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Biomedical subjects

J Jessurun

Publications and source records attributed to J Jessurun.

At least 37 records · Page 2Linked to original sources
PubMed1996

Acute lung injury fibroblast migration and invasion of a fibrin matrix is mediated by CD44.

Fibrosis results when myofibroblasts invade the wound fibrin provisional matrix. Extracellular matrix receptors on the cell surface mediate cell adhesion, migration, and invasion. Recent work with transformed cells indicates that these cells use the cell surface matrix receptor CD44 for migration and invasion. In this study, we examine whether lung fibroblasts, isolated from patients dying with acute alveolar fibrosis, use CD44 to invade a fibrin matrix. Consistent with a role for CD44 in mediating fibroblast invasion and subsequent tissue fibrosis, immunohistochemical analysis of lung tissue from patients who died from acute alveolar fibrosis after lung injury reveals CD44-expressing mesenchymal cells throughout newly formed fibrotic tissue. PCR, Western, and immunoprecipitation analysis demonstrate that the 85-kD CD44 isoform is expressed by acute lung injury fibroblasts. Consistent with a role in mediating matrix adhesion and migration ultrastructurally, CD44 was found uniformly over the cell surface and was found densely labeling filopodia and lamellipodia, highly motile structures involved in cell migration. To determine if lung injury fibroblasts use CD44 to invade fibrin, a fibrin gel model of fibrosis was used. By blocking the function of CD44 with monoclonal antibodies, fibroblast invasion into a fibrin matrix was inhibited. To examine the mechanism by which CD44 mediates fibroblast invasion, the role of CD44 in fibroblast migration and adhesion was evaluated. Anti-CD44 antibody blocked fibroblast migration on the provisional matrix proteins fibronectin, fibrinogen, and hyaluronic acid. Additionally, fibroblast CD44 mediated adhesion to the provisional matrix proteins fibronectin, fibrin, and hyaluronic acid, but not to laminin, a component of the basement membrane. These findings support the hypothesis that fibroblast CD44 functions as an adhesion receptor for provisional matrix proteins and is capable of mediating fibroblast migration and invasion of the wound provisional matrix resulting in the formation of fibrotic tissue.

Cell Adhesion↗
PubMed1996

Total lymphoid irradiation, without intrathymic injection of donor cells, induces indefinite acceptance of heart but not islet or skin allografts in rats.

Allograft tolerance occurs in rodents given a dose of antilymphocyte serum (ALS) and intrathymic injection (ITI) of donor splenocytes (SC) 1-3 weeks prior to transplant (TX). The purpose of our study was to test total lymphoid irradiation (TLI) as an alternative to ALS in ITI tolerance induction to heart, islet, and skin allografts. Prepubertal Wistar Furth rats were recipients. ITI of donor (Lewis) SC was done at the end of the TLI course. Rats received either a heterotopic heart, a skin graft, or 2300 islets (diabetic recipients) intraportally from Lewis donors. TLI (without ITI) in a dose of 200 rads/day for 5 consecutive days, followed by TX in 3 weeks resulted in indefinite acceptance of heart (but not islet or skin) grafts in 60% of the recipients. These data indicate that TLI by a dose schedule of 200 rads/day for 5 days should be tested for clinical relevance in large animal recipients of immediately vascularized grafts.

Animals↗
PubMed1996

Noninvasive diagnosis of cardiac allograft rejection in an orthotopic canine model.

BACKGROUND: A decline in the R wave voltage obtained from surface electrocardiograms once correlated with cardiac allograft rejection. With cyclosporine therapy, however, these electrocardiographic findings became inconsistent, occurring only during severe rejection episodes. Despite cyclosporine use, intramyocardial unipolar peak-to-peak amplitudes obtained from plunge electrodes are reported to be highly sensitive and specific for diagnosing rejection. These reports are based on heterotopic grafts, which atrophy over time, making long-term voltage changes during rejection difficult to interpret. The purpose of this study was to use analysis of unipolar peak-to-peak amplitudes as a prospective monitoring tool for diagnosing orthotopic cardiac allograft rejection. METHODS: Ten adult mongrel dogs underwent orthotopic heart transplantation with the attachment of four intramyocardial leads. The unipolar peak-to-peak amplitudes were measured daily and compared with endomyocardial biopsy results. RESULTS: We found that intramyocardial unipolar peak-to-peak amplitude analysis had a sensitivity and a specificity of 100% for diagnosing rejection. We also found that as the number of myocardial leads increased, the sensitivity of detecting rejection also increased. CONCLUSIONS: We conclude that unipolar peak-to-peak amplitude analysis is an accurate noninvasive means for early detection of cardiac allograft rejection in an orthotopic model. Its success should allow less frequent, more selective use of endomyocardial biopsy.

Animals↗
PubMed1996

Methotrexate for lung transplant recipients with steroid-resistant acute rejection.

BACKGROUND: Steroid-resistant or recurrent acute rejection is a risk factor for the development of chronic graft failure in lung transplant recipients. The best treatment for these patients is not known. Methotrexate has been used successfully in heart transplant recipients with persistent or recurrent acute rejection. This study was performed to evaluate the efficacy of methotrexate in lung transplant recipients with steroid-resistant acute rejection. METHODS: From January 1991 to December 1995, 12 patients with steroid-resistant acute rejection were treated with methotrexate given weekly for 6 weeks and dose-adjusted according to laboratory data and clinical side effects. After completion of therapy, all patients underwent transbronchial biopsy to evaluate the efficacy of methotrexate treatment. RESULTS: Twelve patients underwent treatment with methotrexate for steroid-resistant acute rejection. Acute rejection resolved in all patients completing at least 4 weeks of therapy; 10 of 12 patients (83%) had no further episodes of acute rejection during a mean follow-up period of 12.5 months (range 1 to 42 months). Acute rejection recurred in two patients 6 and 16 months after methotrexate therapy. Both resolved with high-dose corticosteroid therapy. One patient had asymptomatic cytomegalovirus shedding 8 weeks after completion of methotrexate therapy. One patient had aseptic meningitis after her fourth dose of methotrexate. Neither infectious complication was associated with neutropenia. One patient had bone marrow suppression and neutropenic fevers after augmentation of her methotrexate dose. Two patients received shortened methotrexate courses because of gastrointestinal side effects. CONCLUSIONS: Methotrexate is efficacious in the treatment of lung transplant recipients with steroid-resistant acute rejection. Patients must be monitored for side effects during therapy and dosing must be individualized based on laboratory and clinical parameters.

Acute Disease↗
PubMed1995

Cystic fibrosis-associated colitis and fibrosing colonopathy.

OBJECTIVE: To describe our experience with cystic fibrosis (CF)-associated colitis and fibrosing colonopathy, and to assess treatment strategies. STUDY DESIGN: We reviewed hospital charts and autopsy reports of all University of Minnesota patients with CF between 1975 and August 1994. We identified six patients with colonopathy and compared them with a cohort of 79 patients with CF in the same age range and seen during the same period. RESULTS: All patients with colonopathy had bloody diarrhea; five of the six had abdominal pain. Stool frequency and related symptoms distinguished the patients with colonopathy from the cohort population. All took a higher median dose of pancreatic enzymes than the cohort population during the 3 months preceding the onset of symptoms (p < 0.002). For all six patients, barium studies revealed loss of haustration, and shortening and diffuse narrowing of the colonic lumen with relative rectal sparing. The distal ileal mucosa was irregular in four patients. A histopathologic study reveal fibrosis of the submucosa or lamina propria, and focal acute cryptitis in all six patients. Other features included ascites (2/6) and nodular regenerative hyperplasia of the liver (1/6). One patient continues to have symptoms, three had subtotal colectomy, and the condition of two improved after a regimen including a low-fat diet, withholding of pancreatic enzymes, and supplemental parenteral nutrition was initiated. CONCLUSIONS: Fibrosing colonopathy represents a newly recognized gastrointestinal complication of cystic fibrosis. Affected persons have taken larger doses of pancreatic enzymes than similar patients with cystic fibrosis, and have bloody diarrhea. We developed a medical protocol that may avoid surgical resection of the colon in some of these patients.

Biopsy↗
PubMed1995

Autologous islet transplantation to prevent diabetes after pancreatic resection.

BACKGROUND: Extensive pancreatic resection for small-duct chronic pancreatitis is often required for pain relief, but the risk of diabetes is a major deterrent. OBJECTIVE: Incidence of pain relief, prevention of diabetes, and identification of factors predictive of success were the goals in this series of 48 patients who underwent pancreatectomy and islet autotransplantation for chronic pancreatitis. PATIENTS AND METHODS: Of the 48 patients, 43 underwent total or near-total (> 95%) pancreatectomy and 5 underwent partial pancreatectomy. The resected pancreas was dispersed by either old (n = 26) or new (n = 22) methods of collagenase digestion. Islets were injected into the portal vein of 46 of the 48 patients and under the kidney capsule in the remaining 2. Postoperative morbidity, mortality, pain relief, and need for exogenous insulin were determined, and actuarial probability of postoperative insulin independence was calculated based on several variables. RESULTS: One perioperative death occurred. Surgical complications occurred in 12 of the 48 patients (25%): of these, 3 had a total (n = 27); 8, a near-total (n = 16); and 1, a partial pancreatectomy (p = 0.02). Most of the 48 patients had a transient increase in portal venous pressure after islet infusion, but no serious sequelae developed. More than 80% of patients experienced significant pain relief after pancreatectomy. Of the 39 patients who underwent total or near-total pancreatectomy, 20 (51%) were initially insulin independent. Between 2 and 10 years after transplantation, 34% were insulin independent, with no grafts failing after 2 years. The main predictor of insulin independence was the number of islets transplanted (of 14 patients who received > 300,000 islets, 74% were insulin independent at > 2 years after transplantation). In turn, the number of islets recovered correlated with the degree of fibrosis (r = -0.52, p = 0.006) and the dispersion method (p = 0.005). CONCLUSION: Pancreatectomy can relieve intractable pain caused by chronic pancreatitis. Islet autotransplantation is safe and can prevent long-term diabetes in more than 33% of patients and should be an adjunct to any pancreatic resection. A given patient's probability of success can be predicted by the morphologic features of the pancreas.

Adolescent↗
PubMed1995

Ferritin protects endothelial cells from oxidized low density lipoprotein in vitro.

Low density lipoprotein (LDL), if it becomes oxidized, develops several unique properties including the capacity to provoke endothelial cytotoxicity via metal-catalyzed free radical-mediated mechanisms. As were previously have shown that iron-catalyzed oxidant injury to endothelial cells can be attenuated by the addition of exogenous iron chelators such as the lazaroids and deferoxamine, we have examined whether the endogenous iron chelator, ferritin, might provide protection from oxidized LDL. LDL oxidized by iron-containing hemin and H2O2 is toxic to endothelial cells in a time- and dose-dependent fashion. Endothelial cell ferritin content is increased by pretreatment of cells with iron compounds or by the direct addition of exogenous apoferritin; ferritin-loaded cells are markedly resistant to the toxicity caused by oxidized LDL. Iron inactivation by ferritin depends on its ferroxidase activity. When a recombinant human ferritin heavy chain mutant, 222, which is devoid of ferroxidase activity, is added to endothelial cells, unlike the excellent protection afforded by the wild-type recombinant heavy chain, endothelial cells are not protected from oxidized LDL. To assess the in vivo relevance of our observation, we examined human coronary arteries of cardiac explants taken from patients with end-stage atherosclerosis. Large amounts of immunoreactive ferritin are focally detected in atherosclerotic lesions, specifically in the myofibroblasts, macrophages, and endothelium without a notable increase in Prussian blue-detectable iron. These findings suggest that ferritin may modulate vascular cell injury in vivo.

Animals↗
PubMed1995

Gallstone composition in Mexican patients.

Prevalence of gallstone disease in Mexico is similar to that found in some European countries. Patients from those industrialized Western countries primarily develop cholesterol gallstones; however, we do not have information related to the chemical composition of gallstones in the Mexican population. The aim of this study was to determine the physiochemical characteristics of gallstones from patients undergoing surgery for symptomatic cholelithiasis. We analyzed gallstone specimens from 59 patients (17 male and 42 female) from five Mexican states and Mexico City by X-ray diffraction. The chemical analysis revealed that 71.2% of the patients had stones of mixed composition. We concluded that the chemical composition of gallstones found in Mexican patients is similar to that found in patients from other Western countries.

Adult↗
PubMed1994

Experimental large-animal model of obliterative bronchiolitis after lung transplantation.

Obliterative bronchiolitis is a major cause of long-term morbidity after lung transplantation. It is characterized by small-airway inflammation and occlusion by fibrous tissue. The pathogenesis is uncertain. To study this disease, we developed a model of posttransplantation obliterative bronchiolitis using genetically defined miniature swine. Group 1 (n = 2) received a left lung autograft; group 2 (n = 7), a left lung allograft. Group 2 recipients were given cyclosporine, prednisone, and azathioprine for 3 months, then immunosuppression was tapered and discontinued over 1 month. The animals were observed for an additional 2 months, then sacrificed. Lung grafts in both groups were monitored with serial bronchoalveolar lavages and transbronchial biopsies for 6 months. After sacrifice, lung grafts underwent histopathologic and immunohistochemical examination. No allograft had histologic evidence of acute rejection or peribronchiolar infiltrate during the first 3 months of immunosuppression. During the tapering period, airway changes characterized by severe peribronchiolar lymphocytic infiltrates were seen. Bronchoalveolar lavages of allografts showed significantly increased lymphocyte counts with CD8+ cells predominating. After the discontinuation of immunosuppression, transbronchial biopsy and autopsy specimens showed progressive fibrous inflammatory occlusion of bronchioles. Immunohistochemical staining demonstrated increased expression of MCH class II antigen on the bronchiolar epithelium and increased dendritic cells and CD4+ lymphocytes. None of these changes were seen in group 1. Our findings suggest obliterative bronchiolitis is an immunologically mediated phenomenon related to chronic graft rejection after lung transplantation. This model will allow systematic study of the pathogenesis of obliterative bronchiolitis and possible therapeutic intervention.

Animals↗
PubMed1994

Cellular rejection in discordant xenografts when hyperacute rejection is prevented: analysis using adoptive and passive transfer.

Hyperacute rejection of discordant xenografts occurs rapidly, precluding cellular infiltration. Thus the role of cellular rejection in discordant xenografts is debated. Using adoptive transfer of sensitized splenocytes and passive transfer of sensitized serum, we evaluated the influence of cellular and humoral elements on cellular infiltration and rejection in the guinea-pig-to-rat discordant xenograft model. Guinea-pig hearts were transplanted into Lewis rats. Pretransplant, rats underwent splenectomy and plasma exchange and were started on daily cobra venom factor injections. Xenografts rejected faster after adoptive (1, 2, 2 and 2 days) or passive (1, 1, 2 and 2 days) transfer than controls (4, 4, 4 and 4 days; p < 0.05). Macrophages and neutrophils were predominant in early prerejection specimens. Over time, cellular infiltrates were dominated by mononuclear cells. Natural killer cells were present in all groups, as were interleukin 2 receptor positive cells. Our data suggest that either sensitized serum or sensitized cells are capable of initiating an accelerated rejection characterized by cellular infiltration. Despite subtle differences, the population of infiltrating cells was similar in each group. Thus, although rejection may be initiated by either cellular or humoral influences, the ultimate result is the same. We have, therefore, established a small animal model to study cellular rejection in discordant xenografts. This model will help evaluate the role of cell subsets and xenoantibodies in xenograft rejection and will help determine the precise relationship between the two when hyperacute rejection is prevented.

Acute Disease↗
PubMed1994

Arteriovenous hemangioma: a clinicopathological and immunohistochemical study.

The clinicopathological and immunohistochemical properties of 6 examples of arteriovenous hemangioma, including 2 intraoral lesions, were reviewed. This distinct benign, acquired vascular lesion, infrequently encountered in the literature, is characterized by multiple thick- and thin-walled vascular spaces resembling arteries and veins, respectively. In our study, we performed elastic stains that revealed a prominent venular component, whereas the arterial aspect was inconspicuous to absent. Our aim was also to elucidate the possible histogenesis of this lesion. Previous reports suggest as pathogenetic mechanisms hamartomatous proliferation either of the subpapillary vascular plexus or of the Suquet-Hoyer canal of the true glomus. Our immunohistochemical studies failed to identify typical glomus cells. In addition, we investigated the mast cell count in all lesions and it was found increased. These findings, as well as recent evidence directly implicating mast cells in angiogenesis, can support the theory of hamartomatous proliferation of the subpapillary plexus. One should also not exclude the possibility of a reactive process resulting in the characteristic features of arteriovenous hemangioma.

Adult↗
PubMed1994

Skewed T-cell receptor usage and junctional heterogeneity among isletitis alpha beta and gamma delta T-cells in human IDDM [corrected].

Because of anatomical limitations, molecular characterization of islet-inflammatory T-cells in human insulin-dependent diabetes mellitus (IDDM) has remained elusive. We have isolated isletitis T-cells from pancreas graft biopsies of two patients (syngeneic and allogeneic, respectively) shortly after onset of recurrent IDDM and have characterized their repertoire by sequencing T-cell receptor (TcR)-specific cDNAs. Histopathological analysis of the grafts revealed selective beta-cell loss and isletitis characteristic of recurrent disease with no evidence of chronic inflammation or rejection. Most of the in vivo-activated isletitis T-cells were CD8+TcR alpha beta+ and CD4-CD8-TcR gamma delta+ in both patients. Comparison of the different TcR alpha,beta,gamma, and delta sequences revealed V(D)J junctional heterogeneity but skewed TcR usage within patients. Eighth of 13 different isletitis TcR beta sequences (19 of 26 cDNAs) from the syngeneic graft of patient 1 were V beta 3+, as opposed to only 1 of 31 peripheral TcR beta sequences (1 of 31 cDNAs) (61.5 vs. 3.2%, P < 0.0001). Of the 19 different isletitis TcR alpha clonotypes of this patient (24 of 42 cDNAs), 5 were V alpha 14+. The isletitis TcR beta clonotypes of the human leukocyte antigen-identical allogeneic graft of patient 2 showed selective J beta, but not V beta, gene usage. Two of three predominant isletitis clonotypes of patient 2 were V alpha 22+ (19 of 28 cDNAs) and the other (5 of 28 cDNAs) was also V alpha 14+.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Prevalence of gallstone disease in Mexico. A necropsy study.

The prevalence of gallstone disease in Mexico was investigated by studying a sample of 21,446 necropsies performed at the Department of Pathology of the General Hospital of Mexico City during a 35-year period (1953-1988). For each decade, 1000 necropsy cases were randomly selected. The crude prevalence of gallstone disease was 14.3%, 8.5% for males and 20.4% for females. The age groups ranged from 20 to more than 80 years old; the age-standardized prevalence for males was 5.6% and for females 16.2%. These rates are intermediate between those found in Chile and some African countries, comparable to some European studies, and less than those found in Mexican-Americans. No significant trend in the prevalence of gallstone disease was found when the different decades were compared.

Adult↗
PubMed1993

Increased risk of early colorectal neoplasms after hepatic transplant in patients with inflammatory bowel disease.

UNLABELLED: Inflammatory bowel disease (IBD) is associated with an increase in colon and rectal carcinoma. Immunosuppression after transplantation increases the incidence of certain types of tumors. PURPOSE: We reviewed the postoperative course of IBD patients who had undergone hepatic transplantation for primary sclerosing cholangitis to see whether there was an increase in the rate of colorectal neoplasms. METHODS: The charts of 44 patients from two institutions who had undergone a hepatic transplant for primary sclerosing cholangitis were reviewed. Of these 44 patients, 33 had IBD (32 chronic ulcerative colitis, 1 Crohn's). Of these 33 patients, 2 had previously undergone total colectomy/proctectomy and 4 died in the perioperative period. The remaining 27 patients had all undergone colonoscopic evaluation just prior to transplant. Postoperatively all patients were given prednisone, cyclosporine, and azathioprine. Minimum follow-up was 12 months; mean follow-up was 39 months. RESULTS: Three of the 27 patients (11.1 percent) developed early colorectal neoplasms (2 cancers, 1 large villous adenoma with severe dysplasia) at 9, 12, and 13 months post-transplant. All three patients were successfully treated with a total colectomy/proctectomy or resection of any remaining colon. These 3 patients had a mean 19-year history of IBD (range, 9-27 years), while the 24 patients without tumors had a mean 18-year history of IBD (range, 6-39 years). CONCLUSION: There is a subset of transplant patients with primary sclerosing cholangitis and IBD who rapidly develop colorectal neoplasms. Frequent surveillance is recommended for IBD patients in the post-transplant period.

Adult↗