PubMed Health⌕ Search

Biomedical subjects

S Moritz

Publications and source records attributed to S Moritz.

50 records · Page 3Linked to original sources
PubMed1997

Analysis of cell cycle disruptions in cultures of rat pleural mesothelial cells exposed to asbestos fibers.

The control of DNA integrity in mammalian cells is important to maintain the cell homeostasis and prevent neoplastic transformation. Control of cell division and cell death permits repair or elimination of damaged cells. Since asbestos fibers can produce DNA damage, chromosome alterations and apoptosis in several sorts of cells, including mesothelial cells, it was interesting to investigate cell cycle disturbances in rat pleural mesothelial cells (RPMC) treated with asbestos fibers. Cell cycle analyses were performed in RPMC exposed to crocidolite (10 and 20 microg/cm2) and chrysotile (5 and 10 microg/cm2) for different times (4 to 48 h). Both fiber types entailed a G2/M accumulation in agreement with a delay in the mitosis course. Chrysotile fibers produced a G0/G1 accumulation associated with a time-dependent p53 and p21 expression. Crocidolite exposure resulted in a delay in the G1/S transition paralleling a low rate of p53 expression. These results are in agreement with a DNA damaging potential of asbestos fibers since similar results were found following RPMC exposure to gamma rays. In asbestos-treated RPMC, a low rate of apoptosis was found suggesting that RPMC may follow a DNA repair pathway that could contribute to the formation of DNA lesions. In addition, the cell cycle disturbances at the G2/M checkpoint suggest that genetically altered cells have progressed through the cycle and support the already published findings on the ability of asbestos fibers to impair cell division.

Animals↗
PubMed1996

Expression of adhesion molecules on circulating PMN during hyperdynamic endotoxemia.

In a porcine model of hyperdynamic endotoxemia, we studied the numerical expression of L-selectin and beta 2-integrins on circulating polymorphonuclear leukocytes (PMN). Functional changes of beta 2-integrins were determined by the adhesion of PMN to C3-coated zymosan particles. Anesthesized pigs received a continuous infusion of Salmonella abortus-equi endotoxin (5 micrograms.kg body wt-1.h-1) for 270 min (endotoxin group; n = 7). A control group received 0.9% NaCl (n = 6). L-selectin had decreased 30 min after the induction of endotoxemia [59.1 +/- 11.9 vs. 91.6 +/- 15.5 relative fluorescence units (RFU) at baseline; P < 0.05], reaching minimal values after 150 min (23.9 +/- 3.9 RFU in endotoxin group vs. 95.2 +/- 30.4 RFU in control group; P < 0.05). PMN adhesion to C3-coated zymosan increased at 30 min (41.3 +/- 9.9% in endotoxin group vs. 2.4 +/- 1.1% in control group; P < 0.05) and remained significantly elevated thereafter. In contrast to the rapid shedding of L-selectin and functional upregulation of beta 2-integrins, the numerical expression of beta 2-integrins remained unchanged until 60 min (44.8 +/- 2.8 vs. 32.2 +/- 1.7 RFU at baseline; P < 0.05); compared with the control group, significantly elevated values were observed 150 min after the start of endotoxin (48.9 +/- 2.4 RFU in endotoxin group vs. 36.5 +/- 2.7 RFU in control group; P < 0.05). We conclude that numerical and functional expressions of beta 2-integrins are dissociated during endotoxemia. Although upregulation of beta 2-integrins might render PMN more adhesive to the vascular endothelium, the presence of activated PMN in the circulation suggests that low expression of L-selectin might impede adhesion.

Animals↗
PubMed1993

Hexokinase II mRNA and gene structure, regulation by insulin, and evolution.

A DNA segment that is highly conserved in glucokinase (hexokinase IV) and hexokinase I cDNA was used to identify specific cDNAs in a library prepared from rat adipose tissue mRNA. Some of these cDNAs were identified as being hexokinase I cDNA. Others, although similar to both the glucokinase and hexokinase I cDNAs, were unique. Two of these unique cDNAs overlapped and contained an open reading frame that encoded a protein of 103 kDa which, when expressed in Escherichia coli, had kinetic properties characteristic of hexokinase II. The entire hexokinase II mRNA sequence and the exon-intron structure of the hexokinase II gene were determined. A single transcription initiation site and two distinct termination sites account for the two observed hexokinase II RNA species of 5500 and 4400 nucleotides that were detected when either of the cDNAs was used as a hybridization probe against poly(A)+ RNA isolated from rat adipose tissue. Hexokinase II mRNA was decreased in adipose tissue from diabetic rats, but was restored by insulin treatment to levels found in nondiabetic control rats. Insulin also induced hexokinase II mRNA in two adipose cell lines (3T3-F442A and BFC-1B) and two skeletal muscle cell lines (C2C12 and L6). In L6 cells, this increase was accounted for by a corresponding increase of hexokinase II gene transcription. Comparison of the structures of the hexokinase II and glucokinase genes support the hypothesis that the 100-kDa hexokinase arose by gene duplication and tandem ligation of a 50-kDa glucokinase-like ancestral gene.

Adipose Tissue↗
PubMed1986

[Immunopathological study of acute interstitial nephropathy induced by clometacin].

Clometacin is an antalgic drug with a chemical structure very similar to that of indomethacin; it is widely used in France. We report evidence for a cell-mediated immune mechanism in the pathogenesis of clometacin-induced acute interstitial nephritis. In the interstitial infiltrate of a female patient presenting with this condition, T cells constituted 75% of the total lymphocyte population. Cytotoxic/suppressor T cells predominated over helper/inducer T cells with a ratio of two to one. IgA-secreting plasmocytes were also present (about 23% of the inflammatory infiltrate). Peripheral blood lymphocyte studies showed that pre-incubation of the patient's cells with clometacin resulted in an increased sensitivity to interleukin 2 and a positive syngeneic mixed lymphocyte culture. This study seems to be relevant to the pathogenesis of acute interstitial nephritis induced by nonsteroidal anti-inflammatory drugs.

Acute Disease↗
PubMed1986

Cytotoxic T cell response and thymic hormonal dysfunction in graft-vs-host mice.

As an approach to dissect complex mechanisms that lead to graft-vs-host (GvH)-associated immune disorders, we have compared the splenic cytotoxic T lymphocyte (CTL) response and thymic hormonal function in nonirradiated F1 hybrid mice injected with parental spleen cells. Thymic secretory function was studied by the determination of serum thymulin levels, and the number of thymic epithelial cells containing thymulin as assessed by indirect immunofluorescence with the use of an anti-thymulin monoclonal antibody. In addition, the epithelial cell network was analyzed with an anti-keratin serum, and the general histology pattern was studied by conventional histologic methods. An initial analysis was performed on day 15, which was characterized by CTL suppression mediated by parental suppressor T cells. No thymic abnormalities were detected at this time. By day 45 after GvH induction, active CTL suppression had decreased, and GvH was associated with a progressive decline in thymic hormonal function. Finally, by day 60 and thereafter, F1 GvH mice recovered normal in vitro CTL responsiveness, which contrasted with profound alterations of the epithelial cell network and severely reduced serum thymulin levels. This hormonal dysfunction was shown to be directly associated with a reduction in the number of thymulin-containing cells. Moreover, no anti-thymulin auto-antibodies could be detected. The results are discussed with respect to the role of thymic hormonal dysfunction in the modulation of F1 CTL responses observed during the course of a GvH reaction, and the additional analogy of this GvH model with human immunodeficiency.

Animals↗
PubMed1985

Lymphopenia and abnormal balance of T-lymphocyte subpopulations in toxic epidermal necrolysis.

A lymphopenia (peripheral-blood-lymphocyte count less than 1,000/mm3) was observed in seven out of ten patients with toxic epidermal necrolysis (TEN). The enumeration of T-lymphocyte subsets with monoclonal antibodies showed a decreased number of pan T-lymphocytes (OKT3-positive), which was related to a profound depletion of OKT4-positive cells. In contrast, OKT8-positive cell counts were not significantly changed. This abnormal balance of T-lymphocytes was linked to the acute phase of the disease and was not found after recovery. The pathogenetic mechanisms of such T-lymphocyte abnormalities in TEN remain unclear.

Adolescent↗
PubMed1985

Involvement of macrophages in the pathology of toxic epidermal necrolysis.

In toxic epidermal necrolysis (TEN), as in the 'epidermal type' of erythema multiforme, the necrotic epidermis is infiltrated with mononuclear cells. We studied the epidermal infiltrate in seven cases of TEN. About half the cells obtained from pieces of cleaved epidermis dissociated by trypsin were non-epithelial. On cytologic analysis, 80% of these foreign cells exhibited markers of macrophages, 15% were granulocytes and only 5% were lymphocytes (almost exclusively OKT8 T lymphocytes). Semi-thin sections of early prenecrotic lesions showed exocytosis of mononuclear cells within the epidermis with features of satellite cell necrosis and formation of colloid bodies. Almost all these mononuclear cells were macrophages as evidenced by endogenous peroxidase-positive granules. These findings suggest that some kind of macrophage-mediated cytotoxicity may play a role in the necrosis of epidermal cells during TEN.

Adolescent↗
PubMed1985

Lymphocyte transformation test in drug-induced toxic epidermal necrolysis.

Lymphocyte transformation tests (LTT) to drugs remain widely used in drug reactions, despite controversies about their real usefulness. We tested the lymphocytes of 12 patients recovering from a drug-induced Toxic epidermal necrolysis (TEN). There was no difference between the amounts of thymidine incorporated when patients' lymphocytes were cultivated with culprit or innocent drugs. In both situations the lymphocytes from patients reacted like the lymphocytes from controls cultivated with the same panel of drugs. These negative results do not exclude that a hypersensitivity reaction may play a role in the physiopathology of TEN. Anyhow, they clearly indicate that testing lymphocyte transformation to drugs has no practical value in the diagnosis of TEN.

Adolescent↗
PubMedDate not supplied

The impact of neuroleptic dosage and extrapyramidal side effects on schizophrenic basic symptoms.

The impact of neuroleptic medication and extrapyramidal symptoms on abnormal subjective experiences in schizophrenia, also termed basic symptoms, as assessed with the Frankfurt Complaint Questionnaire (FCQ) was investigated in 40 schizophrenic patients medicated with conventional neuroleptics. Basic symptoms are thought to reflect the subjective side of schizophrenic vulnerability and to underlie schizophrenic symptomatology. It was expected that basic symptoms would inversely correlate with chlorpromazine equivalents, since neuroleptics not only improve acute schizophrenic symptoms but also have prophylactic properties. However, a significant positive correlation with neuroleptic dosage and extrapyramidal symptoms emerged, suggesting that basic symptoms as operationalized in the FCQ partly reflect neuroleptic-induced deficits. The results remained unchanged when global psychopathology was controlled for. In line with previous research, basic symptoms correlated with thought disorder but not with positive symptoms. However, when the effects of neuroleptic-induced disturbances were controlled for, thought disorder also insignificantly correlated with basic symptoms. Our findings confirm previous results that question the construct validity of the FCQ. Moreover, the need to control for confounding variables (such as medication) is emphasized by comparing different psychiatric groups.

Adult↗
PubMedDate not supplied

Subjective cognitive dysfunction in first-episode and chronic schizophrenic patients.

Previous studies indicate that first-episode and chronic schizophrenic patients do not differ regarding neuropsychological performance as assessed with standard cognitive tasks. For the present study, it was investigated whether first-episode and chronic schizophrenics report similar subjective cognitive deficits. The Frankfurt Complaint Questionnaire (FCQ), a scale devised for assessing subjective cognitive disturbances in schizophrenia, was administered to 20 first-episode and 36 chronic schizophrenic patients, as well as 20 healthy controls. The schizophrenic subsamples did not differ on any of the FCQ subscales or on a "lie scale," measuring illness denial. Psychopathological ratings were comparable for both groups. As expected, healthy subjects reported significantly less cognitive and perceptual problems than schizophrenic patients. In marked contrast to a Kraepelinian view of schizophrenia, the present data confirm previous studies conducted with objective neuropsychological tests that schizophrenia is a neurodevelopmental rather than a neurodegenerative disorder.

Adult↗
PubMedDate not supplied

Cognitive dysfunction at baseline predicts symptomatic 1-year outcome in first-episode schizophrenics.

The present study addresses the consequences of cognitive disturbances on symptomatic outcome. Fifty-three first-episode schizophrenics were reassessed (n = 32) 1 year after admission. Simple regression analyses revealed that several self-perceived cognitive deficits at baseline as measured with the Frankfurt Complaint Questionnaire significantly predicted increased Brief Psychiatric Rating Scale global scores at follow-up (p = 0.05 to p = 0.005). A stepwise regression analysis proved memory dysfunction to be the strongest predictor of symptomatic worsening (p = 0.005). It is suggested that the exploration and treatment of neuropsychological deficits in schizophrenia is of great clinical importance with regard to its impact on both functional and symptomatic outcome in schizophrenia.

Acute Disease↗