahl, J B; Rosenberg, J; Hansen, B L

    1992-01-01

    elective major abdominal surgery. All patients in addition received systemic piroxicam (20 mg daily). No significant differences were observed between the groups at any assessment of pain at rest (P greater than 0.05), whereas pain in the morphine/bupivacaine group was significantly reduced during...

  19. Major histocompatibility complex I proteins in brain development and plasticity

    Science.gov (United States)

    Elmer, Bradford M.; McAllister, A. Kimberley

    2012-01-01

    Proper development of the central nervous system (CNS) requires the establishment of appropriate connections between neurons. Recent work suggests that this process is controlled by a balance between synaptogenic molecules and proteins that negatively regulate synapse formation and plasticity. Surprisingly, many of these newly identified synapse-limiting molecules are classic “immune” proteins. In particular, major histocompatibility complex class I (MHCI) molecules regulate neurite outgrowth, the establishment and function of cortical connections, activity-dependent refinement in the visual system, and long-term and homeostatic plasticity. This review summarizes our current understanding of MHCI expression and function in the CNS, as well as the potential mechanisms used by MHCI to regulate brain development and plasticity. PMID:22939644

  20. Analysis of Major Histocompatibility Complex (MHC) Immunopeptidomes Using Mass Spectrometry.

    Science.gov (United States)

    Caron, Etienne; Kowalewski, Daniel J; Chiek Koh, Ching; Sturm, Theo; Schuster, Heiko; Aebersold, Ruedi

    2015-12-01

    The myriad of peptides presented at the cell surface by class I and class II major histocompatibility complex (MHC) molecules are referred to as the immunopeptidome and are of great importance for basic and translational science. For basic science, the immunopeptidome is a critical component for understanding the immune system; for translational science, exact knowledge of the immunopeptidome can directly fuel and guide the development of next-generation vaccines and immunotherapies against autoimmunity, infectious diseases, and cancers. In this mini-review, we summarize established isolation techniques as well as emerging mass spectrometry-based platforms (i.e. SWATH-MS) to identify and quantify MHC-associated peptides. We also highlight selected biological applications and discuss important current technical limitations that need to be solved to accelerate the development of this field. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Exploration of the Conformational Dynamics of Major Histocompatibility Complex Molecules.

    Science.gov (United States)

    Yanaka, Saeko; Sugase, Kenji

    2017-01-01

    Major histocompatibility complex (MHC) molecules are loaded with a wide variety of self- and non-self-peptides in their binding grooves and present these to T cell receptors (TCRs) in order to activate the adaptive immune system. A large number of crystal structures of different MHC alleles with different bound peptides have been determined, and they have been found to be quite similar to one another regardless of the bound peptide sequence. The structures do not change markedly even when forming complexes with TCRs. Nonetheless, the degree of TCR activation does differ markedly depending on the peptide presented by the MHC. Recent structural studies in solution rather than as crystals have suggested that the conformational dynamics of MHC molecules may be responsible for the MHC stability differences. Furthermore, it was shown that the conformational dynamics of MHC molecules is important for peptide loading and presentation to TCR. Here, we describe the static and dynamic structures of MHC molecules and appropriate methods to analyze them. We focus particularly on nuclear magnetic resonance (NMR), one of the most powerful tools to study dynamic properties of proteins. The number of such studies in the literature is limited, but in this review, we show that NMR is valuable for elucidating the structural dynamics of MHC molecules.

  2. Molecular Genotype Identification of Different Chickens: Major Histocompatibility Complex

    Directory of Open Access Journals (Sweden)

    Hongzhi Wang

    2014-09-01

    Full Text Available Chicken is a main poultry in China. Molecular breeding for disease resistance plays an important role in the control of diseases, especially infectious diseases. Choice of genes for disease resistance is the key technology of molecular breeding. The major histocompatibility complex (MHC is of great interest to poultry breeding scientists for its extraordinary polymorphism and close relation with traits of resistance against infectious diseases. The MHC-B haplotype plays an important role in the study of disease resistance in chicken. The traditional chicken MHC-B haplotype is commonly defined by serologic reactions of erythrocytes and the majority of studies have been conducted in Leghorn and broiler but study about other chicken breeds is little. In this study, firstly, the microsatellite marker LEI0258 which is located within the MHC was sequenced by using target sequence capture assay in different chicken breeds, and then according to the number of repeated structures and polymorphic sequences in microsatellite, sequence information for the region defined by LEI0258 was obtained for different haplotypes. Afterwards, we identified the relation between MHC-B haplotypes and disease resistance. Collectively, these observed results provided the reference data for disease-resistant breeding association with blood type and for further study of MHC gene function in poultry.

  3. Value of a step-up diagnosis plan: CRP and CT-scan to diagnose and manage postoperative complications after major abdominal surgery

    Directory of Open Access Journals (Sweden)

    Jennifer Straatman

    2014-12-01

    Full Text Available Postoperative complications frequently follow major abdominal surgery and are associated with increased morbidity and mortality. Early diagnosis and treatment of complications is associated with improved patient outcome. In this study we assessed the value of a step-up diagnosis plan by C-reactive protein and CT-scan (computed tomography-scan imaging for detection of postoperative complications following major abdominal surgery. An observational cohort study was conducted of 399 consecutive patients undergoing major abdominal surgery between January 2009 and January 2011. Indication for operation, type of surgery, postoperative morbidity, complications according to the Clavien-Dindo classification and mortality were recorded. Clinical parameters were recorded until 14 days postoperatively or until discharge. Regular C-reactive protein (CPR measurements in peripheral blood and on indication -enhanced CT-scans were performed. Eighty-three out of 399 (20.6 % patients developed a major complication in the postoperative course after a median of seven days (IQR 4-9 days. One hundred and thirty two patients received additional examination consisting of enhanced CT-scan imaging, and treatment by surgical reintervention or intensive care observation. CRP levels were significantly higher in patients with postoperative complications. On the second postoperative day CRP levels were on average 197.4 mg/L in the uncomplicated group, 220.9 mg/L in patients with a minor complication and 280.1 mg/L in patients with major complications (p < 0,001. CT-scan imaging showed a sensitivity of 91.7 % and specificity of 100 % in diagnosis of major complications. Based on clinical deterioration and the increase of CRP, an additional enhanced CT-scan offered clear discrimination between patients with major abdominal complications and uncomplicated patients. Adequate treatment could then be accomplished.

  4. Haplessly hoping: macaque major histocompatibility complex made easy.

    Science.gov (United States)

    Wiseman, Roger W; Karl, Julie A; Bohn, Patrick S; Nimityongskul, Francesca A; Starrett, Gabriel J; O'Connor, David H

    2013-01-01

    Major histocompatibility complex (MHC) gene products control the repertoire of T cell responses that an individual may create against pathogens and foreign tissues. This text will review the current understanding of MHC genetics in nonhuman primates, with a focus on Mauritian-origin cynomolgus macaques (Macaca fascicularis) and Indian-origin rhesus macaques (Macaca mulatta). These closely related macaque species provide important experimental models for studies of infectious disease pathogenesis, vaccine development, and transplantation research. Recent advances resulting from the application of several cost effective, high-throughput approaches, with deep sequencing technologies have revolutionized our ability to perform MHC genotyping of large macaque cohorts. Pyrosequencing of cDNA amplicons with a Roche/454 GS Junior instrument, provides excellent resolution of MHC class I allelic variants with semi-quantitative estimates of relative levels of transcript abundance. Introduction of the Illumina MiSeq platform significantly increased the sample throughput, since the sample loading workflow is considerably less labor intensive, and each instrument run yields approximately 100-fold more sequence data. Extension of these sequencing methods from cDNA to genomic DNA amplicons further streamlines the experimental workflow and opened opportunities for retrospective MHC genotyping of banked DNA samples. To facilitate the reporting of MHC genotypes, and comparisons between groups of macaques, this text also introduces an intuitive series of abbreviated rhesus MHC haplotype designations based on a major Mamu-A or Mamu-B transcript characteristic for ancestral allele combinations. The authors believe that the use of MHC-defined macaques promises to improve the reproducibility, and predictability of results from pre-clinical studies for translation to humans.

  5. Safety and efficacy of combined epidural/general anesthesia during major abdominal surgery in patients with increased intracranial pressure: a cohort study.

    Science.gov (United States)

    Zabolotskikh, Igor; Trembach, Nikita

    2015-05-15

    The increased intracranial pressure can significantly complicate the perioperative period in major abdominal surgery, increasing the risk of complications, the length of recovery from the surgery, worsening the outcome. Epidural anesthesia has become a routine component of abdominal surgery, but its use in patients with increased intracranial pressure remains controversial. The goal of the study was to evaluate the safety and efficacy of epidural anesthesia, according to monitoring of intracranial pressure in patients with increased intracranial pressure. The study includes 65 surgical patients who were routinely undergone the major abdominal surgery under combined epidural/general anesthesia. Depending on the initial ICP all patients were divided into 2 groups: 1 (N group) - patients with the normal intracranial pressure (≤12 mm Hg, n = 35) and 2 (E group) - patients with the elevated intracranial pressure (ICP > 12 mm Hg, n = 30). During the surgery we evaluated ICP, blood pressure, cerebral perfusion pressure (CPP). The parameters of recovery from anesthesia and the effectiveness of postoperative analgesia were also assessed. In N group ICP remained stable. In E group ICP decreased during anesthesia, the overall decline was 40% at the end of the operation (from 15 to 9 mm Hg (P intracranial pressure undergoing elective abdominal surgery under the condition of maintaining the arterial pressure. Its use is not associated with the increase in intracranial pressure during the anesthesia, but it needs an intraoperative monitoring of ICP in order to prevent CPP reduction.

  6. Transmembrane signaling through major histocompatibility complex (MHC) encoded molecules

    International Nuclear Information System (INIS)

    Newell, M.K.

    1987-01-01

    The importance of the major histocompatibility complex (MHC) encoded molecules has traditionally been ascribed to the role these molecules play as restriction elements for T lymphocytes. This is, in order for T cell activation to occur the T cell must recognize antigen in association with MHC molecules. More controversial, however, is the potential role MHC molecules play as signal transducing receptors/acceptors to the B lymphocyte. In other words, do class II MHC molecules (Ia antigens) actively transduce a signal to the B cell which drives its differentiation into an antibody secreting cell? Two approaches to this question are described. The first involves biochemical characterization of those molecules which consistently copurify with I-A/sup k/ by two dimensional gel electrophoresis. The second approach utilizes two types of analyses: first, an examination of the biochemical changes which occur in the cell as a result of Ia ligation; and second, analysis of changes in the B cell's physiological response as a result of Ia perturbation. Molecules were examined which may couple the antigen binding event in the B lymphocyte to the antigen driven signal transduction cascade which ultimately leads to immunoglobulin secretion. In these experiments, cells were labelled with [ 32 P] and stimulated cells with phorbol myristate acetate. The membrane form of immunoglobulin was then isolated from detergent lysates of whole cells and passed over an anti-k affinity column. The eluates were analyzed by SDS-PAGE

  7. Major Histocompatibility Complex (MHC) Markers in Conservation Biology

    Science.gov (United States)

    Ujvari, Beata; Belov, Katherine

    2011-01-01

    Human impacts through habitat destruction, introduction of invasive species and climate change are increasing the number of species threatened with extinction. Decreases in population size simultaneously lead to reductions in genetic diversity, ultimately reducing the ability of populations to adapt to a changing environment. In this way, loss of genetic polymorphism is linked with extinction risk. Recent advances in sequencing technologies mean that obtaining measures of genetic diversity at functionally important genes is within reach for conservation programs. A key region of the genome that should be targeted for population genetic studies is the Major Histocompatibility Complex (MHC). MHC genes, found in all jawed vertebrates, are the most polymorphic genes in vertebrate genomes. They play key roles in immune function via immune-recognition and -surveillance and host-parasite interaction. Therefore, measuring levels of polymorphism at these genes can provide indirect measures of the immunological fitness of populations. The MHC has also been linked with mate-choice and pregnancy outcomes and has application for improving mating success in captive breeding programs. The recent discovery that genetic diversity at MHC genes may protect against the spread of contagious cancers provides an added impetus for managing and protecting MHC diversity in wild populations. Here we review the field and focus on the successful applications of MHC-typing for conservation management. We emphasize the importance of using MHC markers when planning and executing wildlife rescue and conservation programs but stress that this should not be done to the detriment of genome-wide diversity. PMID:21954351

  8. Major histocompatibility complex-linked social signalling affects female fertility.

    Science.gov (United States)

    Burger, D; Thomas, S; Aepli, H; Dreyer, M; Fabre, G; Marti, E; Sieme, H; Robinson, M R; Wedekind, C

    2017-12-06

    Genes of the major histocompatibility complex (MHC) have been shown to influence social signalling and mate preferences in many species, including humans. First observations suggest that MHC signalling may also affect female fertility. To test this hypothesis, we exposed 191 female horses ( Equus caballus ) to either an MHC-similar or an MHC-dissimilar stimulus male around the time of ovulation and conception. A within-subject experimental design controlled for non-MHC-linked male characteristics, and instrumental insemination with semen of other males ( n = 106) controlled for potential confounding effects of semen or embryo characteristics. We found that females were more likely to become pregnant if exposed to an MHC-dissimilar than to an MHC-similar male, while overall genetic distance to the stimulus males (based on microsatellite markers on 20 chromosomes) had no effect. Our results demonstrate that early pregnancy failures can be due to maternal life-history decisions (cryptic female choice) influenced by MHC-linked social signalling. © 2017 The Author(s).

  9. High-sensitive cardiac troponin T measurements in prediction of non-cardiac complications after major abdominal surgery

    NARCIS (Netherlands)

    Noordzij, P. G.; van Geffen, O.; Dijkstra, I. M.; Boerma, D.; Meinders, A. J.; Rettig, T. C D; Eefting, F. D.; van Loon, D.; van de Garde, E. M W; van Dongen, E. P A

    2015-01-01

    BACKGROUND: Postoperative non-cardiac complication rates are as high as 11-28% after high-risk abdominal procedures. Emerging evidence indicates that postoperative cardiac troponin T elevations are associated with adverse outcome in non-cardiac surgery. The aim of this study was to determine the

  10. Diagnostic value of C-reactive protein to rule out infectious complications after major abdominal surgery: a systematic review and meta-analysis.

    Science.gov (United States)

    Gans, Sarah L; Atema, Jasper J; van Dieren, Susan; Groot Koerkamp, Bas; Boermeester, Marja A

    2015-07-01

    Infectious complications occur frequently after major abdominal surgery and have a major influence on patient outcome and hospital costs. A marker that can rule out postoperative infectious complications (PICs) could aid patient selection for safe and early hospital discharge. C-reactive protein (CRP) is a widely available, fast, and cheap marker that might be of value in detecting PIC. Present meta-analysis evaluates the diagnostic value of CRP to rule out PIC following major abdominal surgery, aiding patient selection for early discharge. A systematic literature search of Medline, PubMed, and Cochrane was performed identifying all prospective studies evaluating the diagnostic value of CRP after abdominal surgery. Meta-analysis was performed according to the PRISMA statement. Twenty-two studies were included for qualitative analysis of which 16 studies were eligible for meta-analysis, representing 2215 patients. Most studies analyzed the value of CRP in colorectal surgery (eight studies). The pooled negative predictive value (NPV) improved each day after surgery up to 90% at postoperative day (POD) 3 for a pooled CRP cutoff of 159 mg/L (range 92-200). Maximum predictive values for PICs were reached on POD 5 for a pooled CRP cutoff of 114 mg/L (range 48-150): a pooled sensitivity of 86% (95% confidence interval (CI) 79-91%), specificity of 86% (95% CI 75-92%), and a positive predictive value of 64% (95% CI 49-77%). The pooled sensitivity and specificity were significantly higher on POD 5 than on other PODs (p < 0.001). Infectious complications after major abdominal surgery are very unlikely in patients with a CRP below 159 mg/L on POD 3. This can aid patient selection for safe and early hospital discharge and prevent overuse of imaging.

  11. Phage display of peptide / major histocompatibility class I complexes

    DEFF Research Database (Denmark)

    Vest Hansen, N; Ostergaard Pedersen, L; Stryhn, A

    2001-01-01

    and subsequently that ot the T cell receptor for peptide-MHC-I complex), we have fused a single chain peptide-MHC-I complex to the phage minor coat protein, gpIII, and displayed it on filamentous phage. Expression of peptide-MHC-I complexes was shown with relevant conformation-specific monoclonal antibodies and......, more importantly, with a unique "T cell receptor-like" (i. e. peptide-specific, MHC-I-restricted) antibody. Thus, properly assembled and folded peptide-MHC-I complexes can be displayed on filamentous phage. Despite the successful display, interaction with T cells could not be demonstrated....

  12. Sarcopenia and sarcopenic obesity in patients with complex abdominal wall hernias.

    Science.gov (United States)

    Rinaldi, John M; Geletzke, Abby K; Phillips, Brett E; Miller, Jamie; Dykes, Thomas M; Soybel, David I

    2016-11-01

    Chronic muscle wasting, or sarcopenia, has been associated with poor-health outcomes after major surgical procedures. Here, we explore the utility of CT-generated determinations of sarcopenia as markers of risk in patients undergoing evaluation for complex ventral hernia repair. In 148 successive patients being evaluated for complex ventral hernia repair, CT scans were analyzed retrospectively for attributes of the hernia and indices of core-muscle mass, correlating them with preoperative clinical/laboratory profiles and outcomes in 82 patients who had undergone surgery. Prevalence of sarcopenia, and sarcopenia corrected for obesity, was 26% and 20% respectively. Sarcopenia was associated with age, some laboratory indicators, and increased hospital length of stay but not with a higher likelihood of surgical site occurrence. Obesity may obscure the value of sarcopenia as a marker of metabolic disturbance and postoperative outcome. Image-based measurements of core-muscle mass should be used with caution as predictors of risk in similar surgical populations. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. The effect of TISSEEL fibrin sealant on seroma formation following complex abdominal wall hernia repair: a single institutional review and derived cost analysis.

    Science.gov (United States)

    Azoury, S C; Rodriguez-Unda, N; Soares, K C; Hicks, C W; Baltodano, P A; Poruk, K E; Hu, Q L; Cooney, C M; Cornell, P; Burce, K; Eckhauser, F E

    2015-12-01

    The authors evaluated the ability of a fibrin sealant (TISSEEL™: Baxter Healthcare Corp, Deerfield, IL, USA) to reduce the incidence of post-operative seroma following abdominal wall hernia repair. We performed a 4-year retrospective review of patients undergoing abdominal wall hernia repair, with and without TISSEEL, by a single surgeon (FEE) at The Johns Hopkins Hospital. Demographics, surgical risk factors, operative data and 30-day outcomes, including wound complications and related interventions, were compared. The quantity and cost of Tisseel per case was reviewed. A total of 250 patients were evaluated: 127 in the TISSEEL group and 123 in the non-TISSEEL control group. The average age for both groups was 56.6 years (P = 0.97). The majority of patients were female (TISSEEL 52.8%, non-TISSEEL 56.1%, P = 0.59) and ASA Class III (TISSEEL 56.7%, non-TISSEEL 58.5%, P = 0.40). There was no difference in the average defect size for both groups (TISSEEL 217 ± 187.6 cm(2), non-TISSEEL 161.3 ± 141.5 cm(2), P = 0.36). Surgical site occurrences occurred in 18.1% of the TISSEEL and 13% of the non-TISSEEL group (P = 0.27). There was a trend towards an increased incidence of seroma in the TISSEEL group (TISSEEL 11%, non-TISSEEL 4.9%, P = 0.07). A total of $124,472.50 was spent on TISSEEL, at an average cost of $995.78 per case. In the largest study to date, TISSEEL™ application offered no advantage for the reduction of post-operative seroma formation following complex abdominal hernia repair. Moreover, the use of this sealant was associated with significant costs.

  14. The effects of the academic performance of college students whose major is sports on body composition and abdominal fat rates.

    Science.gov (United States)

    Hong, Hyeon-Ok; Lee, Bo-Ae

    2016-08-01

    The subjects of this research are 30 students of Dong-Eui Institute of Technology in Busan city, who were grouped into two categories after applying the curriculum of the second semester of the freshman year to their classes: those whose academic performance was at the top 20% (15 students) and those whose academic performance was at the bottom 20% (15 students). For the measurement items, we measured their weight, body fat mass, body fat rates, body mass index, and abdominal fat rates by using a body composition testing machine. We then analyzed the t-test results by using the IBM SPSS ver. 18.0 program. Through this research, we found that there was a significant difference among those in the group of students whose academic performance was at the top 20% in terms of body fat mass and body fat rates, which means that academic performance has relatively little effect on body composition and abdominal fat rates.

  15. Value of a step-up diagnosis plan: CRP and CT-scan to diagnose and manage postoperative complications after major abdominal surgery Value of a step-up diagnosis plan: CRP and CT-scan to diagnose and manage postoperative complications after major abdominal surgery

    NARCIS (Netherlands)

    Straatman, Jennifer; Cuesta, Miguel A.; Gisbertz, Suzanne S.; van der Peet, Donald L.

    2014-01-01

    Postoperative complications frequently follow major abdominal surgery and are associated with increased morbidity and mortality. Early diagnosis and treatment of complications is associated with improved patient outcome. In this study we assessed the value of a step-up diagnosis plan by C-reactive

  16. Abdominal wall reconstruction with components separation and mesh reinforcement in complex hernia repair.

    Science.gov (United States)

    Nockolds, Claire L; Hodde, Jason P; Rooney, Paul S

    2014-04-30

    Abdominal closure in the presence of enterocutaneous fistula, stoma or infection can be challenging. A single-surgeon's experience of performing components separation abdominal reconstruction and reinforcement with mesh in the difficult abdomen is presented. Medical records from patients undergoing components separation and reinforcement with hernia mesh at Royal Liverpool Hospital from 2009 to 2012 were reviewed. Patients were classified by the Ventral Hernia Working Group (VHWG) grading system. Co-morbidities, previous surgeries, specific type of reconstruction technique, discharge date, complications and hernia recurrence were recorded. Twenty-three patients' (15 males, 8 females) notes were reviewed. Median age was 57 years (range 20-76 years). Median follow-up at the time of review was 17 months (range 2-48 months). There were 13 grade III hernias and 10 grade IV hernias identified. Synthetic mesh was placed to reinforce the abdomen in 6 patients, cross-linked porcine dermis was used in 3, and a Biodesign® Hernia Graft was placed in 14. Complications included wound infection (13%), superficial wound dehiscence (22%), seroma formation (22%) and stoma complications (9%). To date, hernias have recurred in 3 patients (13%). Components separation and reinforcement with biological mesh is a successful technique in the grade III and IV abdomen with acceptable rate of recurrence and complications.

  17. Measuring complexity, nonextensivity and chaos in the DNA sequence of the Major Histocompatibility Complex

    Science.gov (United States)

    Pavlos, G. P.; Karakatsanis, L. P.; Iliopoulos, A. C.; Pavlos, E. G.; Xenakis, M. N.; Clark, Peter; Duke, Jamie; Monos, D. S.

    2015-11-01

    We analyze 4 Mb sequences of the Major Histocompatibility Complex (MHC), which is a DNA segment on chromosome 6 with high gene density, controlling many immunological functions and associated with many diseases. The analysis is based on modern theoretical and mathematical tools of complexity theory, such as nonlinear time series analysis and Tsallis non-extensive statistics. The results revealed that the DNA complexity and self-organization can be related to fractional dynamical nonlinear processes with low-dimensional deterministic chaotic and non-extensive statistical character, which generate the DNA sequences under the extremization of Tsallis q-entropy principle. While it still remains an open question as to whether the DNA walk is a fractional Brownian motion (FBM), a static anomalous diffusion process or a non-Gaussian dynamical fractional anomalous diffusion process, the results of this study testify for the latter, providing also a possible explanation for the previously observed long-range power law correlations of nucleotides, as well as the long-range correlation properties of coding and non-coding sequences present in DNA sequences.

  18. The effects of the academic performance of college students whose major is sports on body composition and abdominal fat rates

    OpenAIRE

    Hong, Hyeon-Ok; Lee, Bo-Ae

    2016-01-01

    The subjects of this research are 30 students of Dong-Eui Institute of Technology in Busan city, who were grouped into two categories after applying the curriculum of the second semester of the freshman year to their classes: those whose academic performance was at the top 20% (15 students) and those whose academic performance was at the bottom 20% (15 students). For the measurement items, we measured their weight, body fat mass, body fat rates, body mass index, and abdominal fat rates by usi...

  19. Signal transduction by the major histocompatibility complex class I molecule

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Skov, S; Bregenholt, S

    1999-01-01

    Ligation of cell surface major histocompatibility class I (MHC-I) proteins by antibodies, or by their native counter receptor, the CD8 molecule, mediates transduction of signals into the cells. MHC-I-mediated signaling can lead to both increased and decreased activity of the MHC-I-expressing cell...

  20. 454 sequencing reveals extreme complexity of the class II Major Histocompatibility Complex in the collared flycatcher

    Directory of Open Access Journals (Sweden)

    Gustafsson Lars

    2010-12-01

    Full Text Available Abstract Background Because of their functional significance, the Major Histocompatibility Complex (MHC class I and II genes have been the subject of continuous interest in the fields of ecology, evolution and conservation. In some vertebrate groups MHC consists of multiple loci with similar alleles; therefore, the multiple loci must be genotyped simultaneously. In such complex systems, understanding of the evolutionary patterns and their causes has been limited due to challenges posed by genotyping. Results Here we used 454 amplicon sequencing to characterize MHC class IIB exon 2 variation in the collared flycatcher, an important organism in evolutionary and immuno-ecological studies. On the basis of over 152,000 sequencing reads we identified 194 putative alleles in 237 individuals. We found an extreme complexity of the MHC class IIB in the collared flycatchers, with our estimates pointing to the presence of at least nine expressed loci and a large, though difficult to estimate precisely, number of pseudogene loci. Many similar alleles occurred in the pseudogenes indicating either a series of recent duplications or extensive concerted evolution. The expressed alleles showed unambiguous signals of historical selection and the occurrence of apparent interlocus exchange of alleles. Placing the collared flycatcher's MHC sequences in the context of passerine diversity revealed transspecific MHC class II evolution within the Muscicapidae family. Conclusions 454 amplicon sequencing is an effective tool for advancing our understanding of the MHC class II structure and evolutionary patterns in Passeriformes. We found a highly dynamic pattern of evolution of MHC class IIB genes with strong signals of selection and pronounced sequence divergence in expressed genes, in contrast to the apparent sequence homogenization in pseudogenes. We show that next generation sequencing offers a universal, affordable method for the characterization and, in perspective

  1. Childhood abdominal cystic lymphangioma

    Energy Technology Data Exchange (ETDEWEB)

    Konen, Osnat; Rathaus, Valeria; Shapiro, Myra [Department of Diagnostic Imaging, Meir General Hospital, Sapir Medical Centre, Kfar Saba (Israel); Dlugy, Elena [Department of Paediatric Surgery, Schneider Medical Centre, Sackler School of Medicine, Tel-Aviv University (Israel); Freud, Enrique [Department of Paediatric Surgery, Sapir Medical Centre, Sackler School of Medicine, Tel-Aviv University (Israel); Kessler, Ada [Department of Diagnostic Imaging, Sourasky Medical Centre, Tel-Aviv (Israel); Horev, Gadi [Department of Diagnostic Imaging, Schneider Medical Centre, Tel-Aviv (Israel)

    2002-02-01

    Background: Abdominal lymphangioma is a rare benign congenital malformation of the mesenteric and/or retroperitoneal lymphatics. Clinical presentation is variable and may be misleading; therefore, complex imaging studies are necessary in the evaluation of this condition. US and CT have a major role in the correct preoperative diagnosis and provide important information regarding location, size, adjacent organ involvement, and expected complications. Objective: To evaluate the clinical and imaging findings of seven children with proven abdominal cystic lymphangioma. Materials and methods: Clinical and imaging files of seven children with pathologically proven abdominal lymphangioma, from three university hospitals, were retrospectively evaluated. Patient's ages ranged from 1 day to 6 years (mean, 2.2 years). Symptoms and signs included evidence of inflammation, abnormal prenatal US findings, chronic abdominal pain, haemorrhage following trauma, clinical signs of intestinal obstruction, and abdominal distension with lower extremities lymphoedema. Plain films of five patients, US of six patients and CT of five patients were reviewed. Sequential imaging examinations were available in two cases. Results: Abdominal plain films showed displacement of bowel loops by a soft tissue mass in five of six patients, two of them with dilatation of small bowel loops. US revealed an abdominal multiloculated septated cystic mass in five of six cases and a single pelvic cyst in one which changed in appearance over 2 months. Ascites was present in three cases. CT demonstrated a septated cystic mass of variable sizes in all available five cases. Sequential US and CT examinations in two patients showed progressive enlargement of the masses, increase of fluid echogenicity, and thickening of walls or septa in both cases, with multiplication of septa in one case. At surgery, mesenteric lymphangioma was found in five patients and retroperitoneal lymphangioma in the other two

  2. Static assignment of complex stochastic tasks using stochastic majorization

    Science.gov (United States)

    Nicol, David; Simha, Rahul; Towsley, Don

    1992-01-01

    We consider the problem of statically assigning many tasks to a (smaller) system of homogeneous processors, where a task's structure is modeled as a branching process, and all tasks are assumed to have identical behavior. We show how the theory of majorization can be used to obtain a partial order among possible task assignments. Our results show that if the vector of numbers of tasks assigned to each processor under one mapping is majorized by that of another mapping, then the former mapping is better than the latter with respect to a large number of objective functions. In particular, we show how measurements of finishing time, resource utilization, and reliability are all captured by the theory. We also show how the theory may be applied to the problem of partitioning a pool of processors for distribution among parallelizable tasks.

  3. The LIPPSMAck POP (Lung Infection Prevention Post Surgery - Major Abdominal - with Pre-Operative Physiotherapy) trial: study protocol for a multi-centre randomised controlled trial.

    Science.gov (United States)

    Boden, Ianthe; Browning, Laura; Skinner, Elizabeth H; Reeve, Julie; El-Ansary, Doa; Robertson, Iain K; Denehy, Linda

    2015-12-15

    Post-operative pulmonary complications are a significant problem following open upper abdominal surgery. Preliminary evidence suggests that a single pre-operative physiotherapy education and preparatory lung expansion training session alone may prevent respiratory complications more effectively than supervised post-operative breathing and coughing exercises. However, the evidence is inconclusive due to methodological limitations. No well-designed, adequately powered, randomised controlled trial has investigated the effect of pre-operative education and training on post-operative respiratory complications, hospital length of stay, and health-related quality of life following upper abdominal surgery. The Lung Infection Prevention Post Surgery - Major Abdominal- with Pre-Operative Physiotherapy (LIPPSMAck POP) trial is a pragmatic, investigator-initiated, bi-national, multi-centre, patient- and assessor-blinded, parallel group, randomised controlled trial, powered for superiority. Four hundred and forty-one patients scheduled for elective open upper abdominal surgery at two Australian and one New Zealand hospital will be randomised using concealed allocation to receive either i) an information booklet or ii) an information booklet, plus one additional pre-operative physiotherapy education and training session. The primary outcome is respiratory complication incidence using standardised diagnostic criteria. Secondary outcomes include hospital length of stay and costs, pneumonia diagnosis, intensive care unit readmission and length of stay, days/h to mobilise >1 min and >10 min, and, at 6 weeks post-surgery, patient reported complications, health-related quality of life, and physical capacity. The LIPPSMAck POP trial is a multi-centre randomised controlled trial powered and designed to investigate whether a single pre-operative physiotherapy session prevents post-operative respiratory complications. This trial standardises post-operative assisted ambulation and

  4. A multi-step method with signal quality assessment and fine-tuning procedure to locate maternal and fetal QRS complexes from abdominal ECG recordings

    International Nuclear Information System (INIS)

    Liu, Chengyu; Li, Peng; Zhao, Lina; Di Maria, Costanzo; Zhang, Henggui; Chen, Zhiqing

    2014-01-01

    Non-invasive monitoring of fetal electrocardiogram (fECG) plays an important role in detecting and diagnosing fetal diseases. This study aimed to develop a multi-step method for locating both maternal and fetal QRS complexes from abdominal ECG (aECG) recordings. The proposed method included four major steps: abdominal ECG pre-processing, maternal QRS complex locating, maternal ECG cancellation and fetal QRS complex locating. Signal quality assessment (SQA) and fine-tuning for maternal ECG (FTM) were implemented in the first and third steps, respectively. The method was then evaluated using 75 non-invasive 4-channel aECG recordings provided by the PhysioNet/Computing in Cardiology Challenge 2013. The F 1 measure, which is a new index introduced by Behar et al (2013 Proc. Comput. Cardiol. 40 297–300), was used to assess the locating accuracy. The other two indices, mean squared error of heart rate (MSE H R) between the fetal HR signals estimated from the reference and our method (MSE H R in bpm 2 ) and root mean squared difference between the corresponding fetal RR intervals (MSE R R in ms) were also used to assess the locating accuracy. Overall, for the maternal QRS complex, the F 1 measure was 98.4% from the method without the implementation of SQA, and it was improved to 99.8% with SQA. For the fetal QRS complex, the F 1 measure, MSE H R and MSE R R were 84.9%, 185.6 bpm 2 and 19.4 ms for the method without both SQA and FTM procedures. They were improved to 93.9%, 47.5 bpm 2 and 7.6 ms with both SQA and FTM procedures. These improvements were observed from each individual subject. It can be concluded that implementing both SQA and FTM procedures could achieve better performance for locating both maternal and fetal QRS complexes. (paper)

  5. Signal transduction by the major histocompatibility complex class I molecule

    DEFF Research Database (Denmark)

    Pedersen, A E; Skov, Svend; Bregenholt, S

    1999-01-01

    Ligation of cell surface major histocompatibility class I (MHC-I) proteins by antibodies, or by their native counter receptor, the CD8 molecule, mediates transduction of signals into the cells. MHC-I-mediated signaling can lead to both increased and decreased activity of the MHC-I-expressing cell...... and functioning, MHC-I molecules might be of importance for the maintenance of cellular homeostasis not only within the immune system, but also in the interplay between the immune system and other organ systems....

  6. Tuberculosis abdominal Abdominal tuberculosis

    OpenAIRE

    T. Rubio; M. T. Gaztelu; A. Calvo; M. Repiso; H. Sarasíbar; F. Jiménez Bermejo; A. Martínez Echeverría

    2005-01-01

    La tuberculosis abdominal cursa con un cuadro inespecífico, con difícil diagnóstico diferencial respecto a otras entidades de similar semiología. Presentamos el caso de un varón que ingresa por presentar dolor abdominal, pérdida progresiva y notoria de peso corporal y fiebre de dos meses de evolución. El cultivo de la biopsia de colon mostró presencia de bacilo de Koch.Abdominal tuberculosis develops according to a non-specific clinical picture, with a difficult differential diagnosis with re...

  7. Fetal abdominal wall defects.

    Science.gov (United States)

    Prefumo, Federico; Izzi, Claudia

    2014-04-01

    The most common fetal abdominal wall defects are gastroschisis and omphalocele, both with a prevalence of about three in 10,000 births. Prenatal ultrasound has a high sensitivity for these abnormalities already at the time of the first-trimester nuchal scan. Major unrelated defects are associated with gastroschisis in about 10% of cases, whereas omphalocele is associated with chromosomal or genetic abnormalities in a much higher proportion of cases. Challenges in management of gastroschisis are related to the prevention of late intrauterine death, and the prediction and treatment of complex forms. With omphalocele, the main difficulty is the exclusion of associated conditions, not all diagnosed prenatally. An outline of the postnatal treatment of abdominal wall defects is given. Other rarer forms of abdominal wall defects are pentalogy of Cantrell, omphalocele, bladder exstrophy, imperforate anus, spina bifida complex, prune-belly syndrome, body stalk anomaly, and bladder and cloacal exstrophy; they deserve multidisciplinary counselling and management. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Major intrinsic proteins (MIPs) in plants: a complex gene family with major impacts on plant phenotype.

    Science.gov (United States)

    Forrest, Kerrie L; Bhave, Mrinal

    2007-10-01

    The ubiquitous cell membrane proteins called aquaporins are now firmly established as channel proteins that control the specific transport of water molecules across cell membranes in all living organisms. The aquaporins are thus likely to be of fundamental significance to all facets of plant growth and development affected by plant-water relations. A majority of plant aquaporins have been found to share essential structural features with the human aquaporin and exhibit water-transporting ability in various functional assays, and some have been shown experimentally to be of critical importance to plant survival. Furthermore, substantial evidence is now available from a number of plant species that shows differential gene expression of aquaporins in response to abiotic stresses such as salinity, drought, or cold and clearly establishes the aquaporins as major players in the response of plants to conditions that affect water availability. This review summarizes the function and regulation of these genes to develop a greater understanding of the response of plants to water insufficiency, and particularly, to identify tolerant genotypes of major crop species including wheat and rice and plants that are important in agroforestry.

  9. Abdominal Wall Hernia in Complex Patients incidences, risk factors and timing of repair

    NARCIS (Netherlands)

    J. Verhelst (Joost)

    2016-01-01

    markdownabstractThis thesis consists of two parts: __part 1__ describes a new prosthesis for the treatment of large and complex incisional hernia. Furthermore the natural course and consequences of conservative treatment are described; __part 2__ focusses on three complex groups of patients

  10. Abdominal emergencies

    International Nuclear Information System (INIS)

    Raissaki, M.

    2012-01-01

    children and young individuals with abdominal pain. Sensitivity and specificity for US in diagnosing intussusception, midgut volvulus, urinary tract abnormalities and appendicitis is over 90%. US, occasionally with x-rays, usually suffice for an accurate diagnosis. Upper GI contrast studies are indicated in suspected malrotation, volvulus and atypical high obstruction cases. Lower GI contrast studies are indicated in low/colonic obstruction. CT and/or MRI should be reserved for atypical, complex cases when US and conventional radiography are equivocal or inconclusive. The radiologist should engage oneself to act immediately, consider and actively exclude those diagnoses that could be a threat to the child's health or life. The appropriate modality should be chosen and proper technique should be applied. Radiologists should function as clinicians, take initiative and discuss options and alternative diagnoses. Lack of experience should not delay performance of tests. Our job is finished when a diagnostic test has a written report provided that we make sure the child is managed properly.

  11. Influence of non-dietary factors on the prevalence of abdominal obesity as a major component of the metabolic syndrome among 17-18-year-old youth.

    Science.gov (United States)

    Piotrowska, Ewa; Broniecka, Anna; Biernat, Jadwiga; Wyka, Joanna; Bronkowska, Monika

    2015-01-01

    Youth nutrition and their nutritional status are conditioned by many factors, some of the main ones being: economic, social, climatic, cultural, and psychological factors as well as nutritional knowledge. With the growing problem of overweight and obesity among children and young people, the incidence of the metabolic syndrome is also increasing. The aim of the study was to assess the impact of demographic, sociological and psychological factors on the incidence of obesity among 17-18-year-old adolescents from Wroclaw and vicinity as a major risk factor for the development of the metabolic syndrome. The study was conducted in three upper-secondary schools in Wroclaw, Poland. In the surveyed group (17-18 years old, n = 269) girls accounted for 59.5% and boys constituted 40.5%. Majority of young people were Wroclaw citizens (72.9%). Centile charts elaborated by the Children's Memorial Health Institute were adopted for the evaluation of anthropometric parameters. Evaluation of the impact of non-dietary factors on the manner of nutrition was carried out using own questionnaire. Based on the tests, abdominal obesity was determined among 34.5% of adolescents aged 17 years and among 65.5% of these aged 18 years. Obesity was more common in girls carrying genetic burden of the disease. Youth with the largest waist circumference most often declared to use slimming diets - 6.7%, and the lowest hunger sensation in stress - 3.4%. In addition, 30.5% of the adolescents with the smallest waist circumference and 11.5% with the largest waist circumference declared to be non-smoking. Occasional alcohol consumption was declared by 30.1% of young people with the smallest waist circumference, and 13.4% with the largest waist circumference. Youth with abdominal obesity significantly more likely than those with normal waist circumference applied slimming diets. Significant impact on the formation of abdominal obesity among girls had inherited disease burden.

  12. Timing of Thiopurine or Anti-TNF Initiation Is Associated with the Risk of Major Abdominal Surgery in Crohn's Disease: A Retrospective Cohort Study.

    Science.gov (United States)

    González-Lama, Yago; Suárez, Cristina; González-Partida, Irene; Calvo, Marta; Matallana, Virginia; de la Revilla, Juan; Magaz, Marta; Bernardo, Cristina; Agudo, Belén; Ibarrola, Pilar; Relea, Lucía; Arévalo, Juan; Vera, María Isabel; Abreu, Luis

    2016-01-01

    Early stages of Crohn's disease [CD] are predominantly inflammatory and early treatment could be useful to change the natural history of CD. We aimed to evaluate the impact of early treatment in our cohort of CD patients. We retrospectively reviewed clinical records of all CD patients at our centre who have received immunomodulators. Time from diagnosis to first CD-related major abdominal surgery or end of follow-up was considered. Dates of diagnosis, of starting immunomodulators (thiopurines / anti-tumour necrosis factor [TNF]), and of the first CD-related surgery when appropriate were collected. Of 422 patients who received thiopurines, 189 operated patients started thiopurines after a median of 117 months (interquartile range [IQR] 44-196) since diagnosis; non-operated patients, after a median of 30 months [IQR 6-128], p risk of major abdominal surgery in Crohn's disease. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  13. Younger, premenopausal women with major depressive disorder have more abdominal fat and increased serum levels of prothrombotic factors: implications for greater cardiovascular risk.

    Science.gov (United States)

    Eskandari, Farideh; Mistry, Sejal; Martinez, Pedro E; Torvik, Sara; Kotila, Christine; Sebring, Nancy; Drinkard, Bart E; Levy, Catherine; Reynolds, James C; Csako, Gyorgy; Gold, Philip W; Horne, McDonald; Cizza, Giovanni

    2005-07-01

    Major depressive disorder (MDD) is one of the most common psychiatric illnesses in the adult population. It is often associated with an increased risk of cardiovascular disease. We measured body fat distribution as well as plasminogen activator inhibitor-1 (PAI-1) concentration and factor VIII (fVIII) activity at 8:00 am and 8:00 pm in 45 premenopausal women with MDD vs 28 healthy controls (age, 37 +/- 6.8 vs 35 +/- 6.5; weight [kg], 75.3 +/- 17.2 vs 67.9 +/- 10.2; mean +/- SD] participating in a prospective study of bone turnover, the POWER Study. At the time of evaluation, women with MDD were mildly depressed and mostly in clinical remission on antidepressants. After adjusting for body weight, women with MDD had greater waist circumference and abdominal fat as well as significantly higher evening (8:00 pm) PAI-1 and fVIII levels than controls. Even when age-, race-, and body mass index-matched subsets were compared, the MDD group continued to exhibit statistically higher PAI-1 and fVIII levels. The observed alterations in body fat distribution (increased abdominal fat) and prothrombotic factors (increased PAI-1 and fVIII) may be in part responsible for the increased risk of cardiovascular disease reported in association with major depression.

  14. Abdominal tap

    Science.gov (United States)

    Peritoneal tap; Paracentesis; Ascites - abdominal tap; Cirrhosis - abdominal tap; Malignant ascites - abdominal tap ... You then receive a local numbing medicine. The tap needle is inserted 1 to 2 inches (2. ...

  15. Cost-analysis of robotic-assisted laparoscopic hysterectomy versus total abdominal hysterectomy for women with endometrial cancer and atypical complex hyperplasia.

    Science.gov (United States)

    Herling, Suzanne F; Palle, Connie; Møller, Ann M; Thomsen, Thordis; Sørensen, Jan

    2016-03-01

    The aim of this study was to analyse the hospital cost of treatment with robotic-assisted laparoscopic hysterectomy and total abdominal hysterectomy for women with endometrial cancer or atypical complex hyperplasia and to identify differences in resource use and cost. This cost analysis was based on two cohorts: women treated with robotic-assisted laparoscopic hysterectomy (n = 202) or with total abdominal hysterectomy (n = 158) at Copenhagen University Hospital, Herlev, Denmark. We conducted an activity-based cost analysis including consumables and healthcare professionals' salaries. As cost-drivers we included severe complications, duration of surgery, anesthesia and stay at the post-anesthetic care unit, as well as number of hospital bed-days. Ordinary least-squares regression was used to explore the cost variation. The primary outcome was cost difference in Danish kroner between total abdominal hysterectomy and robotic-assisted laparoscopic hysterectomy. The average cost of consumables was 12,642 Danish kroner more expensive per patient for robotic-assisted laparoscopic hysterectomy than for total abdominal hysterectomy (2014 price level: 1€ = 7.50 Danish kroner). When including all cost-drivers, the analysis showed that the robotic-assisted laparoscopic hysterectomy procedure was 9386 Danish kroner (17%) cheaper than the total abdominal hysterectomy (p = 0.003). When the robot investment was included, the cost difference reduced to 4053 Danish kroner (robotic-assisted laparoscopic hysterectomy was 7% cheaper than total abdominal hysterectomy) (p = 0.20). Increasing age and Type 2 diabetes appeared to influence the overall costs. For women with endometrial cancer or atypical complex hyperplasia, robotic-assisted laparoscopic hysterectomy was cheaper than total abdominal hysterectomy, mostly due to fewer complications and shorter length of hospital stay. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

  16. Outcomes of fenestrated and branched endovascular repair of complex abdominal and thoracoabdominal aortic aneurysms.

    Science.gov (United States)

    Schanzer, Andres; Simons, Jessica P; Flahive, Julie; Durgin, Jonathan; Aiello, Francesco A; Doucet, Danielle; Steppacher, Robert; Messina, Louis M

    2017-09-01

    More than 80% of infrarenal aortic aneurysms are treated by endovascular repair. However, adoption of fenestrated and branched endovascular repair for complex aortic aneurysms has been limited, despite high morbidity and mortality associated with open repair. There are few published reports of consecutive outcomes, inclusive of all fenestrated and branched endovascular repairs, starting from the inception of a complex aortic aneurysm program. Therefore, we examined a single center's consecutive experience of fenestrated and branched endovascular repair of complex aortic aneurysms. This is a single-center, prospective, observational cohort study evaluating 30-day and 1-year outcomes in all consecutive patients who underwent fenestrated and branched endovascular repair of complex aortic aneurysms (definition: requiring one or more fenestrations or branches). Data were collected prospectively through an Institutional Review Board-approved registry and a physician-sponsored investigational device exemption clinical trial (G130210). We performed 100 consecutive complex endovascular aortic aneurysm repairs (November 2010 to March 2016) using 58 (58%) commercially manufactured custom-made devices and 42 (42%) physician-modified devices to treat 4 (4%) common iliac, 42 (42%) juxtarenal, 18 (18%) pararenal, and 36 (36%) thoracoabdominal aneurysms (type I, n = 1; type II, n = 4; type III, n = 12; type IV, n = 18; arch, n = 1). The repairs included 309 fenestrations, branches, and scallops (average of 3.1 branch arteries/case). All patients had 30-day follow-up for 30-day event rates: three (3%) deaths; six (6%) target artery occlusions; five (5%) progressions to dialysis; eight (8%) access complications; one (1%) paraparesis; one (1%) bowel ischemia; and no instances of myocardial infarction, paralysis, or stroke. Of 10 type I or type III endoleaks, 8 resolved (7 with secondary intervention, 1 without intervention). Mean follow-up time was 563 days (interquartile range

  17. Detection of segments with fetal QRS complex from abdominal maternal ECG recordings using support vector machine

    Science.gov (United States)

    Delgado, Juan A.; Altuve, Miguel; Nabhan Homsi, Masun

    2015-12-01

    This paper introduces a robust method based on the Support Vector Machine (SVM) algorithm to detect the presence of Fetal QRS (fQRS) complexes in electrocardiogram (ECG) recordings provided by the PhysioNet/CinC challenge 2013. ECG signals are first segmented into contiguous frames of 250 ms duration and then labeled in six classes. Fetal segments are tagged according to the position of fQRS complex within each one. Next, segment features extraction and dimensionality reduction are obtained by applying principal component analysis on Haar-wavelet transform. After that, two sub-datasets are generated to separate representative segments from atypical ones. Imbalanced class problem is dealt by applying sampling without replacement on each sub-dataset. Finally, two SVMs are trained and cross-validated using the two balanced sub-datasets separately. Experimental results show that the proposed approach achieves high performance rates in fetal heartbeats detection that reach up to 90.95% of accuracy, 92.16% of sensitivity, 88.51% of specificity, 94.13% of positive predictive value and 84.96% of negative predictive value. A comparative study is also carried out to show the performance of other two machine learning algorithms for fQRS complex estimation, which are K-nearest neighborhood and Bayesian network.

  18. Ringer's lactate, but not hydroxyethyl starch, prolongs the food intolerance time after major abdominal surgery; an open-labelled clinical trial.

    Science.gov (United States)

    Li, Yuhong; He, Rui; Ying, Xiaojiang; Hahn, Robert G

    2015-05-06

    The infusion of large amounts of Ringer's lactate prolongs the functional gastrointestinal recovery time and increases the number of complications after open abdominal surgery. We performed an open-labelled clinical trial to determine whether hydroxyethyl starch or Ringer's lactate exerts these adverse effects when the surgery is performed by laparoscopy. Eighty-eight patients scheduled for major abdominal cancer surgery (83% by laparoscopy) received a first-line fluid treatment with 9 ml/kg of either 6% hydroxyethyl starch 130/0.4 (Voluven) or Ringer's lactate, just after induction of anaesthesia; this was followed by a second-line infusion with 12 ml/kg of either starch or Ringer's lactate over 1 hour. Further therapy was managed at the discretion of the attending anaesthetist. Outcome data consisted of postoperative gastrointestinal recovery time, complications and length of hospital stay. The order of the infusions had no impact on the outcome. Both the administration of ≥ 2 L of Ringer's lactate and the development of a surgical complication were associated with a longer time period of paralytic ileus and food intolerance (two-way ANOVA, P food intolerance time amounted to 2 days each. The infusion of ≥ 1 L of hydroxyethyl starch did not adversely affect gastrointestinal recovery. Ringer's lactate, but not hydroxyethyl starch, prolonged the gastrointestinal recovery time in patients undergoing laparoscopic cancer surgery. Surgical complications prolonged the hospital stay.

  19. Effect of early postextubation high-flow nasal cannula vs conventional oxygen therapy on hypoxaemia in patients after major abdominal surgery: a French multicentre randomised controlled trial (OPERA).

    Science.gov (United States)

    Futier, Emmanuel; Paugam-Burtz, Catherine; Godet, Thomas; Khoy-Ear, Linda; Rozencwajg, Sacha; Delay, Jean-Marc; Verzilli, Daniel; Dupuis, Jeremie; Chanques, Gerald; Bazin, Jean-Etienne; Constantin, Jean-Michel; Pereira, Bruno; Jaber, Samir

    2016-12-01

    High-flow nasal cannula (HFNC) oxygen therapy is attracting increasing interest in acute medicine as an alternative to standard oxygen therapy; however, its use to prevent hypoxaemia after major abdominal surgery has not been evaluated. Our trial was designed to close this evidence gap. A multicentre randomised controlled trial was carried out at three university hospitals in France. Adult patients at moderate to high risk of postoperative pulmonary complications who had undergone major abdominal surgery using lung-protective ventilation were randomly assigned using a computer-generated sequence to receive either HFNC oxygen therapy or standard oxygen therapy (low-flow oxygen delivered via nasal prongs or facemask) directly after extubation. The primary endpoint was absolute risk reduction (ARR) for hypoxaemia at 1 h after extubation and after treatment discontinuation. Secondary outcomes included occurrence of postoperative pulmonary complications within 7 days after surgery, the duration of hospital stay, and in-hospital mortality. The analysis was performed on data from the modified intention-to-treat population. This trial was registered with ClinicalTrials.gov (NCT01887015). Between 6 November 2013 and 1 March 2015, 220 patients were randomly assigned to receive either HFNC (n = 108) or standard oxygen therapy (n = 112); all of these patients completed follow-up. The median duration of the allocated treatment was 16 h (interquartile range 14-18 h) with standard oxygen therapy and 15 h (interquartile range 12-18) with HFNC therapy. Twenty-three (21 %) of the 108 patients treated with HFNC 1 h after extubation and 29 (27 %) of the 108 patients after treatment discontinuation had postextubation hypoxaemia, compared with 27 (24 %) and 34 (30 %) of the 112 patients treated with standard oxygen (ARR 4, 95 % CI -8 to 15 %; p = 0.57; adjusted relative risk [RR] 0.87, 95 % CI 0.53-1.43; p = 0.58). Over the 7-day postoperative follow-up period

  20. Cost-analysis of robotic-assisted laparoscopic hysterectomy versus total abdominal hysterectomy for women with endometrial cancer and atypical complex hyperplasia

    DEFF Research Database (Denmark)

    Herling, Suzanne Forsyth; Palle, Connie; Møller, Ann M

    2016-01-01

    professionals' salaries. As cost-drivers we included severe complications, duration of surgery, anesthesia and stay at the post-anesthetic care unit, as well as number of hospital bed-days. Ordinary least-squares regression was used to explore the cost variation. The primary outcome was cost difference...... in Danish kroner between total abdominal hysterectomy and robotic-assisted laparoscopic hysterectomy. RESULTS: The average cost of consumables was 12,642 Danish kroner more expensive per patient for robotic-assisted laparoscopic hysterectomy than for total abdominal hysterectomy (2014 price level: 1€ = 7......INTRODUCTION: The aim of this study was to analyse the hospital cost of treatment with robotic-assisted laparoscopic hysterectomy and total abdominal hysterectomy for women with endometrial cancer or atypical complex hyperplasia and to identify differences in resource use and cost. MATERIAL...

  1. Differential analgesic effects of low-dose epidural morphine and morphine-bupivacaine at rest and during mobilization after major abdominal surgery

    DEFF Research Database (Denmark)

    Dahl, J B; Rosenberg, J; Hansen, B L

    1992-01-01

    In a double-blind, randomized study, epidural infusions of low-dose morphine (0.2 mg/h) combined with low-dose bupivacaine (10 mg/h) were compared with epidural infusions of low-dose morphine (0.2 mg/h) alone for postoperative analgesia at rest and during mobilization and cough in 24 patients after...... elective major abdominal surgery. All patients in addition received systemic piroxicam (20 mg daily). No significant differences were observed between the groups at any assessment of pain at rest (P greater than 0.05), whereas pain in the morphine/bupivacaine group was significantly reduced during...... mobilization from the supine into the sitting position 12 and 30 h after surgical incision and during cough 8, 12, and 30 h after surgical incision (P less than 0.05). We conclude, that low-dose epidural bupivacaine potentiates postoperative low-dose epidural morphine analgesia during mobilization and cough...

  2. Differential changes in free and total insulin-like growth factor I after major, elective abdominal surgery

    DEFF Research Database (Denmark)

    Skjærbæk, Christian; Frystyk, Jan; Ørskov, Hans

    1998-01-01

    Major surgery is accompanied by extensive proteolysis of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3). Proteolysis of IGFBP-3 is generally believed to increase IGF bioavailability due to a diminished affinity of the IGFBP-3 fragments for IGFs. We have investigated 18 patients...... undergoing elective ileo-anal J-pouch surgery. Patients were randomized to treatment with GH (12 IU/day; n = 9) or placebo (n = 9) from 2 days before to 7 days after operation. Free IGF-I and IGF-II were measured by ultrafiltration of serum, and IGFBP-3 proteolytic activity was determined by a [125I...

  3. Weighted abdominal traction for assistance in abdominal closure

    Directory of Open Access Journals (Sweden)

    Wendy Jo Svetanoff

    2018-02-01

    Discussion: One of the concerns with temporary abdominal closure is retraction of the fascia. We report three cases where the fascia and abdominal wall were placed on weighted traction, which allowed for retention of abdominal domain and delayed primary closure without grafts or mesh. This approach adds to the options available to aid in closure of the complex abdomen.

  4. Skeletal muscle major histocompatibility complex class I and II expression differences in adult and juvenile dermatomyositis.

    Science.gov (United States)

    Shinjo, Samuel Katsuyuki; Sallum, Adriana Maluf Elias; Silva, Clovis Artur; Marie, Suely Kazue Nagahashi

    2012-08-01

    To analyze major histocompatibility complex expression in the muscle fibers of juvenile and adult dermatomyositis. In total, 28 untreated adult dermatomyositis patients, 28 juvenile dermatomyositis patients (Bohan and Peter's criteria) and a control group consisting of four dystrophic and five Pompe's disease patients were analyzed. Routine histological and immunohistochemical (major histocompatibility complex I and II, StreptoABComplex/HRP, Dakopatts) analyses were performed on serial frozen muscle sections. Inflammatory cells, fiber damage, perifascicular atrophy and increased connective tissue were analyzed relative to the expression of major histocompatibility complexes I and II, which were assessed as negatively or positively stained fibers in 10 fields (200X). The mean ages at disease onset were 42.0±15.9 and 7.3±3.4 years in adult and juvenile dermatomyositis, respectively, and the symptom durations before muscle biopsy were similar in both groups. No significant differences were observed regarding gender, ethnicity and frequency of organ involvement, except for higher creatine kinase and lactate dehydrogenase levels in adult dermatomyositis (pmajor histocompatibility complex I (96.4% vs. 50.0%, pmajor histocompatibility complex II expression (14.3% vs. 53.6%, p=0.004) was observed in juvenile dermatomyositis. Fiber damage (p=0.006) and increased connective tissue (pmajor histocompatibility complex I was an important finding for the diagnosis of both groups, particularly for juvenile dermatomyositis, whereas there was lower levels of expression of major histocompatibility complex II than major histocompatibility complex I. This finding was particularly apparent in juvenile dermatomyositis.

  5. The value of true-FISP sequence added to conventional gadolinium-enhanced MRA of abdominal aorta and its major branches

    Energy Technology Data Exchange (ETDEWEB)

    Iozzelli, Andrea [University of Milan School of Medicine, Department of Medical and Surgical Sciences, Radiology Unit, IRCCS Policlinico San Donato, via Morandi 30, 20097 San Donato Milanese, Milan (Italy)], E-mail: andrea.iozzelli@poste.it; D' Orta, Giovanni [University of Milan School of Medicine, Department of Medical and Surgical Sciences, Radiology Unit, IRCCS Policlinico San Donato, via Morandi 30, 20097 San Donato Milanese, Milan (Italy)], E-mail: ammos@tiscali.it; Aliprandi, Alberto [University of Milan School of Medicine, Department of Medical and Surgical Sciences, Radiology Unit, IRCCS Policlinico San Donato, via Morandi 30, 20097 San Donato Milanese, Milan (Italy)], E-mail: a.aliprandi@grupposandonato.it; Secchi, Francesco [University of Milan School of Medicine, Department of Medical and Surgical Sciences, Radiology Unit, IRCCS Policlinico San Donato, via Morandi 30, 20097 San Donato Milanese, Milan (Italy)], E-mail: francisecchi@virgilio.it; Di Leo, Giovanni [University of Milan School of Medicine, Department of Medical and Surgical Sciences, Radiology Unit, IRCCS Policlinico San Donato, via Morandi 30, 20097 San Donato Milanese, Milan (Italy)], E-mail: gianni.dileo77@virgilio.it; Sardanelli, Francesco [University of Milan School of Medicine, Department of Medical and Surgical Sciences, Radiology Unit, IRCCS Policlinico San Donato, via Morandi 30, 20097 San Donato Milanese, Milan (Italy)], E-mail: f.sardanelli@grupposandonato.it

    2009-12-15

    To test true-fast imaging with steady-state precession (true-FISP) added to gadolinium-based MR angiography (Gd-MRA) for imaging abdominal aorta and major abdominal vessels, 35 consecutive patients (age 67 {+-} 11 years) with known or suspected abdominal and/or peripheral vascular disease were studied with sagittal and axial 2D true-FISP during free breathing and coronal 3D fast low-angle shot (FLASH) Gd-MRA (breath-holding, 0.2 mmol/kg of Gd-DOTA at 2 ml/s). We evaluated: suprarenal aorta, celiac trunk, superior mesenteric artery, right renal artery, left renal artery, infrarenal aorta, inferior mesenteric artery, aortic bifurcation/common iliac arteries, lumbar arteries and aortic atheromasia. The possible presence of accessory renal arteries, collateral vasculature and vascular prosthesis/stent was evaluated. A quality four-point score was assigned to each item on both sequences, from 0 (not visible) to 3 (good-to-excellent image quality) and Wilcoxon test was used. Main diagnoses resulted: normal or atheromasic aorta (n = 25); aortic aneurysm (n = 2); patent aorto-iliac surgical prosthesis (n = 2); patent vascular iliac stent (n = 2); aneurysm of iliac artery (n = 1); patent aortic endovascular prosthesis (n = 1); patent aorto-femural bypass (n = 1) and aorto-iliac surgical prosthesis endoleak (n = 1). We also found three patients with accessory renal arteries, two with collateral circulation, and three with surgical aorto-iliac prosthesis. The score of true-FISP (25.9 {+-} 4.1, median 27) was significantly higher (p = 0.003) than that of Gd-MRA (23.9 {+-} 3.6, median 24). True-FISP was superior for visualizing inferior mesenteric artery (score 2.5 {+-} 1.1 vs. 1.0 {+-} 1.4; p < 0.001) and atheromasic plaques (2.5 {+-} 1.1 vs. 1.2 {+-} 1.1; p < 0.001). One collateral vasculature was demonstrated only with Gd-MRA. Summarizing, true-FISP is a power and fast non-breath-hold sequence to be added to Gd-MRA, obtaining an information increase.

  6. Examining the evidence for major histocompatibility complex-dependent mate selection in humans and nonhuman primates

    Czech Academy of Sciences Publication Activity Database

    Winternitz, Jamie Caroline; Abbate, J. L.

    2015-01-01

    Roč. 6, 13 May (2015), s. 73-88 ISSN 1179-7274 Institutional support : RVO:68081766 Keywords : major histocompatibility complex * sexual selection * olfaction * facial attraction * parasite resistance * inbreeding avoidance Subject RIV: EB - Genetics ; Molecular Biology

  7. Data on genetic analysis of atherosclerosis identifies a major susceptibility locus in the major histocompatibility complex of mice.

    Science.gov (United States)

    Grainger, Andrew T; Jones, Michael B; Li, Jing; Chen, Mei-Hua; Manichaikul, Ani; Shi, Weibin

    2016-12-01

    The data presented here are related to the research article, entitled Genetic analysis of atherosclerosis identifies a major susceptibility locus in the major histocompatibility complex of mice, published in Atherosclerosis 2016;254:124 (A.T. Grainger, M.B. Jones, J. Li, M.H. Chen, A. Manichaikul, W. Shi, 2016) [1]. The supporting materials include original genotypic and phenotypic data obtained from 206 female F2 mice derived from an intercross between BALB and SMJ inbred mice. The F2 mice were fed 12 weeks of Western diet, starting at 6 weeks of age. Atherosclerotic lesion size in the aortic root of each mouse is the sum of the top 8 lesion areas. The data is provided in the format required for determining QTLs using two independent programs, J/QTL and PLINK.

  8. Plasma levels of plasmin-antiplasmin-complexes are predictive for small abdominal aortic aneurysms expanding to operation-recommendable sizes

    DEFF Research Database (Denmark)

    Lindholt, Jes Sanddal; Jørgensen, B; Fasting, H

    2001-01-01

    Three proteolytic systems seem involved in the aneurysmal degradation of the aortic wall. Plasmin is a common activator of the systems and could thus be predictive for the progression of abdominal aortic aneurysms (AAAs).......Three proteolytic systems seem involved in the aneurysmal degradation of the aortic wall. Plasmin is a common activator of the systems and could thus be predictive for the progression of abdominal aortic aneurysms (AAAs)....

  9. Indications and outcomes of the components separation technique in the repair of complex abdominal wall hernias: experience from the cambridge plastic surgery department.

    Science.gov (United States)

    Adekunle, Shola; Pantelides, Nicholas M; Hall, Nigel R; Praseedom, Raaj; Malata, Charles M

    2013-01-01

    The components separation technique (CST) is a widely described abdominal wall reconstructive technique. There have, however, been no UK reports of its use, prompting the present review. Between 2008 and 2012, 13 patients who underwent this procedure by a single plastic surgeon (C.M.M.) were retrospectively evaluated. The indications, operative details, and clinical outcomes were recorded. There were 7 women and 6 men in the series with a mean age of 53 years (range: 30-80). Patients were referred from a variety of specialties, often as a last resort. The commonest indication for CST was herniation following abdominal surgery. All operations except 1 were jointly performed with general surgeons (for bowel resection, stoma reversal, and hernia dissection). The operations lasted a mean of 5 hours (range: 3-8 hours). There were no major intra- and postoperative problems, except in 1 patient who developed intra-abdominal compartment syndrome, secondary to massive hemorrhage. All patients were satisfied with the cosmetic improvement in their abdominal contours. None of the patients have developed a clinical recurrence after a mean follow-up of 16 months (range: 3-38 months). The components separation technique is an effective method of treating large recalcitrant hernias but appears to be underutilized in the United Kingdom. The management of large abdominal wall defects requires a multidisciplinary approach, with input across a variety of specialities. Liaison with plastic surgery teams should be encouraged at an early stage and the CST should be more widely considered when presented with seemingly intractable abdominal wall defects.

  10. Antigen-B Cell Receptor Complexes Associate with Intracellular major histocompatibility complex (MHC) Class II Molecules*

    Science.gov (United States)

    Barroso, Margarida; Tucker, Heidi; Drake, Lisa; Nichol, Kathleen; Drake, James R.

    2015-01-01

    Antigen processing and MHC class II-restricted antigen presentation by antigen-presenting cells such as dendritic cells and B cells allows the activation of naïve CD4+ T cells and cognate interactions between B cells and effector CD4+ T cells, respectively. B cells are unique among class II-restricted antigen-presenting cells in that they have a clonally restricted antigen-specific receptor, the B cell receptor (BCR), which allows the cell to recognize and respond to trace amounts of foreign antigen present in a sea of self-antigens. Moreover, engagement of peptide-class II complexes formed via BCR-mediated processing of cognate antigen has been shown to result in a unique pattern of B cell activation. Using a combined biochemical and imaging/FRET approach, we establish that internalized antigen-BCR complexes associate with intracellular class II molecules. We demonstrate that the M1-paired MHC class II conformer, shown previously to be critical for CD4 T cell activation, is incorporated selectively into these complexes and loaded selectively with peptide derived from BCR-internalized cognate antigen. These results demonstrate that, in B cells, internalized antigen-BCR complexes associate with intracellular MHC class II molecules, potentially defining a site of class II peptide acquisition, and reveal a selective role for the M1-paired class II conformer in the presentation of cognate antigen. These findings provide key insights into the molecular mechanisms used by B cells to control the source of peptides charged onto class II molecules, allowing the immune system to mount an antibody response focused on BCR-reactive cognate antigen. PMID:26400081

  11. Major histocompatibility complex class I binding predictions as a tool in epitope discovery

    DEFF Research Database (Denmark)

    Lundegaard, Claus; Lund, Ole; Buus, Søren

    2010-01-01

    Over the last decade, in silico models of the major histocompatibility complex (MHC) class I pathway have developed significantly. Before, peptide binding could only be reliably modelled for a few major human or mouse histocompatibility molecules; now, high-accuracy predictions are available...

  12. Collaborative Management of Complex Major Construction Projects: AnyLogic-Based Simulation Modelling

    Directory of Open Access Journals (Sweden)

    Na Zhao

    2016-01-01

    Full Text Available Complex supply chain system collaborative management of major construction projects effectively integrates the different participants in the construction project. This paper establishes a simulation model based on AnyLogic to reveal the collaborative elements in the complex supply chain management system and the modes of action as well as the transmission problems of the intent information. Thus it is promoting the participants to become an organism with coordinated development and coevolution. This study can help improve the efficiency and management of the complex system of major construction projects.

  13. Normal saline versus a balanced crystalloid for goal-directed perioperative fluid therapy in major abdominal surgery: a double-blind randomised controlled study.

    Science.gov (United States)

    Pfortmueller, C A; Funk, G-C; Reiterer, C; Schrott, A; Zotti, O; Kabon, B; Fleischmann, E; Lindner, G

    2018-02-01

    This double-blind randomised controlled trial investigated whether normal saline or a balanced crystalloid has distinct effects on vasopressor use in patients undergoing major abdominal surgery. Patients received either normal saline 0.9% or an acetate-buffered crystalloid for intraoperative volume replacement in a goal-directed fashion. The primary outcome was need for vasopressors; the secondary outcomes were the total dose of catecholamines, total perioperative fluid, and unplanned intensive care admissions. This study was terminated early for safety reasons. A total of 60 out of the planned 240 patients were randomized. Thirty patients received normal saline and 30 patients received the balanced crystalloid, with a total volume of 3427 (2732-4130) ml and 3144 (1673-4926), respectively. The normal-saline group developed hyperchloraemic metabolic acidosis. More patients needed vasopressors for circulatory support in the normal-saline group compared with the buffered crystalloid group (97% vs 67%, respectively; P=0.033). The median weight and anaesthesia duration-adjusted dose of norepinephrine were 0.11 (0.00-0.45) ng kg -1  min -1 and 0.00 (0.00-0.00) kg -1  min -1 in the normal-saline and balanced-crystalloid groups, respectively (P=0.003). Cox regression revealed that the need for vasopressors was related to a high volume of administered fluid, normal-saline resuscitation, and lower mean arterial blood pressure. There was no difference between the groups in total perioperative fluid and unplanned intensive-care-unit admissions. Between-group differences in the duration of anaesthesia did not influence the necessity for a vasopressor. Compared with patients receiving a balanced crystalloid, normal saline in patients undergoing major abdominal surgery was associated with an increased need for vasopressor support. This should be interpreted in view of the large volume of fluid resuscitation and the small sample size because of the preliminary termination of

  14. Structural requirements and biological significance of interactions between peptides and the major histocompatibility complex

    DEFF Research Database (Denmark)

    Grey, H M; Buus, S; Colon, S

    1989-01-01

    Previous studies indicate that T cells recognize a complex between the major histocompatibility complex (MHC) restriction-element and peptide-antigen fragments. Two aspects of this complex formation are considered in this paper: (1) what is the nature of the specificity of the interactions...... that allows a few MHC molecules to serve as restriction elements for a large universe of antigens; and (2) what is the relative contribution of determinant selection (i.e. antigen-MHC complex formation) and T-cell repertoire in determining the capacity of an individual to respond to an antigen? By analysing...

  15. Amino acid infusions started after development of intraoperative core hypothermia do not affect rewarming but reduce the incidence of postoperative shivering during major abdominal surgery: a randomized trial.

    Science.gov (United States)

    Inoue, Satoki; Shinjo, Takeaki; Kawaguchi, Masahiko; Nakajima, Yoshiyuki; Furuya, Hitoshi

    2011-12-01

    Previous studies have demonstrated that amino acid infusions exert enhanced thermogenic effects during general anesthesia. This study was conducted to investigate whether amino acid infusions started after development of intraoperative core hypothermia can accelerate rewarming. Twenty-two patients scheduled for major abdominal surgery were included in this study. When tympanic temperature reached 35.5°C, patients were randomly assigned to receive amino acids (amino acid group; n = 11) or saline (saline group; n = 11). A continuous infusion of a mixture of 18 amino acids or saline was started at 200 ml h(-1). Tympanic, forearm, and digit temperatures were recorded. Forearm minus fingertip skin-surface temperature gradients (temperature gradient) were calculated. Postoperative shivering was also evaluated. Tympanic membrane temperature and temperature gradient were similar between the two groups at each time point during the study period. Temperature gradient at extubation in the amino acid group was significantly lower than in the saline group although tympanic temperature at extubation was similar between the two groups. Postoperative shivering score was significantly lower in the amino acid group than in the saline group. Amino acid infusions started after development of intraoperative core hypothermia failed to accelerate rewarming. However, amino acid infusions reduced the incidence of postoperative shivering. Use of amino acid infusions to reduce thermoregulatory vasoconstriction at emergence might contribute to a decrease in the development of postoperative shivering.

  16. The Combined Effects of Obesity, Abdominal Obesity and Major Depression/Anxiety on Health-Related Quality of Life: the LifeLines Cohort Study.

    Science.gov (United States)

    Nigatu, Yeshambel T; Reijneveld, Sijmen A; de Jonge, Peter; van Rossum, Elisabeth; Bültmann, Ute

    2016-01-01

    Obesity and major depressive disorder (MDD)/anxiety disorders often co-occur and aggravate each other resulting in adverse health-related outcomes. As little is known about the potential effects of interaction between obesity and MDD and/or anxiety disorders on health-related quality of life (HR-QoL), this study was aimed at examining these combined effects. We collected data among N = 89,332 participants from the LifeLines cohort study. We categorized body weight using body mass index (kg/m2) as normal weight (18.5-24.99), overweight (25-29.9), mild obesity (30-34.9) and moderate/severe obesity (≥ 35); we measured abdominal obesity using a waist circumference of ≥102 and ≥ 88 cm for males and females, respectively. MDD and anxiety disorders were diagnosed with the Mini-International Neuropsychiatric Interview. HR-QoL was assessed using the RAND-36 questionnaire to compute physical and mental quality of life scores. We used binary logistic and linear regression analyses. The combined effect of obesity and MDD and/or anxiety disorders on physical QoL was larger than the sum of their separate effects; regression coefficients, B (95%-confidence interval, 95%-CI) were: - 1.32 (-1.75; -0.90). However, the combined effect of obesity and major depression alone on mental QoL was less than the additive effect. With increasing body weight participants report poorer physical QoL; when they also have MDD and/or anxiety disorders participants report even poorer physical QoL. In persons without MDD and/or anxiety disorders, obesity was associated with a better mental QoL. Obesity and MDD and/or anxiety disorders act synergistically on physical and mental QoL. The management of MDD and/or anxiety disorders and weight loss may be important routes to improve HR-QoL.

  17. The bovine class II major histocompatibility complex : serological definition and further characterization of class II haplotypes

    NARCIS (Netherlands)

    Nilsson, P.R.

    1994-01-01

    In this thesis an analysis of the major histocompatibility complex (MHC) class II in cattle is reported, with emphasis on the development of class II serology. First, the production of class II alloantisera, and the serological definition of bovine MHC class II polymorphism is described.

  18. Porcine major histocompatibility complex (MHC) class I molecules and analysis of their peptide-binding specificities

    Science.gov (United States)

    In all vertebrate animals, CD8+ cytotoxic T lymphocytes (CTLs) are controlled by major histocompatibility complex class I (MHC-I) molecules, which are highly polymorphic peptide receptors selecting and presenting endogenously derived epitopes to circulating cytotoxic lymphocytes (CTLs). The polymorp...

  19. Transmembrane Helices Are an Overlooked Source of Major Histocompatibility Complex Class I Epitopes

    NARCIS (Netherlands)

    Bianchi, F.; Textor, J.C.; Bogaart, G. van den

    2017-01-01

    About a fourth of the human proteome is anchored by transmembrane helices (TMHs) to lipid membranes. TMHs require multiple hydrophobic residues for spanning membranes, and this shows a striking resemblance with the requirements for peptide binding to major histocompatibility complex (MHC) class I.

  20. CD1 and major histocompatibility complex II molecules follow a different course during dendritic cell maturation

    NARCIS (Netherlands)

    van der Wel, Nicole N.; Sugita, Masahiko; Fluitsma, Donna M.; Cao, Xaiochun; Schreibelt, Gerty; Brenner, Michael B.; Peters, Peter J.

    2003-01-01

    The maturation of dendritic cells is accompanied by the redistribution of major histocompatibility complex (MHC) class II molecules from the lysosomal MHC class IT compartment to the plasma membrane to mediate presentation of peptide antigens. Besides MHC molecules, dendritic cells also express CD1

  1. NetMHCcons: a consensus method for the major histocompatibility complex class I predictions

    DEFF Research Database (Denmark)

    Karosiene, Edita; Lundegaard, Claus; Lund, Ole

    2012-01-01

    A key role in cell-mediated immunity is dedicated to the major histocompatibility complex (MHC) molecules that bind peptides for presentation on the cell surface. Several in silico methods capable of predicting peptide binding to MHC class I have been developed. The accuracy of these methods...

  2. Major Histocompatibility Complex and Background Genes in Chickens Influence Susceptibility to High Pathogenicity Avian Influenza Virus

    Science.gov (United States)

    The chicken’s major histocompatibility complex (MHC) haplotype has profound influence on the resistance or susceptibility to certain pathogens such as B21 MHC haplotype confers resistance to Marek’s disease (MD). However, non-MHC genes are also important in disease resistance. For example, both line...

  3. Objective Measures of Renal Mass Anatomic Complexity Predict Rates of Major Complications Following Partial Nephrectomy

    Science.gov (United States)

    Simhan, Jay; Smaldone, Marc C.; Tsai, Kevin J.; Canter, Daniel J.; Li, Tianyu; Kutikov, Alexander; Viterbo, Rosalia; Chen, David Y.T.; Greenberg, Richard E.; Uzzo, Robert G.

    2012-01-01

    Background The association between tumor complexity and postoperative complications after partial nephrectomy (PN) has not been well characterized. Objective We evaluated whether increasing renal tumor complexity, quantitated by nephrometry score (NS), is associated with increased complication rates following PN using the Clavien-Dindo classification system (CCS). Design, setting, and participants We queried our prospectively maintained kidney cancer database for patients undergoing PN from 2007 to 2010 for whom NS was available. Interventions All patients underwent PN. Measurements Tumors were categorized into low- (NS: 4–6), moderate- (NS: 7–9), and high-complexity (NS: 10–12) lesions. Complication rates within 30 d were graded (CCS: I–5), stratified as minor (CCS: I or 2) or major (CCS: 3–5), and compared between groups. Results and limitations A total of 390 patients (mean age: 58.0 ± 11.9 yr; 66.9% male) undergoing PN (44.6% open, 55.4% robotic) for low- (28%), moderate- (55.6%), and high-complexity (16.4%) tumors (mean tumor size: 3.74 ± 2.4 cm; median: 3.2 cm) from 2007 to 2010 were identified. Tumor size, estimated blood loss, and ischemia time all significantly differed (p < 0.0001) between groups; patient age, body mass index (BMI), and operative time were comparable. When stratified by CCS, minor and major complication rates for all patients were 26.7% and 11.5%, respectively. Minor complication rates were comparable (26.6 vs 24.9 vs 32.8%; p = 0.45), whereas major complication rates differed (6.4 vs 11.1 vs 21.9%; p = 0.009) among tumor complexity groups. Controlling for age, gender, BMI, type of surgical approach, operative duration, and tumor complexity, prolonged operative time (odds ratio [OR]: 1.01; confidence interval [CI], 1.0–1.02) and high tumor complexity (OR: 5.4; CI, 1.2–24.2) were associated with the postoperative development of a major complication. Lack of external validation is a limitation of this study. Conclusions

  4. The Combined Effects of Obesity, Abdominal Obesity and Major Depression/Anxiety on Health-Related Quality of Life: the LifeLines Cohort Study.

    Directory of Open Access Journals (Sweden)

    Yeshambel T Nigatu

    Full Text Available Obesity and major depressive disorder (MDD/anxiety disorders often co-occur and aggravate each other resulting in adverse health-related outcomes. As little is known about the potential effects of interaction between obesity and MDD and/or anxiety disorders on health-related quality of life (HR-QoL, this study was aimed at examining these combined effects.We collected data among N = 89,332 participants from the LifeLines cohort study. We categorized body weight using body mass index (kg/m2 as normal weight (18.5-24.99, overweight (25-29.9, mild obesity (30-34.9 and moderate/severe obesity (≥ 35; we measured abdominal obesity using a waist circumference of ≥102 and ≥ 88 cm for males and females, respectively. MDD and anxiety disorders were diagnosed with the Mini-International Neuropsychiatric Interview. HR-QoL was assessed using the RAND-36 questionnaire to compute physical and mental quality of life scores. We used binary logistic and linear regression analyses.The combined effect of obesity and MDD and/or anxiety disorders on physical QoL was larger than the sum of their separate effects; regression coefficients, B (95%-confidence interval, 95%-CI were: - 1.32 (-1.75; -0.90. However, the combined effect of obesity and major depression alone on mental QoL was less than the additive effect. With increasing body weight participants report poorer physical QoL; when they also have MDD and/or anxiety disorders participants report even poorer physical QoL. In persons without MDD and/or anxiety disorders, obesity was associated with a better mental QoL.Obesity and MDD and/or anxiety disorders act synergistically on physical and mental QoL. The management of MDD and/or anxiety disorders and weight loss may be important routes to improve HR-QoL.

  5. The Combined Effects of Obesity, Abdominal Obesity and Major Depression/Anxiety on Health-Related Quality of Life: the LifeLines Cohort Study

    Science.gov (United States)

    Nigatu, Yeshambel T.; Reijneveld, Sijmen A.; de Jonge, Peter; van Rossum, Elisabeth; Bültmann, Ute

    2016-01-01

    Background Obesity and major depressive disorder (MDD)/anxiety disorders often co-occur and aggravate each other resulting in adverse health-related outcomes. As little is known about the potential effects of interaction between obesity and MDD and/or anxiety disorders on health-related quality of life (HR-QoL), this study was aimed at examining these combined effects. Methods We collected data among N = 89,332 participants from the LifeLines cohort study. We categorized body weight using body mass index (kg/m2) as normal weight (18.5–24.99), overweight (25–29.9), mild obesity (30–34.9) and moderate/severe obesity (≥ 35); we measured abdominal obesity using a waist circumference of ≥102 and ≥ 88 cm for males and females, respectively. MDD and anxiety disorders were diagnosed with the Mini-International Neuropsychiatric Interview. HR-QoL was assessed using the RAND-36 questionnaire to compute physical and mental quality of life scores. We used binary logistic and linear regression analyses. Results The combined effect of obesity and MDD and/or anxiety disorders on physical QoL was larger than the sum of their separate effects; regression coefficients, B (95%-confidence interval, 95%-CI) were: - 1.32 (-1.75; -0.90). However, the combined effect of obesity and major depression alone on mental QoL was less than the additive effect. With increasing body weight participants report poorer physical QoL; when they also have MDD and/or anxiety disorders participants report even poorer physical QoL. In persons without MDD and/or anxiety disorders, obesity was associated with a better mental QoL. Conclusions Obesity and MDD and/or anxiety disorders act synergistically on physical and mental QoL. The management of MDD and/or anxiety disorders and weight loss may be important routes to improve HR-QoL. PMID:26866920

  6. Assembly and function of the major histocompatibility complex (MHC) I peptide-loading complex are conserved across higher vertebrates.

    Science.gov (United States)

    Hinz, Andreas; Jedamzick, Johanna; Herbring, Valentina; Fischbach, Hanna; Hartmann, Jessica; Parcej, David; Koch, Joachim; Tampé, Robert

    2014-11-28

    Antigen presentation to cytotoxic T lymphocytes via major histocompatibility complex class I (MHC I) molecules depends on the heterodimeric transporter associated with antigen processing (TAP). For efficient antigen supply to MHC I molecules in the ER, TAP assembles a macromolecular peptide-loading complex (PLC) by recruiting tapasin. In evolution, TAP appeared together with effector cells of adaptive immunity at the transition from jawless to jawed vertebrates and diversified further within the jawed vertebrates. Here, we compared TAP function and interaction with tapasin of a range of species within two classes of jawed vertebrates. We found that avian and mammalian TAP1 and TAP2 form heterodimeric complexes across taxa. Moreover, the extra N-terminal domain TMD0 of mammalian TAP1 and TAP2 as well as avian TAP2 recruits tapasin. Strikingly, however, only TAP1 and TAP2 from the same taxon can form a functional heterodimeric translocation complex. These data demonstrate that the dimerization interface between TAP1 and TAP2 and the tapasin docking sites for PLC assembly are conserved in evolution, whereas elements of antigen translocation diverged later in evolution and are thus taxon specific. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. The dichotomy between disease phenotype databases and the implications for understanding complex diseases involving the major histocompatibility complex.

    Science.gov (United States)

    Clark, P M; Kunkel, M; Monos, D S

    2015-12-01

    Many genes related to innate and adaptive immunity reside within the major histocompatibility complex (MHC) and have been associated with a multitude of complex, immune-related disorders. Despite years of genetic study, this region has seen few causative determinants discovered for immune-mediated diseases. Reported associations have been curated in various databases including the Genetic Association Database, NCBI database of clinically relevant variants (ClinVar) and the Human Gene Mutation Database and together capture genetic associations and annotated pathogenic loci within the MHC and across the genome for a variety of complex, immune-mediated diseases. A review of these three distinct databases reveals disparate annotations between associated genes and pathogenic loci, alluding to the polygenic, multifactorial nature of immune-mediated diseases and the pleiotropic character of genes within the MHC. The technical limitations and inherent biases imposed by current approaches and technologies in studying the MHC create a strong case for the need to perform targeted deep sequencing of the MHC and other immunologically relevant loci in order to fully elucidate and study the causative elements of complex immune-mediated diseases. © 2015 The Authors. International Journal of Immunogenetics Published by John Wiley & Sons Ltd.

  8. Microsatellite markers for evaluating the diversity of the natural killer complex and major histocompatibility complex genomic regions in domestic horses.

    Science.gov (United States)

    Horecky, C; Horecka, E; Futas, J; Janova, E; Horin, P; Knoll, A

    2018-04-01

    Genotyping microsatellite markers represents a standard, relatively easy, and inexpensive method of assessing genetic diversity of complex genomic regions in various animal species, such as the major histocompatibility complex (MHC) and/or natural killer cell receptor (NKR) genes. MHC-linked microsatellite markers have been identified and some of them were used for characterizing MHC polymorphism in various species, including horses. However, most of those were MHC class II markers, while MHC class I and III sub-regions were less well covered. No tools for studying genetic diversity of NKR complex genomic regions are available in horses. Therefore, the aims of this work were to establish a panel of markers suitable for analyzing genetic diversity of the natural killer complex (NKC), and to develop additional microsatellite markers of the MHC class I and class III genomic sub-regions in horses. Nine polymorphic microsatellite loci were newly identified in the equine NKC. Along with two previously reported microsatellites flanking this region, they constituted a panel of 11 loci allowing to characterize genetic variation in this functionally important part of the horse genome. Four newly described MHC class I/III-linked markers were added to 11 known microsatellites to establish a panel of 15 MHC markers with a better coverage of the class I and class III sub-regions. Major characteristics of the two panels produced on a group of 65 horses of 13 breeds and on five Przewalski's horses showed that they do reflect genetic variation within the horse species. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Abdominal trauma

    International Nuclear Information System (INIS)

    Giordany, B.R.

    1985-01-01

    Abdominal injury is an important cause of morbidity and mortality in childhood. Ten percent of trauma-related deaths are due to abdominal injury. Thousands of children are involved in auto accidents annually; many suffer severe internal injury. Child abuse is a second less frequent but equally serious cause of internal abdominal injury. The descriptions of McCort and Eisenstein and their associates in the 1960s first brought to attention the frequency and severity of visceral injury as important manifestations of the child abuse syndrome. Blunt abdominal trauma often causes multiple injuries; in the past, many children have been subjected to exploratory surgery to evaluate the extent of possible hidden injury. Since the advent of noninvasive radiologic imaging techniques including radionuclide scans and ultrasound and, especially, computed tomography (CT), the radiologist has been better able to assess (accurately) the extent of abdominal injury and thus allow conservative therapy in many cases. Penetrating abdominal trauma occurs following gunshot wounds, stabbing, and other similar injury. This is fortunately, a relatively uncommon occurrence in most pediatric centers and will not be discussed specifically here, although many principles of blunt trauma diagnosis are valid for evaluation of penetrating abdominal trauma. If there is any question that a wound has extended intraperitonelly, a sinogram with water-soluble contrast material allows quick, accurate diagnosis. The presence of large amounts of free intraperitoneal gas suggests penetrating injury to the colon or other gas-containing viscus and is generally considered an indication for surgery

  10. Molecular mapping of the human major histocompatibility complex by pulsed-field gel electrophoresis.

    OpenAIRE

    Dunham, I; Sargent, C A; Trowsdale, J; Campbell, R D

    1987-01-01

    Pulsed-field gel electrophoresis and "cosmid walking" have been used to establish a molecular map of the human major histocompatibility complex (MHC). We have isolated approximately equal to 230 kilobases (kb) of genomic DNA in overlapping cosmid clones covering the genes for the second and fourth components of complement (C2 and C4, respectively), factor B, and steroid 21-hydroxylase, and approximately equal to 82 kb of genomic DNA surrounding the genes for the tumor necrosis factors alpha a...

  11. Acute incarcerated external abdominal hernia

    OpenAIRE

    Yang, Xue-Fei; Liu, Jia-Lin

    2014-01-01

    External abdominal hernia occurs when abdominal organs or tissues leave their normal anatomic site and protrude outside the skin through the congenital or acquired weakness, defects or holes on the abdominal wall, including inguinal hernia, umbilical hernia, femoral hernia and so on. Acute incarcerated hernia is a common surgical emergency. With advances in minimally invasive devices and techniques, the diagnosis and treatment have witnessed major changes, such as the use of laparoscopic surg...

  12. Abdominal Pain

    Science.gov (United States)

    ... are at greater risk of having anxiety as young adults [2] . Abdominal pain or bellyaches in children What ... can help the overall situation for the child. Teaching kids self-hypnosis [8] or guided imagery [8a] ...

  13. Abdominal exploration

    Science.gov (United States)

    ... diverticulitis ) Inflammation of the pancreas ( acute or chronic pancreatitis ) Liver abscess Pockets of infection (retroperitoneal abscess, abdominal abscess , pelvic abscess) Pregnancy outside of the uterus ( ectopic pregnancy ) Scar tissue ...

  14. Abdominal Pain

    Science.gov (United States)

    ... to ease your pain. For instance, eat smaller meals if your pain is accompanied by indigestion. Avoid ... http://www.mayoclinic.org/symptoms/abdominal-pain/basics/definition/SYM-20050728 . Mayo Clinic Footer Legal Conditions and ...

  15. ABDOMINAL TRAUMA

    Directory of Open Access Journals (Sweden)

    Alojz Pleskovič

    2003-12-01

    Full Text Available Background. The most common cause of abdominal trauma is blunt trauma, gunshot wounds and stab wounds are rare. Most commonly injured organs in abdominal cavity are the spleen and the liver.Conclusions. Early diagnosis is very important and include precise phisical examination and all available diagnostic methods. The final decission about the method of treatmet depends on patients clinical condition, surgeon’s experience and other local conditions.

  16. A recombinant antibody with the antigen-specific, major histocompatibility complex-restricted specificity of T cells

    DEFF Research Database (Denmark)

    Andersen, P S; Stryhn, A; Hansen, B E

    1996-01-01

    Specific recognition of peptide/major histocompatibility complex (MHC) molecule complexes by the T-cell receptor is a key reaction in the specific immune response. Antibodies against peptide/MHC complexes would therefore be valuable tools in studying MHC function and T-cell recognition and might...... peptide/MHC complexes....

  17. The PSA-2 glycoprotein complex of Leishmania major is a glycosylphosphatidylinositol-linked promastigote surface antigen.

    Science.gov (United States)

    Murray, P J; Spithill, T W; Handman, E

    1989-12-15

    Polyclonal rabbit antiserum to the Triton X-114 phase material of Leishmania major, which comprises the surface and internal integral membrane proteins of the parasite, was used to screen a lambda gt11 genomic expression library. A recombinant clone producing a Mr 123,000 beta-galactosidase fusion protein was isolated. Antibodies affinity-purified on this fusion protein recognized a complex of three surface-oriented proteins of promastigotes of L. major of Mr 94,000, 90,000, and 80,000 that we have termed the promastigote surface Ag 2 (PSA-2) complex. The DNA sequence of the insert in this clone predicted the 3' end of an open reading frame encoding a hydrophobic C-terminus. The inferred C-terminal sequence was suggestive of a glycosylphosphatidyl-inositol membrane anchoring mechanism. Phosphatidylinositol-specific phospholipase C treatment of the native PSA-2 proteins caused a shift in their electrophoretic mobility with an apparent reduction in the molecular weight of the PSA-2 complex. After phospholipase C treatment these proteins also displayed the cryptic cross-reacting determinant recognized by antibodies to the Trypanosoma brucei variant surface Ag. Moreover, PSA-2, which previously partitioned in the detergent phase after Triton X-114 phase separation, became water-soluble after phospholipase C treatment. Immunoprecipitation of the PSA-2 proteins with sera directed to lectin-binding proteins indicated that these polypeptides may be differentially glycosylated. Finally, these PSA-2 proteins were recognized by sera from some patients with cutaneous leishmaniasis.

  18. Comparison of multi-modal early oral nutrition for the tolerance of oral nutrition with conventional care after major abdominal surgery: a prospective, randomized, single-blind trial.

    Science.gov (United States)

    Sun, Da-Li; Li, Wei-Ming; Li, Shu-Min; Cen, Yun-Yun; Xu, Qing-Wen; Li, Yi-Jun; Sun, Yan-Bo; Qi, Yu-Xing; Lin, Yue-Ying; Yang, Ting; Lu, Qi-Ping; Xu, Peng-Yuan

    2017-02-10

    Early oral nutrition (EON) has been shown to improve recovery of gastrointestinal function, length of stay and mortality after abdominal surgery; however, early oral nutrition often fails during the first week after surgery. Here, a multi-modal early oral nutrition program is introduced to promote recovery of gastrointestinal function and tolerance of oral nutrition. Consecutive patients scheduled for abdominal surgery were randomized to the multimodal EON group or a group receiving conventional care. The primary endpoint was the time of first defecation. The secondary endpoints were outcomes and the cost-effectiveness ratio in treating infectious complications. The rate of infectious-free patients was regarded as the index of effectiveness. One hundred seven patients were randomly assigned to groups. Baseline characteristics were similar for both groups. In intention-to-treat analysis, the success rate of oral nutrition during the first week after surgery in the multimodal EON group was 44 (83.0%) versus 31 (57.4%) in the conventional care group (P = 0.004). Time to first defecation, time to flatus, recovery time of bowel sounds, and prolonged postoperative ileus were all less in the multimodal EON group (P oral nutrition group (P oral nutrition program was an effective way to improve tolerance of oral nutrition during the first week after surgery, decrease the length of stay and improve cost-effectiveness after abdominal surgery. Registration number: ChiCTR-TRC-14004395 . Registered 15 March 2014.

  19. T cell receptor reversed polarity recognition of a self-antigen major histocompatibility complex.

    Science.gov (United States)

    Beringer, Dennis X; Kleijwegt, Fleur S; Wiede, Florian; van der Slik, Arno R; Loh, Khai Lee; Petersen, Jan; Dudek, Nadine L; Duinkerken, Gaby; Laban, Sandra; Joosten, Antoinette; Vivian, Julian P; Chen, Zhenjun; Uldrich, Adam P; Godfrey, Dale I; McCluskey, James; Price, David A; Radford, Kristen J; Purcell, Anthony W; Nikolic, Tatjana; Reid, Hugh H; Tiganis, Tony; Roep, Bart O; Rossjohn, Jamie

    2015-11-01

    Central to adaptive immunity is the interaction between the αβ T cell receptor (TCR) and peptide presented by the major histocompatibility complex (MHC) molecule. Presumably reflecting TCR-MHC bias and T cell signaling constraints, the TCR universally adopts a canonical polarity atop the MHC. We report the structures of two TCRs, derived from human induced T regulatory (iT(reg)) cells, complexed to an MHC class II molecule presenting a proinsulin-derived peptide. The ternary complexes revealed a 180° polarity reversal compared to all other TCR-peptide-MHC complex structures. Namely, the iT(reg) TCR α-chain and β-chain are overlaid with the α-chain and β-chain of MHC class II, respectively. Nevertheless, this TCR interaction elicited a peptide-reactive, MHC-restricted T cell signal. Thus TCRs are not 'hardwired' to interact with MHC molecules in a stereotypic manner to elicit a T cell signal, a finding that fundamentally challenges our understanding of TCR recognition.

  20. Restriction fragment polymorphisms in the major histocompatibility complex of diabetic BB rats

    DEFF Research Database (Denmark)

    Kastern, W.; Dyrberg, T.; Scholler, J.

    1984-01-01

    DNA isolated from diabetic BB (BB/Hagedorn) rats was examined for restriction fragment length differences within the major histocompatibility complex (MHC) as compared with nondiabetic (W-subline) BB rats. Polymorphisms were detected using a mouse class I MHC gene as probe. Specifically, a 2-kb Bam......HI fragment was present in all the nondiabetic rats examined, but absent in the diabetic rats. Similar polymorphisms were observed with various other restriction enzymes, particularly XbaI, HindII, and SacI. There were no polymorphisms detected using either a human DR-alpha (class II antigen heavy chain...

  1. Invariant chain can function as a chaperone protein for class II major histocompatibility complex molecules.

    OpenAIRE

    Anderson, M S; Miller, J

    1992-01-01

    During biosynthesis, class II major histocompatibility complex molecules are intimately associated with invariant chain (Ii). The Ii-class II association has been shown to block peptide-class II binding and to affect the ultimate conformation of class II expressed on the cell surface. To assess the biochemical basis for the effects of Ii on class II, we have analyzed the biosynthesis of class II in EL4 cells transfected with I-Ad with and without Ii. In these studies, we found that Ii had a p...

  2. Major histocompatibility complex-controlled protective influences on experimental autoimmune encephalomyelitis are peptide specific

    DEFF Research Database (Denmark)

    Issazadeh-Navikas, Shohreh; Kjellén, P; Olsson, T

    1997-01-01

    The myelin basic protein (MBP) peptide 63-88-induced experimental autoimmune encephalomyelitis (EAE) and its associated T cell cytokine profile are influenced by the rat major histocompatibility complex (MHC). There is an allele-specific protective influence of the MHC class I region, whereas......-101 peptide, except in LEW.1N (RT1 pi) rats which were relatively resistant. Only this strain responded with additional Th2-like and transforming growth factor-beta responses to the peptide in vitro. In vivo depletion of CD8+ cells aggravated the disease in this strain. We conclude that both MHC-controlled...

  3. Major histocompatibility complex (MHC) molecules: their common characteristics and relations with diseases

    OpenAIRE

    Başak Yalçın

    2013-01-01

    Major histocompatibility complex (MHC) molecules or human leukocyte antigens (HLA) are the cell surface molecules responsible from antigen presentation and activation of T cells. At the same time MHC molecules determine direction of T cell response. Unlike T cells, antigen specificity of MHC molecules is not high and they can not differenciate self and non-self antigens from each other. MHC molecules are classified as MHC I (HLA- A, B, C) and MHC II (HLA-DP, DR, DQ) molecules which are struct...

  4. Allogeneic major histocompatibility complex-mismatched equine bone marrow-derived mesenchymal stem cells are targeted for death by cytotoxic anti-major histocompatibility complex antibodies.

    Science.gov (United States)

    Berglund, A K; Schnabel, L V

    2017-07-01

    Allogeneic mesenchymal stem cells (MSCs) are a promising cell source for treating musculoskeletal injuries in horses. Controversy exists, however, over whether major histocompatibility complex (MHC)-mismatched MSCs are recognised by the recipient immune system and targeted for death by a cytotoxic antibody response. To determine if cytotoxic anti-MHC antibodies generated in vivo following MHC-mismatched MSC injections are capable of initiating complement-dependent cytotoxicity of MSCs. Experimental controlled study. Antisera previously collected at Days 0, 7, 14 and 21 post-injection from 4 horses injected with donor MHC-mismatched equine leucocyte antigen (ELA)-A2 haplotype MSCs and one control horse injected with donor MHC-matched ELA-A2 MSCs were utilised in this study. Antisera were incubated with ELA-A2 MSCs before adding complement in microcytotoxicity assays and cell death was analysed via eosin dye exclusion. ELA-A2 peripheral blood leucocytes (PBLs) were used in the assays as a positive control. Antisera from all 4 horses injected with MHC-mismatched MSCs contained antibodies that caused the death of ELA-A2 haplotype MSCs in the microcytotoxicity assays. In 2 of the 4 horses, antibodies were present as early as Day 7 post-injection. MSC death was consistently equivalent to that of ELA-A2 haplotype PBL death at all time points and antisera dilutions. Antisera from the control horse that was injected with MHC-matched MSCs did not contain cytotoxic ELA-A2 antibodies at any of the time points examined. This study examined MSC death in vitro only and utilized antisera from a small number of horses. The cytotoxic antibody response induced in recipient horses following injection with donor MHC-mismatched MSCs is capable of killing donor MSCs in vitro. These results suggest that the use of allogeneic MHC-mismatched MSCs must be cautioned against, not only for potential adverse events, but also for reduced therapeutic efficacy due to targeted MSC death. © 2016 The

  5. MaHCO: an ontology of the major histocompatibility complex for immunoinformatic applications and text mining.

    Science.gov (United States)

    DeLuca, David S; Beisswanger, Elena; Wermter, Joachim; Horn, Peter A; Hahn, Udo; Blasczyk, Rainer

    2009-08-15

    The high level of polymorphism associated with the major histocompatibility complex (MHC) poses a challenge to organizing associated bioinformatic data, particularly in the area of hematopoietic stem cell transplantation. Thus, this area of research has great potential to profit from the ongoing development of biomedical ontologies, which offer structure and definition to MHC-data related communication and portability issues. We introduce the design considerations, methodological foundations and implementational issues underlying MaHCO, an ontology which represents the alleles and encoded molecules of the major histocompatibility complex. Importantly for human immunogenetics, it includes a detailed level of human leukocyte antigen (HLA) classification. We then present an ontology browser, search interfaces for immunogenetic fact and document retrieval, and the specification of an annotation language for semantic metadata, based on MaHCO. These use cases are intended to demonstrate the utility of ontology-driven bioinformatics in the field of immunogenetics. The MaHCO Ontology is available via the BioPortal: http://www.bioontology.org/tools/portal/bioportal.html, and at: http://purl.org/stemnet/.

  6. Abdominal Sepsis.

    Science.gov (United States)

    De Waele, Jan J

    2016-08-01

    Abdominal infections are an important challenge for the intensive care physician. In an era of increasing antimicrobial resistance, selecting the appropriate regimen is important and, with new drugs coming to the market, correct use is important more than ever before and abdominal infections are an excellent target for antimicrobial stewardship programs. Biomarkers may be helpful, but their exact role in managing abdominal infections remains incompletely understood. Source control also remains an ongoing conundrum, and evidence is increasing that its importance supersedes the impact of antibiotic therapy. New strategies such as open abdomen management may offer added benefit in severely ill patients, but more data are needed to identify its exact role. The role of fungi and the need for antifungal coverage, on the other hand, have been investigated extensively in recent years, but at this point, it remains unclear who requires empirical as well as directed therapy.

  7. Surgical treatment of chronic multivascular mesenteric ischemia in a patient with antiphospholipid syndrome, abdominal aortic aneurism, and renal cancer: when planning overwhelms complexity.

    Science.gov (United States)

    Paliogiannis, Panagiotis; Ginesu, Giorgio Carlo; Feo, Claudio Francesco; Cossu, Maria Laura; Pinna, Antonio; Farina, Giulia; Vidili, Gianpaolo; Porcu, Alberto

    2016-12-20

    Chronic mesenteric ischemia is a clinical condition caused by obstructive or occlusive disease of the mesenteric vessels, with potentially lethal consequences. We describe a case of open multiple revascularization in a patient affected by antiphospholipid syndrome and diffuse atherosclerosis, with an abdominal aortic aneurism, a contracted kidney, a renal cancer affecting the contralateral kidney, and as a consequence, a chronic renal failure and hypertension. We revascularized the celiac trunk, the superior and inferior mesenteric arteries, and the right renal artery using saphenous grafts; the aneurism was corrected, and the renal tumor was treated by radiofrequency ablation. Despite the invasiveness and complexity, the surgical strategy adopted allowed to save the patient's life, to treat the chronic mesenteric ischemia and the renal cancer, and to improve the chronic renal insufficiency and hypertension. Graft, Mesenteric ischemia, Occlusion, Revascularization.

  8. Latissimus dorsi free flap reconstruction of major abdominal defect in treatment of giant Marjolin’s ulcer: a short report focused on preoperative imaging

    International Nuclear Information System (INIS)

    Steffensen, Signe Muus; Thomassen, Anders; Jensen, Jesper Poul Naested; Soerensen, Jens Ahm

    2014-01-01

    We present a case of a 56-year-old man with a giant carcinoma in the abdominal wall. Based on positron emission tomography/computed tomography (PET/CT) scan there were FDG-avid lymph nodes in the ipsilateral axillary and groin, suspicious for metastases. At contrast-enhanced CT the parietal peritoneum seemed free of tumor invasion, which was essential to radical surgery planning. The tumor was completely removed with clear margins of resection and no metastasis in the resected lymph nodes. The PET/CT scan was repeated after 4 months, showing no signs of recurrence

  9. Diacylglycerol kinase α regulates tubular recycling endosome biogenesis and major histocompatibility complex class I recycling.

    Science.gov (United States)

    Xie, Shuwei; Naslavsky, Naava; Caplan, Steve

    2014-11-14

    Major histocompatibility complex class I (MHC I) presents intracellular-derived peptides to cytotoxic T lymphocytes and its subcellular itinerary is important in regulating the immune response. While a number of diacylglycerol kinase isoforms have been implicated in clathrin-dependent internalization, MHC I lacks the typical motifs known to mediate clathrin-dependent endocytosis. Here we show that depletion of diacylglycerol kinase α (DGKα), a kinase devoid of a clathrin-dependent adaptor protein complex 2 binding site, caused a delay in MHC I recycling to the plasma membrane without affecting the rate of MHC I internalization. We demonstrate that DGKα knock-down causes accumulation of intracellular and surface MHC I, resulting from decreased degradation. Furthermore, we provide evidence that DGKα is required for the generation of phosphatidic acid required for tubular recycling endosome (TRE) biogenesis. Moreover, we show that DGKα forms a complex with the TRE hub protein, MICAL-L1. Given that MICAL-L1 and the F-BAR-containing membrane-tubulating protein Syndapin2 associate selectively with phosphatidic acid, we propose a positive feedback loop in which DGKα generates phosphatidic acid to drive its own recruitment to TRE via its interaction with MICAL-L1. Our data support a novel role for the involvement of DGKα in TRE biogenesis and MHC I recycling. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. How a T Cell Receptor-like Antibody Recognizes Major Histocompatibility Complex-bound Peptide

    Energy Technology Data Exchange (ETDEWEB)

    Mareeva, T.; Martinez-Hackert, E; Sykulev, Y

    2008-01-01

    We determined the crystal structures of the T cell receptor (TCR)-like antibody 25-D1.16 Fab fragment bound to a complex of SIINFEKL peptide from ovalbumin and the H-2Kb molecule. Remarkably, this antibody directly 'reads' the structure of the major histocompatibility complex (MHC)-bound peptide, employing the canonical diagonal binding mode utilized by most TCRs. This is in marked contrast with another TCR-like antibody, Hyb3, bound to melanoma peptide MAGE-A1 in association with HLA-A1 MHC class I. Hyb3 assumes a non-canonical orientation over its cognate peptide-MHC and appears to recognize a conformational epitope in which the MHC contribution is dominant. We conclude that TCR-like antibodies can recognize MHC-bound peptide via two different mechanisms: one is similar to that exploited by the preponderance of TCRs and the other requires a non-canonical antibody orientation over the peptide-MHC complex.

  11. Plasticity of empty major histocompatibility complex class I molecules determines peptide-selector function.

    Science.gov (United States)

    van Hateren, Andy; Bailey, Alistair; Werner, Jörn M; Elliott, Tim

    2015-12-01

    Major histocompatibility complex class I (MHC I) proteins provide protection from intracellular pathogens and cancer via each of a cell's MHC I molecules binding and presenting a peptide to cytotoxic T lymphocytes. MHC I genes are highly polymorphic and can have significant diversity, with polymorphisms predominantly localised in the peptide-binding groove where they can change peptide-binding specificity. However, polymorphic residues may also determine other functional properties, such as how dependent MHC I alleles are on the peptide-loading complex for optimal acquisition of peptide cargo. We describe how differences in the peptide-binding properties of two MHC I alleles correlates with altered conformational flexibility in the peptide-empty state. We hypothesise that plasticity is an intrinsic property encoded by the protein sequence, and that co-ordinated movements of the membrane-proximal and membrane-distal domains collectively determines how dependent MHC I are on the peptide-loading complex for efficient assembly with high affinity peptides. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Ancestral polymorphism at the major histocompatibility complex (MHCIIß in the Nesospiza bunting species complex and its sister species (Rowettia goughensis

    Directory of Open Access Journals (Sweden)

    van Rensburg Alexandra

    2012-08-01

    Full Text Available Abstract Background The major histocompatibility complex (MHC is an important component of the vertebrate immune system and is frequently used to characterise adaptive variation in wild populations due to its co-evolution with pathogens. Passerine birds have an exceptionally diverse MHC with multiple gene copies and large numbers of alleles compared to other avian taxa. The Nesospiza bunting species complex (two species on Nightingale Island; one species with three sub-species on Inaccessible Island represents a rapid adaptive radiation at a small, isolated archipelago, and is thus an excellent model for the study of adaptation and speciation. In this first study of MHC in Nesospiza buntings, we aim to characterize MHCIIß variation, determine the strength of selection acting at this gene region and assess the level of shared polymorphism between the Nesospiza species complex and its putative sister taxon, Rowettia goughensis, from Gough Island. Results In total, 23 unique alleles were found in 14 Nesospiza and 2 R. goughensis individuals encoding at least four presumably functional loci and two pseudogenes. There was no evidence of ongoing selection on the peptide binding region (PBR. Of the 23 alleles, 15 were found on both the islands inhabited by Nesospiza species, and seven in both Nesospiza and Rowettia; indications of shared, ancestral polymorphism. A gene tree of Nesospiza MHCIIß alleles with several other passerine birds shows three highly supported Nesospiza-specific groups. All R. goughensis alleles were shared with Nesospiza, and these alleles were found in all three Nesospiza sequence groups in the gene tree, suggesting that most of the observed variation predates their phylogenetic split. Conclusions Lack of evidence of selection on the PBR, together with shared polymorphism across the gene tree, suggests that population variation of MHCIIß among Nesospiza and Rowettia is due to ancestral polymorphism rather than local selective

  13. A recombinant antibody with the antigen-specific, major histocompatibility complex-restricted specificity of T cells

    DEFF Research Database (Denmark)

    Andersen, P S; Stryhn, A; Hansen, B E

    1996-01-01

    Specific recognition of peptide/major histocompatibility complex (MHC) molecule complexes by the T-cell receptor is a key reaction in the specific immune response. Antibodies against peptide/MHC complexes would therefore be valuable tools in studying MHC function and T-cell recognition and might ...

  14. Structural Requirements and Biological Significance of Interactions between Peptides and the Major Histocompatibility Complex

    Science.gov (United States)

    Grey, H. M.; Buus, S.; Colon, S.; Miles, C.; Sette, A.

    1989-06-01

    Previous studies indicate that T cells recognize a complex between the major histocompatibility complex (MHC) restriction-element and peptide-antigen fragments. Two aspects of this complex formation are considered in this paper: (1) what is the nature of the specificity of the interactions that allows a few MHC molecules to serve as restriction elements for a large universe of antigens; and (2) what is the relative contribution of determinant selection (i.e. antigen-MHC complex formation) and Tcell repertoire in determining the capacity of an individual to respond to an antigen? By analysing single amino acid substitution analogues of a peptide antigen (Ova 325-335) as well as by analysing the structural similarities between unrelated peptides capable of binding to the same MHC molecule, we have been able to document the very permissive nature of the antigen--MHC interaction. Despite this permissiveness of binding, it is possible to define certain structural features of peptides that are associated with the capacity to bind to a particular MHC specificity. With respect to the question of the relative role of determinant selection' and 'holes in the T-cell repertoire' in determining immune responsiveness, we present data that suggest both mechanisms operate in concert with one another. Thus only about 30% of a collection of peptides that in sum represent the sequence of a protein molecule were found to bind to Ia. Although immunogenicity was restricted to those peptides that were capable of binding to Ia (i.e. determinant selection was operative), we found that about 40% of Ia-binding peptides were not immunogenic (i.e. there were also 'holes in the T-cell repertoire').

  15. A prospective, randomised, controlled, double-blind phase I-II clinical trial on the safety of A-Part® Gel as adhesion prophylaxis after major abdominal surgery versus non-treated group

    Directory of Open Access Journals (Sweden)

    Weis Christine

    2010-07-01

    Full Text Available Abstract Background Postoperative adhesions occur when fibrous strands of internal scar tissue bind anatomical structures to one another. The most common cause of intra-abdominal adhesions is previous intra-abdominal surgical intervention. Up to 74% of intestinal obstructions are caused by post surgical adhesions. Although a variety of methods and agents have been investigated to prevent post surgical adhesions, the problem of peritoneal adhesions remains largely unsolved. Materials serving as an adhesion barrier are much needed. Methods/Design This is a prospective, randomised, controlled, patient blinded and observer blinded, single centre phase I-II trial, which evaluates the safety of A-Part® Gel as an adhesion prophylaxis after major abdominal wall surgery, in comparison to an untreated control group. 60 patients undergoing an elective median laparotomy without prior abdominal surgery are randomly allocated into two groups of a 1:1- ratio. Safety parameter and primary endpoint of the study is the occurrence of wound healing impairment or peritonitis within 28 (+10 days after surgery. The frequency of anastomotic leakage within 28 days after operation, occurrence of adverse and serious adverse events during hospital stay up to 3 months and the rate of adhesions along the scar within 3 months are defined as secondary endpoints. After hospital discharge the investigator will examine the enrolled patients at 28 (+10 days and 3 months (±14 days after surgery. Discussion This trial aims to assess, whether the intra-peritoneal application of A-Part® Gel is safe and efficacious in the prevention of post-surgical adhesions after median laparotomy, in comparison to untreated controls. Trial registration NCT00646412

  16. Quantitative online prediction of peptide binding to the major histocompatibility complex.

    Science.gov (United States)

    Hattotuwagama, Channa K; Guan, Pingping; Doytchinova, Irini A; Zygouri, Christianna; Flower, Darren R

    2004-01-01

    With its implications for vaccine discovery, the accurate prediction of T cell epitopes is one of the key aspirations of computational vaccinology. We have developed a robust multivariate statistical method, based on partial least squares, for the quantitative prediction of peptide binding to major histocompatibility complexes (MHC), the principal checkpoint on the antigen presentation pathway. As a service to the immunobiology community, we have made a Perl implementation of the method available via a World Wide Web server. We call this server MHCPred. Access to the server is freely available from the URL: http://www.jenner.ac.uk/MHCPred. We have exemplified our method with a model for peptides binding to the common human MHC molecule HLA-B*3501.

  17. Expression of major histocompatibility complex class II and costimulatory molecules in oral carcinomas in vitro.

    Science.gov (United States)

    Villarroel-Dorrego, Mariana; Speight, Paul M; Barrett, A William

    2005-01-01

    Recognition in the 1980 s that keratinocytes can express class II molecules of the Major Histocompatibility Complex (MHC) first raised the possibility that these cells might have an immunological function, and may even act as antigen presenting cells (APC). For effective T lymphocyte activation, APC require, in addition to MHC II, appropriate costimulatory signals. The aim of this study was to determine the expression of MHC class II and the co-stimulatory molecules CD40, CD80 and CD86 in keratinocytes derived from healthy oral mucosa and oral carcinomas. Using flow cytometry, it was confirmed that oral keratinocytes, switch on, expression of MHC class II molecules after stimulation with IFNgamma in vitro. All keratinocyte lines expressed CD40 constitutively; by contrast, CD80 and CD86 were universally absent. Loss of CD80 and CD86 may be one means whereby tumours escape immunological surveillance.

  18. Porcine major histocompatibility complex (MHC) class I molecules and analysis of their peptide-binding specificities

    DEFF Research Database (Denmark)

    Pedersen, Lasse Eggers; Harndahl, Mikkel; Rasmussen, Michael

    2011-01-01

    In all vertebrate animals, CD8+ cytotoxic T lymphocytes (CTLs) are controlled by major histocompatibility complex class I (MHC-I) molecules. These are highly polymorphic peptide receptors selecting and presenting endogenously derived epitopes to circulating CTLs. The polymorphism of the MHC...... effectively individualizes the immune response of each member of the species. We have recently developed efficient methods to generate recombinant human MHC-I (also known as human leukocyte antigen class I, HLA-I) molecules, accompanying peptide-binding assays and predictors, and HLA tetramers for specific...... CTL staining and manipulation. This has enabled a complete mapping of all HLA-I specificities (“the Human MHC Project”). Here, we demonstrate that these approaches can be applied to other species. We systematically transferred domains of the frequently expressed swine MHC-I molecule, SLA-1*0401, onto...

  19. Humans with chimpanzee-like major histocompatibility complex-specificities control HIV-1 infection

    DEFF Research Database (Denmark)

    Hoof, Ilka; Kesmir, Can; Lund, Ole

    2008-01-01

    Background: Major histocompatibility complex (MHC) class I molecules allow immune surveillance by presenting a snapshot of the intracellular state of a cell to circulating cytotoxic T lymphocytes. The MHC class I alleles of an HIV-1 infected individual strongly influence the level of viremia...... in their MHC class I repertoire. Methods: We compared the specificity of groups of human MHC molecules associated with different levels of viremia in HIV-1 infected individuals with those of chimpanzee. Results and conclusion: We demonstrate that human MHC with control of HIV-1 viral load share binding motifs...... with chimpanzee MHC. Moreover, we find that chimpanzee and human MHC associated with low viral load are predicted to elicit broader Gag-specific immune responses than human MHC associated with high viral load, thus supporting earlier findings that Gag-specific immune responses are essential for HIV-1 control....

  20. The porcine Major Histocompatibility Complex and related paralogous regions: a review

    Directory of Open Access Journals (Sweden)

    Vaiman Marcel

    2000-03-01

    Full Text Available Abstract The physical alignment of the entire region of the pig major histocompatibility complex (MHC has been almost completed. In swine, the MHC is called the SLA (swine leukocyte antigen and most of its class I region has been sequenced. Over one hundred genes have been characterised, including the classical class I and class I-related genes, as well as the class II gene families. These results in swine provide new evidence for the striking conservation during the evolution of a general MHC framework, and are consistent with the location of the class I genes on segments referred to as permissive places within the MHC class I region. Recent results confirm the involvement of the SLA region in numerous quantitative traits.

  1. Class I major histocompatibility complex anchor substitutions alter the conformation of T cell receptor contacts.

    Science.gov (United States)

    Sharma, A K; Kuhns, J J; Yan, S; Friedline, R H; Long, B; Tisch, R; Collins, E J

    2001-06-15

    An immunogenic peptide (GP2) derived from HER-2/neu binds to HLA-A2.1 very poorly. Some altered-peptide ligands (APL) of GP2 have increased binding affinity and generate improved cytotoxic T lymphocyte recognition of GP2-presenting tumor cells, but most do not. Increases in binding affinity of single-substitution APL are not additive in double-substitution APL. A common first assumption about peptide binding to class I major histocompatibility complex is that each residue binds independently. In addition, immunologists interested in immunotherapy frequently assume that anchor substitutions do not affect T cell receptor contact residues. However, the crystal structures of two GP2 APL show that the central residues change position depending on the identity of the anchor residue(s). Thus, it is clear that subtle changes in the identity of anchor residues may have significant effects on the positions of the T cell receptor contact residues.

  2. Multiple major histocompatibility complex class I genes in Asian anurans: Ontogeny and phylogeny.

    Science.gov (United States)

    Didinger, Chelsea; Eimes, John A; Lillie, Mette; Waldman, Bruce

    2017-05-01

    Amphibians, as the first terrestrial vertebrates, offer a window into early major histocompatibility complex (MHC) evolution. We characterized the MHC class I of two Korean amphibians, the Asiatic toad (Bufo gargarizans) and the Japanese tree frog (Hyla japonica). We found at least four transcribed MHC class I (MHC I) loci, the highest number confirmed in any anuran to date. Furthermore, we identified MHC I transcripts in terrestrial adults, and possibly in aquatic larvae, of both species. We conducted a phylogenetic analysis based on MHC I sequence data and found that B. gargarizans and H. japonica cluster together in the superfamily Nobleobatrachia. We further identified three supertypes shared by the two species. Our results reveal substantial variation in the number of MHC I loci in anurans and suggest that certain supertypes have particular physiochemical properties that may confer pathogen resistance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Characterisation of four major histocompatibility complex class II genes of the koala (Phascolarctos cinereus).

    Science.gov (United States)

    Lau, Quintin; Jobbins, Sarah E; Belov, Katherine; Higgins, Damien P

    2013-01-01

    Major histocompatibility complex (MHC) class II molecules have an integral role in the adaptive immune response, as they bind and present antigenic peptides to T helper lymphocytes. In this study of koalas, species-specific primers were designed to amplify exon 2 of the MHC class II DA and DB genes, which contain much of the peptide-binding regions of the α and β chains. A total of two DA α1 domain variants and eight DA β1 (DAB), three DB α1 and five DB β1 variants were amplified from 20 koalas from two free-living populations from South East Queensland and the Port Macquarie region in northern New South Wales. We detected greater variation in the β1 than in the α1 domains as well as evidence of positive selection in DAB. The present study provides a springboard to future investigation of the role of MHC in disease susceptibility in koalas.

  4. Characterisation of major histocompatibility complex class I transcripts in an Australian dragon lizard.

    Science.gov (United States)

    Hacking, Jessica; Bertozzi, Terry; Moussalli, Adnan; Bradford, Tessa; Gardner, Michael

    2018-07-01

    Characterisation of squamate major histocompatibility complex (MHC) genes has lagged behind other taxonomic groups. MHC genes encode cell-surface glycoproteins that present self- and pathogen-derived peptides to T cells and play a critical role in pathogen recognition. Here we characterise MHC class I transcripts for an agamid lizard (Ctenophorus decresii) and investigate the evolution of MHC class I in Iguanian lizards. An iterative assembly strategy was used to identify six full-length C. decresii MHC class I transcripts, which were validated as likely to encode classical class I MHC molecules. Evidence for exon shuffling recombination was uncovered for C. decresii transcripts and Bayesian phylogenetic analysis of Iguanian MHC class I sequences revealed a pattern expected under a birth-and-death mode of evolution. This work provides a stepping stone towards further research on the agamid MHC class I region. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Genetics of graft-versus-host disease: the major histocompatibility complex.

    Science.gov (United States)

    Petersdorf, Effie W

    2013-01-01

    Graft-versus-host disease (GVHD) is a potentially life-threatening complication of allogeneic hematopoietic cell transplantation. Many genes are presumed to be involved in GVHD, but the best characterized genetic system is that of the human major histocompatibility complex (MHC) located on chromosome 6. Among the hundreds of genes located within the MHC region, the best known and characterized are the classical HLA genes, HLA-A, C, B, DRB1, DQB1, and DPB1. They play a fundamental role in T cell immune responses, and HLA-A, C, and B also function as ligands for the natural killer cell immunoglobulin-like receptors involved in innate immunity. This review highlights the state-of-the art in the field of histocompatibility and immunogenetics of the MHC with respect to genetic risk factors for GVHD. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Transmembrane Helices Are an Overlooked Source of Major Histocompatibility Complex Class I Epitopes

    Science.gov (United States)

    Bianchi, Frans; Textor, Johannes; van den Bogaart, Geert

    2017-01-01

    About a fourth of the human proteome is anchored by transmembrane helices (TMHs) to lipid membranes. TMHs require multiple hydrophobic residues for spanning membranes, and this shows a striking resemblance with the requirements for peptide binding to major histocompatibility complex (MHC) class I. It, therefore, comes as no surprise that bioinformatics analysis predicts an over-representation of TMHs among strong MHC class I (MHC-I) binders. Published peptide elution studies confirm that TMHs are indeed presented by MHC-I. This raises the question how membrane proteins are processed for MHC-I (cross-)presentation, with current research focusing on soluble antigens. The presentation of membrane-buried peptides is likely important in health and disease, as TMHs are considerably conserved and their presentation might prevent escape mutations by pathogens. Therefore, it could contribute to the disease correlations described for many human leukocyte antigen haplotypes. PMID:28959259

  7. Divergent selection on locally adapted major histocompatibility complex immune genes experimentally proven in the field

    Science.gov (United States)

    Eizaguirre, Christophe; Lenz, Tobias L; Kalbe, Martin; Milinski, Manfred

    2012-01-01

    Although crucial for the understanding of adaptive evolution, genetically resolved examples of local adaptation are rare. To maximize survival and reproduction in their local environment, hosts should resist their local parasites and pathogens. The major histocompatibility complex (MHC) with its key function in parasite resistance represents an ideal candidate to investigate parasite-mediated local adaptation. Using replicated field mesocosms, stocked with second-generation lab-bred three-spined stickleback hybrids of a lake and a river population, we show local adaptation of MHC genotypes to population-specific parasites, independently of the genetic background. Increased allele divergence of lake MHC genotypes allows lake fish to fight the broad range of lake parasites, whereas more specific river genotypes confer selective advantages against the less diverse river parasites. Hybrids with local MHC genotype gained more body weight and thus higher fitness than those with foreign MHC in either habitat, suggesting the evolutionary significance of locally adapted MHC genotypes. PMID:22583762

  8. The major histocompatibility complex: a model for understanding graft-versus-host disease.

    Science.gov (United States)

    Petersdorf, Effie W

    2013-09-12

    Acute graft-versus-host disease (GVHD) afflicts as much as 80% of all patients who receive an unrelated donor hematopoietic cell transplant (HCT) for the treatment of blood disorders, even with optimal donor HLA matching and use of prophylactic immunosuppressive agents. Of patients who develop acute GVHD, many are at risk for chronic GVHD and bear the burden of considerable morbidity and lowered quality of life years after transplantation. The immunogenetic basis of GVHD has been the subject of intensive investigation, with the classic HLA genetic loci being the best-characterized determinants. Recent information on the major histocompatibility complex (MHC) region of chromosome 6 as an important source of untyped genetic variation has shed light on novel GVHD determinants. These data open new paradigms for understanding the genetic basis of GVHD.

  9. Genotyping strategy matters when analyzing hypervariable major histocompatibility complex-Experience from a passerine bird.

    Science.gov (United States)

    Rekdal, Silje L; Anmarkrud, Jarl Andreas; Johnsen, Arild; Lifjeld, Jan T

    2018-02-01

    Genotyping of classical major histocompatibility complex (MHC) genes is challenging when they are hypervariable and occur in multiple copies. In this study, we used several different approaches to genotype the moderately variable MHC class I exon 3 (MHCIe3) and the highly polymorphic MHC class II exon 2 (MHCIIβe2) in the bluethroat ( Luscinia svecica ). Two family groups (eight individuals) were sequenced in replicates at both markers using Ion Torrent technology with both a single- and a dual-indexed primer structure. Additionally, MHCIIβe2 was sequenced on Illumina MiSeq. Allele calling was conducted by modifications of the pipeline developed by Sommer et al. (BMC Genomics, 14, 2013, 542) and the software AmpliSAS. While the different genotyping strategies gave largely consistent results for MHCIe3, with a maximum of eight alleles per individual, MHCIIβe2 was remarkably complex with a maximum of 56 MHCIIβe2 alleles called for one individual. Each genotyping strategy detected on average 50%-82% of all MHCIIβe2 alleles per individual, but dropouts were largely allele-specific and consistent within families for each strategy. The discrepancies among approaches indicate PCR biases caused by the platform-specific primer tails. Further, AmpliSAS called fewer alleles than the modified Sommer pipeline. Our results demonstrate that allelic dropout is a significant problem when genotyping the hypervariable MHCIIβe2. As these genotyping errors are largely nonrandom and method-specific, we caution against comparing genotypes across different genotyping strategies. Nevertheless, we conclude that high-throughput approaches provide a major advance in the challenging task of genotyping hypervariable MHC loci, even though they may not reveal the complete allelic repertoire.

  10. The Use of Peptide–Major-Histocompatibility-Complex Multimers in Type 1 Diabetes Mellitus

    Science.gov (United States)

    Gojanovich, Greg S; Murray, Sabrina L; Buntzman, Adam S; Young, Ellen F; Vincent, Benjamin G; Hess, Paul R; DVM

    2012-01-01

    Major histocompatibility complex (MHC) class I and MHC class II molecules present short peptides that are derived from endogenous and exogenous proteins, respectively, to cognate T-cell receptors (TCRs) on the surface of T cells. The exquisite specificity with which T cells recognize particular peptide–major-histocompatibility-complex (pMHC) combinations has permitted development of soluble pMHC multimers that bind exclusively to selected T-cell populations. Because the pathogenesis of type 1 diabetes mellitus (T1DM) is driven largely by islet-reactive T-cell activity that causes β-cell death, these reagents are useful tools for studying and, potentially, for treating this disease. When coupled to fluorophores or paramagnetic nanoparticles, pMHC multimers have been used to visualize the expansion and islet invasion of T-cell effectors during diabetogenesis. Administration of pMHC multimers to mice has been shown to modulate T-cell responses by signaling through the TCR or by delivering a toxic moiety that deletes the targeted T cell. In the nonobese diabetic mouse model of T1DM, a pMHC-I tetramer coupled to a potent ribosome-inactivating toxin caused long-term elimination of a specific diabetogenic cluster of differentiation 8+ T-cell population from the pancreatic islets and delayed the onset of diabetes. This review will provide an overview of the development and use of pMHC multimers, particularly in T1DM, and describe the therapeutic promise these reagents have as an antigen-specific means of ameliorating deleterious T-cell responses in this autoimmune disease. PMID:22768881

  11. Increased Treatment Complexity for Major Depressive Disorder for Inpatients With Comorbid Personality Disorder.

    Science.gov (United States)

    Wiegand, Hauke F; Godemann, Frank

    2017-05-01

    The study examined inpatient treatment for major depressive disorder (MDD) when it is complicated by comorbid personality disorder. In this descriptive analysis of a large data sample from 2013 (German VIPP data set) of 58,913 cases from 75 hospitals, three groups were compared: patients with MDD, patients with MDD and a comorbid personality disorder, and patients with a main diagnosis of personality disorder. Compared with MDD patients, those with comorbid personality disorder had higher rates of recurrent depression and nearly twice as many readmissions within one year, despite longer mean length of stay. Records of patients with comorbidities more often indicated accounting codes for "complex diagnostic procedures," "crisis intervention," and "constant observation." Patients with comorbid disorders differed from patients with a main diagnosis of personality disorder in treatment indicator characteristics and distribution of personality disorder diagnoses. Personality disorder comorbidity made MDD treatment more complex, and recurrence of MDD episodes and hospital readmission occurred more often than if patients had a sole MDD diagnosis.

  12. Contribution of chromosomal abnormalities and genes of the major histocompatibility complex to early pregnancy losses

    Directory of Open Access Journals (Sweden)

    Tkach I. R.

    2015-02-01

    Full Text Available Aim. The determination of chromosomal abnormalities in samples from early pregnancy losses and allelic polymorphism of HLA–DRB1 and DQA1 genes in couples with recurrent miscarriage. Methods. Banding cytogenetic and interphase mFISH analysis, DNA extraction by salting method, PCR, agarose gel electrophoresis. Results. Cytogenetic and molecular-cytogenetic investigations of SA material identified karyotype anomalies in 32.4 % of cases with prevalence of autosomal trisomy – 42.65 %, triploidy – 30.38 % and monosomy X – 19.11 %. Complex analysis of frequency and distribution of allelic variants of genes HLA-DRB1 and HLA-DQA1 allowed establishing the alleles DRB1*0301, DRB1*1101-1104 and DQA1*0501 to be aggressor alleles in women with recurrent pregnancy loss (RPL. The cumulative homology of allelic polymorphism of more than 50 % of HLA-DRB1 and HLA-DQA1 loci between partners increases the risk of RPL by almost four times. Conclusion. The detected chromosome aneuploidies in the samples from products of conception and the changes in the major histocompatibility complex genes can cause the failure of a couples reproductive function and can lead to an early fetal loss.

  13. DNA variation of the mammalian major histocompatibility complex reflects genomic diversity and population history

    International Nuclear Information System (INIS)

    Yuhki, Naoya; O'Brien, S.J.

    1990-01-01

    The major histocompatibility complex (MHC) is a multigene complex of tightly linked homologous genes that encode cell surface antigens that play a key role in immune regulation and response to foreign antigens. In most species, MHC gene products display extreme antigenic polymorphism, and their variability has been interpreted to reflect an adaptive strategy for accommodating rapidly evolving infectious agents that periodically afflict natural populations. Determination of the extent of MHC variation has been limited to populations in which skin grafting is feasible or for which serological reagents have been developed. The authors present here a quantitative analysis of restriction fragment length polymorphism of MHC class I genes in several mammalian species (cats, rodents, humans) known to have very different levels of genetic diversity based on functional MHC assays and on allozyme surveys. When homologous class I probes were employed, a notable concordance was observed between the extent of MHC restriction fragment variation and functional MHC variation detected by skin grafts or genome-wide diversity estimated by allozyme screens. These results confirm the genetically depauperate character of the African cheetah, Acinonyx jubatus, and the Asiatic lion, Panthera leo persica; further, they support the use of class I MHC molecular reagents in estimating the extent and character of genetic diversity in natural populations

  14. Major histocompatibility complex variation and the evolution of resistance to amphibian chytridiomycosis.

    Science.gov (United States)

    Fu, Minjie; Waldman, Bruce

    2017-08-01

    Chytridiomycosis, caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd), has been implicated in population declines and species extinctions of amphibians around the world. Susceptibility to the disease varies both within and among species, most likely attributable to heritable immunogenetic variation. Analyses of transcriptional expression in hosts following their infection by Bd reveal complex responses. Species resistant to Bd generally show evidence of stronger innate and adaptive immune system responses. Major histocompatibility complex (MHC) class I and class II genes of some susceptible species are up-regulated following host infection by Bd, but resistant species show no comparable changes in transcriptional expression. Bd-resistant species share similar pocket conformations within the MHC-II antigen-binding groove. Among susceptible species, survivors of epizootics bear alleles encoding these conformations. Individuals with homozygous resistance alleles appear to benefit by enhanced resistance, especially in environmental conditions that promote pathogen virulence. Subjects that are repeatedly infected and subsequently cleared of Bd can develop an acquired immune response to the pathogen. Strong directional selection for MHC alleles that encode resistance to Bd may deplete genetic variation necessary to respond to other pathogens. Resistance to chytridiomycosis incurs life-history costs that require further study.

  15. Prediction of peptide binding to a major histocompatibility complex class I molecule based on docking simulation

    Science.gov (United States)

    Ishikawa, Takeshi

    2016-10-01

    Binding between major histocompatibility complex (MHC) class I molecules and immunogenic epitopes is one of the most important processes for cell-mediated immunity. Consequently, computational prediction of amino acid sequences of MHC class I binding peptides from a given sequence may lead to important biomedical advances. In this study, an efficient structure-based method for predicting peptide binding to MHC class I molecules was developed, in which the binding free energy of the peptide was evaluated by two individual docking simulations. An original penalty function and restriction of degrees of freedom were determined by analysis of 361 published X-ray structures of the complex and were then introduced into the docking simulations. To validate the method, calculations using a 50-amino acid sequence as a prediction target were performed. In 27 calculations, the binding free energy of the known peptide was within the top 5 of 166 peptides generated from the 50-amino acid sequence. Finally, demonstrative calculations using a whole sequence of a protein as a prediction target were performed. These data clearly demonstrate high potential of this method for predicting peptide binding to MHC class I molecules.

  16. Detection of autoreactive CD4 T cells using major histocompatibility complex class II dextramers

    Directory of Open Access Journals (Sweden)

    Kuszynski Charles

    2011-07-01

    Full Text Available Abstract Background Tetramers are useful tools to enumerate the frequencies of antigen-specific T cells. However, unlike CD8 T cells, CD4 T cells - especially self-reactive cells - are challenging to detect with major histocompatibility complex (MHC class II tetramers because of low frequencies and low affinities of their T cell receptors to MHC-peptide complexes. Here, we report the use of fluorescent multimers, designated MHC dextramers that contain a large number of peptide-MHC complexes per reagent. Results The utility of MHC dextramers was evaluated in three autoimmune disease models: 1 proteolipid protein (PLP 139-151-induced experimental autoimmune encephalomyelitis in SJL/J (H-2s mice; 2 myelin oligodendrocyte glycoprotein (MOG 35-55-induced experimental autoimmune encephalomyelitis in C57Bl/6 (H-2b mice; and 3 cardiac myosin heavy chain (Myhc-α 334-352-induced experimental autoimmune myocarditis in A/J (H-2a mice. Flow cytometrically, we demonstrate that IAs/PLP 139-151, IAb/MOG 35-55 and IAk/Myhc-α 334-352 dextramers detect the antigen-sensitized cells with specificity, and with a detection sensitivity significantly higher than that achieved with conventional tetramers. Furthermore, we show that binding of dextramers, but not tetramers, is less dependent on the activation status of cells, permitting enumeration of antigen-specific cells ex vivo. Conclusions The data suggest that MHC dextramers are useful tools to track the generation and functionalities of self-reactive CD4 cells in various experimental systems.

  17. Direct evidence for conformational dynamics in major histocompatibility complex class I molecules.

    Science.gov (United States)

    van Hateren, Andy; Anderson, Malcolm; Bailey, Alistair; Werner, Jörn M; Skipp, Paul; Elliott, Tim

    2017-12-08

    Major histocompatibility complex class I molecules (MHC I) help protect jawed vertebrates by binding and presenting immunogenic peptides to cytotoxic T lymphocytes. Peptides are selected from a large diversity present in the endoplasmic reticulum. However, only a limited number of peptides complement the polymorphic MHC specificity determining pockets in a way that leads to high-affinity peptide binding and efficient antigen presentation. MHC I molecules possess an intrinsic ability to discriminate between peptides, which varies in efficiency between allotypes, but the mechanism of selection is unknown. Elucidation of the selection mechanism is likely to benefit future immune-modulatory therapies. Evidence suggests peptide selection involves transient adoption of alternative, presumably higher energy conformations than native peptide-MHC complexes. However, the instability of peptide-receptive MHC molecules has hindered characterization of such conformational plasticity. To investigate the dynamic nature of MHC, we refolded MHC proteins with peptides that can be hydrolyzed by UV light and thus released. We compared the resultant peptide-receptive MHC molecules with non-hydrolyzed peptide-loaded MHC complexes by monitoring the exchange of hydrogen for deuterium in solution. We found differences in hydrogen-deuterium exchange between peptide-loaded and peptide-receptive molecules that were negated by the addition of peptide to peptide-receptive MHC molecules. Peptide hydrolysis caused significant increases in hydrogen-deuterium exchange in sub-regions of the peptide-binding domain and smaller increases elsewhere, including in the α3 domain and the non-covalently associated β 2 -microglobulin molecule, demonstrating long-range dynamic communication. Comparing two MHC allotypes revealed allotype-specific differences in hydrogen-deuterium exchange, consistent with the notion that MHC I plasticity underpins peptide selection. © 2017 by The American Society for

  18. Major histocompatibility complex haplotypes and class II genes in non-Jewish patients with pemphigus vulgaris

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, A.R. (Harvard School of Dental Medicine, Boston, MA (United States) Center for Blood Research, Boston, MA (United States) American Red Cross Blood Services-Northeast Region, Dedham, MA (United States)); Wagner, R.; Khatri, K.; Notani, G.; Awdeh, Z.; Alper, C.A. (Center for Blood Research, Boston, MA (United States)); Yunis, E.J. (Center for Blood Research, Boston, MA (United States) American Red Cross Blood Services-Northeast Region, Dedham, MA (United States))

    1991-06-01

    Previous studies demonstrated that HLA-DR4 was markedly increased among Ashkenazi Jewish patients with pemphigus vulgaris (PV), almost entirely as the common Jewish extended haplotype (HLA-B38, SC21, DR4, DQw8) or as the haplotype HLA-B35, SC31, DR4, DQw8, and that HLA-DR4, DQw8 was distributed among patients in a manner consistent with dominant expression of a class II (D-region or D-region-linked) susceptibility gene. In the present study of major histocompatibility complex (MHC) halotypes in 25 non-Jewish PV patients, DR4, DQw8 was found in 12 of the patients and DRw6, DQw5 was found in 15. Only 3 patients had neither. The non-Jewish patients were of more Southern European extraction than our controls. This suggests that there are two major MHC susceptibility alleles in American patients with PV. The more ancient apparently arose on a haplotype in the Jews, HLA-B38(35), SC21(SC31), DR4, DQw8, and spread to other populations largely as D-region segments. The other arose in or near Italy on the haplotype HLA-Bw55, SB45, DRw14, DQw5 amd has also partially fragmented so that many patients carry only DRw14, DQw5. The available data do not permit the specific localization of either the DR4, DQw8-or the DRw14, DQw5-linked susceptibility genes.

  19. Passive Immunotherapy for Retroviral Disease: Influence of Major Histocompatibility Complex Type and T-Cell Responsiveness

    Science.gov (United States)

    Hasenkrug, Kim J.; Brooks, Diane M.; Chesebro, Bruce

    1995-11-01

    Administration of virus-specific antibodies is known to be an effective early treatment for some viral infections. Such immunotherapy probably acts by antibody-mediated neutralization of viral infectivity and is often thought to function independently of T-cell-mediated immune responses. In the present experiments, we studied passive antibody therapy using Friend murine leukemia virus complex as a model for an immunosuppressive retroviral disease in adult mice. The results showed that antibody therapy could induce recovery from a well-established retroviral infection. However, the success of therapy was dependent on the presence of both CD4^+ and CD8^+ T lymphocytes. Thus, cell-mediated responses were required for recovery from infection even in the presence of therapeutic levels of antibody. The major histocompatibility type of the mice was also an important factor determining the relative success of antibody therapy in this system, but it was less critical for low-dose than for high-dose infections. Our results imply that limited T-cell responsiveness as dictated by major histocompatibility genes and/or stage of disease may have contributed to previous immunotherapy failures in AIDS patients. Possible strategies to improve the efficacy of future therapies are discussed.

  20. Macrophage cell lines derived from major histocompatibility complex II-negative mice

    Science.gov (United States)

    Beharka, A. A.; Armstrong, J. W.; Chapes, S. K.; Spooner, B. S. (Principal Investigator)

    1998-01-01

    Two bone-marrow-derived macrophage cell lines, C2D and C2Dt, were isolated from major histocompatibility class II negative knock-out mice. The C2D cell line was stabilized by continuous culture in colony-stimulating factor-1 and the C2Dt cell line was transformed with SV40 virus large T antigen. These cells exhibited phenotypic properties of macrophages including morphology and expression of Mac 1 and Mac 2 cell surface molecules. These cells also had comparable growth to the bone-marrow-derived macrophage cell line B6MP102. These new cell lines were not spontaneously cytotoxic and were only capable of modest killing of F5b tumor cells when stimulated with LPS and interferon-gamma, but not when stimulated with LPS alone or with staphylococcal exotoxin. C2D and C2Dt cells phagocytosed labeled Staphylococcus aureus similarly to B6MP102 cells but less well than C2D peritoneal macrophages. These cell lines secreted interleukin-6, but not tumor necrosis factor or nitric oxide in response to LPS or staphlococcal enterotoxins A or B C2D(t) cells were tumorigenic in C2D and C57BL/6J mice but C2D cells were not. These data suggest that macrophage cell lines can be established from bone marrow cells of major histocompatibility complex II-negative mice.

  1. Examining the evidence for major histocompatibility complex-dependent mate selection in humans and nonhuman primates

    Directory of Open Access Journals (Sweden)

    Winternitz JC

    2015-05-01

    Full Text Available Jamie C Winternitz,1,2,* Jessica L Abbate3,4,* 1Institute of Vertebrate Biology, Czech Academy of Sciences, v.v.i, Kvetná, Brno, Czech Republic; 2Institute of Botany, Czech Academy of Sciences, v.v.i, Lidická, Brno, Czech Republic; 3Institute of Ecology and Evolution, University of Bern, Bern, Switzerland; 4INRA-UMR 1062 CBGP (INRA, IRD, CIRAD, Montpellier SupAgro, Montferrier-sur-Lez, France*These authors contributed equally to this workAbstract: Compounds of the major histocompatibility complex (MHC are integral for effective vertebrate adaptive immune response, and are also implicated as cues for sexual selection. The evidence for this is supportive of MHC-based preference for diverse and dissimilar mating partners, in a range of vertebrates from fish to nonhuman primates. However, the evidence for a similar role of these genes and the evolutionary benefits of their diversity in human mate choice has been more controversial. Here, we review the results of 34 primary studies on MHC-mediated mate choice in humans and nonhuman primates in an effort to understand what processes may underscore, or belie, such differences. Both human and nonhuman primate studies show evidence of mate selection for MHC-dissimilarity and diversity, with fewer results in support of mate selection for optimal diversity or for specific “good gene”. In general, stronger support comes from female-choice studies as opposed to male-choice studies (though male preferences and choice are investigated less often. This review suggests that the majority of mate choice results from contemporary human studies are consistent with our evolutionary history, but also reveals that only in humans do we find evidence for preference for mates with similar MHC composition. Overall, we show that contextual nuances, namely, population structure, multiple sensory cues that signal different information, and hormonal influences may explain the conflicting results observed for the role of

  2. Preformed purified peptide/major histocompatibility class I complexes are potent stimulators of class I-restricted T cell hybridomas

    DEFF Research Database (Denmark)

    Stryhn, A; Pedersen, L O; Ortiz-Navarrete, V

    1994-01-01

    A panel of antigen-specific, major histocompatibility complex class I-restricted T cell hybridomas has been generated to examine the capacity of peptide/class I complexes to stimulate T cells at the molecular level. Peptide/class I complexes were generated in detergent solution, purified...... be detected by the T cells. Preformed complexes were about 500,000 times more potent than free peptide in terms of T cell stimulation, demonstrating the physiological relevancy of the biochemically generated complexes. Surprisingly, the majority (including the most sensitive of the hybridomas) had lost CD8...... and quantitated. Latex particles were subsequently coated with known amounts of preformed complexes and used to stimulate the T cell hybridomas. Stimulation was specific, i.e. only the appropriate peptide/class I combination were stimulatory, and quite sensitive, i.e. as little as 300 complexes per bead could...

  3. Major Histocompatibility Complex (MHC) Class I and MHC Class II Proteins: Conformational Plasticity in Antigen Presentation.

    Science.gov (United States)

    Wieczorek, Marek; Abualrous, Esam T; Sticht, Jana; Álvaro-Benito, Miguel; Stolzenberg, Sebastian; Noé, Frank; Freund, Christian

    2017-01-01

    Antigen presentation by major histocompatibility complex (MHC) proteins is essential for adaptive immunity. Prior to presentation, peptides need to be generated from proteins that are either produced by the cell's own translational machinery or that are funneled into the endo-lysosomal vesicular system. The prolonged interaction between a T cell receptor and specific pMHC complexes, after an extensive search process in secondary lymphatic organs, eventually triggers T cells to proliferate and to mount a specific cellular immune response. Once processed, the peptide repertoire presented by MHC proteins largely depends on structural features of the binding groove of each particular MHC allelic variant. Additionally, two peptide editors-tapasin for class I and HLA-DM for class II-contribute to the shaping of the presented peptidome by favoring the binding of high-affinity antigens. Although there is a vast amount of biochemical and structural information, the mechanism of the catalyzed peptide exchange for MHC class I and class II proteins still remains controversial, and it is not well understood why certain MHC allelic variants are more susceptible to peptide editing than others. Recent studies predict a high impact of protein intermediate states on MHC allele-specific peptide presentation, which implies a profound influence of MHC dynamics on the phenomenon of immunodominance and the development of autoimmune diseases. Here, we review the recent literature that describe MHC class I and II dynamics from a theoretical and experimental point of view and we highlight the similarities between MHC class I and class II dynamics despite the distinct functions they fulfill in adaptive immunity.

  4. Identification of susceptibility and protective major histocompatibility complex haplotypes in canine diabetes mellitus.

    Science.gov (United States)

    Kennedy, L J; Davison, L J; Barnes, A; Short, A D; Fretwell, N; Jones, C A; Lee, A C; Ollier, W E R; Catchpole, B

    2006-12-01

    Diabetes mellitus occurs spontaneously in dogs, which is believed to have an autoimmune component and to be a model of human latent autoimmune diabetes of adults (LADA). Some dog breeds (e.g. Samoyed) are particularly predisposed, whereas others (e.g. Boxer) are highly resistant. With the completion of the Dog Genome Assembly, comparative genomic studies of complex diseases in dogs, including diabetes, could provide an important investigative approach into such disorders. Type 1 diabetes in humans is strongly associated with major histocompatibility complex (MHC) class II polymorphisms. We have investigated whether canine dog leucocyte antigen (DLA) class II haplotypes are associated with diabetes. DNA from 460 cases and 1047 controls were genotyped for DLA-DRB1, DLA-DQA1 and DLA-DQB1 using sequence-based typing. Three DLA haplotypes, DRB1*009/DQA1*001/DQB1*008, DRB1*015/DQA1*0061/DQB1*023 and DRB1*002/DQA1*009/DQB1*001, were found at significantly increased frequency in cases with diabetes compared with controls. One DLA-DQ haplotype, DQA1*004/DQB1*013, was significantly reduced in cases with diabetes. Further analysis showed that DQA1 alleles carrying arginine at codon 55 of DQA1 were increased in dogs with diabetes. To our knowledge, this is the first report of a comparative study of MHC and diabetes in a non-rodent species. Since no laboratory model of LADA exists and dogs and humans share similar environments, further research into canine diabetes is warranted.

  5. Major histocompatibility complex linked databases and prediction tools for designing vaccines.

    Science.gov (United States)

    Singh, Satarudra Prakash; Mishra, Bhartendu Nath

    2016-03-01

    Presently, the major histocompatibility complex (MHC) is receiving considerable interest owing to its remarkable role in antigen presentation and vaccine design. The specific databases and prediction approaches related to MHC sequences, structures and binding/nonbinding peptides have been aggressively developed in the past two decades with their own benchmarks and standards. Before using these databases and prediction tools, it is important to analyze why and how the tools are constructed along with their strengths and limitations. The current review presents insights into web-based immunological bioinformatics resources that include searchable databases of MHC sequences, epitopes and prediction tools that are linked to MHC based vaccine design, including population coverage analysis. In T cell epitope forecasts, MHC class I binding predictions are very accurate for most of the identified MHC alleles. However, these predictions could be further improved by integrating proteasome cleavage (in conjugation with transporter associated with antigen processing (TAP) binding) prediction, as well as T cell receptor binding prediction. On the other hand, MHC class II restricted epitope predictions display relatively low accuracy compared to MHC class I. To date, pan-specific tools have been developed, which not only deliver significantly improved predictions in terms of accuracy, but also in terms of the coverage of MHC alleles and supertypes. In addition, structural modeling and simulation systems for peptide-MHC complexes enable the molecular-level investigation of immune processes. Finally, epitope prediction tools, and their assessments and guidelines, have been presented to immunologist for the design of novel vaccine and diagnostics. Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  6. Population-dependent contribution of the major histocompatibility complex region to schizophrenia susceptibility.

    Science.gov (United States)

    Yamada, Kazuo; Hattori, Eiji; Iwayama, Yoshimi; Toyota, Tomoko; Iwata, Yasuhide; Suzuki, Katsuaki; Kikuchi, Mitsuru; Hashimoto, Tasuku; Kanahara, Nobuhisa; Mori, Norio; Yoshikawa, Takeo

    2015-10-01

    There is consistent data from European cohorts suggesting a genetic contribution from the major histocompatibility complex (MHC) to the pathogenesis of schizophrenia. However, the genomic complexity and ethnicity-specific diversity found in the MHC cause difficulties in identifying causal variants or genes, and there is a need for studies encompassing the entire MHC region in multiple ethnic populations. Here, we report on association signals in the MHC region, with schizophrenia in the Japanese population. We genotyped and imputed a total of 10,131 single nucleotide polymorphisms (SNPs), spanning the entire MHC interval. The analysis included 3302 participants (1518 schizophrenics and 1784 healthy controls) from the Japanese population. In this study, we present evidence for association at rs494620, located in the SLC44A4 gene. The association survived after correction for multiple testing (unadjusted P=7.78×10(-5), empirical P=0.0357). The imputation results detected the highest association at rs707937 in the MSH5-SAPCD1 gene (imputed P=8.40×10(-5)). In expression analysis using postmortem brains from schizophrenia and control samples, MSH5-SAPCD1 showed marginally significant expression differences in Brodmann's area 46 (P=0.044 by unpaired t test with Welch's correction, P=0.099 by Mann-Whitney U test). Our study further strengthens evidence for the involvement of the MHC in schizophrenia across populations, and provides insight into population-specific mechanisms for the MHC region in schizophrenia susceptibility. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Major Histocompatibility Complex (MHC) Class I and MHC Class II Proteins: Conformational Plasticity in Antigen Presentation

    Science.gov (United States)

    Wieczorek, Marek; Abualrous, Esam T.; Sticht, Jana; Álvaro-Benito, Miguel; Stolzenberg, Sebastian; Noé, Frank; Freund, Christian

    2017-01-01

    Antigen presentation by major histocompatibility complex (MHC) proteins is essential for adaptive immunity. Prior to presentation, peptides need to be generated from proteins that are either produced by the cell’s own translational machinery or that are funneled into the endo-lysosomal vesicular system. The prolonged interaction between a T cell receptor and specific pMHC complexes, after an extensive search process in secondary lymphatic organs, eventually triggers T cells to proliferate and to mount a specific cellular immune response. Once processed, the peptide repertoire presented by MHC proteins largely depends on structural features of the binding groove of each particular MHC allelic variant. Additionally, two peptide editors—tapasin for class I and HLA-DM for class II—contribute to the shaping of the presented peptidome by favoring the binding of high-affinity antigens. Although there is a vast amount of biochemical and structural information, the mechanism of the catalyzed peptide exchange for MHC class I and class II proteins still remains controversial, and it is not well understood why certain MHC allelic variants are more susceptible to peptide editing than others. Recent studies predict a high impact of protein intermediate states on MHC allele-specific peptide presentation, which implies a profound influence of MHC dynamics on the phenomenon of immunodominance and the development of autoimmune diseases. Here, we review the recent literature that describe MHC class I and II dynamics from a theoretical and experimental point of view and we highlight the similarities between MHC class I and class II dynamics despite the distinct functions they fulfill in adaptive immunity. PMID:28367149

  8. Family-assisted inference of the genetic architecture of major histocompatibility complex variation.

    Science.gov (United States)

    Gaigher, A; Burri, R; Gharib, W H; Taberlet, P; Roulin, A; Fumagalli, L

    2016-11-01

    With their direct link to individual fitness, genes of the major histocompatibility complex (MHC) are a popular system to study the evolution of adaptive genetic diversity. However, owing to the highly dynamic evolution of the MHC region, the isolation, characterization and genotyping of MHC genes remain a major challenge. While high-throughput sequencing technologies now provide unprecedented resolution of the high allelic diversity observed at the MHC, in many species, it remains unclear (i) how alleles are distributed among MHC loci, (ii) whether MHC loci are linked or segregate independently and (iii) how much copy number variation (CNV) can be observed for MHC genes in natural populations. Here, we show that the study of allele segregation patterns within families can provide significant insights in this context. We sequenced two MHC class I (MHC-I) loci in 1267 European barn owls (Tyto alba), including 590 offspring from 130 families using Illumina MiSeq technology. Coupled with a high per-individual sequencing coverage (~3000×), the study of allele segregation patterns within families provided information on three aspects of the architecture of MHC-I variation in barn owls: (i) extensive sharing of alleles among loci, (ii) strong linkage of MHC-I loci indicating tandem architecture and (iii) the presence of CNV in the barn owl MHC-I. We conclude that the additional information that can be gained from high-coverage amplicon sequencing by investigating allele segregation patterns in families not only helps improving the accuracy of MHC genotyping, but also contributes towards enhanced analyses in the context of MHC evolutionary ecology. © 2016 John Wiley & Sons Ltd.

  9. Fine mapping major histocompatibility complex associations in psoriasis and its clinical subtypes.

    Science.gov (United States)

    Okada, Yukinori; Han, Buhm; Tsoi, Lam C; Stuart, Philip E; Ellinghaus, Eva; Tejasvi, Trilokraj; Chandran, Vinod; Pellett, Fawnda; Pollock, Remy; Bowcock, Anne M; Krueger, Gerald G; Weichenthal, Michael; Voorhees, John J; Rahman, Proton; Gregersen, Peter K; Franke, Andre; Nair, Rajan P; Abecasis, Gonçalo R; Gladman, Dafna D; Elder, James T; de Bakker, Paul I W; Raychaudhuri, Soumya

    2014-08-07

    Psoriasis vulgaris (PsV) risk is strongly associated with variation within the major histocompatibility complex (MHC) region, but its genetic architecture has yet to be fully elucidated. Here, we conducted a large-scale fine-mapping study of PsV risk in the MHC region in 9,247 PsV-affected individuals and 13,589 controls of European descent by imputing class I and II human leukocyte antigen (HLA) genes from SNP genotype data. In addition, we imputed sequence variants for MICA, an MHC HLA-like gene that has been associated with PsV, to evaluate association at that locus as well. We observed that HLA-C(∗)06:02 demonstrated the lowest p value for overall PsV risk (p = 1.7 × 10(-364)). Stepwise analysis revealed multiple HLA-C(∗)06:02-independent risk variants in both class I and class II HLA genes for PsV susceptibility (HLA-C(∗)12:03, HLA-B amino acid positions 67 and 9, HLA-A amino acid position 95, and HLA-DQα1 amino acid position 53; p major clinical subtypes of PsV, psoriatic arthritis (PsA; n = 3,038) and cutaneous psoriasis (PsC; n = 3,098). We found that risk heterogeneity between PsA and PsC might be driven by HLA-B amino acid position 45 (Pomnibus = 2.2 × 10(-11)), indicating that different genetic factors underlie the overall risk of PsV and the risk of specific PsV subphenotypes. Our study illustrates the value of high-resolution HLA and MICA imputation for fine mapping causal variants in the MHC. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Zika Virus Escapes NK Cell Detection by Upregulating Major Histocompatibility Complex Class I Molecules.

    Science.gov (United States)

    Glasner, Ariella; Oiknine-Djian, Esther; Weisblum, Yiska; Diab, Mohammad; Panet, Amos; Wolf, Dana G; Mandelboim, Ofer

    2017-11-15

    NK cells are innate lymphocytes that participate in many immune processes encompassing cancer, bacterial and fungal infection, autoimmunity, and even pregnancy and that specialize in antiviral defense. NK cells express inhibitory and activating receptors and kill their targets when activating signals overpower inhibitory signals. The NK cell inhibitory receptors include a uniquely diverse array of proteins named killer cell immunoglobulin-like receptors (KIRs), the CD94 family, and the leukocyte immunoglobulin-like receptor (LIR) family. The NK cell inhibitory receptors recognize mostly major histocompatibility complex (MHC) class I (MHC-I) proteins. Zika virus has recently emerged as a major threat due to its association with birth defects and its pandemic potential. How Zika virus interacts with the immune system, and especially with NK cells, is unclear. Here we show that Zika virus infection is barely sensed by NK cells, since little or no increase in the expression of activating NK cell ligands was observed following Zika infection. In contrast, we demonstrate that Zika virus infection leads to the upregulation of MHC class I proteins and consequently to the inhibition of NK cell killing. Mechanistically, we show that MHC class I proteins are upregulated via the RIGI-IRF3 pathway and that this upregulation is mediated via beta interferon (IFN-β). Potentially, countering MHC class I upregulation during Zika virus infection could be used as a prophylactic treatment against Zika virus. IMPORTANCE NK cells are innate lymphocytes that recognize and eliminate various pathogens and are known mostly for their role in controlling viral infections. NK cells express inhibitory and activating receptors, and they kill or spare their targets based on the integration of inhibitory and activating signals. Zika virus has recently emerged as a major threat to humans due to its pandemic potential and its association with birth defects. The role of NK cells in Zika virus

  11. Susceptibility genes for lung diseases in the major histocompatibility complex revealed by lung expression quantitative trait loci analysis

    NARCIS (Netherlands)

    Lamontagne, Maxime; Joubert, Philippe; Timens, Wim; Postma, Dirkje S.; Hao, Ke; Nickle, David; Sin, Don D.; Pare, Peter D.; Laviolette, Michel; Bosse, Yohan

    The major histocompatibility complex (MHC) has been linked with hundreds of diseases [1]. The MHC is one of the most complex regions of the human genome, because of the high gene density, extended linkage disequilibrium (LD) and sequence diversity [2]. Recent genome-wide association studies (GWAS)

  12. Red Queen Processes Drive Positive Selection on Major Histocompatibility Complex (MHC) Genes.

    Science.gov (United States)

    Ejsmond, Maciej Jan; Radwan, Jacek

    2015-11-01

    Major Histocompatibility Complex (MHC) genes code for proteins involved in the incitation of the adaptive immune response in vertebrates, which is achieved through binding oligopeptides (antigens) of pathogenic origin. Across vertebrate species, substitutions of amino acids at sites responsible for the specificity of antigen binding (ABS) are positively selected. This is attributed to pathogen-driven balancing selection, which is also thought to maintain the high polymorphism of MHC genes, and to cause the sharing of allelic lineages between species. However, the nature of this selection remains controversial. We used individual-based computer simulations to investigate the roles of two phenomena capable of maintaining MHC polymorphism: heterozygote advantage and host-pathogen arms race (Red Queen process). Our simulations revealed that levels of MHC polymorphism were high and driven mostly by the Red Queen process at a high pathogen mutation rate, but were low and driven mostly by heterozygote advantage when the pathogen mutation rate was low. We found that novel mutations at ABSs are strongly favored by the Red Queen process, but not by heterozygote advantage, regardless of the pathogen mutation rate. However, while the strong advantage of novel alleles increased the allele turnover rate, under a high pathogen mutation rate, allelic lineages persisted for a comparable length of time under Red Queen and under heterozygote advantage. Thus, when pathogens evolve quickly, the Red Queen is capable of explaining both positive selection and long coalescence times, but the tension between the novel allele advantage and persistence of alleles deserves further investigation.

  13. Crystal structure of spinach major light-harvesting complex at 2.72Å resolution

    Science.gov (United States)

    Liu, Zhenfeng; Yan, Hanchi; Wang, Kebin; Kuang, Tingyun; Zhang, Jiping; Gui, Lulu; An, Xiaomin; Chang, Wenrui

    2004-03-01

    The major light-harvesting complex of photosystem II (LHC-II) serves as the principal solar energy collector in the photosynthesis of green plants and presumably also functions in photoprotection under high-light conditions. Here we report the first X-ray structure of LHC-II in icosahedral proteoliposome assembly at atomic detail. One asymmetric unit of a large R32 unit cell contains ten LHC-II monomers. The 14 chlorophylls (Chl) in each monomer can be unambiguously distinguished as eight Chla and six Chlb molecules. Assignment of the orientation of the transition dipole moment of each chlorophyll has been achieved. All Chlb are located around the interface between adjacent monomers, and together with Chla they are the basis for efficient light harvesting. Four carotenoid-binding sites per monomer have been observed. The xanthophyll-cycle carotenoid at the monomer-monomer interface may be involved in the non-radiative dissipation of excessive energy, one of the photoprotective strategies that have evolved in plants.

  14. Correlation in chicken between the marker LEI0258 alleles and Major Histocompatibility Complex sequences

    DEFF Research Database (Denmark)

    Chazara, Olympe; Juul-Madsen, Helle Risdahl; Chang, Chi-Seng

    Background The LEI0258 marker is located within the B region of the chicken Major Histocompatibility Complex (MHC), and is surprisingly well associated with serology. Therefore, the correlation between the LEI0258 alleles and the MHC class I and the class II alleles at the level of sequences...... is worth investigating in chickens. Here we describe to which extent the LEI0258 alleles are associated with alleles of classical class I genes and non-classical class II genes, in reference animals as well as local breeds with unknown MHC haplotypes. Methods For the class I region, in an exploratory...... project, we studied 10 animals from 3 breeds: Rhode Island Red, White Leghorn and Fayoumi chickens, by cloning and sequencing B-F1 and B-F2 cDNA from exon 1 to 3’UTR. For the class II region, we reconstructed haplotypes of the 8.8 kb genomic region encompassing three non-classical class II genes: B-DMA, B...

  15. Characterisation of major histocompatibility complex class I genes in Japanese Ranidae frogs.

    Science.gov (United States)

    Lau, Quintin; Igawa, Takeshi; Komaki, Shohei; Satta, Yoko

    2016-11-01

    The major histocompatibility complex (MHC) is a key component of adaptive immunity in all jawed vertebrates, and understanding the evolutionary mechanisms that have shaped these genes in amphibians, one of the earliest terrestrial tetrapods, is important. We characterised MHC class I variation in three common Japanese Rana species (Rana japonica, Rana ornativentris and Rana tagoi tagoi) and identified a total of 60 variants from 21 individuals. We also found evolutionary signatures of gene duplication, recombination and balancing selection (including trans-species polymorphism), all of which drive increased MHC diversity. A unique feature of MHC class I from these three Ranidae species includes low synonymous differences per site (d S ) within species, which we attribute to a more recent diversification of these sequences or recent gene duplication. The resulting higher d N /d S ratio relative to other anurans studied could be related to stronger selection pressure at peptide binding sites. This is one of the first studies to investigate MHC in Japanese amphibians and permits further exploration of the polygenetic factors associated with resistance to infectious diseases.

  16. Red Queen Processes Drive Positive Selection on Major Histocompatibility Complex (MHC Genes.

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    Maciej Jan Ejsmond

    2015-11-01

    Full Text Available Major Histocompatibility Complex (MHC genes code for proteins involved in the incitation of the adaptive immune response in vertebrates, which is achieved through binding oligopeptides (antigens of pathogenic origin. Across vertebrate species, substitutions of amino acids at sites responsible for the specificity of antigen binding (ABS are positively selected. This is attributed to pathogen-driven balancing selection, which is also thought to maintain the high polymorphism of MHC genes, and to cause the sharing of allelic lineages between species. However, the nature of this selection remains controversial. We used individual-based computer simulations to investigate the roles of two phenomena capable of maintaining MHC polymorphism: heterozygote advantage and host-pathogen arms race (Red Queen process. Our simulations revealed that levels of MHC polymorphism were high and driven mostly by the Red Queen process at a high pathogen mutation rate, but were low and driven mostly by heterozygote advantage when the pathogen mutation rate was low. We found that novel mutations at ABSs are strongly favored by the Red Queen process, but not by heterozygote advantage, regardless of the pathogen mutation rate. However, while the strong advantage of novel alleles increased the allele turnover rate, under a high pathogen mutation rate, allelic lineages persisted for a comparable length of time under Red Queen and under heterozygote advantage. Thus, when pathogens evolve quickly, the Red Queen is capable of explaining both positive selection and long coalescence times, but the tension between the novel allele advantage and persistence of alleles deserves further investigation.

  17. Major Histocompatibility Complex and Hematopoietic Stem Cell Transplantation: Beyond the Classical HLA Polymorphism

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    Alice Bertaina

    2018-02-01

    Full Text Available Allogeneic hematopoietic stem cell transplantation (HSCT represents a curative treatment for many patients with hematological malignant or non-malignant disorders. Evaluation of potential donors for HSCT includes a rigorous assessment of the human leukocyte antigens (HLA match status of family members, and the identification of suitable unrelated donors. Genes encoding transplantation antigens are placed both within and outside the major histocompatibility complex (MHC. The human MHC is located on the short arm of chromosome 6 and contains a series of genes encoding two distinct types of highly polymorphic cell surface glycoproteins. Donors for HSCT are routinely selected based on the level of matching for HLA-A, -B, -C, -DRB1, and -DQB1 loci. However, disease relapse, graft-versus-host-disease, and infection remain significant risk factors of morbidity and mortality. In the same breath, in high-risk patients, graft-versus-leukemia effects inherent in HLA mismatching play a substantial immunological role to limit the recurrence of post-transplant disease. The definition of a suitable donor is ever changing, shaped not only by current typing technology, but also by the specific transplant procedure. Indeed, a more complete understanding of permissible HLA mismatches and the role of Killer Immunoglobulin-like receptors’ genes increases the availability of HLA-haploidentical and unrelated donors.

  18. Diversity at the major histocompatibility complex Class II in the platypus, Ornithorhynchus anatinus.

    Science.gov (United States)

    Lillie, Mette; Woodward, Rachael E; Sanderson, Claire E; Eldridge, Mark D B; Belov, Katherine

    2012-07-01

    The platypus (Ornithorhynchus anatinus) is the sole survivor of a previously widely distributed and diverse lineage of ornithorhynchid monotremes. Its dependence on healthy water systems imposes an inherent sensitivity to habitat degradation and climate change. Here, we compare genetic diversity at the major histocompatibility complex (MHC) Class II-DZB gene and 3 MHC-associated microsatellite markers with diversity at 6 neutral microsatellite markers in 70 platypuses from across their range, including the mainland of Australia and the isolated populations of Tasmania, King Island, and Kangaroo Island. Overall, high DZB diversity was observed in the platypus, with 57 DZB β1 alleles characterized. Significant positive selection was detected within the DZB peptide-binding region, promoting variation in this domain. Low levels of genetic diversity were detected at all markers in the 2 island populations, King Island (endemic) and Kangaroo Island (introduced), with the King Island platypuses monomorphic at the DZB locus. Loss of MHC diversity on King Island is of concern, as the population may have compromised immunological fitness and reduced ability to resist changing environmental conditions.

  19. Enhanced Direct Major Histocompatibility Complex Class I Self-Antigen Presentation Induced by Chlamydia Infection.

    Science.gov (United States)

    Cram, Erik D; Simmons, Ryan S; Palmer, Amy L; Hildebrand, William H; Rockey, Daniel D; Dolan, Brian P

    2016-02-01

    The direct major histocompatibility complex (MHC) class I antigen presentation pathway ensures intracellular peptides are displayed at the cellular surface for recognition of infected or transformed cells by CD8(+) cytotoxic T lymphocytes. Chlamydia spp. are obligate intracellular bacteria and, as such, should be targeted by CD8(+) T cells. It is likely that Chlamydia spp. have evolved mechanisms to avoid the CD8(+) killer T cell responses by interfering with MHC class I antigen presentation. Using a model system of self-peptide presentation which allows for posttranslational control of the model protein's stability, we tested the ability of various Chlamydia species to alter direct MHC class I antigen presentation. Infection of the JY lymphoblastoid cell line limited the accumulation of a model host protein and increased presentation of the model-protein-derived peptides. Enhanced self-peptide presentation was detected only when presentation was restricted to defective ribosomal products, or DRiPs, and total MHC class I levels remained unaltered. Skewed antigen presentation was dependent on a bacterial synthesized component, as evidenced by reversal of the observed phenotype upon preventing bacterial transcription, translation, and the inhibition of bacterial lipooligosaccharide synthesis. These data suggest that Chlamydia spp. have evolved to alter the host antigen presentation machinery to favor presentation of defective and rapidly degraded forms of self-antigen, possibly as a mechanism to diminish the presentation of peptides derived from bacterial proteins. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  20. Genetic variation of major histocompatibility complex genes in the endangered red-crowned crane.

    Science.gov (United States)

    Akiyama, Takuya; Kohyama, Tetsuo I; Nishida, Chizuko; Onuma, Manabu; Momose, Kunikazu; Masuda, Ryuichi

    2017-07-01

    Populations that have drastically decreased in the past often have low genetic variation, which may increase the risk of extinction. The genes of major histocompatibility complex (MHC) play an important role in the adaptive immune response of jawed vertebrates. Maintenance of adaptive genetic diversity such as that of MHC genes is important for wildlife conservation. Here, we determined genotypes of exon 3 of MHC class IA genes (MHCIA) and exon 2 of MHC class IIB genes (MHCIIB) to evaluate genetic variation of the endangered red-crowned crane population on Hokkaido Island, Japan, which experienced severe population decline in the past. We identified 16 and 6 alleles of MHCIA and MHCIIB, respectively, from 152 individuals. We found evidence of a positive selection at the antigen-binding sites in MHCIA exon 3 and MHCIIB exon 2. The phylogenetic analyses indicated evidence of trans-species polymorphism among the crane MHC genes. The genetic variability in both classes of MHC genes at the population level was low. No geographic structure was found based on the genetic diversity of microsatellite and MHC genes. Our study provides useful data for the optimal management of the red-crowned crane population in Hokkaido and can contribute to future studies on MHC genes of the continental populations of the red-crowned crane and other crane species.

  1. Molecular mapping of the human major histocompatibility complex by pulsed-field gel electrophoresis

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    Dunham, I.; Sargent, C.A.; Trowsdale, J.; Campbell, R.D.

    1987-10-01

    Pulsed-field gel electrophoresis and cosmid walking have been used to establish a molecular map of the human major histocompatibility complex (MHC). The authors have isolated approx. = 230 kilobases (kb) of genomic DNA in overlapping cosmid clones covering the genes for the second and fourth components of complement (C2 and C4, respectively), factor B, and steroid 21-hydroxylase, and approx. = 82 kb of genomic DNA surrounding the genes for the tumor necrosis factors ..cap alpha.. and ..beta... Single-copy hybridization probes isolated from these cosmid clusters and probes for the known MHC gene loci were hybridized to Southern blots of genomic DNA that had been digested with infrequently cutting restriction endonucleases and separated on pulsed-field gels. The data obtained allowed the construction of a long-range genomic restriction map and indicated that the MHC spans 3800 kb. This map orients the MHC class III gene cluster with respect to the DR subregion; the C2 gene is on the telomeric side of the 21-hydroxylase B gene. In addition they have defined the positions of the genes for the tumor necrosis factors ..cap alpha.. and ..beta.. in the human MHC. Genes for the ..cap alpha.. chain of DR and 21-hydroxylase B are separated by at least 300 kb, while the distance between the genes for C2 and tumor necrosis factor ..cap alpha.. is 390 kb. The HLA-B locus lies approx. = 250 kb on the telomeric side of the tumor necrosis factor genes.

  2. Molecular mapping of the human major histocompatibility complex by pulsed-field gel electrophoresis

    International Nuclear Information System (INIS)

    Dunham, I.; Sargent, C.A.; Trowsdale, J.; Campbell, R.D.

    1987-01-01

    Pulsed-field gel electrophoresis and cosmid walking have been used to establish a molecular map of the human major histocompatibility complex (MHC). The authors have isolated ≅ 230 kilobases (kb) of genomic DNA in overlapping cosmid clones covering the genes for the second and fourth components of complement (C2 and C4, respectively), factor B, and steroid 21-hydroxylase, and ≅ 82 kb of genomic DNA surrounding the genes for the tumor necrosis factors α and β. Single-copy hybridization probes isolated from these cosmid clusters and probes for the known MHC gene loci were hybridized to Southern blots of genomic DNA that had been digested with infrequently cutting restriction endonucleases and separated on pulsed-field gels. The data obtained allowed the construction of a long-range genomic restriction map and indicated that the MHC spans 3800 kb. This map orients the MHC class III gene cluster with respect to the DR subregion; the C2 gene is on the telomeric side of the 21-hydroxylase B gene. In addition they have defined the positions of the genes for the tumor necrosis factors α and β in the human MHC. Genes for the α chain of DR and 21-hydroxylase B are separated by at least 300 kb, while the distance between the genes for C2 and tumor necrosis factor α is 390 kb. The HLA-B locus lies ≅ 250 kb on the telomeric side of the tumor necrosis factor genes

  3. Tapasin dependence of major histocompatibility complex class I molecules correlates with their conformational flexibility.

    Science.gov (United States)

    Garstka, Malgorzata Anna; Fritzsche, Susanne; Lenart, Izabela; Hein, Zeynep; Jankevicius, Gytis; Boyle, Louise H; Elliott, Tim; Trowsdale, John; Antoniou, Antony N; Zacharias, Martin; Springer, Sebastian

    2011-11-01

    Major histocompatibility complex (MHC) class I molecules present cell internally derived peptides at the plasma membrane for surveillance by cytotoxic T lymphocytes. The surface expression of most class I molecules at least partially depends on the endoplasmic reticulum protein, tapasin, which helps them to bind peptides of the right length and sequence. To determine what makes a class I molecule dependent on support by tapasin, we have conducted in silico molecular dynamics (MD) studies and laboratory experiments to assess the conformational state of tapasin-dependent and -independent class I molecules. We find that in the absence of peptide, the region around the F pocket of the peptide binding groove of the tapasin-dependent molecule HLA-B*44:02 is in a disordered conformational state and that it is converted to a conformationally stable state by tapasin. This novel chaperone function of tapasin has not been described previously. We demonstrate that the disordered state of class I is caused by the presence of two adjacent acidic residues in the bottom of the F pocket of class I, and we suggest that conformational disorder is a common feature of tapasin-dependent class I molecules, making them essentially unable to bind peptides on their own. MD simulations are a useful tool to predict such conformational disorder of class I molecules.

  4. Spatial variation and low diversity in the major histocompatibility complex in walrus (Odobenus rosmarus)

    Science.gov (United States)

    Sonsthagen, Sarah A.; Fales, Krystal; Jay, Chadwick V.; Sage, George K.; Talbot, Sandra L.

    2014-01-01

    Increased global temperature and associated changes to Arctic habitats will likely result in the northward advance of species, including an influx of pathogens novel to the Arctic. How species respond to these immunological challenges will depend in part on the adaptive potential of their immune response system. We compared levels of genetic diversity at a gene associated with adaptive immune response [Class II major histocompatibility complex (MHC), DQB exon 2] between populations of walrus (Odobenus rosmarus), a sea ice-dependent Arctic species. Walrus was represented by only five MHC DQB alleles, with frequency differences observed between Pacific and Atlantic populations. MHC DQB alleles appear to be under balancing selection, and most (80 %; n = 4/5) of the alleles were observed in walruses from both oceans, suggesting broad scale differences in the frequency of exposure and diversity of pathogens may be influencing levels of heterozygosity at DQB in walruses. Limited genetic diversity at MHC, however, suggests that walrus may have a reduced capacity to respond to novel immunological challenges associated with shifts in ecological communities and environmental stressors predicted for changing climates. This is particularly pertinent for walrus, since reductions in summer sea ice may facilitate both northward expansion of marine species and associated pathogens from more temperate regions, and exchange of marine mammals and associated pathogens through the recently opened Northwest Passage between the Atlantic and Pacific Oceans in the Canadian high Arctic.

  5. MAJOR HYSTOCOMPATIBILITY COMPLEX: STRUKTUR, FUNGSI, HUBUNGAN DENGAN PENYAKIT DAN PEMANFAATAN DALAM RESPON IMUN

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    Basundari Sri Utama

    2012-10-01

    Full Text Available Respon imun terhadap antigen asing dapat terjadi karena kemampuan dari organisme untuk membedakan "non self" dengan "self", sehingga dapat terhindar dari efek patogen dari antigen yang masuk. Hal ini terjadi karena kemampuan polimorfisme dari komponen molekul yang terdapat pada permukaan sel presentan pada saat proses respon imun terjadi. Komponen molekul tersebut disebut MHC (Major Hystocompatibility Complex pada tikus diberi kode H-2 atau HLA (Human Leucocyt Antifen pada manusia. Pengkode genetik MHC pada tikus terletak pada kromosom 17, pada manusia terletak pada kromosom 6. MHC tersebar pada hampir semua permukaan sel tubuh. Pada tikus MHC kelas 1 terdapat sel-sel yang berinti, platelet dan sel darah merah. Pada manusia terdapat pada sel-sel yang berinti dan platelet. MHC pada tikus terutama terdapat pada sel B, makrofag, sel epithel, sel limfosit T. Pada manusia terutama terdapat pada sel B dan makrofag. Fungsi MHC kelas I diantaranya adalah reaksi penolakan jaringan, stimulasi produksi antibodi, proses interaksi antigen dengan sel T. MHC kelas II diperlukan dalam proses presentasi antigen. Pengetahuan tentang MHC/HLA seseorang, dapat dipakai untuk memperkirakan risiko seseorang mendapatkan penyakit yang bersifat herediter atau kelainan imunologik. Dengan mengetahui bahwa MHC/HLA hanya dapat mengikat peptida, hal ini dapat dimanfaatkan untuk pencegahan reaksi alergi.

  6. Human Herpesvirus 7 U21 Tetramerizes To Associate with Class I Major Histocompatibility Complex Molecules

    Science.gov (United States)

    May, Nathan A.; Wang, Qiuhong; Balbo, Andrea; Konrad, Sheryl L.; Buchli, Rico; Hildebrand, William H.; Schuck, Peter

    2014-01-01

    ABSTRACT The U21 gene product from human herpesvirus 7 binds to and redirects class I major histocompatibility complex (MHC) molecules to a lysosomal compartment. The molecular mechanism by which U21 reroutes class I MHC molecules to lysosomes is not known. Here, we have reconstituted the interaction between purified soluble U21 and class I MHC molecules, suggesting that U21 does not require additional cellular proteins to interact with class I MHC molecules. Our results demonstrate that U21, itself predicted to contain an MHC class I-like protein fold, interacts tightly with class I MHC molecules as a tetramer, in a 4:2 stoichiometry. These observations have helped to elucidate a refined model describing the mechanism by which U21 escorts class I MHC molecules to the lysosomal compartment. IMPORTANCE In this report, we show that the human herpesvirus 7 (HHV-7) immunoevasin U21, itself a class I MHC-like protein, binds with high affinity to class I MHC molecules as a tetramer and escorts them to lysosomes, where they are degraded. While many class I MHC-like molecules have been described in detail, this unusual viral class I-like protein functions as a tetramer, associating with class I MHC molecules in a 4:2 ratio, illuminating a functional significance of homooligomerization of a class I MHC-like protein. PMID:24390327

  7. Sexual conflict inhibits female mate choice for major histocompatibility complex dissimilarity in Chinook salmon.

    Science.gov (United States)

    Garner, Shawn R; Bortoluzzi, Romina N; Heath, Daniel D; Neff, Bryan D

    2010-03-22

    In many species females prefer major histocompatibility complex (MHC) dissimilar mates, which may improve offspring resistance to pathogens. However, sexual conflict may interfere with female preference when males attempt to mate with all females, regardless of compatibility. Here we used semi-natural spawning channels to examine how mating behaviour and genetic similarity at the MHC class II peptide binding region affected parentage patterns in Chinook salmon (Oncorhynchus tshawytscha). We found that females directed aggression at more MHC-similar males than expected by chance, providing a possible mechanism of female MHC choice in salmon. Males also directed aggression towards MHC-similar females, which was consistent with males harassing unreceptive mates. Males' aggression was positively correlated with their reproductive success, and it appeared to overcome female aversion to mating with MHC-similar males, as females who were the target of high levels of male aggression had lower than expected MHC divergence in their offspring. Indeed, offspring MHC divergence was highest when the sex ratio was female-biased and male harassment was likely to be less intense. These data suggest that male harassment can reduce female effectiveness in selecting MHC-compatible mates, and sexual conflict can thus have an indirect cost to females.

  8. Characterization of the major histocompatibility complex class II genes in miiuy croaker.

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    Tianjun Xu

    Full Text Available Major histocompatibility complex (MHC has a central role in the adaptive immune system by presenting foreign peptide to the T-cell receptor. In order to study the molecular function and genomic characteristic of class II genes in teleost, the full lengths of MHC class IIA and IIB cDNA and genomic sequence were cloned from miiuy croaker (Miichthys miiuy. As in other teleost, four exons and three introns were identified in miiuy croaker class IIA gene; but the difference is that six exons and five introns were identified in the miiuy croaker class IIB gene. The deduced amino acid sequence of class IIA and class IIB had 26.3-85.7% and 11.0-88.8% identity with those of mammal and teleost, respectively. Real-time quantitative RT-PCR demonstrated that the MHC class IIA and IIB were ubiquitously expressed in ten normal tissues; expression levels of MHC genes were found first upregulated and then downregulated, and finally by a recovery to normal level throughout the pathogenic bacteria infection process. In addition, we report on the underlying mechanism that maintains sequences diversity among many fish species. A series of site-model tests implemented in the CODEML program revealed that positive Darwinian selection is likely the cause of the molecular evolution in the fish MHC class II genes.

  9. Major histocompatibility complex loci are associated with susceptibility of Atlantic salmon to infectious hematopoietic necrosis virus

    Science.gov (United States)

    Miller, Kristina M.; Winton, James R.; Schulze, Angela D.; Purcell, Maureen K.; Ming, Tobi J.

    2004-01-01

    Infectious hematopoietic necrosis virus (IHNV) is one of the most significant viral pathogens of salmonids and is a leading cause of death among cultured juvenile fish. Although several vaccine strategies have been developed, some of which are highly protective, the delivery systems are still too costly for general use by the aquaculture industry. More cost effective methods could come from the identification of genes associated with IHNV resistance for use in selective breeding. Further, identification of susceptibility genes may lead to an improved understanding of viral pathogenesis and may therefore aid in the development of preventive and therapeutic measures. Genes of the major histocompatibility complex (MHC), involved in the primary recognition of foreign pathogens in the acquired immune response, are associated with resistance to a variety of diseases in vertebrate organisms. We conducted a preliminary analysis of MHC disease association in which an aquaculture strain of Atlantic salmon was challenged with IHNV at three different doses and individual fish were genotyped at three MHC loci using denaturing gradient gel electrophoresis (PCR-DGGE), followed by sequencing of all differentiated alleles. Nine to fourteen alleles per exon-locus were resolved, and alleles potentially associated with resistance or susceptibility were identified. One allele (Sasa-B-04) from a potentially non-classical class I locus was highly associated with resistance to infectious hematopoietic necrosis (p < 0.01). This information can be used to design crosses of specific haplotypes for family analysis of disease associations.

  10. The Emerging Role of the Major Histocompatibility Complex Class I in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Chiarotto, Gabriela Bortolança; Nardo, Giovanni; Trolese, Maria Chiara; França, Marcondes Cavalcante; Bendotti, Caterina; Rodrigues de Oliveira, Alexandre Leite

    2017-11-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting upper and lower motoneurons (MNs). The etiology of the disease is still unknown for most patients with sporadic ALS, while in 5-10% of the familial cases, several gene mutations have been linked to the disease. Mutations in the gene encoding Cu, Zn superoxide dismutase (SOD1), reproducing in animal models a pathological scenario similar to that found in ALS patients, have allowed for the identification of mechanisms relevant to the ALS pathogenesis. Among them, neuroinflammation mediated by glial cells and systemic immune activation play a key role in the progression of the disease, through mechanisms that can be either neuroprotective or neurodetrimental depending on the type of cells and the MN compartment involved. In this review, we will examine and discuss the involvement of major histocompatibility complex class I (MHCI) in ALS concerning its function in the adaptive immunity and its role in modulating the neural plasticity in the central and peripheral nervous system. The evidence indicates that the overexpression of MHCI into MNs protect them from astrocytes' toxicity in the central nervous system (CNS) and promote the removal of degenerating motor axons accelerating collateral reinnervation of muscles.

  11. Major Histocompatibility Complex and Hematopoietic Stem Cell Transplantation: Beyond the Classical HLA Polymorphism.

    Science.gov (United States)

    Bertaina, Alice; Andreani, Marco

    2018-02-22

    Allogeneic hematopoietic stem cell transplantation (HSCT) represents a curative treatment for many patients with hematological malignant or non-malignant disorders. Evaluation of potential donors for HSCT includes a rigorous assessment of the human leukocyte antigens (HLA) match status of family members, and the identification of suitable unrelated donors. Genes encoding transplantation antigens are placed both within and outside the major histocompatibility complex (MHC). The human MHC is located on the short arm of chromosome 6 and contains a series of genes encoding two distinct types of highly polymorphic cell surface glycoproteins. Donors for HSCT are routinely selected based on the level of matching for HLA-A, -B, -C, -DRB1, and -DQB1 loci. However, disease relapse, graft-versus-host-disease, and infection remain significant risk factors of morbidity and mortality. In the same breath, in high-risk patients, graft-versus-leukemia effects inherent in HLA mismatching play a substantial immunological role to limit the recurrence of post-transplant disease. The definition of a suitable donor is ever changing, shaped not only by current typing technology, but also by the specific transplant procedure. Indeed, a more complete understanding of permissible HLA mismatches and the role of Killer Immunoglobulin-like receptors' genes increases the availability of HLA-haploidentical and unrelated donors.

  12. Persistent Ehrlichia chaffeensis infection occurs in the absence of functional major histocompatibility complex class II genes

    Science.gov (United States)

    Ganta, Roman Reddy; Wilkerson, Melinda J.; Cheng, Chuanmin; Rokey, Aaron M.; Chapes, Stephen K.

    2002-01-01

    Human monocytic ehrlichiosis is an emerging tick-borne disease caused by the rickettsia Ehrlichia chaffeensis. We investigated the impact of two genes that control macrophage and T-cell function on murine resistance to E. chaffeensis. Congenic pairs of wild-type and toll-like receptor 4 (tlr4)- or major histocompatibility complex class II (MHC-II)-deficient mice were used for these studies. Wild-type mice cleared the infection within 2 weeks, and the response included macrophage activation and the synthesis of E. chaffeensis-specific Th1-type immunoglobulin G response. The absence of a functional tlr4 gene depressed nitric oxide and interleukin 6 secretion by macrophages and resulted in short-term persistent infections for > or =30 days. In the absence of MHC-II alleles, E. chaffeensis infections persisted throughout the entire 3-month evaluation period. Together, these data suggest that macrophage activation and cell-mediated immunity, orchestrated by CD4(+) T cells, are critical for conferring resistance to E. chaffeensis.

  13. Major histocompatibility complex selection dynamics in pathogen-infected túngara frog (Physalaemus pustulosus) populations.

    Science.gov (United States)

    Kosch, Tiffany A; Bataille, Arnaud; Didinger, Chelsea; Eimes, John A; Rodríguez-Brenes, Sofia; Ryan, Michael J; Waldman, Bruce

    2016-08-01

    Pathogen-driven selection can favour major histocompatibility complex (MHC) alleles that confer immunological resistance to specific diseases. However, strong directional selection should deplete genetic variation necessary for robust immune function in the absence of balancing selection or challenges presented by other pathogens. We examined selection dynamics at one MHC class II (MHC-II) locus across Panamanian populations of the túngara frog, Physalaemus pustulosus, infected by the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd). We compared MHC-II diversity in highland túngara frog populations, where amphibian communities have experienced declines owing to Bd, with those in the lowland region that have shown no evidence of decline. Highland region frogs had MHC variants that confer resistance to Bd. Variant fixation appeared to occur by directional selection rather than inbreeding, as overall genetic variation persisted in populations. In Bd-infected lowland sites, however, selective advantage may accrue to individuals with only one Bd-resistance allele, which were more frequent. Environmental conditions in lowlands should be less favourable for Bd infection, which may reduce selection for specific Bd resistance in hosts. Our results suggest that MHC selection dynamics fluctuate in túngara frog populations as a function of the favourability of habitat to pathogen spread and the vulnerability of hosts to infection. © 2016 The Author(s).

  14. Odour-based discrimination of similarity at the major histocompatibility complex in birds.

    Science.gov (United States)

    Leclaire, Sarah; Strandh, Maria; Mardon, Jérôme; Westerdahl, Helena; Bonadonna, Francesco

    2017-01-11

    Many animals are known to preferentially mate with partners that are dissimilar at the major histocompatibility complex (MHC) in order to maximize the antigen binding repertoire (or disease resistance) in their offspring. Although several mammals, fish or lizards use odour cues to assess MHC similarity with potential partners, the ability of birds to assess MHC similarity using olfactory cues has not yet been explored. Here we used a behavioural binary choice test and high-throughput-sequencing of MHC class IIB to determine whether blue petrels can discriminate MHC similarity based on odour cues alone. Blue petrels are seabirds with particularly good sense of smell, they have a reciprocal mate choice and are known to preferentially mate with MHC-dissimilar partners. Incubating males preferentially approached the odour of the more MHC-dissimilar female, whereas incubating females showed opposite preferences. Given their mating pattern, females were, however, expected to show preference for the odour of the more MHC-dissimilar male. Further studies are needed to determine whether, as in women and female mice, the preference varies with the reproductive cycle in blue petrel females. Our results provide the first evidence that birds can use odour cues only to assess MHC dissimilarity. © 2017 The Author(s).

  15. Differentiation and major histocompatibility complex antigen expression in human liver-derived stem cells.

    Science.gov (United States)

    Lee, J-H; Park, H-J; Kim, Y-A; Lee, D-H; Noh, J-K; Kwon, C H D; Jung, S-M; Lee, S-K

    2012-05-01

    Stem cells are a promising source for liver repopulation after cell transplantation, but whether the adult liver contains hepatic stem cells is controversial. The purpose of this study was to characterize the properties and expression profile of major histocompatibility complex (MHC) antigens on the surface of human-derived stem cells. Human liver-derived stem cells (HLSC7) were isolated from the nontumorous tissue of a patient who underwent a resection of an hepatic hemangioendothelioma. We characterized HLSC7 using a fluorescence-activated cell sorter, polymerase chain reactions, and immunofluorescence assays. HLSC7 expressed mesenchymal but not hematopoietic stem cell markers. HLSC7 underwent osteogenic, chondrogenic, and hepatogenic differentiation when cultured in appropriate differentiation media. However, HLSC7 did not differentiate into adipocytes. In addition, HLSC7 did not express MHC class II (HLA-DP, -DQ, and -DR) antigens. However, they did express MHC class I antigens. These results suggest that human liver-derived stem cells express MHC class I antigens and thus may be rejected on transplantation. Therefore, in addition to studies on stem cell differentiation, one must overcome immunologic barriers for successful clinical application of this therapy. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Identification of 32 major histocompatibility complex class I alleles in African green monkeys.

    Science.gov (United States)

    Cao, Y; Li, A; Li, L; Yan, X; Fa, Y; Zeng, L; Fan, J; Liu, B; Sun, Z

    2014-09-01

    The African green monkey may be an ideal replacement for the rhesus monkey in biomedical research, but relatively little is known about the genetic background of major histocompatibility complex (MHC) class I molecules. In analysis of 12 African green monkeys, 13 Chae-A and 19 Chae-B alleles were identified. Among these alleles, 12 Chae-A and 9 Chae-B were new lineages. The full amino acid length deduced for Chae-A genes is 365 amino acids, but for Chae-B genes, the lengths are 365, 362, 361, and 359 amino acids, respectively. There were 1-3 Chae-A alleles and 2-5 Chae-B alleles in each animal. In African green monkeys, rhesus monkeys, and cynomolgus monkeys, the MHC-A and MHC-B alleles display trans-species polymorphism, rather than being clustered in a species-specific fashion. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Soluble major histocompatibility complex molecules in immune regulation: highlighting class II antigens.

    Science.gov (United States)

    Bakela, Katerina; Athanassakis, Irene

    2018-03-01

    The involvement of major histocompatibility complex (MHC) antigens in the development and regulation of immune response has been well defined over the years, starting from maturation, antigenic peptide loading, migration to the cell membrane for recognition by the T-cell receptor and recycling for immune response cessation. During this intracellular trafficking, MHC antigens find a way to be excreted by the cells, because they can be found as soluble MHC class I (sMHC-I) and class II (sMHC-II) molecules in all body fluids. Although secretion mechanisms have not been sufficiently studied, sMHC molecules have been shown to display important immunoregulatory properties. Their levels in the serum have been shown to be altered in a variety of diseases, including viral infections, inflammation, autoimmunities and cancer, etc. while they seem to be involved in a number of physiological reactions, including maintenance of tolerance, reproduction, as well as mate choice vis-à-vis species evolution. The present review aims to present the thus far existing literature on sMHC molecules and point out the importance of these molecules in the maintenance of immune homeostasis. © 2017 John Wiley & Sons Ltd.

  18. Chemical composition of preen wax reflects major histocompatibility complex similarity in songbirds.

    Science.gov (United States)

    Slade, J W G; Watson, M J; Kelly, T R; Gloor, G B; Bernards, M A; MacDougall-Shackleton, E A

    2016-11-16

    In jawed vertebrates, genes of the major histocompatibility complex (MHC) play a key role in immunity by encoding cell-surface proteins that recognize and bind non-self antigens. High variability at MHC suggests that these loci may also function in social signalling such as mate choice and kin recognition. This requires that MHC genotype covaries with some perceptible phenotypic trait. In mammals and fish, MHC is signalled chemically through volatile and non-volatile peptide odour cues, facilitating MHC-dependent mate choice and other behaviours. In birds, despite evidence for MHC-dependent mating, candidate mechanisms for MHC signalling remain largely unexplored. However, feather preen wax has recently been implicated as a potential source of odour cues. We examined whether the chemical composition of preen wax correlates with MHC class IIβ genotypes of wild song sparrows (Melospiza melodia). Pairwise chemical distance reflected amino acid distance at MHC for male-female dyads, although not for same-sex dyads. Chemical diversity did not reflect MHC diversity. We used gas chromatography-mass spectrometry (GC-MS) to characterize preen wax compounds, and identified four wax esters that best reflect MHC similarity. Provided songbirds can detect variation in preen wax composition, this cue may allow individuals to assess MHC compatibility of potential mates. © 2016 The Author(s).

  19. Social and extra-pair mating in relation to major histocompatibility complex variation in common yellowthroats

    Science.gov (United States)

    Bollmer, Jennifer L.; Dunn, Peter O.; Freeman-Gallant, Corey R.; Whittingham, Linda A.

    2012-01-01

    Females are thought to gain better-quality genes for their offspring by mating with particular males. Genes of the major histocompatibility complex (MHC) play a critical role in adaptive immunity, and several studies have examined female mate choice in relation to MHC variation. In common yellowthroats, females prefer males that have larger black facial masks, an ornament associated with MHC variation, immune function and condition. Here we also tested whether mating patterns are directly correlated with MHC diversity or similarity. Using pyrosequencing, we found that the presence of extra-pair young in the brood was not related to male MHC diversity or similarity between the female and her within-pair mate. Furthermore, extra-pair sires did not differ in overall diversity from males they cuckolded, or in their similarity to the female. MHC diversity is extremely high in this species, and it may limit the ability of females to assess MHC variation in males. Thus, mating may be based on ornaments, such as mask size, which are better indicators of overall male health and genetic quality. PMID:23055067

  20. Structure and function of the non-classical major histocompatibility complex molecule MR1.

    Science.gov (United States)

    Krovi, S Harsha; Gapin, Laurent

    2016-08-01

    Polymorphic major histocompatibility complex (MHC) molecules play a central role in the vertebrate adaptive immune system. By presenting short peptides derived from pathogen-derived proteins, these "classical" MHC molecules can alert the T cell branch of the immune system of infected cells and clear the pathogen. There exist other "non-classical" MHC molecules, which while similar in structure to classical MHC proteins, are contrasted by their limited polymorphism. While the functions of many class Ib MHC molecules have still to be elucidated, the nature and diversity of antigens (if any) that some of them might present to the immune system is expected to be more restricted and might function as another approach to distinguish self from non-self. The MHC-related 1 (MR1) molecule is a member of this family of non-classical MHC proteins. It was recently shown to present unique antigens in the form of vitamin metabolites found in certain microbes. MR1 is strongly conserved genetically, structurally, and functionally through mammalian evolution, indicating its necessity in ensuring an effective immune system for members of this class. Although MR1 will be celebrating 21 years this year since its discovery, most of our understanding of how this molecule functions has only been uncovered in the past decade. Herein, we discuss where MR1 is expressed, how it selectively is able to bind to its appropriate antigens and how it, then, is able to specifically activate a distinct population of T cells.

  1. Adaptive tolerance to a pathogenic fungus drives major histocompatibility complex evolution in natural amphibian populations.

    Science.gov (United States)

    Savage, Anna E; Zamudio, Kelly R

    2016-03-30

    Amphibians have been affected globally by the disease chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), and we are just now beginning to understand how immunogenetic variability contributes to disease susceptibility. Lineages of an expressed major histocompatibility complex (MHC) class II locus involved in acquired immunity are associated with chytridiomycosis susceptibility in controlled laboratory challenge assays. Here, we extend these findings to natural populations that vary both in exposure and response to Bd We find that MHC alleles and supertypes associated with Bd survival in the field show a molecular signal of positive selection, while those associated with susceptibility do not, supporting the hypothesis that heritable Bd tolerance is rapidly evolving. We compare MHC supertypes to neutral loci to demonstrate where selection versus demography is shaping MHC variability. One population with Bd tolerance in nature shows a significant signal of directional selection for the same allele (allele Q) that was significantly associated with survival in an earlier laboratory study. Our findings indicate that selective pressure for Bd survival drives rapid immunogenetic adaptation in some natural populations, despite differences in environment and demography. Our field-based analysis of immunogenetic variation confirms that natural amphibian populations have the evolutionary potential to adapt to chytridiomycosis. © 2016 The Authors.

  2. Binding and activation of major histocompatibility complex class II-deficient macrophages by staphylococcal exotoxins

    Science.gov (United States)

    Beharka, A. A.; Armstrong, J. W.; Iandolo, J. J.; Chapes, S. K.; Spooner, B. S. (Principal Investigator)

    1994-01-01

    Macrophages from C2D transgenic mice deficient in the expression of major histocompatibility complex (MHC) class II proteins were used to identify binding sites for superantigens distinct from the MHC class II molecule. Iodinated staphylococcal enterotoxins A and B (SEA and SEB) and exfoliative toxins A and B (ETA and ETB) bound to C2D macrophages in a concentration-dependent and competitive manner. All four toxins increased F-actin concentration within 30 s of their addition to C2D macrophages, indicating that signal transduction occurred in response to toxin in the absence of class II MHC. Furthermore, ETA, ETB, SEA, and, to a lesser extent, SEB induced C2D macrophages to produce interleukin 6. Several molecular species on C2D macrophages with molecular masses of 140, 97, 61, 52, 43, and 37 kDa bound SEA in immunoprecipitation experiments. These data indicate the presence of novel, functionally active toxin binding sites on murine macrophages distinct from MHC class II molecules.

  3. Molecular modeling of class I and II alleles of the major histocompatibility complex in Salmo salar

    Science.gov (United States)

    Cárdenas, Constanza; Bidon-Chanal, Axel; Conejeros, Pablo; Arenas, Gloria; Marshall, Sergio; Luque, F. Javier

    2010-12-01

    Knowledge of the 3D structure of the binding groove of major histocompatibility (MHC) molecules, which play a central role in the immune response, is crucial to shed light into the details of peptide recognition and polymorphism. This work reports molecular modeling studies aimed at providing 3D models for two class I and two class II MHC alleles from Salmo salar ( Sasa), as the lack of experimental structures of fish MHC molecules represents a serious limitation to understand the specific preferences for peptide binding. The reliability of the structural models built up using bioinformatic tools was explored by means of molecular dynamics simulations of their complexes with representative peptides, and the energetics of the MHC-peptide interaction was determined by combining molecular mechanics interaction energies and implicit continuum solvation calculations. The structural models revealed the occurrence of notable differences in the nature of residues at specific positions in the binding groove not only between human and Sasa MHC proteins, but also between different Sasa alleles. Those differences lead to distinct trends in the structural features that mediate the binding of peptides to both class I and II MHC molecules, which are qualitatively reflected in the relative binding affinities. Overall, the structural models presented here are a valuable starting point to explore the interactions between MHC receptors and pathogen-specific interactions and to design vaccines against viral pathogens.

  4. Understanding Immune Resistance to Infectious Bronchitis Using Major Histocompatibility Complex Chicken Lines.

    Science.gov (United States)

    da Silva, A P; Hauck, R; Zhou, H; Gallardo, R A

    2017-09-01

    Genetic resistance or susceptibility to infectious diseases has been largely associated with the avian major histocompatibility complex (MHC) genes. Our goal was to determine resistance and susceptibility of MHC B haplotype in congenic and inbred chicken lines in order to establish a resistant-susceptible model. Eight congenic lines (253/B18, 254/B15, 330/B21, 312/B24, 331/B2, 335/B19, 336/B21, and 342/BO), two inbred lines (003/B17 and 077/B19), and three commercial lines (white leghorn, brown layers, and broilers) were used in two experiments. We analyzed and compared immunologic responses and the effect of challenge by measuring viral load, IgG and IgA humoral responses, histopathology and histomorphometry, clinical signs, and immune cell populations in the different MHC B haplotype lines. We found that respiratory signs, tracheal deciliation and inflammation, airsacculitis, viral shedding in tears, and local humoral responses were good parameters to determine resistance or susceptibility. Based on these results, we identified 331/B2 as the most resistant and 335/B19 as the most susceptible congenic chicken lines. These two lines will be used as an animal model in subsequent experiments to understand the mechanisms by which the immune system in chickens generates resistance to infectious bronchitis virus.

  5. Effects of major histocompatibility complex class II knockout on mouse bone mechanical properties during development

    Science.gov (United States)

    Simske, Steven J.; Bateman, Ted A.; Smith, Erin E.; Ferguson, Virginia L.; Chapes, Stephen K.

    2002-01-01

    We investigated the effect of major histocompatibility complex class II (MHC II) knockout on the development of the mouse peripheral skeleton. These C2D mice had less skeletal development at 8, 12 and 16 weeks of age compared to wild-type C57BL/6J (B6) male mice. The C2D mice had decreased femur mechanical, geometric and compositional measurements compared to wild type mice at each of these ages. C2D femur stiffness (S), peak force in 3-pt bending (Pm), and mineral mass (Min-M) were 74%, 64% and 66%, respectively, of corresponding B6 values at 8 weeks of age. Similar differences were measured at 12 weeks (for which C2D femoral S, Pm and Min-M were 71%, 72% and 73%, respectively, of corresponding B6 values) and at 16 weeks (for which C2D femoral S, Pm and Min-M were 80%, 66% and 61%, respectively, of corresponding B6 values). MHC II knockout delays the development of adult bone properties and is accompanied by lower body mass compared to wild-type controls.

  6. Genetic variation of major histocompatibility complex (MHC) in wild Red Junglefowl (Gallus gallus).

    Science.gov (United States)

    Nguyen-Phuc, Hoa; Fulton, Janet E; Berres, Mark E

    2016-02-01

    The major histocompatibility complex (MHC) is a multi-family gene cluster that encodes proteins with immuno-responsive function. While studies of MHC in domesticated poultry are relatively common, very little is known about this highly polymorphic locus in wild Red Junglefowl (Gallus gallus), the natural progenitor of domestic chickens. We investigated the diversity of MHC within and among four wild Red Junglefowl populations across diversified natural habitats in South Central Vietnam. Based on a SNP panel of 84 sites spanning 210 Kb of the MHC-B locus, we identified 310 unique haplotypes in 398 chromosomes. None of these haplotypes have been described before and we did not observe any of the wild Red Junglefowl haplotypes in domesticated chickens. Analysis of molecular variance (AMOVA) revealed that 94.51% of observed haplotype variation was accounted for at the within individual level. Little genetic variance was apportioned within and among populations, the latter accounting only for 0.83%. We also found evidence of increased recombination, including numerous hotspots, and limited linkage disequilibrium among the 84 SNP sites. Compared to an average haplotype diversity of 3.55% among seventeen lines of domestic chickens, our results suggest extraordinarily high haplotype diversity remains in wild Red Junglefowl and is consistent with a pattern of balancing selection. Wild Red Junglefowl in Vietnam, therefore, represent a rich resource of natural genomic variation independent from artificial selection. © 2016 Poultry Science Association Inc.

  7. Differential transmembrane domain GXXXG motif pairing impacts major histocompatibility complex (MHC) class II structure.

    Science.gov (United States)

    Dixon, Ann M; Drake, Lisa; Hughes, Kelly T; Sargent, Elizabeth; Hunt, Danielle; Harton, Jonathan A; Drake, James R

    2014-04-25

    Major histocompatibility complex (MHC) class II molecules exhibit conformational heterogeneity, which influences their ability to stimulate CD4 T cells and drive immune responses. Previous studies suggest a role for the transmembrane domain of the class II αβ heterodimer in determining molecular structure and function. Our previous studies identified an MHC class II conformer that is marked by the Ia.2 epitope. These Ia.2(+) class II conformers are lipid raft-associated and able to drive both tyrosine kinase signaling and efficient antigen presentation to CD4 T cells. Here, we establish that the Ia.2(+) I-A(k) conformer is formed early in the class II biosynthetic pathway and that differential pairing of highly conserved transmembrane domain GXXXG dimerization motifs is responsible for formation of Ia.2(+) versus Ia.2(-) I-A(k) class II conformers and controlling lipid raft partitioning. These findings provide a molecular explanation for the formation of two distinct MHC class II conformers that differ in their inherent ability to signal and drive robust T cell activation, providing new insight into the role of MHC class II in regulating antigen-presenting cell-T cell interactions critical to the initiation and control of multiple aspects of the immune response.

  8. Managing the Organizational and Cultural Precursors to Major Events — Recognising and Addressing Complexity

    International Nuclear Information System (INIS)

    Taylor, R. H.; Carhart, N.; May, J.; Wijk, L. G. A. van

    2016-01-01

    been identified as particular vulnerabilities. Initial work on modelling has shown that the factors involved are both complex and inter-related, but learning from the research is being used to develop good practice. Examples will be given of the use of SD to provide new insights into the dynamics and complexity involved, and to provide new tools for assessing the implications of making changes (‘flight simulation’). It should also enable more informed choices to be made about the most useful indicators to measure before actions are taken which can have unintended consequences — leading, in the worst scenarios, to major events. (author)

  9. Economics of abdominal wall reconstruction.

    Science.gov (United States)

    Bower, Curtis; Roth, J Scott

    2013-10-01

    The economic aspects of abdominal wall reconstruction are frequently overlooked, although understandings of the financial implications are essential in providing cost-efficient health care. Ventral hernia repairs are frequently performed surgical procedures with significant economic ramifications for employers, insurers, providers, and patients because of the volume of procedures, complication rates, the significant rate of recurrence, and escalating costs. Because biological mesh materials add significant expense to the costs of treating complex abdominal wall hernias, the role of such costly materials needs to be better defined to ensure the most cost-efficient and effective treatments for ventral abdominal wall hernias. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Major Histocompatibility Complex Class I Chain-Related A (MICA) Molecules: Relevance in Solid Organ Transplantation

    Science.gov (United States)

    Baranwal, Ajay Kumar; Mehra, Narinder K.

    2017-01-01

    An ever growing number of reports on graft rejection and/or failure even with good HLA matches have highlighted an important role of non-HLA antigens in influencing allograft immunity. The list of non-HLA antigens that have been implicated in graft rejection in different types of organ transplantation has already grown long. Of these, the Major Histocompatibility Complex class I chain-related molecule A (MICA) is one of the most polymorphic and extensively studied non-HLA antigenic targets especially in the kidney transplantation. Humoral response to MICA antigens has repeatedly been associated with lower graft survival and an increased risk of acute and chronic rejection following kidney and liver transplantation with few studies showing conflicting results. Although there are clear indications of MICA antibodies being associated with adverse graft outcome, a definitive consensus on this relationship has not been arrived yet. Furthermore, only a few studies have dealt with the impact of MICA donor-specific antibodies as compared to those that are not donor specific on graft outcome. In addition to the membrane bound form, a soluble isoform of MICA (sMICA), which has the potential to engage the natural killer cell-activating receptor NKG2D resulting in endocytosis and degradation of receptor–ligand interaction complex leading to suppression of NKG2D-mediated host innate immunity, has been a subject of intense discussion. Most studies on sMICA have been directed toward understanding their influence on tumor growth, with limited literature focusing its role in transplant biology. Furthermore, a unique dimorphism (methionine to valine) at position 129 in the α2 domain categorizes MICA alleles into strong (MICA-129 met) and weak (MICA-129 val) binders of NKG2D receptor depending on whether they have methionine or valine at this position. Although the implications of MICA 129 dimorphism have been highlighted in hematopoietic stem cell transplantation, its role in

  11. Adaptive molecular evolution of the Major Histocompatibility Complex genes, DRA and DQA, in the genus Equus.

    Science.gov (United States)

    Kamath, Pauline L; Getz, Wayne M

    2011-05-18

    Major Histocompatibility Complex (MHC) genes are central to vertebrate immune response and are believed to be under balancing selection by pathogens. This hypothesis has been supported by observations of extremely high polymorphism, elevated nonsynonymous to synonymous base pair substitution rates and trans-species polymorphisms at these loci. In equids, the organization and variability of this gene family has been described, however the full extent of diversity and selection is unknown. As selection is not expected to act uniformly on a functional gene, maximum likelihood codon-based models of selection that allow heterogeneity in selection across codon positions can be valuable for examining MHC gene evolution and the molecular basis for species adaptations. We investigated the evolution of two class II MHC genes of the Equine Lymphocyte Antigen (ELA), DRA and DQA, in the genus Equus with the addition of novel alleles identified in plains zebra (E. quagga, formerly E. burchelli). We found that both genes exhibited a high degree of polymorphism and inter-specific sharing of allele lineages. To our knowledge, DRA allelic diversity was discovered to be higher than has ever been observed in vertebrates. Evidence was also found to support a duplication of the DQA locus. Selection analyses, evaluated in terms of relative rates of nonsynonymous to synonymous mutations (dN/dS) averaged over the gene region, indicated that the majority of codon sites were conserved and under purifying selection (dN

  12. Adaptive molecular evolution of the Major Histocompatibility Complex genes, DRA and DQA, in the genus Equus

    Directory of Open Access Journals (Sweden)

    Getz Wayne M

    2011-05-01

    Full Text Available Abstract Background Major Histocompatibility Complex (MHC genes are central to vertebrate immune response and are believed to be under balancing selection by pathogens. This hypothesis has been supported by observations of extremely high polymorphism, elevated nonsynonymous to synonymous base pair substitution rates and trans-species polymorphisms at these loci. In equids, the organization and variability of this gene family has been described, however the full extent of diversity and selection is unknown. As selection is not expected to act uniformly on a functional gene, maximum likelihood codon-based models of selection that allow heterogeneity in selection across codon positions can be valuable for examining MHC gene evolution and the molecular basis for species adaptations. Results We investigated the evolution of two class II MHC genes of the Equine Lymphocyte Antigen (ELA, DRA and DQA, in the genus Equus with the addition of novel alleles identified in plains zebra (E. quagga, formerly E. burchelli. We found that both genes exhibited a high degree of polymorphism and inter-specific sharing of allele lineages. To our knowledge, DRA allelic diversity was discovered to be higher than has ever been observed in vertebrates. Evidence was also found to support a duplication of the DQA locus. Selection analyses, evaluated in terms of relative rates of nonsynonymous to synonymous mutations (dN/dS averaged over the gene region, indicated that the majority of codon sites were conserved and under purifying selection (dN dS. However, the most likely evolutionary codon models allowed for variable rates of selection across codon sites at both loci and, at the DQA, supported the hypothesis of positive selection acting on specific sites. Conclusions Observations of elevated genetic diversity and trans-species polymorphisms supported the conclusion that balancing selection may be acting on these loci. Furthermore, at the DQA, positive selection was

  13. The major histocompatibility complex in Old World camelids and low polymorphism of its class II genes.

    Science.gov (United States)

    Plasil, Martin; Mohandesan, Elmira; Fitak, Robert R; Musilova, Petra; Kubickova, Svatava; Burger, Pamela A; Horin, Petr

    2016-03-01

    The Major Histocompatibility Complex (MHC) is a genomic region containing genes with crucial roles in immune responses. MHC class I and class II genes encode antigen-presenting molecules expressed on the cell surface. To counteract the high variability of pathogens, the MHC evolved into a region of considerable heterogeneity in its organization, number and extent of polymorphism. Studies of MHCs in different model species contribute to our understanding of mechanisms of immunity, diseases and their evolution. Camels are economically important domestic animals and interesting biomodels. Three species of Old World camels have been recognized: the dromedary (Camelus dromedarius), Bactrian camel (Camelus bactrianus) and the wild camel (Camelus ferus). Despite their importance, little is known about the MHC genomic region, its organization and diversity in camels. The objectives of this study were to identify, map and characterize the MHC region of Old World camelids, with special attention to genetic variation at selected class MHC II loci. Physical mapping located the MHC region to the chromosome 20 in Camelus dromedarius. Cytogenetic and comparative analyses of whole genome sequences showed that the order of the three major sub-regions is "Centromere - Class II - Class III - Class I". DRA, DRB, DQA and DQB exon 2 sequences encoding the antigen binding site of the corresponding class II antigen presenting molecules showed high degree of sequence similarity and extensive allele sharing across the three species. Unexpectedly low extent of polymorphism with low numbers of alleles and haplotypes was observed in all species, despite different geographic origins of the camels analyzed. The DRA locus was found to be polymorphic, with three alleles shared by all three species. DRA and DQA sequences retrieved from ancient DNA samples of Camelus dromedarius suggested that additional polymorphism might exist. This study provided evidence that camels possess an MHC comparable to

  14. Fine Mapping Major Histocompatibility Complex Associations in Psoriasis and Its Clinical Subtypes

    Science.gov (United States)

    Okada, Yukinori; Han, Buhm; Tsoi, Lam C.; Stuart, Philip E.; Ellinghaus, Eva; Tejasvi, Trilokraj; Chandran, Vinod; Pellett, Fawnda; Pollock, Remy; Bowcock, Anne M.; Krueger, Gerald G.; Weichenthal, Michael; Voorhees, John J.; Rahman, Proton; Gregersen, Peter K.; Franke, Andre; Nair, Rajan P.; Abecasis, Gonçalo R.; Gladman, Dafna D.; Elder, James T.; de Bakker, Paul I.W.; Raychaudhuri, Soumya

    2014-01-01

    Psoriasis vulgaris (PsV) risk is strongly associated with variation within the major histocompatibility complex (MHC) region, but its genetic architecture has yet to be fully elucidated. Here, we conducted a large-scale fine-mapping study of PsV risk in the MHC region in 9,247 PsV-affected individuals and 13,589 controls of European descent by imputing class I and II human leukocyte antigen (HLA) genes from SNP genotype data. In addition, we imputed sequence variants for MICA, an MHC HLA-like gene that has been associated with PsV, to evaluate association at that locus as well. We observed that HLA-C∗06:02 demonstrated the lowest p value for overall PsV risk (p = 1.7 × 10−364). Stepwise analysis revealed multiple HLA-C∗06:02-independent risk variants in both class I and class II HLA genes for PsV susceptibility (HLA-C∗12:03, HLA-B amino acid positions 67 and 9, HLA-A amino acid position 95, and HLA-DQα1 amino acid position 53; p psoriasis (PsC; n = 3,098). We found that risk heterogeneity between PsA and PsC might be driven by HLA-B amino acid position 45 (pomnibus = 2.2 × 10−11), indicating that different genetic factors underlie the overall risk of PsV and the risk of specific PsV subphenotypes. Our study illustrates the value of high-resolution HLA and MICA imputation for fine mapping causal variants in the MHC. PMID:25087609

  15. Evolution of major histocompatibility complex class I and class II genes in the brown bear

    Science.gov (United States)

    2012-01-01

    Background Major histocompatibility complex (MHC) proteins constitute an essential component of the vertebrate immune response, and are coded by the most polymorphic of the vertebrate genes. Here, we investigated sequence variation and evolution of MHC class I and class II DRB, DQA and DQB genes in the brown bear Ursus arctos to characterise the level of polymorphism, estimate the strength of positive selection acting on them, and assess the extent of gene orthology and trans-species polymorphism in Ursidae. Results We found 37 MHC class I, 16 MHC class II DRB, four DQB and two DQA alleles. We confirmed the expression of several loci: three MHC class I, two DRB, two DQB and one DQA. MHC class I also contained two clusters of non-expressed sequences. MHC class I and DRB allele frequencies differed between northern and southern populations of the Scandinavian brown bear. The rate of nonsynonymous substitutions (dN) exceeded the rate of synonymous substitutions (dS) at putative antigen binding sites of DRB and DQB loci and, marginally significantly, at MHC class I loci. Models of codon evolution supported positive selection at DRB and MHC class I loci. Both MHC class I and MHC class II sequences showed orthology to gene clusters found in the giant panda Ailuropoda melanoleuca. Conclusions Historical positive selection has acted on MHC class I, class II DRB and DQB, but not on the DQA locus. The signal of historical positive selection on the DRB locus was particularly strong, which may be a general feature of caniforms. The presence of MHC class I pseudogenes may indicate faster gene turnover in this class through the birth-and-death process. South–north population structure at MHC loci probably reflects origin of the populations from separate glacial refugia. PMID:23031405

  16. Regulation of major histocompatibility complex class II gene expression in trophoblast cells

    Directory of Open Access Journals (Sweden)

    Choi Jason C

    2004-07-01

    Full Text Available Abstract Trophoblast cells are unique because they are one of the few mammalian cell types that do not express major histocompatibility complex (MHC class II antigens, either constitutively or after exposure to IFN-γ. The absence of MHC class II antigen expression on trophoblast cells has been postulated to be one of the essential mechanisms by which the semi-allogeneic fetus evades immune rejection reactions by the maternal immune system. Consistent with this hypothesis, trophoblast cells from the placentas of women suffering from chronic inflammation of unknown etiology and spontaneous recurrent miscarriages have been reported to aberrantly express MHC class II antigens. The lack of MHC class II antigen expression on trophoblast cells is due to silencing of expression of the class II transactivator (CIITA, a transacting factor that is essential for constitutive and IFN-γ-inducible MHC class II gene transcription. Transfection of trophoblast cells with CIITA expression vectors activates both MHC class II and class Ia antigen expression, which confers on trophoblast cells both the ability to activate helper T cells, and sensitivity to lysis by cytotoxic T lymphocytes. Collectively, these studies strongly suggest that stringent silencing of CIITA (and therefore MHC class II gene expression in trophoblast cells is critical for the prevention of immune rejection responses against the fetus by the maternal immune system. The focus of this review is to summarize studies examining the novel mechanisms by which CIITA is silenced in trophoblast cells. The elucidation of the silencing of CIITA in trophoblast cells may shed light on how the semi-allogeneic fetus evades immune rejection by the maternal immune system during pregnancy.

  17. Low major histocompatibility complex class II DQA diversity in the Giant Panda (Ailuropoda melanoleuca

    Directory of Open Access Journals (Sweden)

    Ruan Xiang-Dong

    2007-06-01

    Full Text Available Abstract Background The giant panda (Ailuropoda melanoleuca is one of the most endangered animals due to habitat fragmentation and loss. Although the captive breeding program for this species is now nearly two decades old, researches on the genetic background of such captive populations, especially on adaptive molecular polymorphism of major histocompatibility complex (MHC, are still limited. In this study, we characterized adaptive variation of the giant panda's MHC DQA gene by PCR amplification of its antigen-recognizing region (i.e. the exon 2 and subsequent single-strand conformational polymorphism (SSCP and sequence analyses. Results The results revealed a low level of DQA exon 2 diversity in this rare animal, presenting 6 alleles from 61 giant panda individuals. The observed polymorphism was restricted to 9 amino acid substitutions, all of which occurred at and adjacent to positions forming the functionally important antigen-binding sites. All the samples were in Hardy-Weinberg proportions. A significantly higher rate of non-synonymous than synonymous substitutions at the antigen-binding sites indicated positive selection for diversity in the locus. Conclusion The DQA allelic diversity of giant pandas was low relative to other vertebrates. Nonetheless, the pandas exhibited more alleles in DQA than those in DRB, suggesting the alpha chain genes would play a leading role when coping with certain pathogens and thus should be included in conservation genetic investigation. The microsatellite and MHC loci might predict long-term persistence potential and short-term survival ability, respectively. Consequently, it is recommended to utilize multiple suites of microsatellite markers and multiple MHC loci to detect overall genetic variation in order to design unbiased conservation strategies.

  18. Evolution of major histocompatibility complex class I and class II genes in the brown bear

    Directory of Open Access Journals (Sweden)

    Kuduk Katarzyna

    2012-10-01

    Full Text Available Abstract Background Major histocompatibility complex (MHC proteins constitute an essential component of the vertebrate immune response, and are coded by the most polymorphic of the vertebrate genes. Here, we investigated sequence variation and evolution of MHC class I and class II DRB, DQA and DQB genes in the brown bear Ursus arctos to characterise the level of polymorphism, estimate the strength of positive selection acting on them, and assess the extent of gene orthology and trans-species polymorphism in Ursidae. Results We found 37 MHC class I, 16 MHC class II DRB, four DQB and two DQA alleles. We confirmed the expression of several loci: three MHC class I, two DRB, two DQB and one DQA. MHC class I also contained two clusters of non-expressed sequences. MHC class I and DRB allele frequencies differed between northern and southern populations of the Scandinavian brown bear. The rate of nonsynonymous substitutions (dN exceeded the rate of synonymous substitutions (dS at putative antigen binding sites of DRB and DQB loci and, marginally significantly, at MHC class I loci. Models of codon evolution supported positive selection at DRB and MHC class I loci. Both MHC class I and MHC class II sequences showed orthology to gene clusters found in the giant panda Ailuropoda melanoleuca. Conclusions Historical positive selection has acted on MHC class I, class II DRB and DQB, but not on the DQA locus. The signal of historical positive selection on the DRB locus was particularly strong, which may be a general feature of caniforms. The presence of MHC class I pseudogenes may indicate faster gene turnover in this class through the birth-and-death process. South–north population structure at MHC loci probably reflects origin of the populations from separate glacial refugia.

  19. Introgression from domestic goat generated variation at the major histocompatibility complex of Alpine ibex.

    Directory of Open Access Journals (Sweden)

    Christine Grossen

    2014-06-01

    Full Text Available The major histocompatibility complex (MHC is a crucial component of the vertebrate immune system and shows extremely high levels of genetic polymorphism. The extraordinary genetic variation is thought to be ancient polymorphisms maintained by balancing selection. However, introgression from related species was recently proposed as an additional mechanism. Here we provide evidence for introgression at the MHC in Alpine ibex (Capra ibex ibex. At a usually very polymorphic MHC exon involved in pathogen recognition (DRB exon 2, Alpine ibex carried only two alleles. We found that one of these DRB alleles is identical to a DRB allele of domestic goats (Capra aegagrus hircus. We sequenced 2489 bp of the coding and non-coding regions of the DRB gene and found that Alpine ibex homozygous for the goat-type DRB exon 2 allele showed nearly identical sequences (99.8% to a breed of domestic goats. Using Sanger and RAD sequencing, microsatellite and SNP chip data, we show that the chromosomal region containing the goat-type DRB allele has a signature of recent introgression in Alpine ibex. A region of approximately 750 kb including the DRB locus showed high rates of heterozygosity in individuals carrying one copy of the goat-type DRB allele. These individuals shared SNP alleles both with domestic goats and other Alpine ibex. In a survey of four Alpine ibex populations, we found that the region surrounding the DRB allele shows strong linkage disequilibria, strong sequence clustering and low diversity among haplotypes carrying the goat-type allele. Introgression at the MHC is likely adaptive and introgression critically increased MHC DRB diversity in the genetically impoverished Alpine ibex. Our finding contradicts the long-standing view that genetic variability at the MHC is solely a consequence of ancient trans-species polymorphism. Introgression is likely an underappreciated source of genetic diversity at the MHC and other loci under balancing selection.

  20. Evolution of major histocompatibility complex class I and class II genes in the brown bear.

    Science.gov (United States)

    Kuduk, Katarzyna; Babik, Wiesław; Bojarska, Katarzyna; Sliwińska, Ewa B; Kindberg, Jonas; Taberlet, Pierre; Swenson, Jon E; Radwan, Jacek

    2012-10-02

    Major histocompatibility complex (MHC) proteins constitute an essential component of the vertebrate immune response, and are coded by the most polymorphic of the vertebrate genes. Here, we investigated sequence variation and evolution of MHC class I and class II DRB, DQA and DQB genes in the brown bear Ursus arctos to characterise the level of polymorphism, estimate the strength of positive selection acting on them, and assess the extent of gene orthology and trans-species polymorphism in Ursidae. We found 37 MHC class I, 16 MHC class II DRB, four DQB and two DQA alleles. We confirmed the expression of several loci: three MHC class I, two DRB, two DQB and one DQA. MHC class I also contained two clusters of non-expressed sequences. MHC class I and DRB allele frequencies differed between northern and southern populations of the Scandinavian brown bear. The rate of nonsynonymous substitutions (dN) exceeded the rate of synonymous substitutions (dS) at putative antigen binding sites of DRB and DQB loci and, marginally significantly, at MHC class I loci. Models of codon evolution supported positive selection at DRB and MHC class I loci. Both MHC class I and MHC class II sequences showed orthology to gene clusters found in the giant panda Ailuropoda melanoleuca. Historical positive selection has acted on MHC class I, class II DRB and DQB, but not on the DQA locus. The signal of historical positive selection on the DRB locus was particularly strong, which may be a general feature of caniforms. The presence of MHC class I pseudogenes may indicate faster gene turnover in this class through the birth-and-death process. South-north population structure at MHC loci probably reflects origin of the populations from separate glacial refugia.

  1. Major histocompatibility complex alleles associated with parasite susceptibility in wild giant pandas.

    Science.gov (United States)

    Zhang, L; Wu, Q; Hu, Y; Wu, H; Wei, F

    2015-01-01

    Major histocompatibility complex (MHC) polymorphism is thought to be driven by antagonistic coevolution between pathogens and hosts, mediated through either overdominance or frequency-dependent selection. However, investigations under natural conditions are still rare for endangered mammals which often exhibit depleted variation, and the mechanism of selection underlying the maintenance of characteristics remains a considerable debate. In this study, 87 wild giant pandas were used to investigate MHC variation associated with parasite load. With the knowledge of the MHC profile provided by the genomic data of the giant panda, seven DRB1, seven DQA1 and eight DQA2 alleles were identified at each single locus. Positive selection evidenced by a significantly higher number of non-synonymous substitutions per non-synonymous codon site relative to synonymous substitutions per synonymous codon site could only be detected at the DRB1 locus, which leads to the speculation that DRB1 may have a more important role in dealing with parasite infection for pandas. Coprological analyses revealed that 55.17% of individuals exhibited infection with 1-2 helminthes and 95.3% of infected pandas carried Baylisascaris shroederi. Using a generalized linear model, we found that Aime-DRB1*10 was significantly associated with parasite infection, but no resistant alleles could be detected. MHC heterozygosity of the pandas was found to be uncorrelated with the infection status or the infection intensity. These results suggested that the possible selection mechanisms in extant wild pandas may be frequency dependent rather than being determined by overdominance selection. Our findings could guide the candidate selection for the ongoing reintroduction or translocation of pandas.

  2. The major histocompatibility complex genes impact pain response in DA and DA.1U rats.

    Science.gov (United States)

    Guo, Yuan; Yao, Fan-Rong; Cao, Dong-Yuan; Li, Li; Wang, Hui-Sheng; Xie, Wen; Zhao, Yan

    2015-08-01

    Our recent studies have shown that the difference in basal pain sensitivity to mechanical and thermal stimulation between Dark-Agouti (DA) rats and a novel congenic DA.1U rats is major histocompatibility complex (MHC) genes dependent. In the present study, we further used DA and DA.1U rats to investigate the role of MHC genes in formalin-induced pain model by behavioral, electrophysiological and immunohistochemical methods. Behavioral results showed biphasic nociceptive behaviors increased significantly following the intraplantar injection of formalin in the hindpaw of DA and DA.1U rats. The main nociceptive behaviors were lifting and licking, especially in DA rats (P<0.001 and P<0.01). The composite pain scores (CPS) in DA rats were significantly higher than those in DA.1U rats in both phases of the formalin test (P<0.01). Electrophysiological results also showed the biphasic increase in discharge rates of C and Aδ fibers of L5 dorsal root in the two strains, and the net change of the discharge rate of DA rats was significantly higher than that of DA.1U rats (P<0.05). The mechanical thresholds decreased after formalin injection in both strains (P<0.01), and the net change in the mechanical threshold in DA was greater than that in DA.1U rats (P<0.05). The expression of RT1-B, representation of MHC class II molecule, in laminae I-II of L4/5 spinal cord in DA rats was significantly higher than that in DA.1U rats in the respective experimental group (P<0.05). These results suggested that both DA and DA.1U rats exhibited nociceptive responses in formalin-induced pain model and DA rats were more sensitive to noxious chemical stimulus than DA.1U rats, indicating that MHC genes might contribute to the difference in pain sensitivity. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. CD9 Regulates Major Histocompatibility Complex Class II Trafficking in Monocyte-Derived Dendritic Cells.

    Science.gov (United States)

    Rocha-Perugini, Vera; Martínez Del Hoyo, Gloria; González-Granado, José María; Ramírez-Huesca, Marta; Zorita, Virginia; Rubinstein, Eric; Boucheix, Claude; Sánchez-Madrid, Francisco

    2017-08-01

    Antigen presentation by dendritic cells (DCs) stimulates naive CD4 + T cells, triggering T cell activation and the adaptive arm of the immune response. Newly synthesized major histocompatibility complex class II (MHC-II) molecules accumulate at MHC-II-enriched endosomal compartments and are transported to the plasma membrane of DCs after binding to antigenic peptides to enable antigen presentation. In DCs, MHC-II molecules are included in tetraspanin-enriched microdomains (TEMs). However, the role of tetraspanin CD9 in these processes remains largely undefined. Here, we show that CD9 regulates the T cell-stimulatory capacity of granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent bone marrow-derived DCs (BMDCs), without affecting antigen presentation by fms-like tyrosine kinase 3 ligand (Flt3L)-dependent BMDCs. CD9 knockout (KO) GM-CSF-dependent BMDCs, which resemble monocyte-derived DCs (MoDCs), induce lower levels of T cell activation than wild-type DCs, and this effect is related to a reduction in MHC-II surface expression in CD9-deficient MoDCs. Importantly, MHC-II targeting to the plasma membrane is largely impaired in immature CD9 KO MoDCs, in which MHC-II remains arrested in acidic intracellular compartments enriched in LAMP-1 (lysosome-associated membrane protein 1), and MHC-II internalization is also blocked. Moreover, CD9 participates in MHC-II trafficking in mature MoDCs, regulating its endocytosis and recycling. Our results demonstrate that the tetraspanin CD9 specifically regulates antigenic presentation in MoDCs through the regulation of MHC-II intracellular trafficking. Copyright © 2017 American Society for Microbiology.

  4. Phenome-wide association study maps new diseases to the human major histocompatibility complex region.

    Science.gov (United States)

    Liu, Jixia; Ye, Zhan; Mayer, John G; Hoch, Brian A; Green, Clayton; Rolak, Loren; Cold, Christopher; Khor, Seik-Soon; Zheng, Xiuwen; Miyagawa, Taku; Tokunaga, Katsushi; Brilliant, Murray H; Hebbring, Scott J

    2016-10-01

    Over 160 disease phenotypes have been mapped to the major histocompatibility complex (MHC) region on chromosome 6 by genome-wide association study (GWAS), suggesting that the MHC region as a whole may be involved in the aetiology of many phenotypes, including unstudied diseases. The phenome-wide association study (PheWAS), a powerful and complementary approach to GWAS, has demonstrated its ability to discover and rediscover genetic associations. The objective of this study is to comprehensively investigate the MHC region by PheWAS to identify new phenotypes mapped to this genetically important region. In the current study, we systematically explored the MHC region using PheWAS to associate 2692 MHC-linked variants (minor allele frequency ≥0.01) with 6221 phenotypes in a cohort of 7481 subjects from the Marshfield Clinic Personalized Medicine Research Project. Findings showed that expected associations previously identified by GWAS could be identified by PheWAS (eg, psoriasis, ankylosing spondylitis, type I diabetes and coeliac disease) with some having strong cross-phenotype associations potentially driven by pleiotropic effects. Importantly, novel associations with eight diseases not previously assessed by GWAS (eg, lichen planus) were also identified and replicated in an independent population. Many of these associated diseases appear to be immune-related disorders. Further assessment of these diseases in 16 484 Marshfield Clinic twins suggests that some of these diseases, including lichen planus, may have genetic aetiologies. These results demonstrate that the PheWAS approach is a powerful and novel method to discover SNP-disease associations, and is ideal when characterising cross-phenotype associations, and further emphasise the importance of the MHC region in human health and disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  5. A Recombinant Antibody with the Antigen-Specific, Major Histocompatibility Complex-Restricted Specificity of T Cells

    Science.gov (United States)

    Andersen, Peter S.; Stryhn, Anette; Hansen, Bjarke E.; Fugger, Lars; Engberg, Jan; Buus, Soren

    1996-03-01

    Specific recognition of peptide/major histocompatibility complex (MHC) molecule complexes by the T-cell receptor is a key reaction in the specific immune response. Antibodies against peptide/MHC complexes would therefore be valuable tools in studying MHC function and T-cell recognition and might lead to novel approaches in immunotherapy. However, it has proven difficult to generate antibodies with the specificity of T cells by conventional hybridoma techniques. Here we report that the phage display technology is a feasible alternative to generate antibodies recognizing specific, predetermined peptide/MHC complexes.

  6. The Combined Effects of Obesity, Abdominal Obesity and Major Depression/Anxiety on Health-Related Quality of Life : the LifeLines Cohort Study

    NARCIS (Netherlands)

    Nigatu, Yeshambel T; Reijneveld, Sijmen A; de Jonge, Peter; van Rossum, Elisabeth; Bültmann, Ute

    2016-01-01

    Background Obesity and major depressive disorder (MDD)/anxiety disorders often co-occur and aggravate each other resulting in adverse health-related outcomes. As little is known about the potential effects of interaction between obesity and MDD and/or anxiety disorders on health-related quality of

  7. Polarisation of Major Histocompatibility Complex II Host Genotype with Pathogenesis of European Brown Hare Syndrome Virus

    Science.gov (United States)

    Iacovakis, Christos; Mamuris, Zissis; Moutou, Katerina A.; Touloudi, Antonia; Hammer, Anne Sofie; Valiakos, George; Giannoulis, Themis; Stamatis, Costas; Spyrou, Vassiliki; Athanasiou, Labrini V.; Kantere, Maria; Asferg, Tommy; Giannakopoulos, Alexios; Salomonsen, Charlotte M.; Bogdanos, Dimitrios; Birtsas, Periklis; Petrovska, Liljana; Hannant, Duncan; Billinis, Charalambos

    2013-01-01

    A study was conducted in order to determine the occurrence of European Brown Hare Syndrome virus (EBHSV) in Denmark and possible relation between disease pathogenesis and Major Histocompatibility Complex (MHC) host genotype. Liver samples were examined from 170 brown hares (hunted, found sick or dead), collected between 2004 and 2009. Macroscopical and histopathological findings consistent with EBHS were detected in 24 (14.1%) hares; 35 (20.6%) had liver lesions not typical of the syndrome, 50 (29.4%) had lesions in other tissues and 61 (35.9%) had no lesions. Sixty five (38.2%) of 170 samples were found to be EBHSV-positive (RT-PCR, VP60 gene). In order to investigate associations between viral pathogenesis and host genotype, variation within the exon 2 DQA gene of MHC was assessed. DQA exon 2 analysis revealed the occurrence of seven different alleles in Denmark. Consistent with other populations examined so far in Europe, observed heterozygosity of DQA (Ho = 0.1180) was lower than expected (He = 0.5835). The overall variation for both nucleotide and amino acid differences (2.9% and 14.9%, respectively) were lower in Denmark than those assessed in other European countries (8.3% and 16.9%, respectively). Within the peptide binding region codons the number of nonsynonymous substitutions (dN) was much higher than synonymous substitutions (dS), which would be expected for MHC alleles under balancing selection. Allele frequencies did not significantly differ between EBHSV-positive and -negative hares. However, allele Leeu-DQA*30 was detected in significantly higher (P = 0.000006) frequency among the positive hares found dead with severe histopathological lesions than among those found sick or apparently healthy. In contrast, the latter group was characterized by a higher frequency of the allele Leeu-DQA*14 as well as the proportion of heterozygous individuals (P = 0.000006 and P = 0.027). These data reveal a polarisation between EBHSV pathogenesis

  8. Shared fine specificity between T-cell receptors and an antibody recognizing a peptide/major histocompatibility class I complex

    DEFF Research Database (Denmark)

    Stryhn, A; Andersen, P S; Pedersen, L O

    1996-01-01

    Cytotoxic T cells recognize mosaic structures consisting of target peptides embedded within self-major histocompatibility complex (MHC) class I molecules. This structure has been described in great detail for several peptide-MHC complexes. In contrast, how T-cell receptors recognize peptide-MHC...... complexes have been less well characterized. We have used a complete set of singly substituted analogs of a mouse MHC class I, Kk-restricted peptide, influenza hemagglutinin (Ha)255-262, to address the binding specificity of this MHC molecule. Using the same peptide-MHC complexes we determined the fine...... each other showing that peptide residues 1, 3, 4, 6, and 7 were exposed on the MHC surface and recognized by the T cells. Thus, the majority, and perhaps all, of the side chains of the non-primary anchor residues may be available for T-cell recognition, and contribute to the stringent specificity of T...

  9. Structure and expression of major histocompatibility complex-binding protein 2, a 275-kDa zinc finger protein that binds to an enhancer of major histocompatibility complex class I genes

    NARCIS (Netherlands)

    Veer, L.J. van 't; Lutz, P.M.; Isselbacher, K.J.; Bernards, R.A.

    1992-01-01

    We have isolated a cDNA encoding a transcription factor that binds to the enhancer of major histocompatibility complex (MHC) class I genes. MHC-binding protein 2 (MBP-2) is a 275-kDa protein, containing two sets of widely separated zinc fingers and a stretch of highly acidic amino acids, a

  10. Expression of hepatitis C virus proteins does not interfere with major histocompatibility complex class I processing and presentation in vitro

    OpenAIRE

    Moradpour, Darius; Grabscheid, Benno; Kammer, Andreas R.; Schmidtke, Gunter; Gröttrup, Marcus; Blum, Hubert E.; Cerny, Andreas

    2001-01-01

    Hepatitis C virus (HCV) infection takes a chronic course in the majority of patients. The mechanisms underlying the evasion of the host immune response and viral persistence are poorly understood. In this context, we investigated interactions of HCV proteins with major histocompatibility complex (MHC) class I processing and presentation pathways using cell lines that allow the tetracycline-regulated expression of viral structural and nonstructural proteins. These well-characterized inducible ...

  11. Distribution of class ii major histocompatibility complex antigenexpressing cells in human dental pulp with carious lesions

    Directory of Open Access Journals (Sweden)

    Tetiana Haniastuti

    2012-09-01

    Full Text Available Background: Dental caries is a bacterial infection which causes destruction of the hard tissues of the tooth. Exposure of the dentin to the oral environment as a result of caries inevitably results in a cellular response in the pulp. The major histocompatibility complex (MHC is a group of genes that code for cell-surface histocompatibility antigens. Cells expressing class II MHC molecules participate in the initial recognition and the processing of antigenic substances to serve as antigen-presenting cells. Purpose: The aim of the study was to elucidate the alteration in the distribution of class II MHC antigen-expressing cells in human dental pulp as carious lesions progressed toward the pulp. Methods: Fifteen third molars with caries at the occlusal site at various stages of decay and 5 intact third molars were extracted and used in this study. Before decalcifying with 10% EDTA solution (pH 7.4, all the samples were observed by micro-computed tomography to confirm the lesion condition three-dimensionally. The specimens were then processed for cryosection and immunohistochemistry using an anti-MHC class II monoclonal antibody. Results: Class II MHC antigen-expressing cells were found both in normal and carious specimens. In normal tooth, the class II MHC-immunopositive cells were observed mainly at the periphery of the pulp tissue. In teeth with caries, class II MHC-immunopositive cells were located predominantly subjacent to the carious lesions. As the caries progressed, the number of class II MHC antigen-expressing cells was increased. Conclusion: The depth of carious lesions affects the distribution of class II MHC antigen-expressing cells in the dental pulp.Latar belakang: Karies merupakan penyakit infeksi bakteri yang mengakibatkan destruksi jaringan keras gigi. Dentin yang terbuka akibat karies akan menginduksi respon imun seluler pada pulpa. Kompleks histokompatibilitas utama (MHC merupakan sekumpulan gen yang mengkode histokompatibilitas

  12. Highly conserved extended haplotypes of the major histocompatibility complex and their relationship to multiple sclerosis susceptibility.

    Directory of Open Access Journals (Sweden)

    Douglas S Goodin

    Full Text Available To determine the relationship between highly-conserved extended-haplotypes (CEHs in the major histocompatibility complex (MHC and MS-susceptibility.Among the ~200 MS-susceptibility regions, which are known from genome-wide analyses of single nucleotide polymorphisms (SNPs, the MHC accounts for roughly a third of the currently explained variance and the strongest MS-associations are for certain Class II alleles (e.g., HLA-DRB1*15:01; HLA-DRB1*03:01; and HLA-DRB1*13:03, which frequently reside on CEHs within the MHC.Autosomal SNPs (441,547 from 11,376 MS cases and 18,872 controls in the WTCCC dataset were phased. The most significant MS associated SNP haplotype was composed of 11 SNPs in the MHC Class II region surrounding the HLA-DRB1 gene. We also phased alleles at the HLA-A, HLA-C, HLA-B, HLA-DRB1, and HLA-DQB1 loci. This data was used to probe the relationship between CEHs and MS susceptibility.We phased a total of 59,884 extended haplotypes (HLA-A, HLA-C, HLA-B, HLA-DRB1, HLA-DQB1 and SNP haplotypes from 29,942 individuals. Of these, 10,078 unique extended haplotypes were identified. The 10 most common CEHs accounted for 22% (13,302 of the total. By contrast, the 8,446 least common extended haplotypes also accounted for approximately 20% (12,298 of the total. This extreme frequency-disparity among extended haplotypes necessarily complicates interpretation of reported disease-associations with specific HLA alleles. In particular, the HLA motif HLA-DRB1*15:01~HLA-DQB1*06:02 is strongly associated with MS risk. Nevertheless, although this motif is almost always found on the a1 SNP haplotype, it can rarely be found on others (e.g., a27 and a36, and, in these cases, it seems to have no apparent disease-association (OR = 0.7; CI = 0.3-1.3 and OR = 0.7; CI = 0.2-2.2, respectively. Furthermore, single copy carriers of the a1 SNP-haplotype without this HLA motif still have an increased disease risk (OR = 2.2; CI = 1.2-3.8. In addition, even among the

  13. Circulating growth hormone (GH)-binding protein complex: a major constituent of plasma GH in man

    International Nuclear Information System (INIS)

    Baumann, G.; Amburn, K.; Shaw, M.A.

    1988-01-01

    The recent discovery of a specific binding protein for human GH (hGH) in human plasma suggests that hGH circulates in part as a complex in association with the binding protein(s). However, the magnitude of the complexed fraction prevailing under physiological conditions is unknown because of 1) dissociation of the complex during analysis and 2) potential differences in the binding characteristics of radiolabeled and native hGH. We conducted experiments designed to minimize dissociation during analysis (gel filtration in prelabeled columns, frontal analysis, and batch molecular sieving) with both native and radioiodinated hGH. All three methods yielded similar estimates for the complexed fraction. In normal plasma the bound fraction for 22 K hGH averaged 50.1% (range, 39-59%), that for 20 K hGH averaged 28.5% (range, 26-31%). Above a hGH level of about 20 ng/ml the bound fraction declines in concentration-dependent manner due to saturation of the binding protein. We conclude that a substantial part of circulating hGH is complexed with carrier proteins. This concept has important implications for the metabolism, distribution, and biological activity of hGH

  14. Modulation of the major histocompatibility complex class II-associated peptide repertoire by human histocompatibility leukocyte antigen (HLA)-DO

    NARCIS (Netherlands)

    van Ham, M.; van Lith, M.; Lillemeier, B.; Tjin, E.; Grüneberg, U.; Rahman, D.; Pastoors, L.; van Meijgaarden, K.; Roucard, C.; Trowsdale, J.; Ottenhoff, T.; Pappin, D.; Neefjes, J.

    2000-01-01

    Antigen presentation by major histocompatibility complex class II molecules is essential for antibody production and T cell activation. For most class II alleles, peptide binding depends on the catalytic action of human histocompatibility leukocyte antigens (HLA)-DM. HLA-DO is selectively expressed

  15. Overall major histocompatibility complex class I expression is not downregulated in cervix cancer, as detected by immunoelectron microscopy

    NARCIS (Netherlands)

    van Eijkeren, MA; Roovers, JP; Oorschot, [No Value; Geuze, HJ

    2004-01-01

    Downregulation of major histocompatibility complex (MHC) class I molecules in cervix cancer has been proposed as a mechanism for cancer cells to escape immunodetection. By means of light microscopic immunohistochemistry, it has been shown that in 20-70% of cervix cancers MHC class I is

  16. The combination of major histocompatibility complex (MHC) and non-MHC genes influences murine lymphocytic choriomeningitis virus pathogenesis

    DEFF Research Database (Denmark)

    Eyler, Y L; Pfau, C J; Broomhall, K S

    1989-01-01

    with the recessive disease phenotype. In all cases, susceptibility was dominant. In backcross progeny obtained from matings of parental strains differing in both major histocompatibility complex (MHC) and non-MHC (SWR; C3H), 90% of the challenged mice died, indicating that at least three loci controlled...

  17. A quantitative assay to measure the interaction between immunogenic peptides and purified class I major histocompatibility complex molecules

    DEFF Research Database (Denmark)

    Olsen, A C; Pedersen, L O; Hansen, A S

    1994-01-01

    A direct and sensitive biochemical assay to measure the interaction in solution between peptides and affinity-purified major histocompatibility complex (MHC) class I molecules has been generated. Specific binding reflecting the known class I restriction of cytotoxic T cell responses was obtained...

  18. Proteolysis of the heavy chain of major histocompatibility complex class I antigens by complement component C1s

    DEFF Research Database (Denmark)

    Eriksson, H; Nissen, Mogens Holst

    1990-01-01

    The major histocompatibility complex (MHC) class I antigens contain a light chain, beta 2-microglobulin, non-covalently associated to the transmembrane heavy alpha-chain carrying the allotypic determinants. Since the C1q complement component is known to associate with beta 2-microglobulin, and we...

  19. Reproducible association with type 1 diabetes in the extended class I region of the major histocompatibility complex

    DEFF Research Database (Denmark)

    Viken, M.K.; Blomhoff, A.; Olsson, M.

    2009-01-01

    The high-risk human leukocyte antigen (HLA)-DRB1, DQA1 and DQB1 alleles cannot explain the entire type 1 diabetes (T1D) association observed within the extended major histocompatibility complex. We have earlier identified an association with D6S2223, located 2.3 Mb telomeric of HLA-A, on the DRB1...

  20. Major histocompatibility complex and host background genes in chickens influence resistance to high pathogenicity avian influenza virus

    Science.gov (United States)

    The chicken’s major histocompatibility complex (MHC) haplotype has a profound influence on the resistance or susceptibility to certain pathogens such as B21 MHC haplotype confers resistance to Marek’s disease (MD). However, non-MHC genes are also important in disease resistance. For example, both li...

  1. Oriented coupling of major histocompatibility complex (MHC) to sensor surfaces using light assisted immobilisation technology

    DEFF Research Database (Denmark)

    Snabe, Torben; Røder, Gustav Andreas; Neves-Petersen, Maria Teresa

    2005-01-01

    histocompatibility complex (MHC class I) to a sensor surface is presented. The coupling was performed using light assisted immobilisation--a novel immobilisation technology which allows specific opening of particular disulphide bridges in proteins which then is used for covalent bonding to thiol-derivatised surfaces...... via a new disulphide bond. Light assisted immobilisation specifically targets the disulphide bridge in the MHC-I molecule alpha(3)-domain which ensures oriented linking of the complex with the peptide binding site exposed away from the sensor surface. Structural analysis reveals that a similar...

  2. Major conformations of the ligand skeleton of a tetranuclear dysprosium (3) tartrate complex

    International Nuclear Information System (INIS)

    Chevela, V.V.; Semenov, V.Eh.; Bezryadin, S.G.; Savitskaya, T.V.; Kolesar, I.R.; Matveev, S.N.; Shamov, G.A.

    1999-01-01

    By the molecular mechanics method (MIND program, stoichiometry was studied and basic conformations of ligand frame of dysprosium (3) tetranuclear complex bis-(d-tartrato) bis-(l-tartrato)tetradysprosiate (3) - anion Dy 4 (d-L) 2 (l-L) 2 4- (1) (d-H 4 L = d-tartaric acid, l-H 4 L = l - tartaric acid) were revealed. It is shown that theoretically calculated mP τ constants for so-called compact conformations of 1, where tartratoligands are in gosh conformation, agree with experimentally obtained constant of paramagnetic birefringence (mP e ) of complex 1 [ru

  3. Posttraumatic abdominal aortic dissection

    International Nuclear Information System (INIS)

    Hahmann, M.; Richter, G.M.; Kauffmann, G.W.; Schuhmacher, H.; Allenberg, J.R.

    2001-01-01

    Dissections due to deceleration trauma are rarely limited to the infradiaphragmal aorta (only 2-3%) and are usually lethal. Here we report the unusual course of an abdominal aortic dissection with aneurysmatic enlargement of the false lumen. Based on diagnostic imaging, a therapeutic stent application was planed in order to close the entry and to prevent rupture. During the intervention sondation of the false lumen revealed that the left renal artery had a reentry. Due to the complexity of the entry - reentry situation of the left renal artery the intervention was not possible, and the patient had to undergo vascular surgery. (orig.) [de

  4. SCP1, a major protein component of synaptonemal complexes of the rat

    NARCIS (Netherlands)

    Meuwissen, R.L.J.

    1997-01-01

    Synaptonemal complexes (SCs) are structures that are formed between homologous chromosomes during meiotic prophase. SCs consist of two proteinaceous axes, one along each homologue, that are connected along their length by numerous transverse filaments (TFs). The assembly and disassembly of

  5. SCP2, a major protein component of the axial elements of synaptonemal complexes

    NARCIS (Netherlands)

    Schalk, J.A.C.

    1999-01-01

    Synaptonemal complexes (SCs) are ladderlike protein structures, which are formed between homologous chromosomes during the prophase of the first meiotic division. SCs consist of two axial elements, one along each chromosome, and transverse filaments (TFs), which connect the axial elements.

  6. Assembly of the Major Light-Harvesting Complex II in Lipid Nanodiscs.

    NARCIS (Netherlands)

    Pandit, A.; Shirzad-Wasei, N.; Wlodarczyk, L.M.; Roon, H. van; Boekema, E.J.; Dekker, J.P.; Grip, W.J. de

    2011-01-01

    Self-aggregation of isolated plant light-harvesting complexes (LHCs) upon detergent extraction is associated with fluorescence quenching and is used as an in vitro model to study the photophysical processes of nonphotochemical quenching (NPQ). In the NPQ state, in vivo induced under excess solar

  7. Assembly of the Major Light-Harvesting Complex II in Lipid Nanodiscs

    NARCIS (Netherlands)

    Pandit, Anjali; Shirzad-Wasei, Nazhat; Wlodarczyk, Lucyna M.; van Roon, Henny; Boekema, Egbert J.; Dekker, Jan P.; de Grip, Willem J.; Brown, Leonid S.

    2011-01-01

    Self-aggregation of isolated plant light-harvesting complexes (LHCs) upon detergent extraction is associated with fluorescence quenching and is used as an in vitro model to study the photophysical processes of nonphotochemical quenching (NPQ). In the NPQ state, in vivo induced under excess solar

  8. Lateral gene transfer of an ABC transporter complex between major constituents of the human gut microbiome

    Directory of Open Access Journals (Sweden)

    Meehan Conor J

    2012-11-01

    Full Text Available Abstract Background Several links have been established between the human gut microbiome and conditions such as obesity and inflammatory bowel syndrome. This highlights the importance of understanding what properties of the gut microbiome can affect the health of the human host. Studies have been undertaken to determine the species composition of this microbiome and infer functional profiles associated with such host properties. However, lateral gene transfer (LGT between community members may result in misleading taxonomic attributions for the recipient organisms, thus making species-function links difficult to establish. Results We identified a peptides/nickel transport complex whose components differed in abundance based upon levels of host obesity, and assigned the encoded proteins to members of the microbial community. Each protein was assigned to several distinct taxonomic groups, with moderate levels of agreement observed among different proteins in the complex. Phylogenetic trees of these proteins produced clusters that differed greatly from taxonomic attributions and indicated that habitat-directed LGT of this complex is likely to have occurred, though not always between the same partners. Conclusions These findings demonstrate that certain membrane transport systems may be an important factor within an obese-associated gut microbiome and that such complexes may be acquired several times by different strains of the same species. Additionally, an example of individual proteins from different organisms being transferred into one operon was observed, potentially demonstrating a functional complex despite the donors of the subunits being taxonomically disparate. Our results also highlight the potential impact of habitat-directed LGT on the resident microbiota.

  9. Connective tissue alteration in abdominal wall hernia

    DEFF Research Database (Denmark)

    Henriksen, N A; Yadete, D H; Sørensen, Lars Tue

    2011-01-01

    The aetiology and pathogenesis of abdominal wall hernia formation is complex. Optimal treatment of hernias depends on a full understanding of the pathophysiological mechanisms involved in their formation. The aim of this study was to review the literature on specific collagen alterations...... in abdominal wall hernia formation....

  10. Chlorophyll b can serve as the major pigment in functional photosystem II complexes of cyanobacteria

    OpenAIRE

    Xu, Hong; Vavilin, Dmitrii; Vermaas, Wim

    2001-01-01

    An Arabidopsis thaliana chlorophyll(ide) a oxygenase gene (cao), which is responsible for chlorophyll b synthesis from chlorophyll a, was introduced and expressed in a photosystem I-less strain of the cyanobacterium Synechocystis sp. PCC 6803. In this strain, most chlorophyll is associated with the photosystem II complex. In line with observations by Satoh et al. [Satoh, S., Ikeuchi, M., Mimuro, M. & Tanaka, A. (2001) J. Biol. Chem. 276, 4293–4297], chlorophyll b was made but accounted for le...

  11. Omphalocele, exstrophy of cloaca, imperforate anus, and spinal defect complex, multiple major reconstructive surgeries needed.

    Science.gov (United States)

    Neel, Nada; Tarabay, Mohmoud Salem

    2018-01-01

    OEIS complex is a rare combination of serious birth defects including omphalocele, exstrophy of cloaca, imperforate anus, and spinal defects. The aim of managements has shifted from merely providing survival to improve patient outcomes and quality of life with higher level of physical and social independence. Multiple complicated reconstructive surgeries always needed for achieving the goals of treatment. In this case report, we aimed to present our surgical approach for this rare abnormality to achieve functionally and socially acceptable outcome.

  12. Omphalocele, exstrophy of cloaca, imperforate anus, and spinal defect complex, multiple major reconstructive surgeries needed

    Directory of Open Access Journals (Sweden)

    Nada Neel

    2018-01-01

    Full Text Available OEIS complex is a rare combination of serious birth defects including omphalocele, exstrophy of cloaca, imperforate anus, and spinal defects. The aim of managements has shifted from merely providing survival to improve patient outcomes and quality of life with higher level of physical and social independence. Multiple complicated reconstructive surgeries always needed for achieving the goals of treatment. In this case report, we aimed to present our surgical approach for this rare abnormality to achieve functionally and socially acceptable outcome.

  13. Elg1, the major subunit of an alternative RFC complex, interacts with SUMO-processing proteins.

    Science.gov (United States)

    Parnas, Oren; Amishay, Rona; Liefshitz, Batia; Zipin-Roitman, Adi; Kupiec, Martin

    2011-09-01

    PCNA is a homotrimeric ring with important roles in DNA replication and repair. PCNA is loaded and unloaded by the RFC complex, which is composed of five subunits (Rfc1-5). Three additional complexes that share with RFC the small subunits (Rfc2-5) and contain alternative large subunits were found in yeast and other eukaryotes. We have recently reported that one of these, the Elg1-RFC complex, interacts with SUMOylated PCNA and may play a role in its unloading during DNA repair. Here we report that a yeast-two-hybrid screen with the N terminus of Elg1(which interacts with SUMOylated PCNA) uncovered interactions with proteins that belong to the SUMO pathway, including Slx5 and Slx8, which form an E3 ubiquitin ligase that ubiquitinates SUMOylated proteins. Mutations in SLX5 result in a genomic instability phenotype similar to that of elg1 mutants. The physical interaction between the N terminus of Elg1 and Slx5 is mediated by poly-SUMO chains but not by PCNA modifications, and requires Siz2, but not Siz1, activity. Thus our results highlight the many important roles played by Elg1, some of which are PCNA-dependent and some PCNA-independent. © 2011 Landes Bioscience

  14. T cell responses affected by aminopeptidase N (CD13)-mediated trimming of major histocompatibility complex class II-bound peptides

    DEFF Research Database (Denmark)

    Larsen, S L; Pedersen, L O; Buus, S

    1996-01-01

    the exopeptidase Aminopeptidase N (APN, CD13) as one of the enzymes involved in the observed cell-surface antigen processing. The NH2-terminal end of the longer peptide could, even while bound to major histocompatibility complex (MHC) class II molecules, be digested by APN with dramatic consequences for T cell......Endocytosed protein antigens are believed to be fragmented in what appears to be a balance between proteolysis and MHC-mediated epitope protection, and the resulting peptide-MHC complexes are transported to the surface of the antigen-presenting cells (APC) and presented to T cells. The events...

  15. Human cytomegalovirus-infected cells have unstable assembly of major histocompatibility complex class I complexes and are resistant to lysis by cytotoxic T lymphocytes.

    OpenAIRE

    Warren, A P; Ducroq, D H; Lehner, P J; Borysiewicz, L K

    1994-01-01

    Viruses which cause persistence in the naturally infected host are predicted to have evolved immune evasion mechanisms. Human cytomegalovirus (HCMV) causes significant morbidity and mortality in immunocompromised patients yet persists without clinical manifestations in seropositive individuals who have normal immune function. We report that HCMV infection in vitro impairs major histocompatibility complex class I (MHC-I) assembly accompanied by resistance to killing by cytotoxic CD8+ T lymphoc...

  16. Functional abdominal pain disorders in children

    NARCIS (Netherlands)

    Rajindrajith, Shaman; Zeevenhooven, Judith; Devanarayana, Niranga Manjuri; Perera, Bonaventure Jayasiri Crispus; Benninga, Marc A.

    2018-01-01

    Chronic abdominal pain is a common problem in pediatric practice. The majority of cases fulfill the Rome IV criteria for functional abdominal pain disorders (FAPDs). At times, these disorders may lead to rather serious repercussions. Area covered: We have attempted to cover current knowledge on

  17. Molecular Architecture of the Major Membrane Ring Component of the Nuclear Pore Complex.

    Science.gov (United States)

    Upla, Paula; Kim, Seung Joong; Sampathkumar, Parthasarathy; Dutta, Kaushik; Cahill, Sean M; Chemmama, Ilan E; Williams, Rosemary; Bonanno, Jeffrey B; Rice, William J; Stokes, David L; Cowburn, David; Almo, Steven C; Sali, Andrej; Rout, Michael P; Fernandez-Martinez, Javier

    2017-03-07

    The membrane ring that equatorially circumscribes the nuclear pore complex (NPC) in the perinuclear lumen of the nuclear envelope is composed largely of Pom152 in yeast and its ortholog Nup210 (or Gp210) in vertebrates. Here, we have used a combination of negative-stain electron microscopy, nuclear magnetic resonance, and small-angle X-ray scattering methods to determine an integrative structure of the ∼120 kDa luminal domain of Pom152. Our structural analysis reveals that the luminal domain is formed by a flexible string-of-pearls arrangement of nine repetitive cadherin-like Ig-like domains, indicating an evolutionary connection between NPCs and the cell adhesion machinery. The 16 copies of Pom152 known to be present in the yeast NPC are long enough to form the observed membrane ring, suggesting how interactions between Pom152 molecules help establish and maintain the NPC architecture. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. High-resolution metagenomics targets major functional types in complex microbial communities

    Energy Technology Data Exchange (ETDEWEB)

    Kalyuzhnaya, Marina G.; Lapidus, Alla; Ivanova, Natalia; Copeland, Alex C.; McHardy, Alice C.; Szeto, Ernest; Salamov, Asaf; Grigoriev, Igor V.; Suciu, Dominic; Levine, Samuel R.; Markowitz, Victor M.; Rigoutsos, Isidore; Tringe, Susannah G.; Bruce, David C.; Richardson, Paul M.; Lidstrom, Mary E.; Chistoserdova, Ludmila

    2009-08-01

    Most microbes in the biosphere remain uncultured and unknown. Whole genome shotgun (WGS) sequencing of environmental DNA (metagenomics) allows glimpses into genetic and metabolic potentials of natural microbial communities. However, in communities of high complexity metagenomics fail to link specific microbes to specific ecological functions. To overcome this limitation, we selectively targeted populations involved in oxidizing single-carbon (C{sub 1}) compounds in Lake Washington (Seattle, USA) by labeling their DNA via stable isotope probing (SIP), followed by WGS sequencing. Metagenome analysis demonstrated specific sequence enrichments in response to different C{sub 1} substrates, highlighting ecological roles of individual phylotypes. We further demonstrated the utility of our approach by extracting a nearly complete genome of a novel methylotroph Methylotenera mobilis, reconstructing its metabolism and conducting genome-wide analyses. This approach allowing high-resolution genomic analysis of ecologically relevant species has the potential to be applied to a wide variety of ecosystems.

  19. Evaluation of two approaches to genotyping major histocompatibility complex class I in a passerine—CE-SSCP and 454 pyrosequencing

    Czech Academy of Sciences Publication Activity Database

    Promerová, Marta; Babik, W.; Bryja, Josef; Albrecht, Tomáš; Stuglik, M.; Radwan, J.

    2012-01-01

    Roč. 12, č. 2 (2012), s. 285-292 ISSN 1755-098X R&D Projects: GA AV ČR IAA600930608; GA ČR GA206/06/0851; GA ČR GAP505/10/1871 Institutional research plan: CEZ:AV0Z60930519 Keywords : avian * Carpodacus erythrinus * major histocompatibility complex * next-generation sequencing * scarlet rosefinch Subject RIV: EG - Zoology Impact factor: 7.432, year: 2012

  20. Major Histocompatibility Complex I and II Expression and Lymphocytic Subtypes in Muscle of Horses with Immune?Mediated Myositis

    OpenAIRE

    Durward?Akhurst, S.A.; Finno, C.J.; Barnes, N.; Shivers, J.; Guo, L.T.; Shelton, G.D.; Valberg, S.J.

    2016-01-01

    Background Major histocompatibility complex (MHC) I and II expression is not normally detected on sarcolemma, but is detected with lymphocytic infiltrates in immune?mediated myositis (IMM) of humans and dogs and in dysferlin?deficient muscular dystrophy. Hypothesis/Objectives To determine if sarcolemmal MHC is expressed in active IMM in horses, if MHC expression is associated with lymphocytic subtype, and if dysferlin is expressed in IMM. Animals Twenty?one IMM horses of Quarter Horse?related...

  1. Downregulation of Major Histocompatibility Complex Class I Molecules by Kaposi's Sarcoma-Associated Herpesvirus K3 and K5 Proteins

    OpenAIRE

    Ishido, Satoshi; Wang, Chunyang; Lee, Bok-Soo; Cohen, George B.; Jung, J. U.

    2000-01-01

    The T-cell-mediated immune response plays a central role in the defense against intracellular pathogens. To avoid this immune response, viruses have evolved elaborate mechanisms that target and modulate many different aspects of the host's immune system. A target common to many of these viruses is the major histocompatibility complex (MHC) class I molecules. Kaposi's sarcoma-associated herpesvirus (KSHV) encodes K3 and K5 zinc finger membrane proteins which remove MHC class I molecules from t...

  2. Recent advances in Major Histocompatibility Complex (MHC) class I antigen presentation: Plastic MHC molecules and TAPBPR-mediated quality control

    OpenAIRE

    Van Hateren, Andrew; Elliott, Timothy; Bailey, Alistair

    2017-01-01

    We have known since the late 1980s that the function of classical major histocompatibility complex (MHC) class I molecules is to bind peptides and display them at the cell surface to cytotoxic T cells. Recognition by these sentinels of the immune system can lead to the destruction of the presenting cell, thus protecting the host from pathogens and cancer. Classical MHC class I molecules (MHC I hereafter) are co-dominantly expressed, polygenic, and exceptionally polymorphic and have significan...

  3. Thoracic epidural anaesthesia for major abdominal surgeries ...

    African Journals Online (AJOL)

    The pulse rate, blood pressure and oxygen saturation were monitored throughout the procedure and recorded. Data were obtained from the ... In a previous study, Consani et al.3 documented the feasibility of thoracic epidural ... thoracostomy and mastectomy in high-risk patients.2,6 Since TEA places less demand on drugs, ...

  4. Efficient assembly of recombinant major histocompatibility complex class I molecules with preformed disulfide bonds

    DEFF Research Database (Denmark)

    Ostergaard Pedersen, L; Nissen, Mogens Holst; Hansen, N J

    2001-01-01

    The expression of major histocompatibility class I (MHC-I) crucially depends upon the binding of appropriate peptides. MHC-I from natural sources are therefore always preoccupied with peptides complicating their purification and analysis. Here, we present an efficient solution to this problem....... Recombinant MHC-I heavy chains were produced in Escherichia coli and subsequently purified under denaturing conditions. In contrast to common practice, the molecules were not reduced during the purification. The oxidized MHC-I heavy chain isoforms were highly active with respect to peptide binding....... This suggests that de novo folding of denatured MHC-I molecules proceed efficiently if directed by preformed disulfide bond(s). Importantly, these molecules express serological epitopes and stain specific T cells; and they bind peptides specifically. Several denatured MHC-I heavy chains were analyzed and shown...

  5. Complex Forms of Soil Organic Phosphorus-A Major Component of Soil Phosphorus.

    Science.gov (United States)

    McLaren, Timothy I; Smernik, Ronald J; McLaughlin, Mike J; McBeath, Therese M; Kirby, Jason K; Simpson, Richard J; Guppy, Christopher N; Doolette, Ashlea L; Richardson, Alan E

    2015-11-17

    Phosphorus (P) is an essential element for life, an innate constituent of soil organic matter, and a major anthropogenic input to terrestrial ecosystems. The supply of P to living organisms is strongly dependent on the dynamics of soil organic P. However, fluxes of P through soil organic matter remain unclear because only a minority (typically soil organic P has been identified as recognizable biomolecules of low molecular weight (e.g., inositol hexakisphosphates). Here, we use (31)P nuclear magnetic resonance spectroscopy to determine the speciation of organic P in soil extracts fractionated into two molecular weight ranges. Speciation of organic P in the high molecular weight fraction (>10 kDa) was markedly different to that of the low molecular weight fraction (soil organic P across the five diverse soils. These soil phosphomonoesters will need to be integrated within current models of the inorganic-organic P cycle of soil-plant terrestrial ecosystems.

  6. A complex RARE is required for the majority of Nedd9 embryonic expression.

    Science.gov (United States)

    Knutson, Danielle C; Clagett-Dame, Margaret

    2015-02-01

    Neural precursor cell expressed, developmentally down-regulated 9 (Nedd9, Casl, Hef1, p105cas, Ef1) is a scaffolding protein that assembles complexes involved in regulating cell adhesion, migration, division, and survival. Nedd9 is found very early in the developing embryonic nervous system. A highly conserved complex retinoic acid response element (RARE) is located 485 base pairs (bp) upstream of exon 2B in the promoter of the Nedd9 gene. Mice transgenic for a 5.2 kilobase (kb) region of the 2B Nedd9 promoter containing the RARE upstream of a lacZ reporter gene [Nedd9(RARE)-lacZ] show a large subset of the normal endogenous Nedd9 expression including that in the caudal hindbrain neuroepithelium, spinal cord, dorsal root ganglia (drg) and migrating neural crest (ncc). However, the transgenic mice do not recapitulate the native Nedd9 expression pattern in presumptive rhombomeres (pr) 3 and 5 of the early hindbrain, the base of the neuroepithelium in the midbrain, nor the forebrain telencephalon. Thus, the 5.2 kb region containing the intact RARE drives a large subset of Nedd9 expression, with additional sequences outside of this region needed to define the full complement of expression. When the 5.2 kb construct is modified (eight point mutations) to eliminate responsiveness of the RARE to all-trans retinoic acid (atRA) [Nedd9(mutRARE)-lacZ], virtually all β-galactosidase (β-gal, lacZ) expression is lost. Exposure of Nedd9(RARE)-lacZ transgenic embryos to excess atRA at embryonic day 8.0 (E8.0) leads to rostral ectopic transgene expression within 6 h whereas the Nedd9(mutRARE)-lacZ mutant does not show this effect. Thus the RARE upstream of the Nedd9 2B promoter is necessary for much of the endogenous gene expression during early development as well as ectopic expression in response to atRA.

  7. The outermost N-terminal region of tapasin facilitates folding of major histocompatibility complex class I

    DEFF Research Database (Denmark)

    Røder, Gustav Andreas; Geironson, Linda; Darabi, Anna

    2009-01-01

    ). Using a biochemical peptide-MHC-I-binding assay, recombinant Tpn(1-87) was found to specifically facilitate peptide-dependent folding of HLA-A*0201. Furthermore, we used Tpn(1-87) to generate a monoclonal antibody, alphaTpn(1-87)/80, specific for natural human Tpn and capable of cellular staining of ER......Tapasin (Tpn) is an ER chaperone that is uniquely dedicated to MHC-I biosynthesis. It binds MHC-I molecules, integrates them into peptide-loading complexes, and exerts quality control of the bound peptides; only when an "optimal peptide" is bound will the MHC-I be released and exported to the cell...... surface for presentation to T cells. The exact mechanisms of Tpn quality control and the criteria for being an optimal peptide are still unknown. Here, we have generated a recombinant fragment of human Tpn, Tpn(1-87) (representing the 87 N-terminal and ER-luminal amino acids of the mature Tpn protein...

  8. Using intein catalysis to probe the origin of major histocompatibility complex class I-presented peptides

    Science.gov (United States)

    Farfán-Arribas, Diego J.; Stern, Lawrence J.; Rock, Kenneth L.

    2012-01-01

    All vertebrate nucleated cells generate peptides from their expressed gene products and then display them at the cell surface bound to MHC class I molecules. This allows CD8+ T cells to detect and eliminate abnormal cells that are synthesizing foreign proteins, e.g., from viruses or mutations. To permit the immune system to more uniformly monitor a cell's proteins, regardless of their half-life or location, it has been thought that the products of rapid degradation of the mistakes of protein synthesis (defective ribosomal products, DRiPs) preferentially contribute to the class I-presented peptides. However, using intein catalysis to generate peptide sequences exclusively by posttranslational splicing of mature proteins, we show here that presented peptides can be generated from fully folded and functional proteins. Remarkably, the presentation of peptides from two model mature proteins is just as efficient as from newly synthesized proteins subject to errors in translation or folding. These results indicate that for the constructs we have analyzed, DRiPs are not a more efficient source of class I peptides for antigen presentation than the turnover of mature functional proteins. Accordingly, our data suggest that one of the major ways the immune system evaluates the health of cells is by monitoring the breakdown products of the proteome. PMID:23027972

  9. Complexity of major UK companies between 2006 and 2010: Hierarchical structure method approach

    Science.gov (United States)

    Ulusoy, Tolga; Keskin, Mustafa; Shirvani, Ayoub; Deviren, Bayram; Kantar, Ersin; Çaǧrı Dönmez, Cem

    2012-11-01

    This study reports on topology of the top 40 UK companies that have been analysed for predictive verification of markets for the period 2006-2010, applying the concept of minimal spanning tree and hierarchical tree (HT) analysis. Construction of the minimal spanning tree (MST) and the hierarchical tree (HT) is confined to a brief description of the methodology and a definition of the correlation function between a pair of companies based on the London Stock Exchange (LSE) index in order to quantify synchronization between the companies. A derivation of hierarchical organization and the construction of minimal-spanning and hierarchical trees for the 2006-2008 and 2008-2010 periods have been used and the results validate the predictive verification of applied semantics. The trees are known as useful tools to perceive and detect the global structure, taxonomy and hierarchy in financial data. From these trees, two different clusters of companies in 2006 were detected. They also show three clusters in 2008 and two between 2008 and 2010, according to their proximity. The clusters match each other as regards their common production activities or their strong interrelationship. The key companies are generally given by major economic activities as expected. This work gives a comparative approach between MST and HT methods from statistical physics and information theory with analysis of financial markets that may give new valuable and useful information of the financial market dynamics.

  10. Lipopeptides: a novel antigen repertoire presented by major histocompatibility complex class I molecules.

    Science.gov (United States)

    Morita, Daisuke; Sugita, Masahiko

    2016-10-01

    Post-translationally modified peptides, such as those containing either phosphorylated or O-glycosylated serine/threonine residues, may be presented to cytotoxic T lymphocytes (CTLs) by MHC class I molecules. Most of these modified peptides are captured in the MHC class I groove in a similar manner to that for unmodified peptides. N-Myristoylated 5-mer lipopeptides have recently been identified as a novel chemical class of MHC class I-presented antigens. The rhesus classical MHC class I allele, Mamu-B*098, was found to be capable of binding N-myristoylated lipopeptides and presenting them to CTLs. A high-resolution X-ray crystallographic analysis of the Mamu-B*098:lipopeptide complex revealed that the myristic group as well as conserved C-terminal serine residue of the lipopeptide ligand functioned as anchors, whereas the short stretch of three amino acid residues located in the middle of the lipopeptides was only exposed externally with the potential to interact directly with specific T-cell receptors. Therefore, the modes of lipopeptide-ligand interactions with MHC class I and with T-cell receptors are novel and fundamentally distinct from that for MHC class I-presented peptides. Another lipopeptide-presenting MHC class I allele has now been identified, leading us to the prediction that MHC class I molecules may be separated on a functional basis into two groups: one presenting long peptides and the other presenting short lipopeptides. Since the N-myristoylation of viral proteins is often linked to pathogenesis, CTLs capable of sensing N-myristoylation may serve to control pathogenic viruses, raising the possibility for the development of a new type of lipopeptide vaccine. © 2016 John Wiley & Sons Ltd.

  11. Characterization and 454 pyrosequencing of Major Histocompatibility Complex class I genes in the great tit reveal complexity in a passerine system

    Directory of Open Access Journals (Sweden)

    Sepil Irem

    2012-05-01

    Full Text Available Abstract Background The critical role of Major Histocompatibility Complex (Mhc genes in disease resistance and their highly polymorphic nature make them exceptional candidates for studies investigating genetic effects on survival, mate choice and conservation. Species that harbor many Mhc loci and high allelic diversity are particularly intriguing as they are potentially under strong selection and studies of such species provide valuable information as to the mechanisms maintaining Mhc diversity. However comprehensive genotyping of complex multilocus systems has been a major challenge to date with the result that little is known about the consequences of this complexity in terms of fitness effects and disease resistance. Results In this study, we genotyped the Mhc class I exon 3 of the great tit (Parus major from two nest-box breeding populations near Oxford, UK that have been monitored for decades. Characterization of Mhc class I exon 3 was adopted and bidirectional sequencing was carried using the 454 sequencing platform. Full analysis of sequences through a stepwise variant validation procedure allowed reliable typing of more than 800 great tits based on 214,357 reads; from duplicates we estimated the repeatability of typing as 0.94. A total of 862 alleles were detected, and the presence of at least 16 functional loci was shown - the highest number characterized in a wild bird species. Finally, the functional alleles were grouped into 17 supertypes based on their antigen binding affinities. Conclusions We found extreme complexity at the Mhc class I of the great tit both in terms of allelic diversity and gene number. The presence of many functional loci was shown, together with a pseudogene family and putatively non-functional alleles; there was clear evidence that functional alleles were under strong balancing selection. This study is the first step towards an in-depth analysis of this gene complex in this species, which will help

  12. The complexity of selection at the major primate β-defensin locus

    Directory of Open Access Journals (Sweden)

    Eastwood Hayden

    2005-05-01

    Full Text Available Abstract Background We have examined the evolution of the genes at the major human β-defensin locus and the orthologous loci in a range of other primates and mouse. For the first time these data allow us to examine selective episodes in the more recent evolutionary history of this locus as well as the ancient past. We have used a combination of maximum likelihood based tests and a maximum parsimony based sliding window approach to give a detailed view of the varying modes of selection operating at this locus. Results We provide evidence for strong positive selection soon after the duplication of these genes within an ancestral mammalian genome. Consequently variable selective pressures have acted on β-defensin genes in different evolutionary lineages, with episodes both of negative, and more rarely positive selection, during the divergence of primates. Positive selection appears to have been more common in the rodent lineage, accompanying the birth of novel, rodent-specific β-defensin genes. These observations allow a fuller understanding of the evolution of mammalian innate immunity. In both the rodent and primate lineages, sites in the second exon have been subject to positive selection and by implication are important in functional diversity. A small number of sites in the mature human peptides were found to have undergone repeated episodes of selection in different primate lineages. Particular sites were consistently implicated by multiple methods at positions throughout the mature peptides. These sites are clustered at positions predicted to be important for the specificity of the antimicrobial or chemoattractant properties of β-defensins. Surprisingly, sites within the prepropeptide region were also implicated as being subject to significant positive selection, suggesting previously unappreciated functional significance for this region. Conclusions Identification of these putatively functional sites has important implications for our

  13. Major Histocompatibility Complex class IIb polymorphism influences gut microbiota composition and diversity.

    Science.gov (United States)

    Bolnick, Daniel I; Snowberg, Lisa K; Caporaso, J Gregory; Lauber, Chris; Knight, Rob; Stutz, William E

    2014-10-01

    Animals harbour diverse communities of symbiotic bacteria, which differ dramatically among host individuals. This heterogeneity poses an immunological challenge: distinguishing between mutualistic and pathogenic members of diverse and host-specific microbial communities. We propose that Major Histocompatibility class II (MHC) genotypes contribute to recognition and regulation of gut microbes, and thus, MHC polymorphism contributes to microbial variation among hosts. Here, we show that MHC IIb polymorphism is associated with among-individual variation in gut microbiota within a single wild vertebrate population of a small fish, the threespine stickleback. We sampled stickleback from Cedar Lake, on Vancouver Island, and used next-generation sequencing to genotype the sticklebacks' gut microbiota (16S sequencing) and their MHC class IIb exon 2 sequences. The presence of certain MHC motifs was associated with altered relative abundance (increase or decrease) of some microbial Families. The effect sizes are modest and entail a minority of microbial taxa, but these results represent the first indication that MHC genotype may affect gut microbiota composition in natural populations (MHC-microbe associations have also been found in a few studies of lab mice). Surprisingly, these MHC effects were frequently sex-dependent. Finally, hosts with more diverse MHC motifs had less diverse gut microbiota. One implication is that MHC might influence the efficacy of therapeutic strategies to treat dysbiosis-associated disease, including the outcome of microbial transplants between healthy and diseased patients. We also speculate that macroparasite-driven selection on MHC has the potential to indirectly alter the host gut microbiota, and vice versa. © 2014 John Wiley & Sons Ltd.

  14. Natural selection of the major histocompatibility complex (Mhc) in Hawaiian honeycreepers (Drepanidinae)

    Science.gov (United States)

    Jarvi, S.I.; Tarr, C.L.; Mcintosh, C.E.; Atkinson, C.T.; Fleischer, R.C.

    2004-01-01

    The native Hawaiian honeycreepers represent a classic example of adaptive radiation and speciation, but currently face one the highest extinction rates in the world. Although multiple factors have likely influenced the fate of Hawaiian birds, the relatively recent introduction of avian malaria is thought to be a major factor limiting honeycreeper distribution and abundance. We have initiated genetic analyses of class II ?? chain Mhc genes in four species of honeycreepers using methods that eliminate the possibility of sequencing mosaic variants formed by cloning heteroduplexed polymerase chain reaction products. Phylogenetic analyses group the honeycreeper Mhc sequences into two distinct clusters. Variation within one cluster is high, with dN > d S and levels of diversity similar to other studies of Mhc (B system) genes in birds. The second cluster is nearly invariant and includes sequences from honeycreepers (Fringillidae), a sparrow (Emberizidae) and a blackbird (Emberizidae). This highly conserved cluster appears reminiscent of the independently segregating Rfp-Y system of genes defined in chickens. The notion that balancing selection operates at the Mhc in the honeycreepers is supported by transpecies polymorphism and strikingly high dN/dS ratios at codons putatively involved in peptide interaction. Mitochondrial DNA control region sequences were invariant in the i'iwi, but were highly variable in the 'amakihi. By contrast, levels of variability of class II ?? chain Mhc sequence codons that are hypothesized to be directly involved in peptide interactions appear comparable between i'iwi and 'amakihi. In the i'iwi, natural selection may have maintained variation within the Mhc, even in the face of what appears to a genetic bottleneck.

  15. Evaluating the complexity of online patient education materials about brain aneurysms published by major academic institutions.

    Science.gov (United States)

    Gupta, Raghav; Adeeb, Nimer; Griessenauer, Christoph J; Moore, Justin M; Patel, Apar S; Kim, Christopher; Thomas, Ajith J; Ogilvy, Christopher S

    2017-08-01

    OBJECTIVE Health care education resources are increasingly available on the Internet. A majority of people reference these resources at one point or another. A threshold literacy level is needed to comprehend the information presented within these materials. A key component of health literacy is the readability of educational resources. The National Institutes of Health (NIH) and the American Medical Association have recommended that patient education materials be written between a 4th- and a 6th-grade education level. The authors assessed the readability of online patient education materials about brain aneurysms that have been published by several academic institutions across the US. METHODS Online patient education materials about brain aneurysms were downloaded from the websites of 20 academic institutions. The materials were assessed via 8 readability scales using Readability Studio software (Oleander Software Solutions), and then were statistically analyzed. RESULTS None of the patient education materials were written at or below the NIH's recommended 6th-grade reading level. The average educational level required to comprehend the texts across all institutions, as assessed by 7 of the readability scales, was 12.4 ± 2.5 (mean ± SD). The Flesch Reading Ease Scale classified the materials as "difficult" to understand, correlating with a college-level education or higher. An ANOVA test found that there were no significant differences in readability among the materials from the institutions (p = 0.215). CONCLUSIONS Brain aneurysms affect 3.2% of adults 50 years or older across the world and can cause significant patient anxiety and uncertainty. Current patient education materials are not written at or below the NIH's recommended 4th- to 6th-grade education level.

  16. Nutritional risk in major abdominal surgery: NURIMAS Liver (DRKS00010923 – protocol of a prospective observational trial to evaluate the prognostic value of different nutritional scores in hepatic surgery

    Directory of Open Access Journals (Sweden)

    Pascal Probst

    Full Text Available Background: Malnutrition is commonly known as a risk factor in surgical procedures. The nutritional status seems particularly relevant to the clinical outcome of patients undergoing hepatic resection. Thus, identifying affected individuals and taking preventive therapeutic actions before surgery is an important task. However, there are only very few studies, that investigate which existing nutritional assessment score (NAS is suited best to predict the postoperative outcome in liver surgery. Objective: Nutritional Risk in Major Abdominal Surgery (NURIMAS Liver is a prospective observational trial that analyses the predictive value of 12 different NAS for postoperative morbidity and mortality after liver resection. Methods: After admission to the surgical department of the University Hospital in Heidelberg or the municipal hospital of Karlsruhe, all patients scheduled for elective liver resection will be screened for eligibility. Participants will fill in a questionnaire and undergo a physical examination in order to evaluate nutritional status according to Nutritional Risk Index, Nutritional Risk Screening Score, Subjective Global Assessment, Malnutrition Universal Screening Tool, Mini Nutritional Assessment, Short Nutritional Assessment Questionnaire, Imperial Nutritional Screening System, Imperial Nutritional Screening System II, Nutritional Risk Classification and the ESPEN malnutrition criteria. Postoperative morbidity and mortality will be tracked prospectively throughout the postoperative course. The association of malnutrition according to each score and occurrence of at least one major complication will be analysed using both chi-squared tests and a multivariable logistic regression analysis. Already established risk factors in liver surgery will be added as covariates. Discussion: NURIMAS Liver is a bicentric, prospective observational trial. The aim of this study is to investigate the predictive value of clinical nutritional assessment

  17. Abdominal wall hernia and pregnancy

    DEFF Research Database (Denmark)

    Jensen, K K; Henriksen, N A; Jorgensen, L N

    2015-01-01

    PURPOSE: There is no consensus as to the treatment strategy for abdominal wall hernias in fertile women. This study was undertaken to review the current literature on treatment of abdominal wall hernias in fertile women before or during pregnancy. METHODS: A literature search was undertaken in Pub......Med and Embase in combination with a cross-reference search of eligible papers. RESULTS: We included 31 papers of which 23 were case reports. In fertile women undergoing sutured or mesh repair, pain was described in a few patients during the last trimester of a subsequent pregnancy. Emergency surgery...... of incarcerated hernias in pregnant women, as well as combined hernia repair and cesarean section appears as safe procedures. No major complications were reported following hernia repair before or during pregnancy. The combined procedure of elective cesarean section and abdominal wall hernia repair was reported...

  18. The impact of the Major Trauma Network: will trauma units continue to treat complex foot and ankle injuries?

    Science.gov (United States)

    Hay-David, A G C; Clint, S A; Brown, R R

    2014-12-01

    April 1st 2012 saw the introduction of National Trauma Networks in England. The aim to optimise the management of major trauma. Patients with an ISS≥16 would be transferred to the regional Major Trauma Centre (level 1). Our premise was that trauma units (level 2) would no longer manage complex foot and ankle injuries thereby obviating the need for a foot and ankle specialist service. Retrospective analysis of the epidemiology of foot and ankle injuries, using the Gloucestershire trauma database, from a trauma unit with a population of 750,000. Rates of open fractures, complex foot and ankle injuries and requirement for stabilisation with external fixation were reviewed before and after the introduction of the regional Trauma Network. Secondly, using the Trauma Audit & Research Network (TARN) database, all foot and ankle injuries triaged to the regional Major Trauma Centre (MTC) were reviewed. Incidence of open foot and ankle injuries was 2.9 per 100,000 per year. There were 5.1% open injuries before the network and 3.2% after (p>0.05). Frequency of complex foot and ankle injuries was 4.2% before and 7.5% after the network commenced, showing no significant change. There was no statistically significant change in the numbers of patients with complex foot and ankle injuries treated by application of external fixators. Analysis of TARN data revealed that only 18% of patients with foot and ankle injuries taken to the MTC had an ISS≥16. The majority of these patients were identified as requiring plastic surgical intervention for open fractures (69%) or were polytrauma patients (43%). Only 4.5% of patients had isolated, closed foot and ankle injuries. We found that at the trauma unit there was no decrease in the numbers of complex foot and ankle injuries, open fractures, or the applications of external fixators, following the introduction of the Trauma Network. These patients will continue to attend trauma units as they usually have an ISScomplex foot and ankle

  19. Abdominal and Pelvic CT

    Medline Plus

    Full Text Available ... accurate. In emergency cases, it can reveal internal injuries and bleeding quickly enough to help save lives. ... kidney and bladder stones. abdominal aortic aneurysms (AAA), injuries to abdominal organs such as the spleen, liver, ...

  20. Abdominal and Pelvic CT

    Medline Plus

    Full Text Available ... pancreas, ovaries and bladder as well as lymphoma. kidney and bladder stones. abdominal aortic aneurysms (AAA), injuries to abdominal organs such as the spleen, liver, kidneys or other internal organs in cases of trauma. ...

  1. DNA methylation profiling of the human major histocompatibility complex: a pilot study for the human epigenome project.

    Directory of Open Access Journals (Sweden)

    Vardhman K Rakyan

    2004-12-01

    Full Text Available The Human Epigenome Project aims to identify, catalogue, and interpret genome-wide DNA methylation phenomena. Occurring naturally on cytosine bases at cytosine-guanine dinucleotides, DNA methylation is intimately involved in diverse biological processes and the aetiology of many diseases. Differentially methylated cytosines give rise to distinct profiles, thought to be specific for gene activity, tissue type, and disease state. The identification of such methylation variable positions will significantly improve our understanding of genome biology and our ability to diagnose disease. Here, we report the results of the pilot study for the Human Epigenome Project entailing the methylation analysis of the human major histocompatibility complex. This study involved the development of an integrated pipeline for high-throughput methylation analysis using bisulphite DNA sequencing, discovery of methylation variable positions, epigenotyping by matrix-assisted laser desorption/ionisation mass spectrometry, and development of an integrated public database available at http://www.epigenome.org. Our analysis of DNA methylation levels within the major histocompatibility complex, including regulatory exonic and intronic regions associated with 90 genes in multiple tissues and individuals, reveals a bimodal distribution of methylation profiles (i.e., the vast majority of the analysed regions were either hypo- or hypermethylated, tissue specificity, inter-individual variation, and correlation with independent gene expression data.

  2. DNA Methylation Profiling of the Human Major Histocompatibility Complex: A Pilot Study for the Human Epigenome Project

    Science.gov (United States)

    Rakyan, Vardhman K; Hildmann, Thomas; Novik, Karen L; Lewin, Jörn; Tost, Jörg; Cox, Antony V; Andrews, T. Dan; Howe, Kevin L; Otto, Thomas; Olek, Alexander; Fischer, Judith; Gut, Ivo G; Berlin, Kurt

    2004-01-01

    The Human Epigenome Project aims to identify, catalogue, and interpret genome-wide DNA methylation phenomena. Occurring naturally on cytosine bases at cytosine–guanine dinucleotides, DNA methylation is intimately involved in diverse biological processes and the aetiology of many diseases. Differentially methylated cytosines give rise to distinct profiles, thought to be specific for gene activity, tissue type, and disease state. The identification of such methylation variable positions will significantly improve our understanding of genome biology and our ability to diagnose disease. Here, we report the results of the pilot study for the Human Epigenome Project entailing the methylation analysis of the human major histocompatibility complex. This study involved the development of an integrated pipeline for high-throughput methylation analysis using bisulphite DNA sequencing, discovery of methylation variable positions, epigenotyping by matrix-assisted laser desorption/ionisation mass spectrometry, and development of an integrated public database available at http://www.epigenome.org. Our analysis of DNA methylation levels within the major histocompatibility complex, including regulatory exonic and intronic regions associated with 90 genes in multiple tissues and individuals, reveals a bimodal distribution of methylation profiles (i.e., the vast majority of the analysed regions were either hypo- or hypermethylated), tissue specificity, inter-individual variation, and correlation with independent gene expression data. PMID:15550986

  3. Structural Evidence for a Germline-Encoded T Cell Receptor - Major Histocompatibility Complex Interaction 'Codon'

    Energy Technology Data Exchange (ETDEWEB)

    Feng, D.; Bond, C.J.; Ely, L.K.; Maynard, J.; Garcia, K.C.

    2009-06-02

    All complexes of T cell receptors (TCRs) bound to peptide-major histocompatibility complex (pMHC) molecules assume a stereotyped binding 'polarity', despite wide variations in TCR-pMHC docking angles. However, existing TCR-pMHC crystal structures have failed to show broadly conserved pairwise interaction motifs. Here we determined the crystal structures of two TCRs encoded by the variable {beta}-chain 8.2 (V{sub {beta}}8.2), each bound to the MHC class II molecule I-A{sup u}, and did energetic mapping of V{sub {alpha}} and V{sub {beta}} contacts with I-A{sup u}. Together with two previously solved structures of V{sub {beta}}8.2-containing TCR-MHC complexes, we found four TCR-I-A complexes with structurally superimposable interactions between the V{sub {beta}} loops and the I-A {alpha}-helix. This examination of a narrow 'slice' of the TCR-MHC repertoire demonstrates what is probably one of many germline-derived TCR-MHC interaction 'codons'.

  4. A Simple and Rapid Method for Quality Control of Major Histocompatibility Complex-Peptide Monomers by Flow Cytometry.

    Science.gov (United States)

    Chandran, P Anoop; Heidu, Sonja; Zelba, Henning; Schmid-Horch, Barbara; Rammensee, Hans-Georg; Pascolo, Steve; Gouttefangeas, Cécile

    2017-01-01

    Major histocompatibility complex (MHC) multimers are essential tools in T cell immunomonitoring, which are employed both in basic and clinical research, as well as for assessing clinical samples during therapy. The generation of MHC monomers loaded with synthetic peptides is an elaborate and time-consuming process. It would be beneficial to assess the quality of these monomers prior to downstream applications. In this technical note, we describe a novel flow cytometry-based, cell-free, quick, and robust assay to check the quality of MHC monomers directly after refolding or after long-term storage.

  5. Membrane proteins PmpG and PmpH are major constituents of Chlamydia trachomatis L2 outer membrane complex

    DEFF Research Database (Denmark)

    Mygind, Per H; Christiansen, Gunna; Roepstorff, P

    2000-01-01

    The outer membrane complex of Chlamydia is involved in the initial adherence and ingestion of Chlamydia by the host cell. In order to identify novel proteins in the outer membrane of Chlamydia trachomatis L2, proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis. By....... By silver staining of the protein profile, a major protein doublet of 100-110 kDa was detected. In-gel tryptic digestion and matrix-assisted laser desorption/ionization mass spectrometry identified these proteins as the putative outer membrane proteins PmpG and PmpH....

  6. Expression of hepatitis C virus proteins does not interfere with major histocompatibility complex class I processing and presentation in vitro.

    Science.gov (United States)

    Moradpour, D; Grabscheid, B; Kammer, A R; Schmidtke, G; Groettrup, M; Blum, H E; Cerny, A

    2001-05-01

    Hepatitis C virus (HCV) infection takes a chronic course in the majority of patients. The mechanisms underlying the evasion of the host immune response and viral persistence are poorly understood. In this context, we investigated interactions of HCV proteins with major histocompatibility complex (MHC) class I processing and presentation pathways using cell lines that allow the tetracycline-regulated expression of viral structural and nonstructural proteins. These well-characterized inducible cell lines were found to efficiently process and present endogenously synthesized HCV proteins via MHC class I. Functional MHC class I cell-surface expression and intracellular proteasome activity were not affected by the expression of HCV proteins. These results suggest that viral evasion of the host immune response does not involve interactions of HCV with MHC class I processing and presentation. Other mechanisms, such as interference with the interferon system, may be operative in HCV infection, leading to viral persistence.

  7. Human cytomegalovirus-infected cells have unstable assembly of major histocompatibility complex class I complexes and are resistant to lysis by cytotoxic T lymphocytes.

    Science.gov (United States)

    Warren, A P; Ducroq, D H; Lehner, P J; Borysiewicz, L K

    1994-05-01

    Viruses which cause persistence in the naturally infected host are predicted to have evolved immune evasion mechanisms. Human cytomegalovirus (HCMV) causes significant morbidity and mortality in immunocompromised patients yet persists without clinical manifestations in seropositive individuals who have normal immune function. We report that HCMV infection in vitro impairs major histocompatibility complex class I (MHC-I) assembly accompanied by resistance to killing by cytotoxic CD8+ T lymphocytes. Pulse-chase metabolic labelling experiments show that MHC-I complexes continue to be assembled by both uninfected and HCMV-infected cells. However, MHC-I molecules are unstable in HCMV-infected cells and are rapidly broken down. Endoglycosidase H treatment of immunoprecipitates indicates that the breakdown of MHC-I complexes in HCMV-infected cells occurs primarily in a pre-Golgi compartment. Interference with normal MHC-I assembly and expression, if relevant in vivo, may have implications for the restriction of the diversity of the CD8+ cytotoxic T lymphocyte repertoire directed against HCMV antigens and may be an important mechanism of viral persistence.

  8. Plain abdominal radiography in acute abdominal pain; past, present, and future

    Directory of Open Access Journals (Sweden)

    Gans SL

    2012-06-01

    Full Text Available Sarah L Gans,1 Jaap Stoker,2 Marja A Boermeester11Department of Surgery, 2Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The NetherlandsAbstract: Several studies have demonstrated that a diagnosis based solely on a patient’s medical history, physical examination, and laboratory tests is not reliable enough, despite the fact that these aspects are essential parts of the workup of a patient presenting with acute abdominal pain. Traditionally, imaging workup starts with abdominal radiography. However, numerous studies have demonstrated low sensitivity and accuracy for plain abdominal radiography in the evaluation of acute abdominal pain as well as various specific diseases such as perforated viscus, bowel obstruction, ingested foreign body, and ureteral stones. Computed tomography, and in particular computed tomography after negative ultrasonography, provides a better workup than plain abdominal radiography alone. The benefits of computed tomography lie in decision-making for management, planning of a surgical strategy, and possibly even avoidance of negative laparotomies. Based on abundant available evidence, major advances in diagnostic imaging, and changes in the management of certain diseases, we can conclude that there is no place for plain abdominal radiography in the workup of adult patients with acute abdominal pain presenting in the emergency department in current practice.Keywords: abdominal x-ray, acute abdomen, acute abdominal pain, emergency department, diagnostic imaging, abdominal radiography

  9. Clinical, immunological and genetic features in eleven Algerian patients with major histocompatibility complex class II expression deficiency

    Directory of Open Access Journals (Sweden)

    Djidjik Réda

    2012-08-01

    Full Text Available Abstract Presenting processed antigens to CD4+ lymphocytes during the immune response involves major histocompatibility complex class II molecules. MHC class II genes transcription is regulated by four transcription factors: CIITA, RFXANK, RFX5 and RFXAP. Defects in these factors result in major histocompatibility complex class II expression deficiency, a primary combined immunodeficiency frequent in North Africa. Autosomal recessive mutations in the RFXANK gene have been reported as being the principal defect found in North African patients with this disorder. In this paper, we describe clinical, immunological and genetic features of 11 unrelated Algerian patients whose monocytes display a total absence of MHC class II molecules. They shared mainly the same clinical picture which included protracted diarrhoea and respiratory tract recurrent infections. Genetic analysis revealed that 9 of the 11 patients had the same RFXANK founder mutation, a 26 bp deletion (named I5E6-25_I5E6+1, also known as 752delG26. Immunological and genetic findings in our series may facilitate genetic counselling implementation for Algerian consanguineous families. Further studies need to be conducted to determine 752delG26 heterozygous mutation frequency in Algerian population.

  10. Clinical, immunological and genetic features in eleven Algerian patients with major histocompatibility complex class II expression deficiency.

    Science.gov (United States)

    Djidjik, Réda; Messaoudani, Nesrine; Tahiat, Azzedine; Meddour, Yanis; Chaib, Samia; Atek, Aziz; Khiari, Mohammed Elmokhtar; Benhalla, Nafissa Keltoum; Smati, Leila; Bensenouci, Abdelatif; Baghriche, Mourad; Ghaffor, Mohammed

    2012-08-03

    Presenting processed antigens to CD4+ lymphocytes during the immune response involves major histocompatibility complex class II molecules. MHC class II genes transcription is regulated by four transcription factors: CIITA, RFXANK, RFX5 and RFXAP. Defects in these factors result in major histocompatibility complex class II expression deficiency, a primary combined immunodeficiency frequent in North Africa. Autosomal recessive mutations in the RFXANK gene have been reported as being the principal defect found in North African patients with this disorder. In this paper, we describe clinical, immunological and genetic features of 11 unrelated Algerian patients whose monocytes display a total absence of MHC class II molecules. They shared mainly the same clinical picture which included protracted diarrhoea and respiratory tract recurrent infections. Genetic analysis revealed that 9 of the 11 patients had the same RFXANK founder mutation, a 26 bp deletion (named I5E6-25_I5E6+1, also known as 752delG26). Immunological and genetic findings in our series may facilitate genetic counselling implementation for Algerian consanguineous families. Further studies need to be conducted to determine 752delG26 heterozygous mutation frequency in Algerian population.

  11. The economics of nuclear energy revisited: lessons from the use of a complex technology subject to major accidents

    International Nuclear Information System (INIS)

    Finon, D.

    2012-01-01

    The Fukushima accident again raises the issue of the social and economic viability of nuclear technology. To reassess this viability, we analyze the methods used to internalize the external costs of nuclear energy. These have over time become increasingly complex technologically and specifically affected by major accidents. This combination has served to upset the classical learning curve, calling into question nuclear cost base, social acceptance in the face of climate change and profitability for investors. It has become essential to put in place independent institutions to regulate the safety aspect of nuclear technology and these form a hindrance to its standardization, in turn affecting competitiveness. Nevertheless, the paper argues that the new sequence of internalization of external costs triggered by Fukushima will have limited effects on overall costs, because of previous measures already taken to improve safety. The complexity of nuclear technology is reaching its asymptote: the challenge of 'learning from major accidents' will decrease. On the other hand, the independence and competence of nuclear safety authorities in all countries must be revamped to maximize safety and minimize residual risks. This cannot just be done by decree. However, it is the only way to preserve this global public good - the social acceptance of nuclear technology

  12. Predicted distribution of major malaria vectors belonging to the Anopheles dirus complex in Asia: ecological niche and environmental influences.

    Science.gov (United States)

    Obsomer, Valerie; Defourny, Pierre; Coosemans, Marc

    2012-01-01

    Methods derived from ecological niche modeling allow to define species distribution based on presence-only data. This is particularly useful to develop models from literature records such as available for the Anopheles dirus complex, a major group of malaria mosquito vectors in Asia. This research defines an innovative modeling design based on presence-only model and hierarchical framework to define the distribution of the complex and attempt to delineate sibling species distribution and environmental preferences. At coarse resolution, the potential distribution was defined using slow changing abiotic factors such as topography and climate representative for the timescale covered by literature records of the species. The distribution area was then refined in a second step using a mask of current suitable land cover. Distribution area and ecological niche were compared between species and environmental factors tested for relevance. Alternatively, extreme values at occurrence points were used to delimit environmental envelopes. The spatial distribution for the complex was broadly consistent with its known distribution and influencing factors included temperature and rainfall. If maps developed from environmental envelopes gave similar results to modeling when the number of sites was high, the results were less similar for species with low number of recorded presences. Using presence-only models and hierarchical framework this study not only predicts the distribution of a major malaria vector, but also improved ecological modeling analysis design and proposed final products better adapted to malaria control decision makers. The resulting maps can help prioritizing areas which need further investigation and help simulate distribution under changing conditions such as climate change or reforestation. The hierarchical framework results in two products one abiotic based model describes the potential maximal distribution and remains valid for decades and the other

  13. Predicted distribution of major malaria vectors belonging to the Anopheles dirus complex in Asia: ecological niche and environmental influences.

    Directory of Open Access Journals (Sweden)

    Valerie Obsomer

    Full Text Available Methods derived from ecological niche modeling allow to define species distribution based on presence-only data. This is particularly useful to develop models from literature records such as available for the Anopheles dirus complex, a major group of malaria mosquito vectors in Asia. This research defines an innovative modeling design based on presence-only model and hierarchical framework to define the distribution of the complex and attempt to delineate sibling species distribution and environmental preferences. At coarse resolution, the potential distribution was defined using slow changing abiotic factors such as topography and climate representative for the timescale covered by literature records of the species. The distribution area was then refined in a second step using a mask of current suitable land cover. Distribution area and ecological niche were compared between species and environmental factors tested for relevance. Alternatively, extreme values at occurrence points were used to delimit environmental envelopes. The spatial distribution for the complex was broadly consistent with its known distribution and influencing factors included temperature and rainfall. If maps developed from environmental envelopes gave similar results to modeling when the number of sites was high, the results were less similar for species with low number of recorded presences. Using presence-only models and hierarchical framework this study not only predicts the distribution of a major malaria vector, but also improved ecological modeling analysis design and proposed final products better adapted to malaria control decision makers. The resulting maps can help prioritizing areas which need further investigation and help simulate distribution under changing conditions such as climate change or reforestation. The hierarchical framework results in two products one abiotic based model describes the potential maximal distribution and remains valid for decades

  14. Effects of pH and polysaccharides on peptide binding to class II major histocompatibility complex molecules

    International Nuclear Information System (INIS)

    Harding, C.V.; Roof, R.W.; Allen, P.M.; Unanue, E.R.

    1991-01-01

    The binding of immunogenic peptides to class II major histocompatibility molecules was examined at various pH values. The authors studied binding of peptides containing residues 52-61 from hen egg lysozyme (HEL) to I-A k on fixed peritoneal macrophages or to solubilized affinity-purified I-A k . Optimum binding occurred at pH 5.5-6.0 with accelerated kinetics relative to pH 7.4; equilibrium binding was also higher at pH 5.5-6.0 than at 7.4. Similar enhancement at pH 5-6 was observed for the binding of hemoglobin-(64-76) to I-E k and of ribonuclease-(41-61) to I-A k . In contrast, the binding of HEL-(35-45) to I-A k was minimally enhanced at acid pH. Dissociation of cell-associated or purified peptide-I-A k complexes was minimal between pH 5.5 and 7.4, with increased dissociation only at or below pH 4.0 [HEL-(46-61)] or pH 5.0 [HEL-(34-45)]. Thus, optimum peptide binding occurs at pH values similar to the endosomal environment, where the complexes appear to be formed during antigen processing. In addition, they examined the effect of a number of polysaccharides on the binding of peptide to I-A k . Polysaccharides do not appear to bind to class II major histocompatibility complex molecules, which explains the T-cell independence of polysaccharide antigens

  15. T cell receptor recognition of a 'super-bulged' major histocompatibility complex class I-bound peptide

    Energy Technology Data Exchange (ETDEWEB)

    Tynan, Fleur E; Burrows, Scott R; Buckle, Ashley M; Clements, Craig S; Borg, Natalie A; Miles, John J; Beddoe, Travis; Whisstock, James C; Wilce, Matthew C; Silins, Sharon L; Burrows, Jacqueline M; Kjer-Nielsen, Lars; Kostenko, Lyudmila; Purcell, Anthony W; McCluskey, James; Rossjohn, Jamie [Queensland; (Monash); (Melbourne)

    2010-07-20

    Unusually long major histocompatibility complex (MHC) class I-restricted epitopes are important in immunity, but their 'bulged' conformation represents a potential obstacle to {alpha}{beta} T cell receptor (TCR)-MHC class I docking. To elucidate how such recognition is achieved while still preserving MHC restriction, we have determined here the structure of a TCR in complex with HLA-B*3508 presenting a peptide 13 amino acids in length. This complex was atypical of TCR-peptide-MHC class I interactions, being dominated at the interface by peptide-mediated interactions. The TCR assumed two distinct orientations, swiveling on top of the centrally bulged, rigid peptide such that only limited contacts were made with MHC class I. Although the TCR-peptide recognition resembled an antibody-antigen interaction, the TCR-MHC class I contacts defined a minimal 'generic footprint' of MHC-restriction. Thus our findings simultaneously demonstrate the considerable adaptability of the TCR and the 'shape' of MHC restriction.

  16. Hard wiring of T cell receptor specificity for the major histocompatibility complex is underpinned by TCR adaptability

    Energy Technology Data Exchange (ETDEWEB)

    Burrows, Scott R.; Chen, Zhenjun; Archbold, Julia K.; Tynan, Fleur E.; Beddoe, Travis; Kjer-Nielsen, Lars; Miles, John J.; Khanna, Rajiv; Moss, Denis J.; Liu, Yu Chih; Gras, Stephanie; Kostenko, Lyudmila; Brennan, Rebekah M.; Clements, Craig S.; Brooks, Andrew G.; Purcell, Anthony W.; McCluskey, James; Rossjohn, Jamie (Monash); (Queensland Inst. of Med. Rsrch.); (Melbourne)

    2010-07-07

    {alpha}{beta} T cell receptors (TCRs) are genetically restricted to corecognize peptide antigens bound to self-major histocompatibility complex (pMHC) molecules; however, the basis for this MHC specificity remains unclear. Despite the current dogma, evaluation of the TCR-pMHC-I structural database shows that the nongermline-encoded complementarity-determining region (CDR)-3 loops often contact the MHC-I, and the germline-encoded CDR1 and -2 loops frequently participate in peptide-mediated interactions. Nevertheless, different TCRs adopt a roughly conserved docking mode over the pMHC-I, in which three MHC-I residues (65, 69, and 155) are invariably contacted by the TCR in one way or another. Nonetheless, the impact of mutations at these three positions, either individually or together, was not uniformly detrimental to TCR recognition of pHLA-B*0801 or pHLA-B*3508. Moreover, when TCR-pMHC-I recognition was impaired, this could be partially restored by expression of the CD8 coreceptor. The structure of a TCR-pMHC-I complex in which these three (65, 69, and 155) MHC-I positions were all mutated resulted in shifting of the TCR footprint relative to the cognate complex and formation of compensatory interactions. Collectively, our findings reveal the inherent adaptability of the TCR in maintaining peptide recognition while accommodating changes to the central docking site on the pMHC-I.

  17. [Major histocompatibility complex (MHC) in mammals' and its importance for studies of rare species (with Felidae family as an example)].

    Science.gov (United States)

    Tarasian, K K; Sorokin, P A; Kholodova, M V; Rozhnov, V V

    2014-01-01

    Major histocompatibility complex (MHC) appears to be a suitable tool for solving various tasks of popu- lationgenetics. Information on genetic basis of immunity facilitates understanding of evolutionary his- tory and assessment of current state and prospects of studied population/species survival. On the one hand, MHC variability is maintained through pathogen dependent mechanisms, i.e., directional selection of individuals resistant to diseases, that are present in the environment and balancing selection which gives advantage to those individuals carrying unusual or rare alleles of MHC genes. On the other hand, MHC genes have an influence on reproduction efficiency of individuals. Because of MHC polygeny, its studying requires an application of methods that introduce additional stages between amplification of a certain gene segment and its sequencing. In the article, different tech- niques of allele separation are considered, as well as a simplified version of MHC variability analysis based on the examination of microsatellite loci. Despite the high information value of MHC, it is still not used in zoological studies as often as it deserves. Using as an example predatory mammals of Felidae family which contains quite a few threatened species, we show that a majority of studies on MHC in wild cats is descriptive ones and only few of them deal with genes comparative analysis. The rise of interest to the studies of major histocompatibility complex in non-model species may help not only in solving the fundamental problems of evolution and phylogenetic structure of the family but also in planning the measures for conservation of rare and endangered species exposed to various anthropogenic stresses.

  18. [Iatrogenes of manipulator character in abdominal surgery].

    Science.gov (United States)

    Ungurian, V M; Grinev, M V; Demko, A E; Povzun, S A

    2013-01-01

    The authors analyzed the data of 281 cases of iatrogenes of manipulator character in abdominal surgery in order to investigate the circumstances and character of origin. There were 187 cases of operative confirmation and 84 cases of unintentional intraoperative retained foreign bodies. It was detected, that primary planned intervention of higher category of complexity should be related to the high risk group of the development of the operative confirmation. Retained foreign bodies with soft fabric base were diagnosed in early postoperative period as the result of the beginning of postoperative complications. The retained foreign bodies with tough backer material as a rule didn't cause the complications in early postoperative period. They were diagnosed in long-term postoperative period in majority of cases.

  19. First report of major histocompatibility complex class II loci from the Amazon pink river dolphin (genus Inia).

    Science.gov (United States)

    Martínez-Agüero, M; Flores-Ramírez, S; Ruiz-García, M

    2006-07-31

    We report the first major histocompatibility complex (MHC) DQB1 sequences for the two species of pink river dolphins (Inia geoffrensis and Inia boliviensis) inhabiting the Amazon and Orinoco River basins. These sequences were found to be polymorphic within the Inia genus and showed shared homology with cetacean DQB-1 sequences, especially, those of the Monodontidae and Phocoenidae. On the other hand, these sequences were shown to be divergent from those described for other riverine dolphin species, such as Lipotes vexillifer, the Chinese river dolphin. Two main conclusions can be drawn from our results: 1) the Mhc DQB1 sequences seem to evolve more rapidly than other nuclear sequences in cetaceans, and 2) differential positive selective pressures acting on these genes cause concomitant divergent evolutionary histories that derive phylogenetic reconstructions that could be inconsistent with widely accepted intertaxa evolutionary relationships elucidated with other molecular markers subjected to a neutral dynamics.

  20. Polymorphism in a second ABC transproter gene located within the class II region of the human major histocompatibility complex

    Energy Technology Data Exchange (ETDEWEB)

    Powis, S.H.; Mockridge, I.; Kelly, A.; Glynne, R.; Beck, S.; Trowsdale, J. (Imperial Cancer Research Fund Labs., London (United Kingdom)); Kerr, L.A. (Guy' s Campus, London (United Kingdom)); Gileadi, U. (Univ. of Oxford (United Kingdom))

    1992-02-15

    Recent studies have identified genes within the major histocompatibility complex (MHC) that may play a role in presentation of antigenic peptides to T cells. The authors have previously described RING4, a gene within the human MHC class II region that has sequence homology with members of the ABC (ATP-binding cassette) transporter superfamily. They now report the nucleotide sequence of RING11, a second ABC transporter gene located approximately 7 kilobases telomeric to RING4. RING11 is {gamma}-interferon inducible, a property shared with other genes involved in antigen presentation. Comparison between the amino acid sequences of RING11 and RING4 reveals strong homology. They propose that they form a heterodimer that transports peptides from the cytoplasm into the endoplasmic reticulum. They have identified two RING11 alleles, which differ in length of their derived protein sequence by 17 amino acids. The more common of these alleles is present in a Caucasoid population at a frequency of 79%.

  1. Mammalian non-classical major histocompatibility complex I and its receptors: Important contexts of gene, evolution, and immunity

    Science.gov (United States)

    Pratheek, B. M.; Nayak, Tapas K.; Sahoo, Subhransu S.; Mohanty, Prafulla K.; Chattopadhyay, Soma; Chakraborty, Ntiya G.; Chattopadhyay, Subhasis

    2014-01-01

    The evolutionary conserved, less-polymorphic, nonclassical major histocompatibility complex (MHC) class I molecules: Qa-1 and its human homologue human leukocyte antigen-E (HLA-E) along with HLA-F, G and H cross-talk with the T-cell receptors and also interact with natural killer T-cells and other lymphocytes. Moreover, these nonclassical MHC molecules are known to interact with CD94/NKG2 heterodimeric receptors to induce immune responses and immune regulations. This dual role of Qa-1/HLA-E in terms of innate and adaptive immunity makes them more interesting. This review highlights the new updates of the mammalian nonclassical MHC-I molecules in terms of their gene organization, evolutionary perspective and their role in immunity. PMID:25400340

  2. Disentangling the low-energy states of the major light-harvesting complex of plants and their role in photoprotection.

    Science.gov (United States)

    Krüger, Tjaart P J; Ilioaia, Cristian; Johnson, Matthew P; Ruban, Alexander V; van Grondelle, Rienk

    2014-07-01

    The ability to dissipate large fractions of their absorbed light energy as heat is a vital photoprotective function of the peripheral light-harvesting pigment-protein complexes in photosystem II of plants. The major component of this process, known as qE, is characterised by the appearance of low-energy (red-shifted) absorption and fluorescence bands. Although the appearance of these red states has been established, the molecular mechanism, their site and particularly their involvement in qE are strongly debated. Here, room-temperature single-molecule fluorescence spectroscopy was used to study the red emission states of the major plant light-harvesting complex (LHCII) in different environments, in particular conditions mimicking qE. It was found that most states correspond to peak emission at around 700nm and are unrelated to energy dissipative states, though their frequency of occurrence increased under conditions that mimicked qE. Longer-wavelength emission appeared to be directly related to energy dissipative states, in particular emission beyond 770nm. The ensemble average of the red emission bands shares many properties with those obtained from previous bulk in vitro and in vivo studies. We propose the existence of at least three excitation energy dissipating mechanisms in LHCII, each of which is associated with a different spectral signature and whose contribution to qE is determined by environmental control of protein conformational disorder. Emission at 700nm is attributed to a conformational change in the Lut 2 domain, which is facilitated by the conformational change associated with the primary quenching mechanism involving Lut 1. Copyright © 2014. Published by Elsevier B.V.

  3. Effects of Lung Cotransplantation on Cardiac Allograft Tolerance Across a Full Major Histocompatibility Complex Barrier in Miniature Swine.

    Science.gov (United States)

    Madariaga, M L L; Spencer, P J; Michel, S G; La Muraglia, G M; O'Neil, M J; Mannon, E C; Leblang, C; Rosales, I A; Colvin, R B; Sachs, D H; Allan, J S; Madsen, J C

    2016-03-01

    A 12-day course of high-dose tacrolimus induces tolerance of major histocompatibility complex-mismatched lung allografts in miniature swine but does not induce tolerance of heart allografts unless a kidney is cotransplanted. To determine whether lungs share with kidneys the ability to induce cardiac allograft tolerance, we investigated heart-lung cotransplantation using the same induction protocol. Hearts (n = 3), heart-kidneys (n = 3), lungs (n = 6), and hearts-lungs (n = 3) were transplanted into fully major histocompatibility complex-mismatched recipients treated with high-dose tacrolimus for 12 days. Serial biopsy samples were used to evaluate rejection, and in vitro assays were used to detect donor responsiveness. All heart-kidney recipients and five of six lung recipients demonstrated long-term graft survival for longer than 272 days, while all heart recipients rejected their allografts within 35 days. Tolerant recipients remained free of alloantibody and showed persistent donor-specific unresponsiveness by cell-mediated lympholysis/mixed-lymphocyte reaction. In contrast, heart-lung recipients demonstrated rejection of both allografts (days 47, 55, and 202) and antidonor responsiveness in vitro. In contrast to kidneys, lung cotransplantation leads to rejection of both heart and lung allografts, indicating that lungs do not have the same tolerogenic capacity as kidneys. We conclude that cells or cell products present in kidney, but not heart or lung allografts, have a unique capacity to confer unresponsiveness on cotransplanted organs, most likely by amplifying host regulatory mechanisms. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  4. Influence of early goal-directed therapy using arterial waveform analysis on major complications after high-risk abdominal surgery : study protocol for a multicenter randomized controlled superiority trial

    NARCIS (Netherlands)

    Montenij, Leonard; de Waal, Eric; Frank, Michael; van Beest, Paul; de Wit, Ardine; Kruitwagen, Cas; Buhre, Wolfgang; Scheeren, Thomas

    2014-01-01

    Background:  Early goal-directed therapy refers to the use of predefined hemodynamic goals to optimize tissue oxygen delivery in critically ill patients. Its application in high-risk abdominal surgery is, however, hindered by safety concerns and practical limitations of perioperative hemodynamic

  5. Determinant capture as a possible mechanism of protection afforded by major histocompatibility complex class II molecules in autoimmune disease

    Science.gov (United States)

    1993-01-01

    How peptide-major histocompatibility complex (MHC) class II complexes are naturally generated is still unknown, but accumulating evidence suggests that unfolding proteins or long peptides can become bound to class II molecules at the dominant determinant before proteolytic cleavage. We have compared the immunogenicity of hen egg-white lysozyme (HEL) in nonobese diabetic (NOD), (NOD x BALB/c)F1, and E(d) alpha transgenic NOD mice. We find that a response to the subdominant ANOD- restricted determinant disappears upon introduction of an E(d) molecule, and is restored when scission of HEL separates this determinant from its adjoining, competitively dominant, E(d)-restricted determinant. This suggests that the E(d) molecule binds and protects its dominant determinant on a long peptide while captured neighboring determinants are lost during proteolysis. These results provide clear evidence for "determinant capture" as a mechanism of determinant selection during antigen processing and a possible explanation for MHC- protective effects in insulin-dependent diabetes mellitus. PMID:8228814

  6. IPD-MHC 2.0: an improved inter-species database for the study of the major histocompatibility complex.

    Science.gov (United States)

    Maccari, Giuseppe; Robinson, James; Ballingall, Keith; Guethlein, Lisbeth A; Grimholt, Unni; Kaufman, Jim; Ho, Chak-Sum; de Groot, Natasja G; Flicek, Paul; Bontrop, Ronald E; Hammond, John A; Marsh, Steven G E

    2017-01-04

    The IPD-MHC Database project (http://www.ebi.ac.uk/ipd/mhc/) collects and expertly curates sequences of the major histocompatibility complex from non-human species and provides the infrastructure and tools to enable accurate analysis. Since the first release of the database in 2003, IPD-MHC has grown and currently hosts a number of specific sections, with more than 7000 alleles from 70 species, including non-human primates, canines, felines, equids, ovids, suids, bovins, salmonids and murids. These sequences are expertly curated and made publicly available through an open access website. The IPD-MHC Database is a key resource in its field, and this has led to an average of 1500 unique visitors and more than 5000 viewed pages per month. As the database has grown in size and complexity, it has created a number of challenges in maintaining and organizing information, particularly the need to standardize nomenclature and taxonomic classification, while incorporating new allele submissions. Here, we describe the latest database release, the IPD-MHC 2.0 and discuss planned developments. This release incorporates sequence updates and new tools that enhance database queries and improve the submission procedure by utilizing common tools that are able to handle the varied requirements of each MHC-group. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  7. The role of major histocompatibility complex class I chain-related gene A antibodies in organ transplantation.

    Science.gov (United States)

    Zou, Yizhou; Stastny, Peter

    2009-08-01

    Major histocompatibility complex class I chain-related gene A (MICA) antigens are expressed on the endothelium, they are polymorphic and have been shown to be recognized by antibodies produced by transplant recipients. Methods for detection of these antibodies have become available. In the 15th International Histocompatibility Workshop, a study for MICA antibody testing and of MICA genotyping was organized. Antibodies against MICA antigens have been determined either using cells transfected with MICA alleles or recombinant MICA antigens. MICA epitopes were characterized by empirical study of human sera and by correlation with MICA polymorphic amino acids. Sera were absorbed with cells transfected with MICA alleles and site-directed mutagenesis was employed to analyze complex sera. A number of clinical studies have shown associations of antibodies against MICA with decreased survival of kidney transplants and in one investigation with acute rejection in recipients of heart allografts. In addition to the HLA antigens, which elicit a strong immune response against allografted organs, the MICA antigens may be recognized as foreign and induce the production of MICA-specific antibodies. Antibodies against MICA have been associated with a decrease in the survival of organ allografts. The results suggest the MICA antigens are transplantation antigens that can induce an immune response associated with graft failure.

  8. Analysis of Class I Major Histocompatibility Complex Gene Transcription in Human Tumors Caused by Human Papillomavirus Infection.

    Science.gov (United States)

    Gameiro, Steven F; Zhang, Ali; Ghasemi, Farhad; Barrett, John W; Nichols, Anthony C; Mymryk, Joe S

    2017-09-10

    Oncoproteins from high-risk human papillomaviruses (HPV) downregulate the transcription of the class I major histocompatibility complex (MHC-I) antigen presentation apparatus in tissue culture model systems. This could allow infected or transformed cells to evade the adaptive immune response. Using data from over 800 human cervical and head & neck tumors from The Cancer Genome Atlas (TCGA), we determined the impact of HPV status on the mRNA expression of all six MHC-I heavy chain genes, and the β2 microglobulin light chain. Unexpectedly, these genes were all expressed at high levels in HPV positive (HPV+) cancers compared with normal control tissues. Indeed, many of these genes were expressed at significantly enhanced levels in HPV+ tumors. Similarly, the transcript levels of several other components of the MHC-I peptide-loading complex were also high in HPV+ cancers. The coordinated expression of high mRNA levels of the MHC-I antigen presentation apparatus could be a consequence of the higher intratumoral levels of interferon γ in HPV+ carcinomas, which correlate with signatures of increased infiltration by T- and NK-cells. These data, which were obtained from both cervical and oral tumors in large human cohorts, indicates that HPV oncoproteins do not efficiently suppress the transcription of the antigen presentation apparatus in human tumors.

  9. Molecular Architecture of the Major Histocompatibility Complex Class I-Binding Site of Ly49 Natural Killer Cell Receptors

    Energy Technology Data Exchange (ETDEWEB)

    Deng,L.; Cho, S.; Malchiodi, E.; Kerzic, M.; Dam, J.; Mariuzza, R.

    2008-01-01

    Natural killer (NK) cells play a vital role in the detection and destruction of virally infected and tumor cells during innate immune responses. The highly polymorphic Ly49 family of NK receptors regulates NK cell function by sensing major histocompatibility complex class I (MHC-I) molecules on target cells. Despite the determination of two Ly49-MHC-I complex structures, the molecular features of Ly49 receptors that confer specificity for particular MHC-I alleles have not been identified. To understand the functional architecture of Ly49-binding sites, we determined the crystal structures of Ly49C and Ly49G and completed refinement of the Ly49C-H-2Kb complex. This information, combined with mutational analysis of Ly49A, permitted a structure-based classification of Ly49s that we used to dissect the binding site into three distinct regions, each having different roles in MHC recognition. One region, located at the center of the binding site, has a similar structure across the Ly49 family and mediates conserved interactions with MHC-I that contribute most to binding. However, the preference of individual Ly49s for particular MHC-I molecules is governed by two regions that flank the central region and are structurally more variable. One of the flanking regions divides Ly49s into those that recognize both H-2D and H-2K versus only H-2D ligands, whereas the other discriminates among H-2D or H-2K alleles. The modular design of Ly49-binding sites provides a framework for predicting the MHC-binding specificity of Ly49s that have not been characterized experimentally.

  10. Abdominal Compartment Syndrome

    Directory of Open Access Journals (Sweden)

    Pınar Zeyneloğlu

    2015-04-01

    Full Text Available Intraabdominal hypertension and Abdominal compartment syndrome are causes of morbidity and mortality in critical care patients. Timely diagnosis and treatment may improve organ functions. Intra-abdominal pressure monitoring is vital during evaluation of the patients and in the management algorithms. The incidence, definition and risk factors, clinical presentation, diagnosis and management of intraabdominal hypertension and Abdominal compartment syndrome were reviewed here.

  11. Human major histocompatibility complex contains a minimum of 19 genes between the complement cluster and HLA-B

    International Nuclear Information System (INIS)

    Spies, T.; Bresnahan, M.; Strominger, J.L.

    1989-01-01

    A 600-kilobase (kb) DNA segment from the human major histocompatibility complex (MHC) class III region was isolated by extension of a previous 435-kb chromosome walk. The contiguous series of cloned overlapping cosmids contains the entire 555-kb interval between C2 in the complement gene cluster and HLA-B. This region is known to encode the tumor necrosis factors (TNFs) α and β, B144, and the major heat shock protein HSP70. Moreover, a cluster of genes, BAT1-BAT5 (HLA-B-associated transcripts) have been localized in the vicinity of the genes for TNFα and TNFβ. An additional four genes were identified by isolation of corresponding cDNA clones with cosmid DNA probes. These genes for BAT6-BAT9 were mapped near the gene for C2 within a 120-kb region that includes a HSP70 gene pair. These results, together with complementary data from a similar recent study, indicated the presence of a minimum of 19 genes within the C2-HLA-B interval of the MHC class III region. Although the functional properties of most of these genes are yet unknown, they may be involved in some aspects of immunity. This idea is supported by the genetic mapping of the hematopoietic histocompatibility locus-1 (Hh-1) in recombinant mice between TNFα and H-2S, which is homologous to the complement gene cluster in humans

  12. A complex alloantigen system in Florida sandhill cranes, Grus canadensis pratensis: Evidence for the major histocompatibility (B) system

    Science.gov (United States)

    Jarvi, S.I.; Gee, G.F.; Miller, M.M.; Briles, W.E.

    1995-01-01

    The B blood group system constitutes the major histocompatibility complex (Mhc) in birds. The Mhc is a cluster of genes largely devoted to the processing and presentation of antigen. The Mhc is highly polymorphic in many species and, thus, useful in the evaluation of genetic diversity for fitness traits within populations of a variety of animals. Correlations found between particular Mhc haplotypes and resistance to certain diseases emphasize the importance of understanding the functional significance of diversity of the Mhc, particularly in species threatened with extinction. As part of studies focused on genetic diversity in wild birds, serological techniques were used to define a highly polymorphic alloantigen system in seven families of Florida sandhill cranes (Grus canadensis pratensis). The results of analyses with antisera produced within the crane families and with chicken Mhc antigen-specific reagents revealed a single major alloantigen system that is likely the Mhc of the Florida sandhill crane. Preliminary experiments indicate that these crane alloantisera will provide a means of defining .the Mhc in other species of cranes.

  13. Identification of monoclonal antibodies cross-reactive with bottlenose dolphin orthologues of the major histocompatibility complex and leukocyte differentiation molecules.

    Science.gov (United States)

    Elnaggar, Mahmoud M; Abdellrazeq, Gaber S; Venn-Watson, Stephanie K; Jensen, Eric D; Hulubei, Victoria; Fry, Lindsay M; Sacco, Randy E; Davis, William C

    2017-10-01

    The slow progress in understanding immunotoxic effects of environmental contaminants and their influence on disease susceptibility in whales is largely due to the limited information available on the immune systems and immune function of species included in the Cetancodontamorpha clade. Studies in species in the other major clades included in the Artiodactylamorpha, Ruminantiamorpha, Suinamorpha, and Camelidamorpha have revealed the immune systems are similar, but not identical. The present study was undertaken to expand the available monoclonal antibody reagents needed to gain insight into the composition, function, and evolution of the immune system in Cetancodontamorpha, using the dolphin (Tursiops truncatus) as a model cetacean species. Screening of a set of mAbs that recognize highly conserved epitopes expressed on the major histocompatibility complex (MHC) and leukocyte differentiation molecules (LDMs) in cattle by flow cytometry revealed some of the mAbs recognize epitopes conserved on dolphin orthologues of MHC class I, MHC class II, CD11a, CD14, CD16, CD18, CD163 and CD172a. Comparison of the amino acid sequences of dolphin and bovine orthologues revealed limited changes in sequence have occurred during speciation, suggesting an approach for developing cross-reactive mAbs for use in cetacean research. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Unconventional Peptide Presentation by Major Histocompatibility Complex (MHC) Class I Allele HLA-A*02:01: BREAKING CONFINEMENT.

    Science.gov (United States)

    Remesh, Soumya G; Andreatta, Massimo; Ying, Ge; Kaever, Thomas; Nielsen, Morten; McMurtrey, Curtis; Hildebrand, William; Peters, Bjoern; Zajonc, Dirk M

    2017-03-31

    Peptide antigen presentation by major histocompatibility complex (MHC) class I proteins initiates CD8 + T cell-mediated immunity against pathogens and cancers. MHC I molecules typically bind peptides with 9 amino acids in length with both ends tucked inside the major A and F binding pockets. It has been known for a while that longer peptides can also bind by either bulging out of the groove in the middle of the peptide or by binding in a zigzag fashion inside the groove. In a recent study, we identified an alternative binding conformation of naturally occurring peptides from Toxoplasma gondii bound by HLA-A*02:01. These peptides were extended at the C terminus (PΩ) and contained charged amino acids not more than 3 residues after the anchor amino acid at PΩ, which enabled them to open the F pocket and expose their C-terminal extension into the solvent. Here, we show that the mechanism of F pocket opening is dictated by the charge of the first charged amino acid found within the extension. Although positively charged amino acids result in the Tyr-84 swing, amino acids that are negatively charged induce a not previously described Lys-146 lift. Furthermore, we demonstrate that the peptides with alternative binding modes have properties that fit very poorly to the conventional MHC class I pathway and suggest they are presented via alternative means, potentially including cross-presentation via the MHC class II pathway. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Major histocompatibility complex and mate choice in the polygynous primate: the Sichuan snub-nosed monkey (Rhinopithecus roxellana).

    Science.gov (United States)

    Yang, Banghe; Ren, Baoping; Xiang, Zuofu; Yang, Jingyuan; Yao, Hui; Garber, Paul A; Li, Ming

    2014-11-01

    The highly polymorphic genes within the major histocompatibility complex (MHC) not only play a major role in immunity resistance, but also seem to provide hints for mate choice in some animal populations. In the present study we investigated MHC-related mate choice in a small natural population (group size 40-55 individuals) of a polygynous primate, the Sichuan snub-nosed monkey (Rhinopithecus roxellana). We found that there was no evidence either for MHC-disassortative mating, or for females to mate with males based on MHC heterozygosity or specific alleles. Nevertheless, of the 11 alleles identified, we found that the frequencies of 2 alleles, Rhro-DRB2 (P < 0.01) and Rhro-DRB5 (P < 0.05) were higher in offspring than in their parents. These findings suggest that MHC-DRB in this population of R. roxellana is unlikely to be associated with mating preferences. Limited female opportunities for mate choice are likely due, in part, to the harem breeding structure present in R. roxellana, and the relatively small number of resident adult males in our study band (N = 4-6). In addition, we suggest that differences in the frequency of particular alleles across generations may be linked to parasite resistance in a fluctuating environment; however, confirmation of this finding requires further study. © 2013 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and Wiley Publishing Asia Pty Ltd.

  16. [Pain originating from the abdominal wall: a forgotten diagnostic option].

    Science.gov (United States)

    Rivero Fernández, Miguel; Moreira Vicente, Víctor; Riesco López, José María; Rodríguez Gandía, Miguel Angel; Garrido Gómez, Elena; Milicua Salamero, José María

    2007-04-01

    Chronic abdominal pain is a common clinical problem in primary care, and is usually referred to gastroenterologists or general surgeons. Although up to 20% of cases of idiopathic abdominal pain arise in structures of the abdominal wall, this is frequently overlooked as a possible cause. It includes pain arising from structures of the abdominal wall including skin, parietal peritoneum, cellular subcutaneous tissue, aponeuroses, abdominal muscles and somatosensorial innervation from lower dorsal roots. The diagnosis is based on anamnesis and physical examination. Carnett's sign is a simple maneuver that discriminates between parietal and visceral pain. Management with topical anesthesia is effective in a majority of patients and can help to confirm the diagnosis.

  17. T-cell activation. VI. Inhibitory and stimulatory effects of anti-major histocompatibility complex class I antibodies in allogeneic mixed lymphocyte culture

    DEFF Research Database (Denmark)

    Röpke, M; Röpke, C; Claesson, Mogens Helweg

    1993-01-01

    Murine T splenocytes stimulated in primary allogeneic mixed lymphocyte culture (MLC) were incubated with soluble anti-major histocompatibility complex (MHC) class I monoclonal antibodies. These antibodies induced inhibition in the cytotoxicity of the responding population and this inhibition...

  18. Genetic variation in the extended major histocompatibility complex and susceptibility to childhood acute lymphoblastic leukemia: a review of the evidence

    Directory of Open Access Journals (Sweden)

    Kevin Y Urayama

    2013-12-01

    Full Text Available The enduring suspicion that infections and immunologic response may play a role in the etiology of childhood leukemia, particularly acute lymphoblastic leukemia (ALL, is now supported, albeit still indirectly, by numerous epidemiological studies. The cumulative evidence includes, for example, descriptive observations of a peculiar peak incidence at age 2-5 years for ALL in economically developed countries, clustering of cases in situations of population mixing associated with unusual patterns of personal contacts, associations with various proxy measures for immune modulatory exposures early in life, and genetic susceptibility conferred by variation in genes involved in the immune system. In this review, our focus is the extended major histocompatibility complex (xMHC, an approximately 7.6 megabase region that is well-known for its high density of expressed genes, extensive polymorphisms exhibiting complex linkage disequilibrium patterns, and its disproportionately large number of immune-related genes, including human leukocyte antigen (HLA. First discovered through the role they play in transplant rejection, the classical HLA class I (HLA-A, -B, and -C and class II (HLA-DR, HLA-DQ, and HLA-DP molecules reside at the epicenter of the immune response pathways and are now the targets of many disease susceptibility studies, including those for childhood leukemia. The genes encoding the HLA molecules are only a minority of the over 250 expressed genes in the xMHC, and a growing number of studies are beginning to evaluate other loci through targeted investigations or utilizing a mapping approach with a comprehensive screen of the entire region. Here, we review the current epidemiologic evidence available to date regarding genetic variation contained within this highly unique region of the genome and its relationship with childhood ALL risk.

  19. Laparoscopy In Unexplained Abdominal Pain: Surgeon's Perspective.

    Science.gov (United States)

    Abdullah, Muhammad Tariq; Waqar, Shahzad Hussain; Zahid, Muhammad Abdul

    2016-01-01

    Unexplained abdominal pain is a common but difficult presenting feature faced by the clinicians. Such patients can undergo a number of investigations with failure to reach any diagnosis. The objective of this study was to evaluate the use of laparoscopy in the diagnosis and management of patients with unexplained abdominal pain. This cross-sectional study was conducted at Pakistan Institute of Medical Sciences Islamabad from January 2009 to December 2013. This study included 91 patients of unexplained abdominal pain not diagnosed by routine clinical examination and investigations. These patients were subjected to diagnostic laparoscopy for evaluation of their conditions and to confirm the diagnosis. These patients presented 43% of patients undergoing investigations for abdominal pain. Patients diagnosed with gynaecological problems were excluded to see surgeon's perspective. The findings and the outcomes of the laparoscopy were recorded and data was analyzed. Unexplained abdominal pain is common in females than in males. The most common laparoscopic findings were abdominal tuberculosis followed by appendicitis. Ninety percent patients achieved pain relief after laparoscopic intervention. Laparoscopy is both beneficial and safe in majority of patients with unexplained abdominal pain. General surgeons should acquire training and experience in laparoscopic surgery to provide maximum benefit to these difficult patients.

  20. [Abdominal pregnancy, institutional experience].

    Science.gov (United States)

    Bonfante Ramírez, E; Bolaños Ancona, R; Simón Pereyra, L; Juárez García, L; García-Benitez, C Q

    1998-07-01

    Abdominal pregnancy is a rare entity, which has been classified as primary or secondary by Studiford criteria. A retrospective study, between January 1989 and December 1994, realized at Instituto Nacional de Perinatología, found 35,080 pregnancies, from which 149 happened to be ectopic, and 6 of them were abdominal. All patients belonged to a low income society class, age between 24 and 35 years, and average of gestations in 2.6. Gestational age varied from 15 weeks to 32.2 weeks having only one delivery at term with satisfactory postnatal evolution. One patient had a recurrent abdominal pregnancy, with genital Tb as a conditional factor. Time of hospitalization varied from 4 to 5 days, and no further patient complications were reported. Fetal loss was estimated in 83.4%. Abdominal pregnancy is often the sequence of a tubarian ectopic pregnancy an when present, it has a very high maternal mortality reported in world literature, not found in this study. The stated frequency of abdominal pregnancy is from 1 of each 3372, up to 1 in every 10,200 deliveries, reporting in the study 1 abdominal pregnancy in 5846 deliveries. The study had two characteristic entities one, the recurrence and two, the delivery at term of one newborn. Abdominal pregnancy accounts for 4% of all ectopic pregnancies. Clinical findings in abdominal pregnancies are pain, transvaginal bleeding and amenorrea, being the cardinal signs of ectopic pregnancy.

  1. Staphylococcus-mediated T-cell activation and spontaneous natural killer cell activity in the absence of major histocompatibility complex class II molecules

    Science.gov (United States)

    Chapes, S. K.; Hoynowski, S. M.; Woods, K. M.; Armstrong, J. W.; Beharka, A. A.; Iandolo, J. J.; Spooner, B. S. (Principal Investigator)

    1993-01-01

    We used major histocompatibility complex class II antigen-deficient transgenic mice to show that in vitro natural killer cell cytotoxicity and T-cell activation by staphylococcal exotoxins (superantigens) are not dependent upon the presence of major histocompatibility complex class II molecules. T cells can be activated by exotoxins in the presence of exogenously added interleukin 1 or 2 or in the presence of specific antibody without exogenously added cytokines.

  2. Inferring the evolution of the major histocompatibility complex of wild pigs and peccaries using hybridisation DNA capture-based sequencing.

    Science.gov (United States)

    Lee, Carol; Moroldo, Marco; Perdomo-Sabogal, Alvaro; Mach, Núria; Marthey, Sylvain; Lecardonnel, Jérôme; Wahlberg, Per; Chong, Amanda Y; Estellé, Jordi; Ho, Simon Y W; Rogel-Gaillard, Claire; Gongora, Jaime

    2017-12-18

    The major histocompatibility complex (MHC) is a key genomic model region for understanding the evolution of gene families and the co-evolution between host and pathogen. To date, MHC studies have mostly focused on species from major vertebrate lineages. The evolution of MHC classical (Ia) and non-classical (Ib) genes in pigs has attracted interest because of their antigen presentation roles as part of the adaptive immune system. The pig family Suidae comprises over 18 extant species (mostly wild), but only the domestic pig has been extensively sequenced and annotated. To address this, we used a DNA-capture approach, with probes designed from the domestic pig genome, to generate MHC data for 11 wild species of pigs and their closest living family, Tayassuidae. The approach showed good efficiency for wild pigs (~80% reads mapped, ~87× coverage), compared to tayassuids (~12% reads mapped, ~4× coverage). We retrieved 145 MHC loci across both families. Phylogenetic analyses show that the class Ia and Ib genes underwent multiple duplications and diversifications before suids and tayassuids diverged from their common ancestor. The histocompatibility genes mostly form orthologous groups and there is genetic differentiation for most of these genes between Eurasian and sub-Saharan African wild pigs. Tests of selection showed that the peptide-binding region of class Ib genes was under positive selection. These findings contribute to better understanding of the evolutionary history of the MHC, specifically, the class I genes, and provide useful data for investigating the immune response of wild populations against pathogens.

  3. Children's (Pediatric) Abdominal Ultrasound Imaging

    Medline Plus

    Full Text Available ... What are the limitations of Abdominal Ultrasound Imaging? What is Abdominal Ultrasound Imaging? Ultrasound is safe and ... as the liver or kidneys. top of page What are some common uses of the procedure? Abdominal ...

  4. Emergency abdominal surgery in Zaria, Nigeria

    African Journals Online (AJOL)

    resourced environments with a lack of modern medical facilities. Although ancillary investigations may improve diagnostic accuracy, a reasonable differential diagnosis can be made at the bedside in the majority of patients. The major causes of abdominal emergencies vary from region to region, and even within the same ...

  5. Endoplasmic reticulum resident protein of 90 kilodaltons associates with the T- and B-cell antigen receptors and major histocompatibility complex antigens during their assembly

    NARCIS (Netherlands)

    Hochstenbach, F.; DAVID, V.; WATKINS, S.; Brenner, M. B.

    1992-01-01

    In the endoplasmic reticulum (ER), newly synthesized subunits of the T-cell antigen receptor (TCR), membrane-bound immunoglobulin (mIg), and major histocompatibility complex (MHC) class I antigens must fold correctly and assemble completely into multimeric protein complexes prior to transport to the

  6. Mate choice for major histocompatibility complex genetic divergence as a bet-hedging strategy in the Atlantic salmon (Salmo salar).

    Science.gov (United States)

    Evans, Melissa L; Dionne, Mélanie; Miller, Kristina M; Bernatchez, Louis

    2012-01-22

    Major histocompatibility complex (MHC)-dependent mating preferences have been observed across vertebrate taxa and these preferences are expected to promote offspring disease resistance and ultimately, viability. However, little empirical evidence linking MHC-dependent mate choice and fitness is available, particularly in wild populations. Here, we explore the adaptive potential of previously observed patterns of MHC-dependent mate choice in a wild population of Atlantic salmon (Salmo salar) in Québec, Canada, by examining the relationship between MHC genetic variation and adult reproductive success and offspring survival over 3 years of study. While Atlantic salmon choose their mates in order to increase MHC diversity in offspring, adult reproductive success was in fact maximized between pairs exhibiting an intermediate level of MHC dissimilarity. Moreover, patterns of offspring survival between years 0+ and 1+, and 1+ and 2+ and population genetic structure at the MHC locus relative to microsatellite loci indicate that strong temporal variation in selection is likely to be operating on the MHC. We interpret MHC-dependent mate choice for diversity as a likely bet-hedging strategy that maximizes parental fitness in the face of temporally variable and unpredictable natural selection pressures.

  7. Recent advances in Major Histocompatibility Complex (MHC) class I antigen presentation: Plastic MHC molecules and TAPBPR-mediated quality control.

    Science.gov (United States)

    van Hateren, Andy; Bailey, Alistair; Elliott, Tim

    2017-01-01

    We have known since the late 1980s that the function of classical major histocompatibility complex (MHC) class I molecules is to bind peptides and display them at the cell surface to cytotoxic T cells. Recognition by these sentinels of the immune system can lead to the destruction of the presenting cell, thus protecting the host from pathogens and cancer. Classical MHC class I molecules (MHC I hereafter) are co-dominantly expressed, polygenic, and exceptionally polymorphic and have significant sequence diversity. Thus, in most species, there are many different MHC I allotypes expressed, each with different peptide-binding specificity, which can have a dramatic effect on disease outcome. Although MHC allotypes vary in their primary sequence, they share common tertiary and quaternary structures. Here, we review the evidence that, despite this commonality, polymorphic amino acid differences between allotypes alter the ability of MHC I molecules to change shape (that is, their conformational plasticity). We discuss how the peptide loading co-factor tapasin might modify this plasticity to augment peptide loading. Lastly, we consider recent findings concerning the functions of the non-classical MHC I molecule HLA-E as well as the tapasin-related protein TAPBPR (transporter associated with antigen presentation binding protein-related), which has been shown to act as a second quality-control stage in MHC I antigen presentation.

  8. Characterization of classical major histocompatibility complex (MHC) class II genes in northern pig-tailed macaques (Macaca leonina).

    Science.gov (United States)

    Lian, Xiao-Dong; Zhang, Xi-He; Dai, Zheng-Xi; Zheng, Yong-Tang

    2017-12-01

    The northern pig-tailed macaque (Macaca leonina) has been identified as an independent species from the pig-tailed macaque group. The species is a promising animal model for HIV/AIDS pathogenesis and vaccine studies due to susceptibility to HIV-1. However, the major histocompatibility complex (MHC) genetics in northern pig-tailed macaques remains poorly understood. We have previously studied the MHC class I genes in northern pig-tailed macaques and identified 39 novel alleles. Here, we describe the MHC class II alleles in all six classical loci (DPA, DPB, DQA, DQB, DRA, and DRB) from northern pig-tailed macaques using a sequence-based typing method for the first time. A total of 60 MHC-II alleles were identified of which 27 were shared by other macaque species. Additionally, northern pig-tailed macaques expressed a single DRA and multiple DRB genes similar to the expression in humans and other macaque species. Polymorphism and positive selection were detected, and phylogenetic analysis suggested the presence of a common ancestor in human and northern pig-tailed macaque MHC class II allelic lineages at the DQA, DQB, and DRB loci. The characterization of full-length MHC class II alleles in this study significantly improves understanding of the immunogenetics of northern pig-tailed macaques and provides the groundwork for future animal model studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Proteolysis of the heavy chain of major histocompatibility complex class I antigens by complement component C1s

    DEFF Research Database (Denmark)

    Eriksson, H; Nissen, Mogens Holst

    1990-01-01

    The major histocompatibility complex (MHC) class I antigens contain a light chain, beta 2-microglobulin, non-covalently associated to the transmembrane heavy alpha-chain carrying the allotypic determinants. Since the C1q complement component is known to associate with beta 2-microglobulin, and we...... weights of the fragments are in agreement with the cleavage located in the area between the disulphide loops of the alpha 2-and alpha 3-domains of the heavy chain. In addition human C1s complement is able to cleave H-2 antigens from mouse in a similar fashion but not rat MHC class I antigen or mouse MHC...... class II antigen (I-Ad). Mouse MHC class I antigen-specific determinants could also be detected in supernatant from mouse spleen cells incubated with C1r and C1s. These results indicate the presence in the body fluids of a non-membrane-bound soluble form of the alpha 1-and alpha 2-domains which...

  10. HUBUNGAN ANTARA PERTUMBUHAN DENGAN KEBERADAAN GEN TAHAN PENYAKIT MAJOR HISTOCOMPATIBILITY COMPLEX (MHC PADA IKAN MAS (Cyprinus carpio

    Directory of Open Access Journals (Sweden)

    Erma Primanita Hayuningtyas

    2016-04-01

    Full Text Available Wabah penyakit koi herpes virus (KHV di Indonesia yang terjadi sejak tahun 2002 merupakan salah satu faktor yang memicu kemerosotan produksi ikan mas budidaya. Pembentukan strain unggul ikan mas tahan KHV dapat menjadi solusi bagi permasalahan tersebut. Pemilihan genotip ikan mas tahan KHV dengan marka molekuler gen major histocompatibility complex class II (MHC-II, khususnya pada alel Cyca DAB 1*05 akan membantu dalam kegiatan seleksi. Penelitian ini bertujuan untuk mengetahui keberadaan gen MHC-II pada populasi dasar G0 ikan mas strain Rajadanu dan hubungannya dengan pertumbuhan (bobot. Metode deteksi keberadaan gen MHC-II pada dua kelompok ikan dengan ukuran berbeda dilakukan dengan teknik PCR. Hubungan antara pertumbuhan ikan mas dengan persentase kemunculan gen MHC-II dianalisis dengan menggunakan program SPSS (Statistical Package for the Social Sciences, sehingga diperoleh korelasi di antara keduanya. Hasil penelitian menunjukkan bahwa hubungan antara pertumbuhan dengan persentase keberadaan gen MHC-II berkorelasi negatif dengan nilai R = -0,742. Hal ini mengindikasikan bahwa semakin cepat pertumbuhan populasi ikan mas maka semakin sedikit persentase individu yang mempunyai gen MHC-II pada setiap populasi ikan mas. Sehingga populasi ikan mas yang pertumbuhannya lambat memiliki tingkat persentase positif MHC-II lebih tinggi (85,71%-100% dibandingkan populasi ikan mas yang pertumbuhannya cepat (42,86%-85,71%.

  11. Two putative subunits of a peptide pump encoded in the human major histocompatability complex class 2 region

    International Nuclear Information System (INIS)

    Bahram, S.; Arnold, D.; Bresnahan, M.; Strominger, J.L.; Spies, T.

    1991-01-01

    The class 2 region of the human major histocompatibility complex (MHC) may encode several genes controlling the processing of endogenous antigen and the presentation of peptide epitopes by MHC class 1 molecules to cytotoxic T lymphocytes. A previously described peptide supply factor (PSF1) is a member of the multidrug-resistance family of transporters and may pump cytosolic peptides into the membrane-bound compartment where class 1 molecules assemble. A second transporter gene, PSF2, was identified 10 kilobases (kb) from PSF1, near the class 2 DOB gene. The complete sequences of PSF1 and PSF2 were determined from cDNA clones. The translation products are closely related in sequence and predicted secondary structure. Both contain a highly conserved ATP-binding fold and share 25% homology in a hydrophobic domain with a tentative number of eight membrane-spanning segments. Based on the principle dimeric organization of these two domains in other transporters, PSF1 and PSF2 may function as complementary subunits, independently as homodimers, or both. Taken together with previous genetic evidence, the coregulation of PSF1 and PSF2 by γ interferon and the to-some-degree coordinate transcription of these genes suggest a common role in peptide-loading of class 1 molecules, although a distinct function of PSF2 cannot be ruled out

  12. Genetic variation of the major histocompatibility complex (MHC class II B gene in the threatened Hume's pheasant, Syrmaticus humiae.

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    Weicai Chen

    Full Text Available Major histocompatibility complex (MHC genes are the most polymorphic genes in vertebrates and encode molecules that play a crucial role in pathogen resistance. As a result of their diversity, they have received much attention in the fields of evolutionary and conservation biology. Here, we described the genetic variation of MHC class II B (MHCIIB exon 2 in a wild population of Hume's pheasant (Syrmaticus humiae, which has suffered a dramatic decline in population over the last three decades across its ranges in the face of heavy exploitation and habitat loss. Twenty-four distinct alleles were found in 73 S. humiae specimens. We found seven shared alleles among four geographical groups as well as six rare MHCIIB alleles. Most individuals displayed between one to five alleles, suggesting that there are at least three MHCIIB loci of the Hume's pheasant. The dN ⁄ dS ratio at putative antigen-binding sites (ABS was significantly greater than one, indicating balancing selection is acting on MHCIIB exon 2. Additionally, recombination and gene conversion contributed to generating MHCIIB diversity in the Hume's pheasant. One to three recombination events and seventy-five significant gene conversion events were observed within the Hume's pheasant MHCIIB loci. The phylogenetic tree and network analysis revealed that the Hume's pheasant alleles do not cluster together, but are scattered through the tree or network indicating a trans-species evolutionary mode. These findings revealed the evolution of the Hume's pheasant MHC after suffering extreme habitat fragmentation.

  13. Clinical, Immunological, and Molecular Findings in Five Patients with Major Histocompatibility Complex Class II Deficiency from India

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    Jahnavi Aluri

    2018-02-01

    Full Text Available Major histocompatibility complex (MHC class II deficiency is a rare autosomal recessive form of primary immunodeficiency disorder (PID characterized by the deficiency of MHC class II molecules. This deficiency affects the cellular and humoral immune response by impairing the development of CD4+ T helper (Th cells and Th cell-dependent antibody production by B cells. Affected children typically present with severe respiratory and gastrointestinal tract infections. Hematopoietic stem cell transplantation (HSCT is the only curative therapy available for treating these patients. This is the first report from India wherein we describe the clinical, immunological, and molecular findings in five patients with MHC class II deficiency. Our patients presented with recurrent lower respiratory tract infection as the most common clinical presentation within their first year of life and had a complete absence of human leukocyte antigen-antigen D-related (HLA-DR expression on B cells and monocytes. Molecular characterization revealed novel mutations in RFAXP, RFX5, and CIITA genes. Despite genetic heterogeneity, these patients were clinically indistinguishable. Two patients underwent HSCT but had a poor survival outcome. Detectable level of T cell receptor excision circles (TRECs were measured in our patients, highlighting that this form of PID may be missed by TREC-based newborn screening program for severe combined immunodeficiency.

  14. Myelin-oligodendrocyte glycoprotein is a member of a subset of the immunoglobulin superfamily encoded within the major histocompatibility complex

    Energy Technology Data Exchange (ETDEWEB)

    Pham-Dinh, D.; Dautigny, A. (Institut des Neurosciences, Paris (France)); Mattei, M.G.; Roeckel, N. (Institut National de la Sante et de la Recherche Medicale Unite, Marseille (France)); Nussbaum, J.H.; Roussel, G. (Centre National de la Recherche Scientifique Unite, Strasbourg (France)); Pontarotti, P. (Centre Natinal de la Recherche Scientifique Unite, Toulouse (France)); Mather, I.H. (Univ. of Maryland, College Park, MD (United States)); Artzt, K. (Univ. of Texas, Austin, TX (United States)); Lindahl, K.F. (Univ. of Texas Southwestern Medical Center, Dallas, TX (United States))

    1993-09-01

    Myelin/oligodendrocyte glycoprotein (MOG) is found on the surface of myelinating oligodendrocytes and external lamellae of myelin sheaths in the central nervous system, and it is target antigen in experimental autoimmune encephalomyelitis and multiple sclerosis. The authors have isolated bovine, mouse, and rat MOG cDNA clones and shown that the developmental pattern of MOG expression in the rat central nervous system coincides with the late stages of myelination. The amino-terminal, extracellular domain of MOG has characteristics of an immunoglobulin variable domain and is 46% and 41% identical with the amino terminus of bovine butyrophilin (expressed in the lactating mammary gland) and B-G antigens of the chicken major histocompatibility complex (MHC), respectively; these proteins thus form a subset of the immunoglobulin superfamily. The homology between MOG and B-G extends beyond their structure and genetic mapping to their ability to induce strong antibody responses and has implications for the role of MOG in pathological, autoimmune conditions. The authors colocalized the MOG and BT genes to the human MHC on chromosome 6p21.3-p22. The mouse MOG gene was mapped to the homologous band C of chromosome 17, within the M region of the mouse MHC. 38 refs., 6 figs.

  15. Major histocompatibility complex-unrestricted cytolytic activity of human T cells: analysis of precursor frequency and effector phenotype

    International Nuclear Information System (INIS)

    Patel, S.S.; Thiele, D.L.; Lipsky, P.E.

    1987-01-01

    The frequency and phenotype of human T cells that mediate major histocompatibility complex (MHC)-unrestricted cytolysis were analyzed. T cell clones were generated by culturing adherent cell-depleted peripheral blood mononuclear cells at a density of 0.3 cell/well with phytohemagglutinin, recombinant interleukin 2 (rIL-2), and irradiated autologous peripheral blood mononuclear cells and/or Epstein-Barr virus-transformed lymphoblastoid cell lines. All of the 198 clones generated by this method were T cells (CD2 + , CD3 + , CD4 + or CD2 + , CD3 + , CD8 + ) that possessed potent lytic activity against K562, an erythroleukemia line sensitive to lysis by human natural killer cells, and Cur, a renal carcinoma cell line resistant to human natural killer activity. Cytolysis, measured by 51 Cr release, was MHC-unrestricted, since the clones were able to lyse MHC class I or class II negative targets, as well as MHC class I and class II negative targets. Although the clones produced tissue necrosis factor/lymphotoxin-like molecules, lysis of Cur of K562 was not mediated by a soluble factor secreted by the clones. These data indicate that the capacity for MHC-unrestricted tumoricidal activity and expression of NKH1 and CD11b, but not CD 16, are properties common to all or nearly all human peripheral blood-derived T cell clones regardless of CD4 or CD8 phenotype

  16. Historical perspective on the synonymization of the four major pest species belonging to the Bactrocera dorsalis species complex (Diptera, Tephritidae).

    Science.gov (United States)

    Hee, Alvin K W; Wee, Suk-Ling; Nishida, Ritsuo; Ono, Hajime; Hendrichs, Jorge; Haymer, David S; Tan, Keng-Hong

    2015-01-01

    An FAO/IAEA-sponsored coordinated research project on integrative taxonomy, involving close to 50 researchers from at least 20 countries, culminated in a significant breakthrough in the recognition that four major pest species, Bactrocera dorsalis, Bactrocera philippinensis, Bactrocera papayae and Bactrocera invadens, belong to the same biological species, Bactrocera dorsalis. The successful conclusion of this initiative is expected to significantly facilitate global agricultural trade, primarily through the lifting of quarantine restrictions that have long affected many countries, especially those in regions such as Asia and Africa that have large potential for fresh fruit and vegetable commodity exports. This work stems from two taxonomic studies: a revision in 1994 that significantly increased the number of described species in the Bactrocera dorsalis species complex; and the description in 2005 of Bactrocera invadens, then newly incursive in Africa. While taxonomically valid species, many biologists considered that these were different names for one biological species. Many disagreements confounded attempts to develop a solution for resolving this taxonomic issue, before the FAO/IAEA project commenced. Crucial to understanding the success of that initiative is an accounting of the historical events and perspectives leading up to the international, multidisciplinary collaborative efforts that successfully achieved the final synonymization. This review highlights the 21 year journey taken to achieve this outcome.

  17. Elevation of soluble major histocompatibility complex class I related chain A protein in malignant and infectious diseases in Chinese patients

    Directory of Open Access Journals (Sweden)

    Jiang Xiaoxin

    2012-11-01

    Full Text Available Abstract Background Elevation of soluble major histocompatibility complex class I chain-related gene A (sMICA products in serum has been linked to tissue/organ transplantation, autoimmune diseases and some malignant disorders. Cells infected by microbiological pathogens may release sMICA, whereas less is known whether and to what extent serum sMICA levels may change in infectious diseases. Methods The present study determined serum sMICA levels by enzyme-linked immunosorbent assay (ELISA in a southern China population, including patients (n = 1041 suffering from several types of malignant and infectious diseases and healthy controls (n = 141. Results Relative to controls, serum sMICA elevation was significant in patients of hepatic cancer, and was approaching statistical significance in patients with lung, gastric and nasopharyngeal cancers. sMICA elevation was also associated with some bacterial (Enterobacteriaceae, Mycobacterium tuberculosis, non-fermenting Gram-negative bacteria and Gram-positive cocci, viral (hepatitis B and C and the Microspironema pallidum infections. Conclusion Serum sMICA levels may be informative for the diagnosis of some malignant and infectious diseases. The results also indicate that microbiological infections should be considered as a potential confounding clinical condition causing serum sMICA elevation while using this test to evaluate the status of other disorders, such as cancers, host-graft response and autoimmune diseases.

  18. Recent advances in Major Histocompatibility Complex (MHC) class I antigen presentation: Plastic MHC molecules and TAPBPR-mediated quality control

    Science.gov (United States)

    van Hateren, Andy; Bailey, Alistair; Elliott, Tim

    2017-01-01

    We have known since the late 1980s that the function of classical major histocompatibility complex (MHC) class I molecules is to bind peptides and display them at the cell surface to cytotoxic T cells. Recognition by these sentinels of the immune system can lead to the destruction of the presenting cell, thus protecting the host from pathogens and cancer. Classical MHC class I molecules (MHC I hereafter) are co-dominantly expressed, polygenic, and exceptionally polymorphic and have significant sequence diversity. Thus, in most species, there are many different MHC I allotypes expressed, each with different peptide-binding specificity, which can have a dramatic effect on disease outcome. Although MHC allotypes vary in their primary sequence, they share common tertiary and quaternary structures. Here, we review the evidence that, despite this commonality, polymorphic amino acid differences between allotypes alter the ability of MHC I molecules to change shape (that is, their conformational plasticity). We discuss how the peptide loading co-factor tapasin might modify this plasticity to augment peptide loading. Lastly, we consider recent findings concerning the functions of the non-classical MHC I molecule HLA-E as well as the tapasin-related protein TAPBPR (transporter associated with antigen presentation binding protein-related), which has been shown to act as a second quality-control stage in MHC I antigen presentation. PMID:28299193

  19. Major Histocompatibility Complex I Mediates Immunological Tolerance of the Trophoblast during Pregnancy and May Mediate Rejection during Parturition

    Science.gov (United States)

    Rapacz-Leonard, Anna; Dąbrowska, Małgorzata; Janowski, Tomasz

    2014-01-01

    During pregnancy in larger mammals, the maternal immune system must tolerate the fetus for months while resisting external infection. This tolerance is facilitated by immunological communication between the fetus and the mother, which is mediated by Major Histocompatibility Complex I (MHC I) proteins, by leukocytes, and by the cytokines secreted by the leukocytes. Fetal-maternal immunological communication also supports pregnancy by inducing physiological changes in the mother. If the mother “misunderstands” the signal sent by the fetus during pregnancy, the fetus will be miscarried or delivered preterm. Unlike any other maternal organ, the placenta can express paternal antigens. At parturition, paternal antigens are known to be expressed in cows and may be expressed in horses, possibly so that the maternal immune system will reject the placenta and help to expel it. This review compares fetal-maternal crosstalk that is mediated by the immune system in three species with pregnancies that last for nine months or longer: humans, cattle, and horses. It raises the possibility that immunological communication early in pregnancy may prepare the mother for successful expulsion of fetal membranes at parturition. PMID:24812442

  20. Association Between Major Histocompatibility Complex Class I Chain-Related Gene Polymorphisms and Susceptibility of Systemic Lupus Erythematosus.

    Science.gov (United States)

    Yu, Ping; Zhu, Quan; Chen, Chunjing; Fu, Xiaoling; Li, Yu; Liu, Limin; Luo, Qizhi; Wang, Fuyan; Wang, Yong

    2017-10-01

    Major histocompatibility complex class I chain-related gene (MIC) polymorphisms have been associated with many autoimmune diseases. To explore the correlation between MIC polymorphisms and systemic lupus erythematosus (SLE), we compared the sequence of the MIC gene in Han Chinese patients with SLE from Hainan Island, China, with healthy individuals. In this study, the MIC polymorphisms in 296 subjects (159 patients with SLE and 137 healthy volunteers) of Han ethnicity from Hainan Island were characterized. A chi-square test was performed to evaluate the differences in the allelic frequency of the MIC genes between patients with SLE and the control subjects. The genotyping results indicated that the frequencies of the MICA*010, MICB*014, and MICB*002 alleles were significantly higher in the control subjects than the patients with SLE. Additionally, the results also indicated that the frequency of the MICB*009N in the SLE group was significantly increased compared to that in the matched control subjects. The results of this study suggested that the MICB*009N allele might be a risk factor for SLE, whereas the MICB*014, MICA*010 and MICB*002 alleles were associated with reduced incidence of SLE in the study population. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  1. Association of early onset myasthenia gravis in Newfoundland dogs with the canine major histocompatibility complex class I.

    Science.gov (United States)

    Wolf, Zena; Vernau, Karen; Safra, Noa; Shelton, G Diane; King, Jason; Owen, Joseph; Weich, Kalie; Bannasch, Danika

    2017-05-01

    Acquired Myasthenia Gravis (MG) is an autoimmune neuromuscular disorder whose development in humans has been associated with the Major Histocompatibility Complex (MHC) or Human Leukocyte Antigen (HLA). There is a form of early onset MG (EOMG) in Newfoundland dogs that mimics the clinical presentation in humans and appears to have familial inheritance. Genotyping of three classical Dog Leukocyte Antigen (DLA) class II genes, DLA-DRB1, DLA-DQA1 and DLA-DQB1, in 16 Newfoundlands with EOMG and 46 unaffected Newfoundlands, identified DLA-DQB1 *00301 (p-value = 0.0051 OR: 7.41) as a risk locus for the development of EOMG in this breed. In order to further investigate the extent of the association to the entire MHC region, 208 additional SNPs were genotyped in two phases. Both a risk locus for EOMG to the DLA class I (chr12: 458483-506460) and a protective locus for EOMG susceptibility that extends outside of the DLA class I (chr12: 89701-475348) were identified. Four additional dog breeds with an elevated risk for the development of MG were SNP genotyped, but no shared or significant associations were found. MHC involvement in canine MG disease manifestation overlaps with loci identified in human studies and highlights the value of dogs as a model for genetic studies of naturally occurring diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. The expression of major histocompatibility complex class I in endometrial epithelial cells from dairy cow under a simulating hypoxic environment.

    Science.gov (United States)

    Wu, Haichong; Jiang, Kangfeng; Zhang, Tao; Zhao, Gan; Shaukat, Aftab; Deng, Ganzhen

    2018-01-25

    During the first trimester of pregnancy in dairy cows, the fetus is mainly recognized by the expression of major histocompatibility complex class I (MHC-I) in the maternal immune system. Before the embryo begins to implant in the maternal uterus, it requires a long time to remodel and develop vessels in the placenta. During this stage, the embryos are exposed to a hypoxic environment. However, the expression of bovine MHC-I has not been determined in hypoxic bovine endometrial epithelial cells (bEECs). Hypoxia-inducible factor-1α (HIF-1α) is a marker for hypoxic conditions in cells. In the present study, we used cobalt chloride (CoCl 2 ) to establish a hypoxic cell model and then determined the expression of the classical gene BoLA-A and the non-classical gene MICB. qRT-PCR and western blot assays were applied to determine the expression of HIF-1α. qRT-PCR was performed to detect the levels of BoLA-A and MICB mRNAs. The results showed that HIF-1α expression was increased in the hypoxic cell model. The expression of BoLA-A was increased, but MICB levels were decreased in bEECs. Our study provides a basis for exploring the cattle intrauterine environment during pregnancy. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Mate choice for major histocompatibility complex genetic divergence as a bet-hedging strategy in the Atlantic salmon (Salmo salar)

    Science.gov (United States)

    Evans, Melissa L.; Dionne, Mélanie; Miller, Kristina M.; Bernatchez, Louis

    2012-01-01

    Major histocompatibility complex (MHC)-dependent mating preferences have been observed across vertebrate taxa and these preferences are expected to promote offspring disease resistance and ultimately, viability. However, little empirical evidence linking MHC-dependent mate choice and fitness is available, particularly in wild populations. Here, we explore the adaptive potential of previously observed patterns of MHC-dependent mate choice in a wild population of Atlantic salmon (Salmo salar) in Québec, Canada, by examining the relationship between MHC genetic variation and adult reproductive success and offspring survival over 3 years of study. While Atlantic salmon choose their mates in order to increase MHC diversity in offspring, adult reproductive success was in fact maximized between pairs exhibiting an intermediate level of MHC dissimilarity. Moreover, patterns of offspring survival between years 0+ and 1+, and 1+ and 2+ and population genetic structure at the MHC locus relative to microsatellite loci indicate that strong temporal variation in selection is likely to be operating on the MHC. We interpret MHC-dependent mate choice for diversity as a likely bet-hedging strategy that maximizes parental fitness in the face of temporally variable and unpredictable natural selection pressures. PMID:21697172

  4. Male mate choice relies on major histocompatibility complex class I in a sex-role-reversed pipefish.

    Science.gov (United States)

    Roth, O; Sundin, J; Berglund, A; Rosenqvist, G; Wegner, K M

    2014-05-01

    Mate choice for compatible genes is often based on genes of the major histocompatibility complex (MHC). Although MHC-based mate choice is commonly observed in female choice, male mate choice remains elusive. In particular, if males have intense paternal care and are thus the choosing sex, male choice for females with dissimilar MHC can be expected. Here, we investigated whether male mate choice relies on MHC class I genes in the sex-role reversed pipefish Syngnathus typhle. In a mate choice experiment, we determined the relative importance of visual and olfactory cues by manipulating visibility and olfaction. We found that pipefish males chose females that maximize sequence-based amino acid distance between MHC class I genotypes in the offspring when olfactory cues were present. Under visual cues, large females were chosen, but in the absence of visual cues, the choice pattern was reversed. The use of sex-role reversed species thus revealed that sexual selection can lead to the evolution of male mate choice for MHC class I genes. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  5. Generation of a genomic tiling array of the human Major Histocompatibility Complex (MHC and its application for DNA methylation analysis

    Directory of Open Access Journals (Sweden)

    Ottaviani Diego

    2008-05-01

    Full Text Available Abstract Background The major histocompatibility complex (MHC is essential for human immunity and is highly associated with common diseases, including cancer. While the genetics of the MHC has been studied intensively for many decades, very little is known about the epigenetics of this most polymorphic and disease-associated region of the genome. Methods To facilitate comprehensive epigenetic analyses of this region, we have generated a genomic tiling array of 2 Kb resolution covering the entire 4 Mb MHC region. The array has been designed to be compatible with chromatin immunoprecipitation (ChIP, methylated DNA immunoprecipitation (MeDIP, array comparative genomic hybridization (aCGH and expression profiling, including of non-coding RNAs. The array comprises 7832 features, consisting of two replicates of both forward and reverse strands of MHC amplicons and appropriate controls. Results Using MeDIP, we demonstrate the application of the MHC array for DNA methylation profiling and the identification of tissue-specific differentially methylated regions (tDMRs. Based on the analysis of two tissues and two cell types, we identified 90 tDMRs within the MHC and describe their characterisation. Conclusion A tiling array covering the MHC region was developed and validated. Its successful application for DNA methylation profiling indicates that this array represents a useful tool for molecular analyses of the MHC in the context of medical genomics.

  6. Constraints within major histocompatibility complex class I restricted peptides: Presentation and consequences for T-cell recognition

    Energy Technology Data Exchange (ETDEWEB)

    Theodossis, Alex; Guillonneau, Carole; Welland, Andrew; Ely, Lauren K.; Clements, Craig S.; Williamson, Nicholas A.; Webb, Andrew I.; Wilce, Jacqueline A.; Mulder, Roger J.; Dunstone, Michelle A.; Doherty, Peter C.; McCluskey, James; Purcell, Anthony W.; Turner, Stephen J.; Rossjohn, Jamie (Ian Wark Lab.); (Monash); (Melbourne)

    2010-03-24

    Residues within processed protein fragments bound to major histocompatibility complex class I (MHC-I) glycoproteins have been considered to function as a series of 'independent pegs' that either anchor the peptide (p) to the MHC-I and/or interact with the spectrum of {alpha}{beta}-T-cell receptors (TCRs) specific for the pMHC-I epitope in question. Mining of the extensive pMHC-I structural database established that many self- and viral peptides show extensive and direct interresidue interactions, an unexpected finding that has led us to the idea of 'constrained' peptides. Mutational analysis of two constrained peptides (the HLA B44 restricted self-peptide (B44DP{alpha}-EEFGRAFSF)) and an H2-D{sup b} restricted influenza peptide (D{sup b}PA, SSLENFRAYV) demonstrated that the conformation of the prominently exposed arginine in both peptides was governed by interactions with MHC-I-orientated flanking residues from the peptide itself. Using reverse genetics in a murine influenza model, we revealed that mutation of an MHC-I-orientated residue (SSLENFRAYV {yields} SSLENARAYV) within the constrained PA peptide resulted in a diminished cytotoxic T lymphocyte (CTL) response and the recruitment of a limited pMHC-I specific TCR repertoire. Interactions between individual peptide positions can thus impose fine control on the conformation of pMHC-I epitopes, whereas the perturbation of such constraints can lead to a previously unappreciated mechanism of viral escape.

  7. Female major histocompatibility complex type affects male testosterone levels and sperm number in the horse (Equus caballus).

    Science.gov (United States)

    Burger, D; Dolivo, G; Marti, E; Sieme, H; Wedekind, C

    2015-05-22

    Odours of vertebrates often contain information about the major histocompatibility complex (MHC), and are used in kin recognition, mate choice or female investment in pregnancy. It is, however, still unclear whether MHC-linked signals can also affect male reproductive strategies. We used horses (Equus caballus) to study this question under experimental conditions. Twelve stallions were individually exposed either to an unfamiliar MHC-similar mare and then to an unfamiliar MHC-dissimilar mare, or vice versa. Each exposure lasted over a period of four weeks. Peripheral blood testosterone levels were determined weekly. Three ejaculates each were collected in the week after exposure to both mares (i.e. in the ninth week) to determine mean sperm number and sperm velocity. We found high testosterone levels when stallions were kept close to MHC-dissimilar mares and significantly lower ones when kept close to MHC-similar mares. Mean sperm number per ejaculate (but not sperm velocity) was positively correlated to mean testosterone levels and also affected by the order of presentation of mares: sperm numbers were higher if MHC-dissimilar mares were presented last than if MHC-similar mares were presented last. We conclude that MHC-linked signals influence testosterone secretion and semen characteristics, two indicators of male reproductive strategies. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  8. The evolution of the major histocompatibility complex in upstream versus downstream river populations of the longnose dace.

    Science.gov (United States)

    Crispo, Erika; Tunna, Haley R; Hussain, Noreen; Rodriguez, Silvia S; Pavey, Scott A; Jackson, Leland J; Rogers, Sean M

    2017-05-01

    Populations in upstream versus downstream river locations can be exposed to vastly different environmental and ecological conditions and can thus harbor different genetic resources due to selection and neutral processes. An interesting question is how upstream-downstream directionality in rivers affects the evolution of immune response genes. We used next-generation amplicon sequencing to identify eight alleles of the major histocompatibility complex (MHC) class II β exon 2 in the cyprinid longnose dace ( Rhinichthys cataractae ) from three rivers in Alberta, upstream and downstream of municipal and agricultural areas along contaminant gradients. We used these data to test for directional and balancing selection on the MHC. We also genotyped microsatellite loci to examine neutral population processes in this system. We found evidence for balancing selection on the MHC in the form of increased nonsynonymous variation relative to neutral expectations, and selection occurred at more amino acid residues upstream than downstream in two rivers. We found this pattern despite no population structure or isolation by distance, based on microsatellite data, at these sites. Overall, our results suggest that MHC evolution is driven by upstream-downstream directionality in fish inhabiting this system.

  9. Cross-linking staphylococcal enterotoxin A bound to major histocompatibility complex class I is required for TNF-alpha secretion

    Science.gov (United States)

    Wright, A. D.; Chapes, S. K.

    1999-01-01

    The mechanism of how superantigens function to activate cells has been linked to their ability to bind and cross-link the major histocompatibility complex class II (MHCII) molecule. Cells that lack the MHCII molecule also respond to superantigens, however, with much less efficiency. Therefore, the purpose of this study was to confirm that staphylococcal enterotoxin A (SEA) could bind the MHCI molecule and to test the hypothesis that cross-linking SEA bound to MHCII-deficient macrophages would induce a more robust cytokine response than without cross-linking. We used a capture enzyme-linked immunosorbent assay and an immunprecipitation assay to directly demonstrate that MHCI molecules bind SEA. Directly cross-linking MHCI using monoclonal antibodies or cross-linking bound SEA with an anti-SEA antibody or biotinylated SEA with avidin increased TNF-alpha and IL-6 secretion by MHCII(-/-) macrophages. The induction of a vigorous macrophage cytokine response by SEA/anti-SEA cross-linking of MHCI offers a mechanism to explain how MHCI could play an important role in superantigen-mediated pathogenesis. Copyright 1999 Academic Press.

  10. Membrane-bound versus soluble major histocompatibility complex Class I-related chain A and major histocompatibility complex Class I-related chain B differential expression: Mechanisms of tumor eradication versus evasion and current drug development strategies

    Directory of Open Access Journals (Sweden)

    P K Suresh

    2016-01-01

    Full Text Available Major histocompatibility complex Class I-related chain A/chain B (MICA/MICB is stress-inducible, highly polymorphic ligands whose expression at the transcript level has been detected in all tissues except the central nervous system. However, their restricted protein expression is due to their regulation at the posttranslational level. Its levels are elevated in virally infected and neoplastically transformed cells. Membrane expression of this NKG2DL marks the aberrant cells for elimination by those immune effector cells that express the cognate NKG2D receptor. Among the evasion strategies developed by tumors, the metalloprotease-dependent shedding of MICA/MICB from tumors (either the free or the exosome form can contribute to the inhibition of cytolysis by the immune effector cells (all NK cells, most NKT cells; γδ CD8+ T cells and αβ CD8+ T cells, as well as some αβ CD4+ T cells. There are micro-RNA clusters that regulate surface expression and shedding. Polymorphic variants can be used as susceptibility/associative markers and can also possibly be used to correlate with tumor survival as well as staging/grading of tumors. Variations in the expression level require quantification of this marker for diagnostic/prognostic and therapeutic purposes. Mechanism-based studies would provide a better tumor-specific understanding of their relative roles in the processes of tumor cell elimination versus growth and progression. Last but not least, conventional, interlaboratory validated assays (for, e.g., antibody-based methods should be replaced by robust, reproducible, feasible biophysics-based methods using tumor biopsies. Further, correlative DNA polymorphism-based studies can be done using biological fluids (for, e.g., human saliva that can be sampled by minimally invasive means.

  11. Membrane-bound versus soluble major histocompatibility complex Class I-related chain A and major histocompatibility complex Class I-related chain B differential expression: Mechanisms of tumor eradication versus evasion and current drug development strategies.

    Science.gov (United States)

    Suresh, P K

    2016-01-01

    Major histocompatibility complex Class I-related chain A/chain B (MICA/MICB) is stress-inducible, highly polymorphic ligands whose expression at the transcript level has been detected in all tissues except the central nervous system. However, their restricted protein expression is due to their regulation at the posttranslational level. Its levels are elevated in virally infected and neoplastically transformed cells. Membrane expression of this NKG2DL marks the aberrant cells for elimination by those immune effector cells that express the cognate NKG2D receptor. Among the evasion strategies developed by tumors, the metalloprotease-dependent shedding of MICA/MICB from tumors (either the free or the exosome form) can contribute to the inhibition of cytolysis by the immune effector cells (all NK cells, most NKT cells; γδ CD8+ T cells and αβ CD8+ T cells, as well as some αβ CD4+ T cells). There are micro-RNA clusters that regulate surface expression and shedding. Polymorphic variants can be used as susceptibility/associative markers and can also possibly be used to correlate with tumor survival as well as staging/grading of tumors. Variations in the expression level require quantification of this marker for diagnostic/prognostic and therapeutic purposes. Mechanism-based studies would provide a better tumor-specific understanding of their relative roles in the processes of tumor cell elimination versus growth and progression. Last but not least, conventional, interlaboratory validated assays (for, e.g., antibody-based methods) should be replaced by robust, reproducible, feasible biophysics-based methods using tumor biopsies. Further, correlative DNA polymorphism-based studies can be done using biological fluids (for, e.g., human saliva) that can be sampled by minimally invasive means.

  12. Giant panda BAC library construction and assembly of a 650-kb contig spanning major histocompatibility complex class II region

    Directory of Open Access Journals (Sweden)

    Pan Hui-Juan

    2007-09-01

    Full Text Available Abstract Background Giant panda is rare and endangered species endemic to China. The low rates of reproductive success and infectious disease resistance have severely hampered the development of captive and wild populations of the giant panda. The major histocompatibility complex (MHC plays important roles in immune response and reproductive system such as mate choice and mother-fetus bio-compatibility. It is thus essential to understand genetic details of the giant panda MHC. Construction of a bacterial artificial chromosome (BAC library will provide a new tool for panda genome physical mapping and thus facilitate understanding of panda MHC genes. Results A giant panda BAC library consisting of 205,800 clones has been constructed. The average insert size was calculated to be 97 kb based on the examination of 174 randomly selected clones, indicating that the giant panda library contained 6.8-fold genome equivalents. Screening of the library with 16 giant panda PCR primer pairs revealed 6.4 positive clones per locus, in good agreement with an expected 6.8-fold genomic coverage of the library. Based on this BAC library, we constructed a contig map of the giant panda MHC class II region from BTNL2 to DAXX spanning about 650 kb by a three-step method: (1 PCR-based screening of the BAC library with primers from homologous MHC class II gene loci, end sequences and BAC clone shotgun sequences, (2 DNA sequencing validation of positive clones, and (3 restriction digest fingerprinting verification of inter-clone overlapping. Conclusion The identifications of genes and genomic regions of interest are greatly favored by the availability of this giant panda BAC library. The giant panda BAC library thus provides a useful platform for physical mapping, genome sequencing or complex analysis of targeted genomic regions. The 650 kb sequence-ready BAC contig map of the giant panda MHC class II region from BTNL2 to DAXX, verified by the three-step method, offers a

  13. Abdominal tuberculosis in children

    International Nuclear Information System (INIS)

    Ablin, D.S.; Jain, K.A.; Azouz, E.M.

    1994-01-01

    Four boys with abdominal tuberculosis, one of whom had acquired immunodeficiency syndrome, are presented. Abdominal imaging findings on plain radiography, ultrasonography, computer tomography, and gastrointestinal contrast studies included tuberculous peritonitis and ascites in all patients, tuberculous adenopathy in two, gastrointestinal tuberculosis in two, and omental tuberculosis in two. The radiographic features particularly characteristic of abdominal tuberculosis were: (1) Low attenuating adenopathy with rim enhancement, (2) omental or ileocecal inflammatory mass, (3) high density ascites, and (4) gastrointestinal enteritis involving the ileocecal region. (orig./MG)

  14. Major histocompatibility complex variation in insular populations of the Egyptian vulture: inferences about the roles of genetic drift and selection.

    Science.gov (United States)

    Agudo, Rosa; Alcaide, Miguel; Rico, Ciro; Lemus, Jesus A; Blanco, Guillermo; Hiraldo, Fernando; Donázar, Jose A

    2011-06-01

    Insular populations have attracted the attention of evolutionary biologists because of their morphological and ecological peculiarities with respect to their mainland counterparts. Founder effects and genetic drift are known to distribute neutral genetic variability in these demes. However, elucidating whether these evolutionary forces have also shaped adaptive variation is crucial to evaluate the real impact of reduced genetic variation in small populations. Genes of the major histocompatibility complex (MHC) are classical examples of evolutionarily relevant loci because of their well-known role in pathogen confrontation and clearance. In this study, we aim to disentangle the partial roles of genetic drift and natural selection in the spatial distribution of MHC variation in insular populations. To this end, we integrate the study of neutral (22 microsatellites and one mtDNA locus) and MHC class II variation in one mainland (Iberia) and two insular populations (Fuerteventura and Menorca) of the endangered Egyptian vulture (Neophron percnopterus). Overall, the distribution of the frequencies of individual MHC alleles (n=17 alleles from two class II B loci) does not significantly depart from neutral expectations, which indicates a prominent role for genetic drift over selection. However, our results point towards an interesting co-evolution of gene duplicates that maintains different pairs of divergent alleles in strong linkage disequilibrium on islands. We hypothesize that the co-evolution of genes may counteract the loss of genetic diversity in insular demes, maximize antigen recognition capabilities when gene diversity is reduced, and promote the co-segregation of the most efficient allele combinations to cope with local pathogen communities. © 2011 Blackwell Publishing Ltd.

  15. Novel full-length major histocompatibility complex class I allele discovery and haplotype definition in pig-tailed macaques.

    Science.gov (United States)

    Semler, Matthew R; Wiseman, Roger W; Karl, Julie A; Graham, Michael E; Gieger, Samantha M; O'Connor, David H

    2017-11-13

    Pig-tailed macaques (Macaca nemestrina, Mane) are important models for human immunodeficiency virus (HIV) studies. Their infectability with minimally modified HIV makes them a uniquely valuable animal model to mimic human infection with HIV and progression to acquired immunodeficiency syndrome (AIDS). However, variation in the pig-tailed macaque major histocompatibility complex (MHC) and the impact of individual transcripts on the pathogenesis of HIV and other infectious diseases is understudied compared to that of rhesus and cynomolgus macaques. In this study, we used Pacific Biosciences single-molecule real-time circular consensus sequencing to describe full-length MHC class I (MHC-I) transcripts for 194 pig-tailed macaques from three breeding centers. We then used the full-length sequences to infer Mane-A and Mane-B haplotypes containing groups of MHC-I transcripts that co-segregate due to physical linkage. In total, we characterized full-length open reading frames (ORFs) for 313 Mane-A, Mane-B, and Mane-I sequences that defined 86 Mane-A and 106 Mane-B MHC-I haplotypes. Pacific Biosciences technology allows us to resolve these Mane-A and Mane-B haplotypes to the level of synonymous allelic variants. The newly defined haplotypes and transcript sequences containing full-length ORFs provide an important resource for infectious disease researchers as certain MHC haplotypes have been shown to provide exceptional control of simian immunodeficiency virus (SIV) replication and prevention of AIDS-like disease in nonhuman primates. The increased allelic resolution provided by Pacific Biosciences sequencing also benefits transplant research by allowing researchers to more specifically match haplotypes between donors and recipients to the level of nonsynonymous allelic variation, thus reducing the risk of graft-versus-host disease.

  16. A Comprehensive Calorimetric Investigation of an Entropically Driven T Cell Receptor-Peptide/Major Histocompatibility Complex Interaction

    Science.gov (United States)

    Armstrong, Kathryn M.; Baker, Brian M.

    2007-01-01

    The αβ T cell receptor (TCR) is responsible for recognizing peptides bound and “presented” by major histocompatibility complex (MHC) molecules. We recently reported that at 25°C the A6 TCR, which recognizes the Tax peptide presented by the class I MHC human leukocyte antigen-A*0201 (HLA-A2), binds with a weak ΔH°, a favorable ΔS°, and a moderately negative ΔCp. These observations were of interest given the unfavorable binding entropies and large heat capacity changes measured for many other TCR-ligand interactions, suggested to result from TCR conformational changes occurring upon binding. Here, we further investigated the A6-Tax/HLA-A2 interaction using titration calorimetry. We found that binding results in a pKa shift, complicating interpretation of measured binding thermodynamics. To better characterize the interaction, we measured binding as a function of pH, temperature, and buffer ionization enthalpy. A global analysis of the resulting data allowed determination of both the intrinsic binding thermodynamics separated from the influence of protonation as well as the thermodynamics associated with the pKa shift. Our results indicate that intrinsically, A6 binds Tax/HLA-A2 with a very weak ΔH°, an even more favorable ΔS° than previously thought, and a relatively large negative ΔCp. Comparison of these energetics with the makeup of the protein-protein interface suggests that conformational adjustments are required for binding, but these are more likely to be structural shifts, rather than disorder-to-order transitions. The thermodynamics of the pKa shift suggest protonation may be linked to an additional process such as ion binding. PMID:17449678

  17. Role of major histocompatibility complex class II in resistance of mice to naturally acquired infection with Syphacia obvelata

    Science.gov (United States)

    Stewart, Patricia W.; Chapes, Stephen K.

    2003-01-01

    Genetics plays a substantial role in host resistance in many host-parasite interactions. We examined the prevalence of naturally acquired infection with Syphacia obvelata in a number of mouse strains housed in a non-barrier facility. These mice, which included cross-bred and congenic, inbred strains on various genetic backgrounds, differ in the loci for the immune function genes--major histocompatibility complex class II (MHCII), toll-like receptor 4 (Tlr4), and solute carrier family 11, member 1 (Slc11a1)--which allowed comparisons of the impact of these genes on resistance to pinworm infection. Male and female mice of various ages were sampled over an 18-month period; infection was determined by use of the cellophane tape test. Results indicated that mice that were MHCII+/+ had a significantly lower prevalence of infection than did mice that were MHCII-/-. Differences were not seen between male and female mice. Although MHCII+/+ mice had an age-associated decrease in infection prevalence, such decrease was not seen in MHCII-/- mice. In contrast, infection prevalence in mice with the normal Tlr4 gene (Tlr4(LPS-n/LPS-n)) gene did not differ significantly compared with that in mice that were homozygous for either the point mutation (Tlr4(LPS-d/LPS-d)) or deletion (Tlr4(LPS-del/LPS-del)) of that gene. Likewise, the presence (Sle11a1r/r) or absence (Slc11a1s/s) of functional alleles for Slc11a1 had no effect on the prevalence of infection with S. obvelata. In conclusion, presence of MHCII, but not Tlr4 or Slc11a1 significantly influences prevalence of naturally acquired infection with S. obvelata. These data justify further comprehensive analyses of the immune components that are involved in pinworm resistance.

  18. Selection, trans-species polymorphism, and locus identification of major histocompatibility complex class IIβ alleles of New World ranid frogs

    Science.gov (United States)

    Kiemnec-Tyburczy, Karen M.; Richmond, Jonathan Q.; Savage, Anna E.; Zamudio, Kelly R.

    2010-01-01

    Genes encoded by the major histocompatibility complex (MHC) play key roles in the vertebrate immune system. However, our understanding of the evolutionary processes and underlying genetic mechanisms shaping these genes is limited in many taxa, including amphibians, a group currently impacted by emerging infectious diseases. To further elucidate the evolution of the MHC in frogs (anurans) and develop tools for population genetics, we surveyed allelic diversity of the MHC class II ??1 domain in both genomic and complementary DNA of seven New World species in the genus Rana (Lithobates). To assign locus affiliation to our alleles, we used a "gene walking" technique to obtain intron 2 sequences that flanked MHC class II?? exon 2. Two distinct intron sequences were recovered, suggesting the presence of at least two class II?? loci in Rana. We designed a primer pair that successfully amplified an orthologous locus from all seven Rana species. In total, we recovered 13 alleles and documented trans-species polymorphism for four of the alleles. We also found quantitative evidence of selection acting on amino acid residues that are putatively involved in peptide binding and structural stability of the ??1 domain of anurans. Our results indicated that primer mismatch can result in polymerase chain reaction (PCR) bias, which influences the number of alleles that are recovered. Using a single locus may minimize PCR bias caused by primer mismatch, and the gene walking technique was an effective approach for generating single-copy orthologous markers necessary for future studies of MHC allelic variation in natural amphibian populations. ?? 2010 Springer-Verlag.

  19. Inflammatory bowel diseases influence major histocompatibility complex class I (MHC I) and II compartments in intestinal epithelial cells.

    Science.gov (United States)

    Bär, F; Sina, C; Hundorfean, G; Pagel, R; Lehnert, H; Fellermann, K; Büning, J

    2013-05-01

    Antigen presentation by intestinal epithelial cells (IEC) is crucial for intestinal homeostasis. Disturbances of major histocompatibility complex class I (MHC I)- and II-related presentation pathways in IEC appear to be involved in an altered activation of CD4(+) and CD8(+) T cells in inflammatory bowel disease. However, a comprehensive analysis of MHC I- and II-enriched compartments in IEC of the small and large bowel in the healthy state as opposed to inflammatory bowel diseases is lacking. The aim of this study was to characterize the subcellular expression of MHC I and II in the endocytic pathway of IEC throughout all parts of the intestinal tract, and to identify differences between the healthy state and inflammatory bowel diseases. Biopsies were taken by endoscopy from the duodenum, jejunum, ileum and colon in healthy individuals (n = 20). In Crohn's disease (CD), biopsies were obtained from the ileum and colon and within the colon from ulcerative colitis (UC) patients (n = 15). Analysis of IEC was performed by immunoelectron microscopy. MHC I and II were identified in early endosomes and multi-vesicular, multi-lamellar, electrondense and vacuolar late endosomes. Both molecules were enriched in multi-vesicular bodies. No differences were found between the distinct parts of the gut axis. In CD and UC the expression of MHC I and II showed a shift from multi-vesicular bodies towards the basolateral membranes. Within the multi-vesicular bodies, MHC I and II moved from internal vesicles to the limiting membranes upon inflammation in CD and UC. MHC I- and II-enriched compartments in IEC were identical in all parts of the small and large bowel. CD and UC appear to modulate the MHC I- and II-related presentation pathways of exogenous antigens in IEC. © 2012 British Society for Immunology.

  20. Major Histocompatibility Complex I and II Expression and Lymphocytic Subtypes in Muscle of Horses with Immune-Mediated Myositis.

    Science.gov (United States)

    Durward-Akhurst, S A; Finno, C J; Barnes, N; Shivers, J; Guo, L T; Shelton, G D; Valberg, S J

    2016-07-01

    Major histocompatibility complex (MHC) I and II expression is not normally detected on sarcolemma, but is detected with lymphocytic infiltrates in immune-mediated myositis (IMM) of humans and dogs and in dysferlin-deficient muscular dystrophy. To determine if sarcolemmal MHC is expressed in active IMM in horses, if MHC expression is associated with lymphocytic subtype, and if dysferlin is expressed in IMM. Twenty-one IMM horses of Quarter Horse-related breeds, 3 healthy and 6 disease controls (3 pasture myopathy, 3 amylase-resistant polysaccharide storage myopathy [PSSM]). Immunohistochemical staining for MHC I, II, and CD4+, CD8+, CD20+ lymphocytes was performed on archived muscle of IMM and control horses. Scores were given for MHC I, II, and lymphocytic subtypes. Immunofluorescent staining for dysferlin, dystrophin, and a-sarcoglycan was performed. Sarcolemmal MHC I and II expression was detected in 17/21 and 15/21 of IMM horses, respectively, and in specific fibers of PSSM horses, but not healthy or pasture myopathy controls. The CD4+, CD8+, and CD20+ cells were present in 20/21 IMM muscles with CD4+ predominance in 10/21 and CD8+ predominance in 6/21 of IMM horses. Dysferlin, dystrophin, and a-sarcoglycan staining were similar in IMM and control muscles. Deficiencies of dysferlin, dystrophin, and a-sarcoglycan are not associated with IMM. Sarcolemmal MHC I and II expression in a proportion of myofibers of IMM horses in conjunction with lymphocytic infiltration supports an immune-mediated etiology for IMM. The MHC expression also occured in specific myofibers in PSSM horses in the absence of lymphocytic infiltrates. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  1. Major histocompatibility complex diversity is positively associated with stream water temperatures in proximate populations of sockeye salmon.

    Science.gov (United States)

    Larson, W A; Lisi, P J; Seeb, J E; Seeb, L W; Schindler, D E

    2016-09-01

    Local adaptation to heterogeneous environments generates population diversity within species, significantly increasing ecosystem stability and flows of ecosystem services. However, few studies have isolated the specific mechanisms that create and maintain this diversity. Here, we examined the relationship between water temperature in streams used for spawning and genetic diversity at a gene involved in immune function [the major histocompatibility complex (MHC)] in 14 populations of sockeye salmon (Oncorhynchus nerka) sampled across the Wood River basin in south-western Alaska. The largest influence on MHC diversity was lake basin, but we also found a significant positive correlation between average water temperature and MHC diversity. This positive relationship between temperature and MHC diversity appears to have been produced by natural selection at very local scales rather than neutral processes, as no correlation was observed between temperature and genetic diversity at 90 neutral markers. Additionally, no significant relationship was observed between temperature variability and MHC diversity. Although lake basin was the largest driver of differences in MHC diversity, our results also demonstrate that fine-scale differences in water temperature may generate variable selection regimes in populations that spawn in habitats separated by as little as 1 km. Additionally, our results indicated that some populations may be reaching a maximum level of MHC diversity. We postulate that salmon from populations in warm streams may delay spawning until late summer to avoid thermal stress as well as the elevated levels of pathogen prevalence and virulence associated with warm temperatures earlier in the summer. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  2. Identifying the degree of major histocompatibility complex matching in genetically unrelated dogs with the use of microsatellite markers.

    Science.gov (United States)

    Park, K-M; Kang, H-S; Hussein, K H; Kim, H-M; Kwak, H-H; Woo, H-M

    2015-04-01

    The dog has served as an important experimental model for biomedical research such as transplantation and developing immunosuppressive agents. Although major histocompatibility complex (MHC) in dogs is a dominant factor of graft rejection, it has not been well investigated in dogs compared with human. For that reason, imprecise cross-matching or time-consuming sequence-based typing methods have generally been used to choose specific donor and recipient pairs. Investigation of matching distribution of MHC in dogs with the use of simple and accurate methods would be beneficial for biomedical researchers. The aim of this study was to identify the diversity of dog leukocyte antigen (DLA) types in genetically unrelated dogs by means of microsatellite markers. Thirty-three Beagle and Shih-Tzu dogs, which were negative in cross-matching, were chosen. The genomic DNA was isolated from peripheral blood leukocytes, and highly polymorphic short tandem repeats located in MHC class I and II were amplified with the use of specific primers. Among all of the dogs, MHC matching groups, including class I full match-class II full match (M-M), class I full match-class II haplo match (M-H), class I haplo match-class II full match (H-M), class I haplo match-class II haplo match (H-H) groups, were ∼1.55%, 0.39%, 1.94%, and 6.59%, respectively. MHC class I nonmatch-class II nonmatch (U-U) groups were 58.14% of the total dogs. Because differences of histocompatibility between donor and recipient leads to various allograft rejections, knowledge of the distribution of MHC matching in unrelated dogs would be helpful in designing studies and to get more accurate results from experiments using dog transplantation models. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Major Histocompatibility Complex Genes Map to Two Chromosomes in an Evolutionarily Ancient Reptile, the Tuatara Sphenodon punctatus.

    Science.gov (United States)

    Miller, Hilary C; O'Meally, Denis; Ezaz, Tariq; Amemiya, Chris; Marshall-Graves, Jennifer A; Edwards, Scott

    2015-05-07

    Major histocompatibility complex (MHC) genes are a central component of the vertebrate immune system and usually exist in a single genomic region. However, considerable differences in MHC organization and size exist between different vertebrate lineages. Reptiles occupy a key evolutionary position for understanding how variation in MHC structure evolved in vertebrates, but information on the structure of the MHC region in reptiles is limited. In this study, we investigate the organization and cytogenetic location of MHC genes in the tuatara (Sphenodon punctatus), the sole extant representative of the early-diverging reptilian order Rhynchocephalia. Sequencing and mapping of 12 clones containing class I and II MHC genes from a bacterial artificial chromosome library indicated that the core MHC region is located on chromosome 13q. However, duplication and translocation of MHC genes outside of the core region was evident, because additional class I MHC genes were located on chromosome 4p. We found a total of seven class I sequences and 11 class II β sequences, with evidence for duplication and pseudogenization of genes within the tuatara lineage. The tuatara MHC is characterized by high repeat content and low gene density compared with other species and we found no antigen processing or MHC framework genes on the MHC gene-containing clones. Our findings indicate substantial differences in MHC organization in tuatara compared with mammalian and avian MHCs and highlight the dynamic nature of the MHC. Further sequencing and annotation of tuatara and other reptile MHCs will determine if the tuatara MHC is representative of nonavian reptiles in general. Copyright © 2015 Miller et al.

  4. Non-classical major histocompatibility complex class makes a crucial contribution to reproduction in the dairy cow.

    Science.gov (United States)

    Shu, Lei; Peng, Xiuli; Zhang, Shen; Deng, Ganzhen; Wu, Yue; He, Mingyue; Li, Beibei; Li, Chengye; Zhang, Kechun

    2012-01-01

    The aim of this study was to evaluate the effect of classical and non-classical major histocompatibility complex (MHC) on the reproduction in the dairy cow. Nine pairs of MHC-I genes were chosen according to their homology and possible function, and their transcription levels in maternal peripheral blood mononuclear cells (PBMCs) from all three trimesters and transcription levels in fetal tissues were compared to evaluate their contributions to cattle reproduction. The results showed that three non-classical genes were variably expressed in PBMCs of pregnant cows. MICB was downregulated in the first and second trimesters (P0.05). BoLA-NC1* was upregulated in the first and last trimesters (P0.05). BoLA-NC3* was upregulated in all trimesters (P<0.001). On the other hand, MICB was upregulated in fetal ear tissues (P<0.001), and BoLA-NC1* was almost silent in both fetal placenta and ear tissues (P<0.001); however, BoLA-NC3* was upregulated in both the fetal placenta and ear tissues (P<0.001). These results suggested that non-classical gene BoLA-NC1* increased maternal immunity against the fetus, which was inhibited by BoLA-NC3*. BoLA-NC3* also inhibited fetal autoimmunity. Apoptosis of the fetal placenta could reduce itself expressing MICB, and upregulated expression of MICB in ear tissues was favorable for the fetus to escape autoimmunity. On the other hand, downregulated expression of MICB in the fetal placenta allows for placental decoherence from the maternal placentome, which was beneficial to fetus delivery. Although classical genes were expressed differentially, their effects were restricted because of heavy chain deficiency.

  5. Endometrioma de parede abdominal Abdominal wall endometrioma

    Directory of Open Access Journals (Sweden)

    Italo Accetta

    2011-03-01

    Full Text Available RACIONAL: A incidência exata da endometriose na população geral é desconhecida. A confirmação desta doença só é possível através da análise histopatológica de um fragmento obtido por algum procedimento invasivo, pois não existe até o momento, nenhum marcador clínico seguro. OBJETIVO: Relatar a experiência com as manifestações clínicas e o tratamento cirúrgico em pacientes com endometrioma de parede abdominal. MÉTODO: Análise retrospectiva das pacientes operadas por endometrioma de parede abdominal, dando ênfase aos dados relativos à idade, sintomas, cesariana prévia, relação dos sintomas com o ciclo menstrual, exames físicos e complementares, tratamento cirúrgico, evolução pósoperatória e resultado histopatológico dos espécimes. RESULTADOS: Foram operadas 14 pacientes no período estudado, com idade entre 28 e 40 anos. A presença de massa e dor local que piorava durante a menstruação foram as queixas principais. Ultrassonografia e tomografia computadorizada foram exames importantes em localizar precisamente a doença. O tratamento cirúrgico foi exérese ampla da tumoração e dos tecidos comprometidos. As pacientes evoluíram satisfatoriamente e o histopatológico confirmou a suspeita de endometrioma de parede abdominal em todos os casos. CONCLUSÂO: Foi nítida a relação entre cesariana prévia e endometrioma de parede abdominal e estudos ultrassonográficos e tomográficos auxiliaram a planejar a abordagem cirúrgica permitindo a exérese da tumoração e de todos os tecidos adjacentes comprometidos.BACKGROND: The exact incidence of endometriosis in the general population is unknown. Confirmation of this disease is only possible by histopathological analysis of a fragment obtained by some invasive procedure, because there is so far, no clinical secure marker. AIM: To report the experience with the clinical manifestations and surgical treatment in patients with abdominal wall endometrioma. METHODS

  6. Impact of Surgihoney Reactive Oxygen on surgical site infection (SSI after complex abdominal wall reconstruction (AWR of grade 3 and 4 ventral Hernias: A single arm pilot study

    Directory of Open Access Journals (Sweden)

    Sam Parker

    2017-01-01

    Conclusions: This study will provide an assessment of methods and feasibility of recruiting and following up patients who are treated with SHRO. On the basis of this pilot trial, a full trial may be proposed in the future which will provide additional, robust evidence on the clinical and cost effectiveness of SHRO in wound management following AWR. This may act as a model for the management of wounds in complex patients undergoing AWR.

  7. Structural and Biochemical Analyses of Swine Major Histocompatibility Complex Class I Complexes and Prediction of the Epitope Map of Important Influenza A Virus Strains.

    Science.gov (United States)

    Fan, Shuhua; Wu, Yanan; Wang, Song; Wang, Zhenbao; Jiang, Bo; Liu, Yanjie; Liang, Ruiying; Zhou, Wenzhong; Zhang, Nianzhi; Xia, Chun

    2016-08-01

    The lack of a peptide-swine leukocyte antigen class I (pSLA I) complex structure presents difficulties for the study of swine cytotoxic T lymphocyte (CTL) immunity and molecule vaccine development to eliminate important swine viral diseases, such as influenza A virus (IAV). Here, after cloning and comparing 28 SLA I allelic genes from Chinese Heishan pigs, pSLA-3*hs0202 was crystalized and solved. SLA-3*hs0202 binding with sβ2m and a KMNTQFTAV (hemagglutinin [HA]-KMN9) peptide from the 2009 pandemic swine H1N1 strain clearly displayed two distinct conformations with HA-KMN9 peptides in the structures, which are believed to be beneficial to stimulate a broad spectrum of CTL immune responses. Notably, we found that different HA-KMN9 conformations are caused, not only by the flexibility of the side chains of residues in the peptide-binding groove (PBG), but also by the skewing of α1 and α2 helixes forming the PBG. In addition, alanine scanning and circular-dichroism (CD) spectra confirmed that the B, D, and F pockets play critical biochemical roles in determining the peptide-binding motif of SLA-3*hs0202. Based on biochemical parameters and comparisons to similar pockets in other known major histocompatibility complex class I (MHC-I) structures, the fundamental motif for SLA-3*hs0202 was determined to be X-(M/A/R)-(N/Q/R/F)-X-X-X-X-X-(V/I) by refolding in vitro and multiple mutant peptides. Finally, 28 SLA-3*hs0202-restricted epitope candidates were identified from important IAV strains, and two of them have been found in humans as HLA-A*0201-specific IAV epitopes. Structural and biochemical illumination of pSLA-3*hs0202 can benefit vaccine development to control IAV in swine. We crystalized and solved the first SLA-3 structure, SLA-3*hs0202, and found that it could present the same IAV peptide with two distinct conformations. Unlike previous findings showing that variable peptide conformations are caused only by the flexibility of the side chains in the groove

  8. Abdominal tuberculosis: Imaging features

    International Nuclear Information System (INIS)

    Pereira, Jose M.; Madureira, Antonio J.; Vieira, Alberto; Ramos, Isabel

    2005-01-01

    Radiological findings of abdominal tuberculosis can mimic those of many different diseases. A high level of suspicion is required, especially in high-risk population. In this article, we will describe barium studies, ultrasound (US) and computed tomography (CT) findings of abdominal tuberculosis (TB), with emphasis in the latest. We will illustrate CT findings that can help in the diagnosis of abdominal tuberculosis and describe imaging features that differentiate it from other inflammatory and neoplastic diseases, particularly lymphoma and Crohn's disease. As tuberculosis can affect any organ in the abdomen, emphasis is placed to ileocecal involvement, lymphadenopathy, peritonitis and solid organ disease (liver, spleen and pancreas). A positive culture or hystologic analysis of biopsy is still required in many patients for definitive diagnosis. Learning objectives:1.To review the relevant pathophysiology of abdominal tuberculosis. 2.Illustrate CT findings that can help in the diagnosis

  9. Abdominal and Pelvic CT

    Medline Plus

    Full Text Available ... for tumors as well as monitor response to chemotherapy. top of page How should I prepare? You ... of acute abdominal conditions in babies, such as vomiting or blood in stool. For some conditions, including ...

  10. Abdominal and Pelvic CT

    Medline Plus

    Full Text Available ... be asked to remove hearing aids and removable dental work. Women will be asked to remove bras ... can diagnose many causes of abdominal pain or injury from trauma with very high accuracy, enabling faster ...

  11. Abdominal x-ray

    Science.gov (United States)

    Abdominal film; X-ray - abdomen; Flat plate; KUB x-ray ... There is low radiation exposure. X-rays are monitored and regulated to provide the minimum amount of radiation exposure needed to produce the image. Most ...

  12. Abdominal tuberculosis: Imaging features

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Jose M. [Department of Radiology, Hospital de S. Joao, Porto (Portugal)]. E-mail: jmpjesus@yahoo.com; Madureira, Antonio J. [Department of Radiology, Hospital de S. Joao, Porto (Portugal); Vieira, Alberto [Department of Radiology, Hospital de S. Joao, Porto (Portugal); Ramos, Isabel [Department of Radiology, Hospital de S. Joao, Porto (Portugal)

    2005-08-01

    Radiological findings of abdominal tuberculosis can mimic those of many different diseases. A high level of suspicion is required, especially in high-risk population. In this article, we will describe barium studies, ultrasound (US) and computed tomography (CT) findings of abdominal tuberculosis (TB), with emphasis in the latest. We will illustrate CT findings that can help in the diagnosis of abdominal tuberculosis and describe imaging features that differentiate it from other inflammatory and neoplastic diseases, particularly lymphoma and Crohn's disease. As tuberculosis can affect any organ in the abdomen, emphasis is placed to ileocecal involvement, lymphadenopathy, peritonitis and solid organ disease (liver, spleen and pancreas). A positive culture or hystologic analysis of biopsy is still required in many patients for definitive diagnosis. Learning objectives:1.To review the relevant pathophysiology of abdominal tuberculosis. 2.Illustrate CT findings that can help in the diagnosis.

  13. Abdominal and Pelvic CT

    Medline Plus

    Full Text Available ... experienced radiologist can diagnose many causes of abdominal pain or injury from trauma with very high accuracy, enabling faster treatment and often eliminating the need for additional, more ...

  14. Abdominal and Pelvic CT

    Medline Plus

    Full Text Available ... is done because a potential abnormality needs further evaluation with additional views or a special imaging technique. ... GI) contrast exams and ultrasound are preferred for evaluation of acute abdominal conditions in babies, such as ...

  15. Abdominal Pain Syndrome

    Science.gov (United States)

    ... have a clear idea about the cause of pain. Sometimes a diagnosis is made and treatment can be started. In ... tests. Treatment What treatments are available for abdominal pain? Once a diagnosis is made, treatment can proceed for that condition. ...

  16. Abdominal and Pelvic CT

    Medline Plus

    Full Text Available ... often used to determine the cause of unexplained pain. CT scanning is fast, painless, noninvasive and accurate. ... help diagnose the cause of abdominal or pelvic pain and diseases of the internal organs, small bowel ...

  17. Abdominal and Pelvic CT

    Medline Plus

    Full Text Available ... organs and is often used to determine the cause of unexplained pain. CT scanning is fast, painless, ... procedure is typically used to help diagnose the cause of abdominal or pelvic pain and diseases of ...

  18. Abdominal and Pelvic CT

    Medline Plus

    Full Text Available ... disease such as ulcerative colitis or Crohn's disease , pancreatitis or liver cirrhosis. cancers of the liver, kidneys, ... exams and ultrasound are preferred for evaluation of acute abdominal conditions in babies, such as vomiting or ...

  19. Abdominal and Pelvic CT

    Medline Plus

    Full Text Available ... the technologist verifies that the images are of high enough quality for accurate interpretation. The CT examination ... abdominal pain or injury from trauma with very high accuracy, enabling faster treatment and often eliminating the ...

  20. Abdominal and Pelvic CT

    Medline Plus

    Full Text Available ... abdominal conditions in babies, such as vomiting or blood in stool. For some conditions, including but not limited to some liver, kidney, pancreatic, uterine or ... Content Some imaging tests and treatments have special pediatric considerations. The teddy ...

  1. Abdominal and Pelvic CT

    Medline Plus

    Full Text Available ... the liver, kidneys, pancreas, ovaries and bladder as well as lymphoma. kidney and bladder stones. abdominal aortic ... and properly administer radiation treatments for tumors as well as monitor response to chemotherapy. top of page ...

  2. A major prolactin-binding complex on human milk fat globule membranes contains cyclophilins A and B: the complex is not the prolactin receptor.

    Science.gov (United States)

    Lorenson, Mary Y; Ueda, Eric K; Chen, KuanHui E; Walker, Ameae M

    2012-03-01

    Prolactin (PRL) in milk influences maturation of gastrointestinal epithelium and development of both the hypothalamo-pituitary and immune systems of offspring. Here, we demonstrate that most PRL in human milk is part of a novel, high-affinity, multicomponent binding complex found on the milk fat globule membrane and not in whey. To examine properties of the complex, a sensitive ELISA was developed such that human PRL (hPRL) binding to the complex was measured by loss of hPRL detectability; thus, as much as 50 ng of hPRL was undetectable in the presence of 10 μl of human milk. Using the same methodology, no comparable complex formation was observed with human serum or amniotic fluid. hPRL complexation in milk was rapid, time dependent, and cooperative. Antibodies to or competitors of the hPRL receptor (placental lactogen and growth hormone) showed the hPRL receptor was not involved in the complex. However, hPRL complexation was antagonized by cyclosporine A and anti-cyclophilins. The complex was very stable, resisting dissociation in SDS, urea, and dithiothreitol. Western analysis revealed an ∼75-kDa complex that included hPRL, cyclophilins A and B, and a 16-kDa cyclophilin A. Compared with noncomplexed hPRL, complexed hPRL in whole milk showed similar activation of STAT5 but markedly delayed activation of ERK. Alteration of signaling suggests that complex formation may alter hPRL biological activity. This is the first report of a unique, multicomponent, high-capacity milk fat reservoir of hPRL; all other analyses of milk PRL have utilized defatted milk.

  3. Imaging in Tuberculosis abdominal

    International Nuclear Information System (INIS)

    Suarez, Tatiana; Garcia, Vanessa; Tamara, Estrada; Acosta, Federico

    2010-01-01

    In this article we illustrate and discuss imaging features resulting from Tuberculosis abdominal affectation. We present patients evaluated with several imaging modalities who had abdominal symptoms and findings suggestive of granulomatous disease. Diagnosis was confirm including hystopatology and clinical outgoing. Cases involved presented many affected organs such as lymphatic system, peritoneum, liver, spleen, pancreas, kidneys, ureters, adrenal glands and pelvic organs Tuberculosis, Tuberculosis renal, Tuberculosis hepatic, Tuberculosis splenic Tomography, x-ray, computed

  4. Abdominal Wall Reconstruction in Patients with Digestive Tract Fistulas

    OpenAIRE

    Johnson, Eric K.; Tushoski, Pamela L.

    2010-01-01

    Abdominal wall reconstruction in the digestive tract fistula patient is a complex issue. The authors review the available data and present information regarding the timing of surgery, techniques of abdominal wall reconstruction, hernia repair, and discuss pitfalls associated with the various options. A simple and basic approach to this problem is described.

  5. Major histocompatibility complex (MHC) class III genetics in two Amerindian tribes from southern Brazil: the Kaingang and the Guarani.

    Science.gov (United States)

    Weg-Remers, S; Brenden, M; Schwarz, E; Witzel, K; Schneider, P M; Guerra, L K; Rehfeldt, I R; Lima, M T; Hartmann, D; Petzl-Erler, M L; de Messias, I J; Mauff, G

    1997-10-01

    Population genetic studies of the major histocompatibility complex (MHC) class III region, comprising C2, BF and C4 phenotypes, and molecular genetic data are rarely available for populations other than Caucasoids. We have investigated three Amerindian populations from Southern Brazil: 131 Kaingang from Ivaí (KIV), 111 Kaingang (KRC) and 100 Guarani (GRC) from Rio das Cobras. Extended MHC haplotypes were derived after standard C2, BF, C4 phenotyping and restriction fragment length polymorphism (RFLP) analysis with TaqI, together with HLA data published previously by segregation analysis. C2 and BF frequencies corresponded to other Amerindian populations. C4B*Q0 frequency was high in the GRC (0.429) but low in the Kaingang. Unusual C4 alleles were found, viz. C4A*58, A*55 and C4B*22 (presumably non-Amerindian) and aberrant C4A*3 of Amerindian origin occurring with a frequency of 0.223 in the GRC. C4A*3 bands of homo- and heterozygous individuals carrying this variant were Rodgers 1 positive and Chido 1,3 positive, showed a C4A specific lysis type and a C4A like alpha-chain. Polymerase chain reaction studies and sequencing showed that this is based on a C4A*3 duplication with a regular C4A*3 and a partially converted C4A*0304 carrying the C4B specific epitopes Ch 6 and Ch 1,3. Associations of class III haplotypes with particular RFLP patterns were similar to those reported for Caucasoids. The previously described association between combined C4A and CYP21P deletions and the 6.4 kb TaqI fragment was not seen in these Amerindians. This fragment occurred within a regular two locus gene structure in the Kaingang, representing a "short" gene at C4 locus I. C4 and CYP21 duplications were frequently observed. The distribution of extended MHC haplotypes provides evidence for a close relationship between the KIV and KRC and a larger genetic distance between the two Kaingang groups and the GRC.

  6. Screening for total and abdominal obesity among University of ...

    African Journals Online (AJOL)

    The importance of total body fat and distribution has been stressed as a major risk factor for both adults and children. There is paucity of information concerning total and abdominal obesity among university students in South Africa. The purpose of this study was to screen for total and abdominal obesity among university of ...

  7. A wolf in wolf's clothing the abdominal compartment syndrome

    African Journals Online (AJOL)

    abdomen. These findings are consistent with the diagnosis of intra-abdominal compartment syndrome. In 1 case trauma was remote from the abdomen .... although they tend to develop most often in those who have undergone major vascular operations or suffered abdominal trauma. The effects of the pressure on the bowel ...

  8. Abdominal injuries after high falls: high incidence and increased mortality

    NARCIS (Netherlands)

    van Hensbroek, P. Boele; van Ooijen, M.; Lamers, A. B. G. N.; Ponsen, K.-J.; Goslings, J. C.

    2013-01-01

    Falls from height are a major cause of morbidity and mortality. Injuries to the extremities and head are common. However, little has been reported on abdominal injuries or their treatment. This study aims to assess the abdominal injuries, treatment, and mortality after falls from height. We searched

  9. Penetrating abdominal injury cases admitted in University of Benin ...

    African Journals Online (AJOL)

    The incidence of penetrating abdominal injuries especially through gunshot injuries is on the increase and is a major cause of morbidity and mortality in our community. Control measures and ways of reducing morbidity and mortality are suggested. Keywords: penetrating abdominal injuries, gun shot injuries. Annals of ...

  10. The efficacy of adhesiolysis on chronic abdominal pain

    DEFF Research Database (Denmark)

    Gerner-Rasmussen, Jonas; Burcharth, Jakob; Gögenur, Ismail

    2015-01-01

    INTRODUCTION: Abdominal adhesions are a frequent reason for chronic abdominal pain. The purpose of this systematic review was to investigate the evidence of performing laparoscopic adhesiolysis as a treatment for patients with chronic abdominal pain. METHODS: Medline, Embase, and The Cochrane...... Central Register of Controlled Trials were searched for trials performing lysis of adhesions on patients suffering from chronic abdominal pain. Clinical studies on patients being treated for chronic abdominal pain with surgical adhesiolysis were included. The main outcome of the study...... chronic abdominal pain. A total of 22 trials were identified as case-series and included no control group. Three studies were identified as randomized controlled trials (RCT). A benefit of the intervention varied from 16 to 88 % in the non-randomized studies, with the majority reporting pain relief...

  11. Abdominal emergencies in pediatrics.

    Science.gov (United States)

    Coca Robinot, D; Liébana de Rojas, C; Aguirre Pascual, E

    2016-05-01

    Abdominal symptoms are among the most common reasons for pediatric emergency department visits, and abdominal pain is the most frequently reported symptom. Thorough history taking and physical examination can often reach the correct diagnosis. Knowing the abdominal conditions that are most common in each age group can help radiologists narrow the differential diagnosis. When imaging tests are indicated, ultrasonography is usually the first-line technique, enabling the diagnosis or adding relevant information with the well-known advantages of this technique. Nowadays, plain-film X-ray studies are reserved for cases in which perforation, bowel obstruction, or foreign body ingestion is suspected. It is also important to remember that abdominal pain can also occur secondary to basal pneumonia. CT is reserved for specific indications and in individual cases, for example, in patients with high clinical suspicion of abdominal disease and inconclusive findings at ultrasonography. We review some of the most common conditions in pediatric emergencies, the different imaging tests indicated in each case, and the imaging signs in each condition. Copyright © 2016 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

  12. Systemic lupus erythematosus : abdominal radiologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jae Cheon; Cho, On Koo; Lee, Yong Joo; Bae, Jae Ik; Kim, Yong Soo; Rhim, Hyun Chul; Ko, Byung Hee [Hanyang Univ. College of Medicine, Seoul (Korea, Republic of)

    1999-06-01

    Systemic lupus erythematosus(SLE) is a systemic disease of unknown etiology. Its main pathology is vasculitis and serositis, due to deposition of the immune complex or antibodies. Most findings are nonspecific ; abdominal manifestations include enteritis, hepatomegaly, pancreatic enlargement, serositis, lymphadenopathy, splenomegaly, nephritis, interstitial cystitis, and thrombophlebitis. We described radiologic findings of various organ involvement of SLE; digestive system, serosa, reticuloendothelial system, urinary system, and venous system. Diagnosis of SLE was done according to the criteria of American Rheumatism Association. Understanding of the variable imaging findings in SLE may be helpful for the early detection of abdominal involvement and complications.

  13. Major histocompatibility complex class I peptide presentation after Salmonella enterica serovar typhimurium infection assessed via stable isotope tagging of the B27-presented peptide repertoire

    NARCIS (Netherlands)

    Ringrose, Jeffrey H.; Meiring, Hugo D.; Speijer, Dave; Feltkamp, Theodorus E. W.; van Els, Cecile A. C. M.; de Jong, Ad P. J. M.; Dankert, Jacob

    2004-01-01

    Reactive arthritis (ReA) induced by infection with several gram-negative bacteria is strongly associated with expression of the major histocompatibility complex class I molecule HLA-B27. It is thought that due to the intracellular lifestyle of ReA-inducing bacteria, bacterial fragments can be

  14. The SRCR/SID region of DMBT1 defines a complex multi-allele system representing the major basis for its variability in cancer

    DEFF Research Database (Denmark)

    Mollenhauer, Jan; Müller, Hanna; Kollender, Gaby

    2002-01-01

    seven distinct DMBT1 alleles based on variable numbers of tandem repeats (VNTRs). At least 11 tumors exclusively harbored these VNTRs. The data suggest that the SRCR/SID region defines a complex multi-allele system that has escaped previous analyses and that represents the major basis...

  15. Synthesis and Evaluation of Tc-99m-Labelled Monoclonal Antibody 1D09C3 for Molecular Imaging of Major Histocompatibility Complex Class II Protein Expression

    NARCIS (Netherlands)

    Malviya, Gaurav; de Vries, E. F. J.; Dierckx, Rudi A.; Signore, Alberto

    2011-01-01

    It is known that major histocompatibility complex class II protein HLA-DR is highly expressed in B-cell lymphomas and in a variety of autoimmune and inflammatory diseases. Therefore, a radiolabelled fully humanized IgG4 monoclonal antibody (mAb) can provide useful prognostic and diagnostic

  16. Non-major histocompatibility complex-restricted cytotoxic activity of blood mononuclear cells stimulated with secreted mycobacterial proteins and other mycobacterial antigens

    DEFF Research Database (Denmark)

    Ravn, P; Pedersen, B K

    1994-01-01

    Several observations indicate that non-major histocompatibility complex (MHC)-restricted cytotoxicity, mediated for example by natural killer cells and lymphokine-activated killer cells, may serve as an important antimicrobial defense mechanism. The purpose of the present study was to investigate...

  17. The "adjuvant effect" of the polymorphic B-G antigens of the chicken major histocompatibility complex analyzed using purified molecules incorporated in liposomes

    DEFF Research Database (Denmark)

    Salomonsen, J; Eriksson, H; Skjødt, K

    1991-01-01

    The polymorphic B-G region of the chicken major histocompatibility complex has previously been shown to mediate an "adjuvant effect" on the humoral response to other erythrocyte alloantigens. We demonstrate here that B-G molecules purified with monoclonal antibodies exert this adjuvant effect...

  18. CD54/intercellular adhesion molecule 1 and major histocompatibility complex II signaling induces B cells to express interleukin 2 receptors and complements help provided through CD40 ligation

    DEFF Research Database (Denmark)

    Poudrier, J; Owens, T

    1994-01-01

    We have examined signaling roles for CD54 intercellular adhesion molecule 1 and major histocompatibility complex (MHC) II as contact ligands during T help for B cell activation. We used a T helper 1 (Th1)-dependent helper system that was previously shown to be contact as well as interleukin 2 (IL-2...

  19. Peptide binding specificity of major histocompatibility complex class I resolved into an array of apparently independent subspecificities: quantitation by peptide libraries and improved prediction of binding

    DEFF Research Database (Denmark)

    Stryhn, A; Pedersen, L O; Romme, T

    1996-01-01

    Considerable interest has focused on understanding how major histocompatibility complex (MHC) specificity is generated and characterizing the specificity of MHC molecules with the ultimate goal being to predict peptide binding. We have used a strategy where all possible peptides of a particular...

  20. Expression of bovine non-classical major histocompatibility complex class 1 proteins in mouse P815 and human K562 cells

    Science.gov (United States)

    Major histocompatibility complex class I (MHC-I) proteins can be expressed as cell surface or secreted proteins. To investigate whether bovine non-classical MHC-I proteins are expressed as cell surface or secreted proteins, and to assess the reactivity pattern of monoclonal antibodies with non-class...

  1. Ultrasonography in abdominal emergencies

    International Nuclear Information System (INIS)

    Risi, D.; Alessi, G.; Meli, C.; Marzano, M.; Fiori, E.; Caterino, S.

    1989-01-01

    From February 1986 to March 1988 113 abdominal US exams were performed in emergency situation to evaluate the accuracy of this methodology: 13 were blunt traumas, 18 post-operative complications. A real-time scanner with a linear probe of 5 MHz was employed. The results were confirmed by surgical and/or clinical and instrumental evaluation. In 81% of the examinations, ultrasonography allowed a diagnosis to be made. Gallbladder and biliary pathologies were the most common findings. The results (sensibility 96%, specificity 88%, accuracy 95%) confirm the affidability of ultrasonography in abdominal emergencies, as shown in literature

  2. Laparoscopic surgery in children: abdominal wall complications

    Directory of Open Access Journals (Sweden)

    Vaccaro S.

    2017-06-01

    Full Text Available Minimal invasive surgery has become the standard of care for operations involving the thoracic and abdominal cavities for all ages. Laparoscopic complications can occur as well as more invasive surgical procedures and we can classify them into non-specific and specific. Our goal is to analyze the most influential available scientific literature and to expose important and recognized advices in order to reduce these complications. We examined the mechanism, risk factors, treatment and tried to outline how to prevent two major abdominal wall complications related to laparoscopy: bleeding and port site herniation .

  3. An abdominal tuberculosis case mimicking an abdominal mass ...

    African Journals Online (AJOL)

    Abdominal tuberculosis is rare in childhood. It may be difficult to diagnose as it mimics various disorders. We present a 12-year-old child with an unusual clinical presentation who was diagnosed with abdominal tuberculosis only perioperatively.

  4. The Mr 30,000-33,000 major protein components of the lateral elements of synaptonemal complexes of the rat

    NARCIS (Netherlands)

    Lammers, H.

    1999-01-01

    Synaptonemal complexes (SCs) are intranuclear structures which are formed during meiotic prophase between homologous chromosomes. The SC consists of two protein-rich axes, either of which is found at the basis of one of the homologous chromosomes. These axes, called lateral elements (LEs),

  5. From light-harvesting to photoprotection: structural basis of the dynamic switch of the major antenna complex of plants (LHCII)

    NARCIS (Netherlands)

    Liguori, N.; Periole, X.; Marrink, S.J.; Croce, R.

    2015-01-01

    Light-Harvesting Complex II (LHCII) is largely responsible for light absorption and excitation energy transfer in plants in light-limiting conditions, while in high-light it participates in photoprotection. It is generally believed that LHCII can change its function by switching between different

  6. From light-harvesting to photoprotection : structural basis of the dynamic switch of the major antenna complex of plants (LHCII)

    NARCIS (Netherlands)

    Liguori, Nicoletta; Periole, Xavier; Marrink, Siewert J; Croce, Roberta

    2015-01-01

    Light-Harvesting Complex II (LHCII) is largely responsible for light absorption and excitation energy transfer in plants in light-limiting conditions, while in high-light it participates in photoprotection. It is generally believed that LHCII can change its function by switching between different

  7. Staged abdominal re-operation for abdominal trauma.

    Science.gov (United States)

    Taviloglu, Korhan

    2003-07-01

    To review the current developments in staged abdominal re-operation for abdominal trauma. To overview the steps of damage control laparotomy. The ever increasing importance of the resuscitation phase with current intensive care unit (ICU) support techniques should be emphasized. General surgeons should be familiar to staged abdominal re-operation for abdominal trauma and collaborate with ICU teams, interventional radiologists and several other specialties to overcome this entity.

  8. Spiroacetal biosynthesis in fruit flies is complex: distinguishable origins of the same major spiroacetal released by different Bactrocera spp.

    Science.gov (United States)

    Schwartz, Brett D; Booth, Yvonne K; Fletcher, Mary T; Kitching, William; De Voss, James J

    2010-03-07

    The major spiroacetal ((E,E)-1) of the pestiferous fruit flies, Bactrocera tryoni and Bactrocera cucumis, is biosynthesised from fatty acids by distinguishable pathways which utilise modified beta-oxidation and C-H hydroxylation, generating a putative ketodiol which cyclises.

  9. Conflicting Ideologies and Language Policy in Adult ESL: Complexities of Language Socialization in a Majority-L1 Classroom

    Science.gov (United States)

    Mori, Miki

    2014-01-01

    This study looks at how language ideologies affect and are revealed in language socialization practices in a majority-L1 adult ESL classroom, particularly looking at language use and policy. It draws on recent theories and critiques of language socialization (Bayley & Langman, 2011; Bronson & Watson-Gegeo, 2008; Garrett &…

  10. Abdominal tuberculosis mimicking intra-abdominal malignancy: A ...

    African Journals Online (AJOL)

    Background: Abdominal TB usually presents with nonspecific findings and may thus mimic a multitude of gastrointestinal disorders. Abdominal tuberculosis may therefore present as large and palpable intra-abdominal masses usually arising from lymphadenopathy which may mimic lymphomas and other malignancies.

  11. Abdominal Adiposity Distribution Quantified by Ultrasound Imaging and Incident Hypertension in a General Population

    DEFF Research Database (Denmark)

    Seven, Ekim; Thuesen, Betina H; Linneberg, Allan

    2016-01-01

    Abdominal obesity is a major risk factor for hypertension. However, different distributions of abdominal adipose tissue may affect hypertension risk differently. The main purpose of this study was to explore the association of subcutaneous abdominal adipose tissue (SAT) and visceral adipose tissue...

  12. Endometriosis Abdominal wall

    International Nuclear Information System (INIS)

    Alvarez, M.; Carriquiry, L.

    2003-01-01

    Endometriosis of abdominal wall is a rare entity wi ch frequently appears after gynecological surgery. Case history includes three cases of parietal endometriosis wi ch were treated in Maciel Hospital of Montevideo. The report refers to etiological diagnostic aspects and highlights the importance of total resection in order to achieve definitive healing

  13. Abdominal and Pelvic CT

    Medline Plus

    Full Text Available ... to help diagnose the cause of abdominal or pelvic pain and diseases of the internal organs, small bowel and colon, such as: infections such as appendicitis , pyelonephritis or infected fluid collections, also known as abscesses. inflammatory bowel disease such as ulcerative colitis or Crohn's ...

  14. Adult abdominal hernias.

    LENUS (Irish Health Repository)

    Murphy, Kevin P

    2014-06-01

    Educational Objectives and Key Points. 1. Given that abdominal hernias are a frequent imaging finding, radiologists not only are required to interpret the appearances of abdominal hernias but also should be comfortable with identifying associated complications and postrepair findings. 2. CT is the imaging modality of choice for the assessment of a known adult abdominal hernia in both elective and acute circumstances because of rapid acquisition, capability of multiplanar reconstruction, good spatial resolution, and anatomic depiction with excellent sensitivity for most complications. 3. Ultrasound is useful for adult groin assessment and is the imaging modality of choice for pediatric abdominal wall hernia assessment, whereas MRI is beneficial when there is reasonable concern that a patient\\'s symptoms could be attributable to a hernia or a musculoskeletal source. 4. Fluoroscopic herniography is a sensitive radiologic investigation for patients with groin pain in whom a hernia is suspected but in whom a hernia cannot be identified at physical examination. 5. The diagnosis of an internal hernia not only is a challenging clinical diagnosis but also can be difficult to diagnose with imaging: Closed-loop small-bowel obstruction and abnormally located bowel loops relative to normally located small bowel or colon should prompt assessment for an internal hernia.

  15. Abdominal and Pelvic CT

    Medline Plus

    Full Text Available ... as ulcerative colitis or Crohn's disease , pancreatitis or liver cirrhosis. cancers of the liver, kidneys, pancreas, ovaries and bladder as well as ... injuries to abdominal organs such as the spleen, liver, kidneys or other internal organs in cases of ...

  16. Abdominal and Pelvic CT

    Medline Plus

    Full Text Available ... exams and ultrasound are preferred for evaluation of acute abdominal conditions in babies, such as vomiting or blood in stool. For some conditions, including but not limited to some liver, kidney, pancreatic, uterine or ovarian abnormalities, the evaluation and diagnosis ...

  17. Children's (Pediatric) Abdominal Ultrasound Imaging

    Medline Plus

    Full Text Available ... appendicitis is the most common reason for emergency abdominal surgery. Ultrasound imaging can also: help a physician determine the source of abdominal pain, such as gallstones, kidney stones, abscesses or ...

  18. Children's (Pediatric) Abdominal Ultrasound Imaging

    Medline Plus

    Full Text Available ... particularly valuable for evaluating abdominal, pelvic or scrotal pain in children. Preparation will depend on the type ... help a physician determine the source of abdominal pain, such as gallstones, kidney stones, abscesses or an ...

  19. Incision for abdominal laparoscopy (image)

    Science.gov (United States)

    Abdominal laparoscopy is a useful aid in diagnosing disease or trauma in the abdominal cavity with less scarring than ... as liver and pancreatic resections may begin with laparoscopy to exclude the presence of additional tumors (metastatic ...

  20. Children's (Pediatric) Abdominal Ultrasound Imaging

    Medline Plus

    Full Text Available ... Except for traumatic injury, appendicitis is the most common reason for emergency abdominal surgery. Ultrasound imaging can also: help a physician determine the source of abdominal pain, such as gallstones, kidney stones, ...

  1. Acute traumatic abdominal wall hernia

    OpenAIRE

    Hartog, Dennis; Tuinebreijer, Wim; Oprel, Pim; Patka, Peter

    2011-01-01

    textabstractAlthough blunt abdominal trauma is frequent, traumatic abdominal wall hernias (TAWH) are rare. We describe a large TAWH with associated intra-abdominal lesions that were caused by high-energy trauma. The diagnosis was missed by clinical examination but was subsequently revealed by a computed tomography (CT) scan. Repair consisted of an open anatomical reconstruction of the abdominal wall layers with reinforcement by an intraperitoneal composite mesh. The patient recovered well and...

  2. Intra-abdominal pressure and abdominal wall muscular function: Spinal unloading mechanism.

    Science.gov (United States)

    Stokes, Ian A F; Gardner-Morse, Mack G; Henry, Sharon M

    2010-11-01

    The roles of antagonistic activation of abdominal muscles and of intra-abdominal pressurization remain enigmatic, but are thought to be associated with both spinal unloading and spinal stabilization in activities such as lifting. Biomechanical analyses are needed to understand the function of intra-abdominal pressurization because of the anatomical and physiological complexity, but prior analyses have been over-simplified. To test whether increased intra-abdominal pressure was associated with reduced spinal compression forces for efforts that generated moments about each of the principal axis directions, a previously published biomechanical model of the spine and its musculature was modified by the addition of anatomically realistic three-layers of curved abdominal musculature connected by fascia to the spine. Published values of muscle cross-sectional areas and the active and passive stiffness properties were assigned. The muscle activations were calculated assuming minimized muscle stress and stretch for the model loaded with flexion, extension, lateral bending and axial rotation moments of up to 60 Nm, along with intra-abdominal pressurization of 5 or 10 kPa (37.5 or 75 mm Hg) and partial bodyweight (340 N). The analysis predicted a reduction in spinal compressive force with increase in intra-abdominal pressurization from 5 to 10 kPa. This reduction at 60 Nm external effort was 21% for extension effort, 18% for flexion effort, 29% for lateral bending and 31% for axial rotation. This analysis predicts that intra-abdominal pressure produces spinal unloading, and shows likely muscle activation patterns that achieve this. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. Acute traumatic abdominal wall hernia

    NARCIS (Netherlands)

    D. den Hartog (Dennis); W.E. Tuinebreijer (Wim); P.P. Oprel (Pim); P. Patka (Peter)

    2011-01-01

    textabstractAlthough blunt abdominal trauma is frequent, traumatic abdominal wall hernias (TAWH) are rare. We describe a large TAWH with associated intra-abdominal lesions that were caused by high-energy trauma. The diagnosis was missed by clinical examination but was subsequently revealed by a

  4. Phylogenetic Relationships among Whiteflies in the Bemisia tabaci (Gennadius Species Complex from Major Cassava Growing Areas in Kenya

    Directory of Open Access Journals (Sweden)

    Duke M. Manani

    2017-02-01

    Full Text Available Whiteflies, Bemisia tabaci (Gennadius are major insect pests that affect many crops such as cassava, tomato, beans, cotton, cucurbits, potato, sweet potato, and ornamental crops. Bemisia tabaci transmits viral diseases, namely cassava mosaic and cassava brown streak diseases, which are the main constraints to cassava production, causing huge losses to many small-scale farmers. The aim of this work was to determine the phylogenetic relationships among Bemisia tabaci species in major cassava growing areas of Kenya. Surveys were carried out between 2013 and 2015 in major cassava growing areas (Western, Nyanza, Eastern, and Coast regions, for cassava mosaic disease (CMD and cassava brown streak disease (CBSD. Mitochondrial cytochrome oxidase I (mtCOI-DNA was used to determine the genetic diversity of B. tabaci. Phylogenetic trees were constructed using Bayesian methods to understand the genetic diversity across the study regions. Phylogenetic analysis revealed two B. tabaci species present in Kenya, sub-Saharan Africa 1 and 2 comprising five distinct clades (A–E with percent sequence similarity ranging from 97.7 % to 99.5%. Clades B, C, D, and E are predominantly distributed in the Western and Nyanza regions of Kenya whereas clade B is dominantly found along the coast, the eastern region, and parts of Nyanza. Our B. tabaci clade A groups with sub-Saharan Africa 2-(SSA2 recorded a percent sequence similarity of 99.5%. In this study, we also report the identification of SSA2 after a 15 year absence in Kenya. The SSA2 species associated with CMD has been found in the Western region of Kenya bordering Uganda. More information is needed to determine if these species are differentially involved in the epidemiology of the cassava viruses.

  5. Ruptured Abdominal Aortic Aneurysm

    Directory of Open Access Journals (Sweden)

    Jessica Andrusaitis

    2017-07-01

    Full Text Available History of present illness: A 69-year-old male with poorly controlled hypertension presented with 1 hour of severe low back pain that radiated to his abdomen. The patient was tachycardic and had an initial blood pressure of 70/40. He had a rigid and severely tender abdomen. The patient’s history of hypertension, abnormal vital signs, severity and location of his pain were suspicious for a ruptured abdominal aortic aneurysm (AAA. Therefore, a computed tomography angiogram (CTA was ordered. Significant findings: CTA demonstrated a ruptured 7.4 cm infrarenal abdominal aortic aneurysm with a large left retroperitoneal hematoma. Discussion: True abdominal aortic aneurysm is defined as at least a 3cm dilatation of all three layers of the arterial wall of the abdominal aorta.1 An estimated 15,000 people die per year in the US of this condition.2 Risk factors for AAA include males older than 65, tobacco use, and hypertension.1,3,4 There are also congenital, mechanical, traumatic, inflammatory, and infectious causes of AAA.3 Rupture is often the first manifestation of the disease. The classic triad of abdominal pain, pulsatile mass, and hypotension is seen in only 50% of ruptured AAAs.5 Pain (abdominal, groin, or back is the most common symptom. The most common misdiagnoses of ruptured AAAs are renal colic, diverticulitis, and gastrointestinal hemorrhage.6 Bedside ultrasonography is the fastest way to detect this condition and is nearly 100% sensitive.1 One study showed that bedside ultrasounds performed by emergency physicians had a sensitivity of .94 [95% CI = .86-1.0] and specificity of 1 [95% CI = .98-1.0] for detecting AAAs.7 CTA has excellent sensitivity (approximately 100% and yields the added benefit of facilitating surgical planning and management.1 Without surgical treatment, a ruptured AAA is almost uniformly fatal, and 50% of those who undergo surgery do not survive.1 Early resuscitation and coordination with vascular surgery should be

  6. High resolution X-ray structures of mouse major urinary protein nasal isoform in complex with pheromones

    Energy Technology Data Exchange (ETDEWEB)

    Perez-Miller, Samantha; Zou, Qin; Novotny, Milos V.; Hurley, Thomas D. (Indiana-Med); (Indiana)

    2010-09-07

    In mice, the major urinary proteins (MUP) play a key role in pheromonal communication by binding and transporting semiochemicals. MUP-IV is the only isoform known to be expressed in the vomeronasal mucosa. In comparison with the MUP isoforms that are abundantly excreted in the urine, MUP-IV is highly specific for the male mouse pheromone 2-sec-butyl-4,5-dihydrothiazole (SBT). To examine the structural basis of this ligand preference, we determined the X-ray crystal structure of MUP-IV bound to three mouse pheromones: SBT, 2,5-dimethylpyrazine, and 2-heptanone. We also obtained the structure of MUP-IV with 2-ethylhexanol bound in the cavity. These four structures show that relative to the major excreted MUP isoforms, three amino acid substitutions within the binding calyx impact ligand coordination. The F103 for A along with F54 for L result in a smaller cavity, potentially creating a more closely packed environment for the ligand. The E118 for G substitution introduces a charged group into a hydrophobic environment. The sidechain of E118 is observed to hydrogen bond to polar groups on all four ligands with nearly the same geometry as seen for the water-mediated hydrogen bond network in the MUP-I and MUP-II crystal structures. These differences in cavity size and interactions between the protein and ligand are likely to contribute to the observed specificity of MUP-IV.

  7. Chicken major histocompatibility complex-encoded B-G antigens are found on many cell types that are important for the immune system

    DEFF Research Database (Denmark)

    Salomonsen, J; Dunon, D; Skjødt, K

    1991-01-01

    B-G antigens are a polymorphic multigene family of cell surface molecules encoded by the chicken major histocompatibility complex (MHC). They have previously been described only on cells of the erythroid lineage. By using flow cytometry, section staining, and immunoprecipitation with monoclonal a...... with certain functional data, lead us to suggest that B-G molecules have an important role in the selection of B cells in the chicken bursa. Udgivelsesdato: 1991-Feb-15...

  8. A new method for comparing rankings through complex networks: Model and analysis of competitiveness of major European soccer leagues

    Science.gov (United States)

    Criado, Regino; García, Esther; Pedroche, Francisco; Romance, Miguel

    2013-12-01

    In this paper, we show a new technique to analyze families of rankings. In particular, we focus on sports rankings and, more precisely, on soccer leagues. We consider that two teams compete when they change their relative positions in consecutive rankings. This allows to define a graph by linking teams that compete. We show how to use some structural properties of this competitivity graph to measure to what extend the teams in a league compete. These structural properties are the mean degree, the mean strength, and the clustering coefficient. We give a generalization of the Kendall's correlation coefficient to more than two rankings. We also show how to make a dynamic analysis of a league and how to compare different leagues. We apply this technique to analyze the four major European soccer leagues: Bundesliga, Italian Lega, Spanish Liga, and Premier League. We compare our results with the classical analysis of sport ranking based on measures of competitive balance.

  9. Petrogenesis of the Canindé de São Francisco complex: A major Late Proterozoic gabbroic body in the Sergipe Foldbelt, northeastern Brazil

    Science.gov (United States)

    Oliveira, E. P.; Tarney, J.

    The large Canindé de São Francisco gabbroic complex, with its associated volcanic units, has been widely interpreted as a Late Proterozoic island-arc sequence emplaced onto the margin of the São Francisco craton during the development of the Sergipe Foldbelt. Whole-rock major, trace, and rare earth element data and mineral chemistry data are presented here for the Canindé gabbroic complex and the associated Gentileza and Novo Gosto volcanics. These data show that both the gabbros and the volcanics have compositions that bear little resemblance to island-arc sequences. Instead, much of the complex has trace element characteristics that resemble those of continental flood basalts, such as the Paraná. It is more likely that the Canindé Complex has resulted from remobilization of the subcontinental lithosphere during some thermal event in the Late Proterozoic. The Sergipe Foldbelt, therefore, may not necessarily represent a zone of continental collision. Two distinct magma types are recognized in both the gabbro complex and the volcanic sequence. The dominant leucogabbros and the Gentileza basaltic volcanics are relatively enriched in incompatible trace elements and have multi-element patterns that are similar to those Paraná basalts. However, the Novo Gosto volcanics and the FeTi oxide gabbros are much more depleted in light rare earth and other incompatible trace elements, and have more refractory major element compositions. These rocks cannot be related to the rest of the complex by any conceivable scheme involving fractional crystallization. They have more likely resulted from melting of a more refractory mantle component in the subcontinental lithosphere, or they represent second-stage melting of mantle from which a basalt component had already been removed.

  10. ABDOMINAL TRAUMA- CLINICAL STUDY

    Directory of Open Access Journals (Sweden)

    Vanaja Ratnakumari Billa

    2017-08-01

    Full Text Available BACKGROUND In the recent times there has been increased incidence of abdominal trauma cases due to several causes. Quick and prompt intervention is needed to decrease the mortality of the patients. So we conducted a study to assess the cause and the management of abdominal trauma cases in our institution. The aim of this study was to know the incidence of blunt and penetrating injuries and their causes, age and sex incidence, importance of various investigations, mode of treatment offered and post-operative complications. To study the cause of death and evolve better management. MATERIALS AND METHODS The present study comprises of patients admitted to and operated in various surgical units in the Department of Surgery at Government General Hospital, attached to Guntur Medical College Guntur, from August 2014 to October 2016. RESULTS Increase incidence seen in age group 20-29 years (30%. Male predominance 77.5%. Mechanism of injury–road traffic accidents 65%. Isolated organ injury–colon and rectum 40%. Other associated injuries–chest injuries with rib fractures 7.5%. Complications–wound infection 17.5%. Duration of hospital stay 8–14 days. Bowel injury management–closure of perforation 84.6%. Resection anastomosis 15.38%. CONCLUSION Thorough clinical examination, diagnostic paracentesis, plain X-ray erect abdomen and ultrasound proved to be very helpful in the diagnosis of intra-abdominal injuries. Spleen is the commonest organ involved in blunt trauma and colon is the commonly injured organ in penetrating abdominal trauma, many patients have associated extremity and axial skeleton injuries. With advances in diagnosis and intensive care technologies, most patients of solid visceral injuries with hemodynamic stability can be managed conservatively. Surgical site infection is the most common complication following surgery. The mortality is high; reason might be patient reaching the hospital late, high incidence of postoperative septic

  11. Endometrioma de parede abdominal

    Directory of Open Access Journals (Sweden)

    Italo Accetta

    Full Text Available OBJETIVO: Relatar a experiência dos autores com as manifestações clínicas e o tratamento cirúrgico em pacientes com endometrioma de parede abdominal. MÉTODOS: Análise retrospectiva das pacientes operadas por endometrioma de parede abdominal, dando ênfase aos dados relativos à idade, sintomas, cesariana prévia, relação dos sintomas com o ciclo menstrual, exames físicos e complementares, tratamento cirúrgico, evolução pós-operatória e resultado histopatológico dos espécimes. RESULTADOS: Foram operadas 14 pacientes no período estudado, com idade entre 28 e 40 anos. A presença de massa e dor local que piorava durante a menstruação foram as queixas principais. Ultrassonografia e tomografia computadorizada foram exames importantes em localizar precisamente a doença. O tratamento cirúrgico foi exérese ampla da tumoração e dos tecidos comprometidos. As pacientes evoluíram satisfatoriamente e o histopatológico confirmou a suspeita de endometrioma de parede abdominal em todos os casos. CONCLUSÃO: Foi nítida a relação entre cesariana prévia e endometrioma de parede abdominal e estudos ultrassonográficos e tomográficos auxiliaram a planejar a abordagem cirúrgica permitindo a exérese da tumoração e de todos os tecidos adjacentes comprometidos.

  12. Minimally Invasive Abdominal Surgery

    OpenAIRE

    Richardson, William S.; Carter, Kristine M.; Fuhrman, George M.; Bolton, John S.; Bowen, John C.

    2000-01-01

    In the last decade, laparoscopy has been the most innovative surgical movement in general surgery. Minimally invasive surgery performed through a few small incisions, laparoscopy is the standard of care for the treatment of gallbladder disease and the gold standard for the treatment of reflux disease. The indications for a laparoscopic approach to abdominal disease continue to increase, and many diseases may be treated with laparoscopic techniques. At Ochsner, laparoscopic techniques have dem...

  13. [Abdominal catastrophe--surgeon's view].

    Science.gov (United States)

    Vyhnánek, F

    2010-07-01

    Abdominal catastrophe is a serious clinical condition, usually being a complication arising during treatment of intraabdominal nontraumatic disorders or abdominal injuries. Most commonly, inflamation- secondary peritonitis, is concerned. Abdominal catastrophe also includes secondary signs of sepsis, abdominal compartment syndrome and enterocutaneous fistules. Most septic abdominal disorders which show signs of abdominal catastrophy, require surgical intervention and reinterventions--planned or "on demand" laparotomies. During the postoperative period, the patient requires intensive care management, including steps taken to stabilize his/hers condition, management of sepsis and metabolic and nutritional support measures, as well as adequate indication for reoperations. New technologies aimed at prevention of complications in laparostomies and to improve conditions for final laparotomy closure are used in phase procedures for surgical management of intraabdominal infections. Despite the new technologies, abdominal catastrophe has higher morbidity and lethality risk rates.

  14. Obesity-Associated Abdominal Elephantiasis

    Directory of Open Access Journals (Sweden)

    Ritesh Kohli

    2013-01-01

    Full Text Available Abdominal elephantiasis is a rare entity. Abdominal elephantiasis is an uncommon, but deformative and progressive cutaneous disease caused by chronic lymphedema and recurrent streptococcal or Staphylococcus infections of the abdominal wall. We present 3 cases of patients with morbid obesity who presented to our hospital with abdominal wall swelling, thickening, erythema, and pain. The abdominal wall and legs were edematous, with cobblestone-like, thickened, hyperpigmented, and fissured plaques on the abdomen. Two patients had localised areas of skin erythema, tenderness, and increased warmth. There was purulent drainage from the abdominal wall in one patient. They were managed with antibiotics with some initial improvement. Meticulous skin care and local keratolytic treatment for the lesions were initiated with limited success due to their late presentation. All three patients refused surgical therapy. Conclusion. Early diagnosis is important for the treatment of abdominal elephantiasis and prevention of complications.

  15. Classification of primary and incisional abdominal wall hernias.

    Science.gov (United States)

    Muysoms, F E; Miserez, M; Berrevoet, F; Campanelli, G; Champault, G G; Chelala, E; Dietz, U A; Eker, H H; El Nakadi, I; Hauters, P; Hidalgo Pascual, M; Hoeferlin, A; Klinge, U; Montgomery, A; Simmermacher, R K J; Simons, M P; Smietański, M; Sommeling, C; Tollens, T; Vierendeels, T; Kingsnorth, A

    2009-08-01

    A classification for primary and incisional abdominal wall hernias is needed to allow comparison of publications and future studies on these hernias. It is important to know whether the populations described in different studies are comparable. Several members of the EHS board and some invitees gathered for 2 days to discuss the development of an EHS classification for primary and incisional abdominal wall hernias. To distinguish primary and incisional abdominal wall hernias, a separate classification based on localisation and size as the major risk factors was proposed. Further data are needed to define the optimal size variable for classification of incisional hernias in order to distinguish subgroups with differences in outcome. A classification for primary abdominal wall hernias and a division into subgroups for incisional abdominal wall hernias, concerning the localisation of the hernia, was formulated.

  16. Abdominal aspergillosis: CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Yeom, Suk Keu, E-mail: pagoda20@hanmail.net [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Poongnap2-dong, Songpa-gu, Seoul, 138-736 (Korea, Republic of); Kim, Hye Jin, E-mail: kimhyejin@amc.seoul.kr [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Poongnap2-dong, Songpa-gu, Seoul, 138-736 (Korea, Republic of); Byun, Jae Ho, E-mail: jhbyun@amc.seoul.kr [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Poongnap2-dong, Songpa-gu, Seoul, 138-736 (Korea, Republic of); Kim, Ah Young, E-mail: aykim@amc.seoul.kr [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Poongnap2-dong, Songpa-gu, Seoul, 138-736 (Korea, Republic of); Lee, Moon-Gyu, E-mail: mglee@amc.seoul.kr [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Poongnap2-dong, Songpa-gu, Seoul, 138-736 (Korea, Republic of); Ha, Hyun Kwon, E-mail: hkha@amc.seoul.kr [Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Poongnap2-dong, Songpa-gu, Seoul, 138-736 (Korea, Republic of)

    2011-03-15

    Objective: In order to retrospectively evaluate the CT findings of abdominal aspergillosis in immunocompromised patients. Materials and methods: CT scans were reviewed with regard to the sites, number, morphologic appearance, attenuation, and the contrast enhancement patterns of the lesions in six patients (5 women, 1 man; mean age, 43.4 years; range, 23-59 years) with pathologically proved abdominal aspergillosis by two gastrointestinal radiologists in consensus. Medical records were also reviewed to determine each patient's clinical status and outcome. Results: All patients were immunocompromised state: 4 patients received immunosuppressive therapy for solid organ transplantation and 2 patients received chemotherapy for acute myeloid leukemia. Aspergillosis involved blood vessels (n = 3), liver (n = 2), spleen (n = 2), gastrointestinal tract (n = 2), native kidney (n = 1), transplanted kidney (n = 1), peritoneum (n = 1), and retroperitoneum (n = 1). CT demonstrated solid organ or bowel infarction or perforation secondary to vascular thrombosis or pseudoaneurysm, multiple low-attenuating lesions of solid organs presenting as abscesses, concentric bowel wall thickening mimicking typhlitis, or diffuse or nodular infiltration of the peritoneum and retroperitoneum. Conclusion: Familiarity with findings commonly presenting as angioinvasive features or abscesses on CT, may facilitate the diagnosis of rare and fatal abdominal aspergillosis.

  17. Abdominal emergencies during pregnancy.

    Science.gov (United States)

    Bouyou, J; Gaujoux, S; Marcellin, L; Leconte, M; Goffinet, F; Chapron, C; Dousset, B

    2015-12-01

    Abdominal emergencies during pregnancy (excluding obstetrical emergencies) occur in one out of 500-700 pregnancies and may involve gastrointestinal, gynecologic, urologic, vascular and traumatic etiologies; surgery is necessary in 0.2-2% of cases. Since these emergencies are relatively rare, patients should be referred to specialized centers where surgical, obstetrical and neonatal cares are available, particularly because surgical intervention increases the risk of premature labor. Clinical presentations may be atypical and misleading because of pregnancy-associated anatomical and physiologic alterations, which often result in diagnostic uncertainty and therapeutic delay with increased risks of maternal and infant morbidity. The most common abdominal emergencies are acute appendicitis (best treated by laparoscopic appendectomy), acute calculous cholecystitis (best treated by laparoscopic cholecystectomy from the first trimester through the early part of the third trimester) and intestinal obstruction (where medical treatment is the first-line approach, just as in the non-pregnant patient). Acute pancreatitis is rare, usually resulting from trans-ampullary passage of gallstones; it usually resolves with medical treatment but an elevated risk of recurrent episodes justifies laparoscopic cholecystectomy in the 2nd trimester and endoscopic sphincterotomy in the 3rd trimester. The aim of the present work is to review pregnancy-induced anatomical and physiological modifications, to describe the main abdominal emergencies during pregnancy, their specific features and their diagnostic and therapeutic management. Copyright © 2015. Published by Elsevier Masson SAS.

  18. To revisit economics of nuclear technology. Lessons from the learning of a complex technology by major accidents

    International Nuclear Information System (INIS)

    Finon, Dominique

    2012-05-01

    The Fukushima accident raises again the issue of the social and economic viability of nuclear technology. To re-evaluate this viability, we analyse the past process of internalisation of external costs of nuclear energy, which present the specificities to be chanted by accidents and has had a constant effect of complexification. This process has provoked a de-organisation of the classical learning process reflected in constant cost increases and the change of social preferences, to end up by the lack of competitiveness before climate policies. Independent institutions of safety regulation have become essential elements of the social embeddedness of nuclear technology at the expense of technology stability and standardization, condition of its competitiveness. In this perspective, the paper argues that the new sequence of social costs' internalization opened by Fukushima will have limited effects on costs, because of anterior steps of safety improvements. Nuclear technology complexification reaches its asymptote: it is being to overcome the challenge of 'learning by major accidents'. On the other hand nuclear institutions must be re-designed in such a way that it could guarantee maximum safety records and minimum residual risks by going to the other root of the safety issue, the degree of independence and capabilities of the safety authorities in every country, what cannot be decreed. It is nevertheless at this price that could be preserved the global public good of the social acceptance of nuclear technology by limiting drastically chance of new accidents. (author)

  19. The intestinal tract as the major source of interleukin 6 production during abdominal aortic clamping and hind limb ischaemia-reperfusion injury O trato intestinal como a principal fonte na producao de interleucina 6 durante clampeamento da aorta abdominal e lesão de isquemia/rererfusão de membros inferiores

    Directory of Open Access Journals (Sweden)

    Márcio Benedito Palma Pimenta

    2007-01-01

    Full Text Available PURPOSE: The aim of this study was to investigate whether the hind limbs or intestinal tract is the most important initiator of the inflammatory response secondary aortic clamping and hind limb ischemia/reperfusion injury. METHODS: Blood samples of Wistar rats obtained from posterior cava vein, portal vein, and heart cavity during either laparotomy (control group, n=8 or laparotomy + 2 h of aortic clamping and bilateral hind limb ischemia (ischemia group, n=8, or 2 h after ischemia and 2 h of reperfusion (ischemia-reperfusion group, n=8 were assayed for interleukin 6 (IL-6 and C-reactive protein (CRP. RESULTS: Serum IL-6 at the heart (223.6±197.9 [10-832] pg/mL was higher (pOBJETIVO: Investigar qual o principal mediador da resposta inflamatória na lesao de isquemia/reperfusão após clampeamento da aorta abdominal e isquemia dos membros inferiores: o intestine ou as extremidades inferiores. MÉTODOS: amostra de sangue de ratos Wistar coletados da cava posterior, porta e cavidade cardíaca during tanto laparotomia (grupo controle n=8 ou laparotomia + 2 horas de clampeamento aórtico e isquemia bilateral de membros posteriores (grupo isquemia n=8, ou 2 h de isquemia seguido por 2 horas de reperfusão (grupo isquemia/reperfusão n=8, onde foram dosados interleucina 6 e proteína C-reativa. RESULTADOS: Il-6 no coração (223.6±197.9 [10-832] pg/mL foi maior (p<0.001 tanto na veia porta (133.08±108.52 [4-372] pg/mL quanto na veia cava posterior (127.58±109.15 [8-388] pg/mL. PCR não foi significativamente diferente entre os grupos. CONCLUSÃO: o trato intestinal foi responsável pela resposta inflamatória secundária a lesão de isquemia/reperfusão.

  20. Nucleoporin's Like Charge Regions Are Major Regulators of FG Coverage and Dynamics Inside the Nuclear Pore Complex.

    Science.gov (United States)

    Peyro, Mohaddeseh; Soheilypour, Mohammad; Ghavami, Ali; Mofrad, Mohammad R K

    2015-01-01

    Nucleocytoplasmic transport has been the subject of a large body of research in the past few decades. Recently, the focus of investigations in this field has shifted from studies of the overall function of the nuclear pore complex (NPC) to the examination of the role of different domains of phenylalanine-glycine nucleoporin (FG Nup) sequences on the NPC function. In our recent bioinformatics study, we showed that FG Nups have some evolutionarily conserved sequence-based features that might govern their physical behavior inside the NPC. We proposed the 'like charge regions' (LCRs), sequences of charged residues with only one type of charge, as one of the features that play a significant role in the formation of FG network inside the central channel. In this study, we further explore the role of LCRs in the distribution of FG Nups, using a recently developed coarse-grained molecular dynamics model. Our results demonstrate how LCRs affect the formation of two transport pathways. While some FG Nups locate their FG network at the center of the NPC forming a homogeneous meshwork of FG repeats, other FG Nups cover the space adjacent to the NPC wall. LCRs in the former group, i.e. FG Nups that form an FG domain at the center, tend to regulate the size of the highly dense, doughnut-shaped FG meshwork and leave a small low FG density area at the center of the pore for passive diffusion. On the other hand, LCRs in the latter group of FG Nups enable them to maximize their interactions and cover a larger space inside the NPC to increase its capability to transport numerous cargos at the same time. Finally, a new viewpoint is proposed that reconciles different models for the nuclear pore selective barrier function.