Search PubMed⌕ Search

Biomedical subjects

M Roth

Publications and source records attributed to M Roth.

At least 163 records · Page 9Linked to original sources
PubMed1996

Distinct patterns of immunoglobulin classes and IgG subclasses of autoantibodies in patients with inflammatory bowel disease.

OBJECTIVE: The pathophysiological significance of autoantibodies in inflammatory bowel diseases (IBD) is still unclear. To assess specific immunological abnormalities we examined the distribution and restriction of immunoglobulin classes and subclasses of anti-neutrophil cytoplasmic antibodies (ANCAs) in ulcerative colitis and of antibodies to pancreatic juice (APJs) in Crohn's disease. METHODS: We tested 62 sera of patients with ulcerative colitis and 184 sera of patients with Crohn's disease for their immunoglobulin class and IgG subclass distribution of ANCAs (in ulcerative colitis patients) and APJs (in Crohn's disease patients) by fluorescence isothiocyanate (FITC)-labelled anti-human antibodies in an immunofluorescence assay with human granulocytes or pancreas as substrate. Twenty-five patients with Wegener's granulomatosis were used for comparison. RESULTS: In ulcerative colitis ANCAs were found in 74% of the patients. They were predominantly of the IgG (96%) and IgA class (37%). In Crohn's disease APJs (present in 28% of the cases) were of the IgG (98%) and IgA class (71%). ANCAs in ulcerative colitis were of the IgG1 (73%) and IgG3 (5%) subclasses, APJs in Crohn's disease of the IgG1 (94%), IgG2 (20%) and IgG3 (2%) subclasses. The immunoglobulin class and IgG subclass distributions of ANCAs and APJs resembled the changes in total immunoglobulin classes and IgG subclasses in ulcerative colitis or Crohn's disease. CONCLUSION: The immunoglobulin classes and IgG subclasses of autoantibodies in ulcerative colitis and Crohn's disease differ from each other and from the distribution of autoantibodies in vasculitic diseases (Wegener's granulomatosis, microscopic vasculitis, systemic lupus erythematosus). These alterations reflect specific pathophysiological features of ulcerative colitis and Crohn's disease.

Adolescent↗
PubMed1996

Induction of interleukin 6 and interleukin 8 expression by Broncho-Vaxom (OM-85 BV) via C-Fos/serum responsive element.

BACKGROUND: Broncho-Vaxom (OM-85 BV) increases the resistance of the respiratory tract to bacterial infections by modulating host immune responses. The compound increases serum IgG levels but decreases IgE levels in patients suffering from chronic bronchitis or chronic obstructive pulmonary disease. It increases concentrations of gamma-interferon (IFN-gamma), IgA, and interleukin (IL)-2 in bronchoalveolar lavage fluid of patients with bronchitis. Treatment with OM-85 BV increases the number of T helper and natural killer cells. In this study the effects of OM-85 BV on transcription of cytokines is investigated in human lung fibroblasts. METHODS: Transcription and synthesis of IL-6 and IL-8 were assessed in cultured primary human lung fibroblasts using standard methods of Northern blot analysis for the level of mRNAs and enzyme linked immunosorbent assay for proteins. RESULTS: Broncho-Vaxom (OM-85 BV) at different concentrations induced transcription of IL-6 and IL-8. The effect of the drug on transcription of IL-6 and IL-8 genes correlated with secretion of the proteins into cell supernatants. OM-85 BV-dependent expression of the interleukin genes involved C-Fos/serum responsive element (C-Fos/SRE). CONCLUSIONS: The data suggest that the various immunopharmacological activities of OM-85 BV that have been described in clinical studies may be explained by its ability to induce expression of IL-6 and IL-8.

Adjuvants, Immunologic↗
PubMed1996

Moclobemide in elderly patients with cognitive decline and depression: an international double-blind, placebo-controlled trial.

BACKGROUND: The new reversible MAOl moclobemide was compared with placebo in the treatment of elderly patients with DSM-III diagnosis of dementia and/or of major depression. METHOD: Six hundred and ninety-four elderly patients with symptoms of depression and cognitive decline entered an international, multi-centre, double blind trial in which they were randomly allocated to treatment with either moclobemide 400 mg daily or placebo for 42 days. Five hundred and eleven patients met DSM-III criteria for dementia and were also depressed (DEM+D); 183 did not meet DSM-III criteria for dementia but met the criteria for DSM-III major depressive episode and also suffered from cognitive decline (MDE+CD). RESULTS: Analysis of the 17 and 24-item Hamilton Depression Scale scores showed that moclobemide, compared with placebo, produced significantly greater improvement in both the demented and depressed groups (P = 0.001 both diagnostic groups). There was an improvement in cognitive function as measured by the SCAG Factor 1 in moclobemide treated patients (P = 0.005 DEM+D; P = 0.02 MDE+CD). There was no evidence of decline in cognitive function as the result of treatment. Clinical global assessment of tolerance was 'excellent' and 'good' in 88% of the moclobemide and in 92% of the placebo treated patients. The proportion of patients discontinuing treatment prematurely was similar in both treatment groups. There were no significant differences in side-effects between treatment groups. There were no significant changes in vital signs, ECG or laboratory findings in either treatment group. There were no dietary restrictions and no report of any tyramine reaction. CONCLUSIONS: Moclobemide was shown to be a safe, well tolerated and effective antidepressant, which did not cause impairment of cognitive function in elderly patients with a DSM-III diagnosis of dementia and/or DSM-III major depression.

Aged↗
PubMed1996

A unique temporal bone lesion resembling juvenile active ossifying myxoma.

Juvenile active ossifying fibroma (JAOF) is a lesion characterized by early age of onset, slow growth, frequent recurrence, and locally aggressive behavior. Histologically, it consists of three major components: cellular fibrous stroma, osteoid bodies, and myxomatous matrix, which may become cystic. This article describes a case of a slowly growing destructive lesion of the mastoid in a 2-year-old girl with histologic features resembling those of juvenile active ossifying myxoma (JAOM). Histologically, its prominent features were myxoid and fibromyxoid stroma with cystic areas, vascular spaces, bone, and multinucleated giant cells. This is the first pediatric temporal bone lesion with these features recorded These histologic components led to the diagnosis of JAOM of the temporal bone, probably developing in relation to the development of the mastoid air spaces.

Bone Neoplasms↗
PubMed1996

[Psychopathology, self concept and developmental delay in healthy and chronically ill adolescents. Results of a 4 1/2 year longitudinal study].

Psychopathology, self-concept and developmental delays in healthy and chronically ill adolescents: Results of a 4-1/2-year follow-up study. This contribution presents results obtained in a 4-1/2-year longitudinal study on 91 adolescents with diabetes and 107 healthy adolescents. We addressed the question of whether chronically ill adolescents show more psychopathological behaviors than healthy adolescents, and if so, whether there are changes within a time span of 4-1/2-years. In addition, we investigated whether adolescents with diabetes differ from healthy adolescents in their feelings of self-esteem and in their developmental status. The self-concept of healthy and diabetic adolescents proved to be very similar, and stable over time as well. As regards developmental status, the developmental delays seen in the diabetic subjects at the beginning of the study had disappeared by the end of the study. Throughout the study the diabetic adolescents appeared to be more "normal", showing significantly fewer symptoms of psychopathology than the healthy control group. Furthermore, the consistently higher values in social desirability among the diabetic subjects show that the strong denial in these subjects was stable over the 4-1/2-year period.

Adolescent↗
PubMed1995

Apolipoprotein E type epsilon 4 allele frequency is increased in patients with schizophrenia.

Apolipoprotein E type epsilon 4 alleles are increased in both Alzheimer's disease (AD) and cortical Lewy body dementia, while the epsilon 2 allele has been associated as a protective factor against the development of dementia in AD. We have determined APOE genotype in schizophrenic patients coming to autopsy (age range 19-95 years). The allele frequencies in this group were: epsilon 2, 6.0%; epsilon 3, 67.9%; and epsilon 4, 26.2%. Three patients (14%) were homozygous for the epsilon 4 allele. Thus, schizophrenia is associated with an increased epsilon 4 allele frequency, as compared with controls (P = 0.01), that was indistinguishable from that found in either AD or Lewy body dementia. The increased epsilon 4 allele frequency was not associated with increased age of schizophrenia patient, indicating that it was not due to the co-existence of AD.

Adult↗
PubMed1995

Use of unrelated marrow grafts compensates for reduced graft-versus-leukemia reactivity after T-cell-depleted allogeneic marrow transplantation for chronic myelogenous leukemia.

The effect of donor/recipient histocompatibility on relapse in patients receiving T-cell-depleted (TCD) grafts for chronic myelogenous leukemia (CML) was evaluated. Specifically, we sought to determine whether TCD results in an attenuation of the graft-versus-leukemia (GVL) effect on recipients of unrelated marrow grafts similar to that observed in HLA-identical sibling marrow transplantations. This question was addressed by comparative analysis of the relapse rates in marrow grafts who otherwise received identical preparative regimens and graft-versus-host disease (GVHD) prophylaxis schedules (T-cell depletion with T10B9 monoclonal antibody and complement plus posttransplant cyclosporine) and by serial molecular analyses using the polymerase chain reaction (PCR) to detect the bcr/abl RNA transcript in patients transplanted with unrelated donor grafts. Patients transplanted with advanced disease (accelerated phase or blast crisis) had equally high relapse rates, regardless of whether they received HLA-identical sibling (56%;95% confidence interval [CI], 29% to 82%) or unrelated marrow grafts (8%; 95% CI, 0% to 28%) had a significantly lower incidence of relapse than did patients transplanted with HLA-identical marrow grafts (47%; 95% CI, 23% to 71%; P = .002). Because all patients were similarly treated, these data indicate that the lower relapse rate in these unrelated patients was caused by an augmented GVL effect that was most likely attributable to increased HLA disparity between donor and recipient. The probability of developing both acute and chronic GVHD was significantly increased in chronic-phase recipients of unrelated marrow grafts, suggesting that the enhanced GVL effect was at least partly GVHD-associated. The lack of such a finding in advanced disease patient receiving unrelated marrow grafts raises the possibility that clinically significant GVL effect after TCD marrow transplantation was limited and confined to patients with more indolent disease. Serial PCR analyses for the presence of the bcr/abl RNA transcript showed that the vast majority of patients transplanted in chronic phase with unrelated marrow grafts were persistently PCR-negative, indicating that the GVL effect was durable in these patients. Most of these patients were observed to become PCR negative within 1 to 2 months after transplantation, showing that early eradication of leukemia was possible with TCD marrow grafts. This study shows that the use of unrelated marrow grafts compensates for reduced GVL reactivity associated with TCD in patients transplanted for CML. Furthermore, these data indicate that, in selected patient populations with CML, TCD can be used to reduce GVHD without a commensurate compromise in the GVL effect.

Adolescent↗
PubMed1995

Platelet-derived growth factor stimulates the secretion of hyaluronic acid by proliferating human vascular smooth muscle cells.

Total glycans from the cell layer and the culture medium of human vascular smooth muscle cells (VSMC) that had been cultivated in the presence of platelet-derived growth factor (PDGF) were isolated and purified by gel filtration after Pronase and DNase digestion and alkaliborohydride treatment. Measurements of the content of neutral hexoses and uronic acids revealed that PDGF stimulates total glycan synthesis by proliferating VSMC in a linear fashion from 24 h to 72 h of incubation. In contrast, total glycan synthesis by human fibroblasts, epithelial cells, or endothelial cells was not affected by PDGF, indicating cell-type specificity. Chemical, biochemical, and enzymological characterization of the total glycans synthesized by VSMC showed that PDGF stimulates the secretion of a 340-kDa glycan molecule in a time-dependent manner from 24 h to 72 h. This molecule is highly acidic, shares a common structure with hyaluronic acid, and exhibits a potent antiproliferative activity on VSMC. These results suggest that VSMC in response to PDGF are capable of controlling their own growth and migration by the synthesis of a specific form of hyaluronic acid with antiproliferative potency, which may be involved in the regulation of the local inflammatory responses associated with atherosclerosis.

Amino Acids↗
PubMed1995

Biochemical complementation studies in vitro of gyrase subunits from different species.

To investigate the functional equivalence of DNA gyrase subunits from different bacterial sources hybrid enzymes were formed using purified A and B subunits from three species of Streptomycetes, E. coli and B. subtilis. The activity of gyrase hybrids composed of heterologous gyr A and gyr B proteins and of the gyrases containing homologous subunits was characterized by binding studies and a cleavage assay with two different DNA fragments. Likewise the enzyme activity was monitored by the super-coiling and relaxation assay with pBR322 DNA. We found that cleavage reactions are largely determined by the source of the gyr B subunits whereas DNA supercoiling and relaxation reactions of pBR322 catalyzed by DNA gyrase are limited to a combination of homologous A and B subunits or of heterologous A and B subunits from the taxonomically related bacteria Streptomycetes.

Bacillus subtilis↗
PubMed1995

Silent myocardial rupture in a patient with diabetes and Addison's disease.

We present a case of left ventricular rupture and formation of a pseudoaneurysm after silent myocardial infarction in a patient with Schmidt syndrome (polyglandular deficiency syndrome including Addison's disease, lymphocytic thyroiditis and diabetes mellitus). This case illustrates the possibility of myocardial rupture without hemodynamic collapse and a possible role of chronic steroid substitution.

Addison Disease↗
PubMed1995

Focal white-matter lesions in brain of patients with inflammatory bowel disease.

Inflammatory bowel diseases are often associated with extra-intestinal manifestations, such as arthritis and iritis/uveitis. Using magnetic-resonance imaging we found hyperintense focal white-matter lesions in the brain in 20 of 48 (42%) patients with Crohn's disease, in 11 of 24 (46%) patients with ulcerative colitis, but in only 8 of 50 (16%) healthy age-matched controls (relative risk [95% CI] vs controls 2.6 [1.3-5.3] and 2.9 [1.3-6.2], respectively). These findings may represent another extra-intestinal manifestation of inflammatory bowel disease.

Adult↗
PubMed1995

Intracellular interleukin 6 mediates platelet-derived growth factor-induced proliferation of nontransformed cells.

The functional relevance of interleukin 6 (IL-6) in platelet-derived growth factor (PDGF)-induced cell growth was evaluated in cultures of human fibroblasts, vascular smooth muscle cells, and mesangial cells. The three isoforms of the PDGF--namely, PDGF-AA, -AB, and -BB--induced the expression of the IL-6 gene and proliferation of the nontransformed cells. PDGF-induced transcription, translation, and secretion of IL-6 were diminished in the presence of IL-6 antisense oligonucleotides. While neutralizing anti-IL-6 antibodies failed to affect the growth factor-dependent cell proliferation, IL-6 antisense oligonucleotides inhibited cell division. In addition, IL-6 antisense oligonucleotides abolished PDGF-induced transcription of the genes coding for the cell division cycle 2-related protein (CDC2) and proliferating cell nuclear antigen (PCNA), both of which are regulated in a cell cycle-dependent manner. It is concluded that PDGF-dependent proliferation of nontransformed cells involves the action of intracellular IL-6.

Base Sequence↗
PubMed1995

Parenteral nutrition alters monocyte TNF receptor activity.

The route of nutrient provision has been reported to influence some aspects of the host inflammatory response in both patient populations and normal subjects. The tumor necrosis factor receptor system is a complex regulatory mechanism that modulates the bioavailability of tumor necrosis factor (TNF). We sought to determine whether maintenance on total parenteral nutrition (TPN) can alter host response to endotoxin challenge, specifically as it relates to the TNF receptor system. Seventeen healthy men were randomized to receive either TPN (n = 8) or a defined formula enteral diet (ENT, n = 9) prior to intravenous infusion of endotoxin (Lot EC-5, 20 U/kg). The subjects that received 1 week of antecedent TPN exhibited an increased heart rate and temperature and decreased mean arterial pressure post-LPS compared to those subjects maintained on enteral nutritional support. The TPN subjects also exhibited comparatively higher TNF and interleukin-6 levels in response to endotoxin. Monocyte TNF receptor levels decreased in both groups post-LPS, but TPN subjects exhibited consistently greater expression of this functional membrane-associated TNF receptor. After LPS, soluble tumor necrosis factor receptor II (sTNFr II, p75) peaked three times higher in TPN subjects than in ENT subjects. Conversely, sTNFr I (p55) was higher in the enterally fed group. From these studies it appears that antecedent TPN not only influences clinical manifestations of endotoxin but also modulates the regulation of all associated TNF receptors and shedding of soluble receptors.

Adolescent↗
PubMed1995

Ca(2+)-channel blockers modulate the expression of interleukin-6 and interleukin-8 genes in human vascular smooth muscle cells.

Ca(2+)-channel blockers at therapeutic concentrations were shown to modulate several processes underlying inflammation, such as growth factor-mediated activation of genes coding for the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in human vascular smooth muscle cells (VSMC) (Block et al., 1991), and for interleukins in human mesangial cells (Roth et al., 1992). Two Ca(2+)-channel blockers, Manidipine (Roth et al., 1992) and Verapamil (Walz et al., 1990) have been shown to induce the expression of the gene coding for interleukin-6 (IL-6). Here we demonstrate that the four Ca(2+)-channel blockers, Amlodipine, Felodipine, Isradipine and Manidipine, at nanomolar concentrations, activate the transcription of the genes encoding IL-6 and IL-8 in primary human VSMC and fibroblasts. Ca(2+)-channel blocker-induced transcription is subsequently followed by secretion of the two ILs into the growth medium of the cells. In addition, we compared the action of the Ca(2+)-channel blockers with that of propranolol, a beta-adrenoceptor antagonist, or with furosemide, a diuretic, all of which are known to lower blood pressure. However, in contrast to the dihydropyridines, the two latter drugs failed to affect the expression of the two IL genes.

Adrenergic beta-Antagonists↗
PubMed1995

Bone metabolism in spinal cord injured individuals and in others who have prolonged immobilisation. A review.

Immobilisation or disuse is a condition known to be associated with a decrease in bone mass, osteopenia and in some people leading to osteoporosis with an increased risk of fractures. In this condition, previous histomorphometric and biochemical reports have shown an uncoupling between bone formation and resorption, but the exact sequence of the events resulting in bone loss is still not fully understood. In spinal cord injury for instance, the main finding soon after the onset is decreased osteoblastic activity associated with a dramatic increase in bone degradation. The overall consequence of these metabolic events is the development of a rapid and severe osteoporosis only observed in the paralysed part of the body associated with the loss of biomechanical strength and the biosynthesis of a structurally modified matrix which is unable to sustain normal mechanical stress. This situation dramatically increases the risk of fractures. The same uncoupling phenomenon has been described in healthy individuals who have been submitted to long duration bedrest and also in astronauts during spaceflight; but the timing, intensity and the metabolic subset may be different as these people do recover after cessation of the disuse period, which does not occur in paralysed patients. As new accurate and sensitive non-invasive techniques have become available recently to assess bone and connective tissue metabolism, more information is now available regarding bone loss in paralysed and/or immobilised individuals. These techniques should be definitely helpful in orientating new therapeutic trials with drugs and/or procedures intended to correct the musculoskeletal deleterious effects of disuse. This paper is therefore aimed at a review of bone metabolism in those with a severe spinal cord injury, or with a long duration of bedrest, or with loss of biomechanical function, or with actual or simulated spaceflight, in all instances using non-invasive techniques.

Bed Rest↗