Biomedical subjects
Publications and source records attributed to D Roth.
A case of acute leukemia has two distinct immature blast lines, lineage inconsistency with CD 4 positivity, and trisomy 13q as the effective cytogenetic abnormality. This case represents another instance of trisomy 13 with acute leukemia developing in a more primitive pluripotent stem cell.
We identified 39 patients with acute cocaine intoxication and rhabdomyolysis over an 8-year period. Twenty-three of the patients (59%) demonstrated biochemical evidence for hepatic dysfunction. Sixteen of these patients had severe liver injury as defined by an alanine aminotransferase (ALT) of greater than 400 U/l (group A). Seven had an ALT between 36-399 U/l (group B) and 16 showed no evidence of liver injury (group C). In contrast to those with normal ALT, the clinical course of the group A patients was more often accompanied by profound hypotension (44 vs. 0%, p less than 0.025), disseminated intravascular coagulation (50 vs. 0%, p less than 0.005), hyperpyrexia (75 vs. 25%, p less than 0.025) and acute renal failure (81 vs. 0%, p less than 0.001). Seven of the group A patients expired (44%). Histologic examination of liver tissue obtained from post-mortem samples demonstrated extensive centrilobular and midzonal necrosis in three cases and panlobular necrosis in two others. A mild lymphocytic infiltrate with bile duct proliferation was present in each specimen. We conclude that cocaine intoxication can be accompanied by liver dysfunction which is most likely multifactorial; the presence of severe dysfunction identifies a patient with potentially significant morbidity and mortality.
In this study from two specialized centres 85 patients with histologically proven myocarditis (n = 10) and clinically ascertained perimyocarditis (pericardial effusion and cardiomegaly or segmental wall motion abnormality; n = 75) were followed up for 4.5 + 1.9 years. Immunosuppressive treatment was not applied. After a mean follow-up period of 4.5 + 1.9 years 55% of patients had improved clinically and 35% of patients were completely free of symptoms. Relapses had occurred up to three times. Chronic forms were found in 20% of patients, mostly in those with pericarditis and effusions. Eighteen percent of the patients deteriorated gradually. In 20% of the chronic or deteriorating patients congestive heart failure developed (postmyocarditic heart muscle disease). Fifteen percent of the patients died, mainly from bacterial perimyocarditis and to a lesser extent from inflammatory heart disease from enteroviruses. Patients who succumbed after more than 6 months died either suddenly or from progressive heart failure. A favourable outcome was often accompanied by a decrease in titre, but this decrease was less impressive in those who had antimyolemmal and antisarcolemmal antibodies. The persistence of these antibodies in high titres predominated in patients with poor prognosis and postmyocarditic dilated heart muscle disease, as did cytolytic serum activity.
Explore the source record for details and available documents.
Long-term (10-year) results of kidney transplantation have been analyzed from this center with respect to several variables. In this report the influence of viral disease was added in studying the effect of cadaver versus living-related donor, recipient race, and compliance. Over all, 10-year actuarial patient and graft survival were 68% and 48%, respectively. Cytomegalovirus, hepatitis B and C, and HIV-1 were studied for their effects, and survival curves analyzed statistically. Although cadaver and living-related donor, recipient race, and compliance were 3 main variables influencing graft survival, these 4 viruses were not selective in their effects on any of them. Hepatitis B surface antigen positivity and hepatitis C antibody positivity did not influence overall mortality or graft survival. Only cytomegalovirus seronegative status was important (as opposed to seropositive status, which was not). Of seronegative patients only those receiving a kidney from a seropositive donor were adversely affected. The presence of HIV-1 antibody had an adverse effect on graft survival, but the question remains as to whether overall mortality in HIV seropositive patients is any worse than those receiving dialysis therapy.
Non-A, non-B hepatitis is a significant cause of liver disease among renal allograft recipients. In order to assess the impact and prevalence of hepatitis C in a series of renal allograft recipients, we retrospectively screened 621 consecutive patients transplanted between 1979 and 1989 and 484 cadaver organ donors retrieved in the same interval for serologic evidence of hepatitis C viral (HCV) infection using the enzyme-linked assay for anti-HCV antibody. Of 596 HBsAg negative patients, 180 (30%) were anti-HCV positive at the time of transplant. One-year posttransplant, 117 (22%) had detectable levels of anti-HCV antibody. Chemically significant hepatitis developed in 52/234 (22%) anti-HCV positive patients, and 26 of these followed a clinical course consistent with chronic hepatitis. Significantly more males and patients with antibody to HCV detectable at 1 year posttransplant were in the group experiencing an increase in liver enzymes. Ten-year patient and graft survival was 78% and 50%, respectively, for the anti-HCV positive patients who had an elevation of alanine aminotransferase, and 76% and 57% for the cohort maintaining normal liver function (P = NS). There were also no differences in patient and graft survival among the anti-HCV positive group and the consistently sero-negative patients. Of 484 cadaver organ donors with serum available for analysis (out of 1200 retrieved), 67 (14%) were anti-HCV positive at the time of organ donation. Among 23 anti-HCV negative kidney recipients who received a kidney from an HCV antibody positive donor, only one had seroconverted at 1 year posttransplant. Antibody to HCV appears to be widespread among renal transplant recipients and cadaver organ donors. We were unable to demonstrate any evidence of long-term adverse effects on patient and graft survival among anti-HCV positive patients employing the first generation anti-HCV assay.
Purified hepatocytes (LH), Kupffer cells (LKu), and intrahepatic biliary duct cells (LD) were isolated from canine livers, as well as tubular cells from canine kidneys, by enzymatic digestion, gradient centrifugation, and tissue culture techniques. Incubation of LH, LKu, and LD for 48 hr in a two-compartment diffusion chamber opposite two-way mixed lymphocyte cultures, or with canine gamma interferon purified and standardized in our laboratory, resulted in a significant increase in class II expression. This was detected in the cell analyzer with directly fluoresceinated B1F6, a monoclonal antibody (mab) generated in our laboratory vs. a canine class II monomorphic epitope. An amplification of the allogeneic mixed lymphocyte liver cell cultures (MLLC) of at least 2-fold was observed by preinduction of canine class II expression with IFN-gamma on LKu and LD cells, but an autologous reaction could not be elicited. However, an autologous as well as allogeneic lymphoproliferation against kidney tubular cells (MLKC) could be easily observed without IFN-gamma and amplified with IFN-gamma to stimulation indices of at least 3 times that of noninduced cultures. Dependence of the allogeneic MLLC and allogeneic and autologous MLKC on class II gene expression was also evidenced by blocking of 3H-thymidine uptake seen by incubation with 5 micrograms of B1F6. Another mab, I1F6, generated against tubular cells and inhibiting the autologous and allogeneic MLKC, had no blocking effect on lymphoproliferation with any of the liver cell preparations. No such tissue-specific mab (analogous to I1F6) has thus far been found in response to mouse immunization with LH, LKu, or LD. In the absence of accepted defined molecular probes in the dog as yet, we conclude that, in contrast to kidney tubular cells, cells of the normal canine liver do not readily stimulate a primary lymphoproliferative autoimmune reaction in vitro despite class II amplification. Thus autoreactivity (as opposed to alloreactivity) is much less prominent in immune recognition of purified cellular components of nondiseased liver tissue than of kidney tissue in which tissue-associated epitopes are more operative.
Immunoglobulins derived from sera containing anti-antiidiotypic antibodies (Ab2) generated in renal transplant recipients after OKT3 monoclonal antibody therapy, as reported in our previous study (1), have now been proved to bind to several bands of T cell membrane lysates (TCML) in immunoblotting analyses ranging in molecular weight from 40 to 55 KD. These sera also blocked the expression of the ligand binding to WT31 in flow cytometry. WT31 is a MAb that recognizes a common determinant on the T cell receptor (TCR). Immunoglobulins from these sera suppressed the activation of normal peripheral blood T lymphocytes (PBT) induced by OKT3. All patients (7/32) who developed this Ab2 had distinct culture-proved cytomegaloviral infections. In further immunoblotting studies, alpha F1, another MAb recognizing the framework of the TCR alpha chain, more deeply inserted in the T cell membrane, also showed binding to protein bands of cytomegalovirus pellet lysates derived from virus-infected embryonic fibroblasts. In addition, alpha F1 showed positive binding to several ligands in the membrane lysate of CMV-infected, but not noninfected MRC-5 cells. An anti-CMV MAb recognizing late nuclear antigen (LAb), also strongly bound to a approximately 50 KD band of TCML and several bands (approximately 34, approximately 40, and approximately 50 KD) of H33HJAJ1 (human T leukemia) cell lysate. Furthermore, alpha F1 immunoprecipitated a approximately 96 KD ligand of CMV-infected MRC5 lysate that had the same electrophoretic mobility as one of the proteins precipitable with LAb. Both LAb and alpha F1 also showed positive binding to paraformaldehyde-fixed and Triton X-100-permeabilized PBT in flow cytometry. Sera containing Ab2 blocked alpha F1 binding to acetone-fixed cytofuged PBT preparations on slides. Moreover, both alpha F1 and LAb inhibited mitogen-stimulated lymphocyte activation in vitro. These data support the notion that T cell functional abnormalities associated with CMV infection observed after treatment of transplant recipients with anti-T cell monoclonals might be caused by binding to T cell ligands by a variety of crossreacting human Igs operative in a regulatory network. Confirmatory evidence is the effect of MAbs generated against CMV virion epitopes crossreacting with T cell ligands, and vice versa.
Individuals with anti-phospholipid antibodies are at increased risk for the development of thrombosis and fetal loss. The pathogenesis of these syndromes is unknown, but may involve antibody-mediated alterations in endothelial cell coagulant activity. To address this possibility, we determined the incidence of endothelial cell-reactive antibodies in 76 patients whose plasma contained anti-phospholipid antibodies, but who had no clinically-evident immune disorder. Plasma from 47 patients deposited significantly more immunoglobulin on cultured endothelial cells than control plasma. Positive tests were more frequent in patients with a history of thrombosis than in those without (17/19 v 23/48; P = 0.004). However, we observed no correlation between immunoglobulin deposition on cardiolipin and endothelial cells by individual plasmas. Furthermore, endothelial cell reactivity was not diminished by adsorption of anti-cardiolipin antibodies from patient sera using liposomes. Immunoglobulin fractions prepared from 5/6 patient sera immunoprecipitated a approximately 70 kDa endothelial cell surface protein; 4/5 of these fractions also induced the release of von Willebrand factor from endothelial cells. These results demonstrate that plasma from many patients with anti-phospholipid antibodies, but no clinically-evident autoimmune disease, also contains endothelial cell-reactive antibodies. Detection of such antibodies might help identify individuals in this patient population at greatest risk for thrombosis.
Explore the source record for details and available documents.
With enzymatically isolated smooth muscle cells from primary stenosing lesions cultured in a transfilterculturesystem it is possible to examine multiple steps (e.g. migration and proliferation) involved in the development of restenosing lesions at the same time. By using human atherosclerotic plaque material the clinical relevance of experiments might be improved.
By cultivating smooth muscle cells, isolated from media-pieces of rabbit and human aorta, on microporous filter membranes (transfilter-culture-system), it is possible to examine proliferation and migration of smooth muscle cells at the same time. After addition of Epinephrine to the cultures, an increase in proliferation and migration was observed.
Migration and proliferation of smooth muscle cells (SMC) from the media into the subendothelial space are important steps in the development of restenosing events after angioplasty; therefore a medical inhibition of this activity seems to be of clinical interest. Primary stenosing plaque material of 20 patients and restenosing plaque material of 6 patients was removed by atherectomy (Prof. Höfling, Dr. Bauriedel, Munich). For the isolation of plaque cells a mixture of Collagenase/Elastase was used. The vast majority of plaque cells was identified as smooth muscle cells by positive reaction with monoclonal antibodies against smooth muscle alpha-Actin. Propranolol (10(-4) mol/l to 10(-9) mol/l), Prednisolone (10(-3) mol/l to 10(-8) mol/l) and Etoposide (10(-4) mol/l to 10(-9) mol/l) were added to the cultures one day after seeding. After 3 days cell number and cell size distribution were analysed in a cell counter (Casy I, Schärfe System, Reutlingen). While Propranolol didn't change proliferative activity of SMC, Prednisolone caused a slight, but dose dependent inhibition of SMC-proliferation. Etoposid inhibited SMC-proliferation even below clinical concentrations to 50%. The local application of steroid or cytostatic agents might improve long term results after angioplasty. The clinical relevance of this 'Prescreening System' has to be evaluated by experimental and clinical studies.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
1. The efficacy of fluvoxamine is compared to that of desipramine in a multicenter double blind placebo controlled six-week flexible dose trial of 90 outpatients with major depressive disorder. 2. Although overall drug effects were relatively weak, there were trends suggesting separation of both active drugs from placebo at week six. Both drugs were well tolerated. 3. Studies of major depression ought to be designed to last 8-10 weeks in order to demonstrate placebo active drug differences and the stability of such a difference should it occur in the first six weeks.