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Biomedical subjects

D Vassilopoulos

Publications and source records attributed to D Vassilopoulos.

At least 73 records · Page 4Linked to original sources

TCR/CD3 complex-mediated signal transduction pathway in T cells and T cell lines from patients with systemic lupus erythematosus.

We studied the TCR/CD3 complex-mediated signal transduction pathway in freshly isolated T cells and T cell lines from patients with systemic lupus erythematosus (SLE). The peak and 5-min anti-CD3 mAb-mediated free intracytoplasmic Ca2+ concentration ([Ca2+]i) increase was statistically significant higher in fresh T cells from SLE patients than in control T cells. Increased CD3-mediated [Ca2+]i responses were observed in T cells from patients with SLE but not in T cells from other rheumatic diseases. Furthermore, significantly increased CD3-mediated [Ca2+]i responses were observed in T cell lines from SLE patients but not from controls. Although the [Ca2+]i response did not correlate with the global SLE disease activity or individual clinical manifestations, it was significantly higher in the group of patients who were not on treatment. Both CD4+ and CD8+ T cell subsets from peripheral blood cells and T cell lines displayed higher CD3-mediated [Ca2+]i responses than their normal counterparts. The peak of the response occurred earlier in the patient than in the normal group. The amount of Ca2+ that was released from the intracellular stores was higher in lupus than control T cells. The TCR/CD3-induced production of inositol phosphate metabolites in SLE cells was comparable with controls. The sarcoplasmic and endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin-induced [Ca2+]i response was similar in both SLE and normal T cells. Our experiments demonstrate for the first time a definite abnormality in the early steps of the TCR/CD3-mediated signal transduction pathway in T cells from SLE patients that involves increased release of Ca2+ from intracellular stores.

Adolescent↗

Effects of an aminosteroid inhibitor of phospholipase C-dependent processes on the TCR-mediated signal transduction pathway in human T cells.

Phospholipase C (PLC) is a key enzyme in the T cell antigen receptor (TCR)-mediated signal transduction pathway in human T cells. Agonist-induced PLC activation leads to a cascade of intracellular events that ultimately regulate gene transcription and T cell activation. We studied the effects of U-73122, a putative inhibitor of PLC-dependent events, on TCR/CD3 complex-mediated early and late events in human T cells. Both anti-CD3 monoclonal antibody-induced 1,4,5-inositol trisphosphate (IP3) and free intracytoplasmic calcium [Ca2+]i increases were inhibited by U-73122 (0.05-0.1 microM), but not by the related inactive analog, U-73343. U-73122 did not affect thapsigargin-evoked [Ca2+]i increase in T cells, indicating a specific mode of inhibition of CD3 signaling. Late events in T cell activation like CD3-mediated T cell proliferation and mitogen-induced interleukin 2 receptor (IL2-R) expression were also inhibited by this agent. T cell proliferation induced by a combination of a phorbol ester and ionomycin was not affected by U-73122. Although an agonist effect on basal IP3 and [Ca2+]i levels was observed with high concentrations of U-73122, the inhibitor alone did not induce any proliferative effect or IL2-R expression in T cells. Our results demonstrate for the first time that U-73122 is a specific inhibitor of PLC-dependent processes in human T cells and could serve as a valuable tool for studying T cell signal transduction pathways.

Adjuvants, Immunologic↗

Linkage disequilibrium between the expanded (CAG)n repeat and an allele of the adjacent (CCG)n repeat in Huntington's disease patients of Greek origin.

Huntington's disease (HD) is associated with an expanded unstable (CAG)n repeat in the IT15 gene. This repeat was investigated in 44 HD patients and 59 of their relatives at risk who were members of 29 unrelated families from various parts of Greece. Abnormal elongation of the (CAG)n repeat ranging from 39 to 95 trinucleotide units was found in all but one of the 44 HD patients tested with 70% of these patients showing 42-47 repeats. The size of the expanded sequence correlated inversely with the age at disease onset (r = 0.77, p < 0.00001, n = 43). In a single sporadic case, de novo expansion of the (CAG)n repeat was detected. Twenty-four of 59 asymptomatic family members at risk showed expansion of the (CAG)n repeat in the HD range (39-56 trinucleotide units) while three had intermediate alleles (36-37 repeats). Evaluation of the adjacent polymorphic (CCG)n repeat showed a strong linkage disequilibrium between the 7-unit (CCG)n repeat allele and the HD mutation, with 51% of normal and 93% of HD chromosomes showing this allele (chi 2 = 15.55, p < 0.0001, n - 260). These data on HD patients of Greek origin are consistent with the thesis that the (CAG)n expansion is the primary gene defect of the disease and that this mutation occurred primarily on chromosomes with the (CCG)7 repeat haplotype.

Age of Onset↗

The risk of cancer in relatives of patients with brain neoplasm.

The family trees of 142 patients, suffering from histologically proven brain tumour, were compared to those of an equal number of sex and age matched controls. The results showed no statistically significant differences in the occurrence of malignant neoplasm between the two groups. These results indicate that the risk of cancer among relatives of patients with brain tumours does not exceed that of healthy controls.

Adult↗

Reflex sympathetic dystrophy syndrome and osteogenesis imperfecta. A report and review of the literature.

A case of multifocal reflex sympathetic dystrophy (RSDS) in a patient with the tarda form of osteogenesis imperfecta is described, followed by a review of the literature. Microfractures of the trabecular bone in these patients are proposed to be the initial stimulus in the pathogenesis of RSDS by a mechanism similar to the one involved in the pathogenesis of RSDS complicating other diseases associated with bone fragility.

Adult↗

Neuropathy following acute intoxication with Mecarbam (OP ester)

Only a small number of organophosphorous compounds, of the many thousands circulating on the market, has been reported as causing neuropathy with delayed onset. A case is presented of a young male who in an attempt to commit suicide by taking a massive dose of Mecarbam, developed polyneuropathy accompanied by a mild involvement of the CNS. Mecarbam is herewith reported for the first time as an agent which can affect the peripheral nervous system.

Adult↗

Epidemiological assessment of levodopa use by populations.

This study is an analysis of the measurements of drug use by populations proposed by the Nordic Council on Medicines, conducted from an epidemiological-theoretical perspective. Particular attention is given to levodopa use (LDU). Several measurements of comparative LDU are proposed here for the assessment of levodopa (LD) consumption, from data on LD sales to well defined populations, over known periods of time. The method takes into account possible purposes of LDU evaluations, and is based on a reported model which combines information on Parkinson's Disease prevalence (PD) from surveys, gross levodopa sales, age-structure of the population, the figures for infant mortality rates (IMRs) taken as an indicator of modernization, and the average amount of LD prescribed as daily dose. The evaluation of LDU is implemented following a stepwise procedure.

Cross-Cultural Comparison↗

Amyotrophic lateral sclerosis in southern Greece: an epidemiologic study.

All amyotrophic lateral sclerosis cases hospitalized over a 25-year period in the University Department of Neurology in Athens were surveyed, with emphasis given to the occupation of the patients and the geographic distribution of the disease. The results showed an overrepresentation of farmers among patients and an aggregation of cases in the region of Cephalonia. These findings might suggest that environmental factors could be involved in the etiology of the disease.

Adult↗

Skeletal muscle CK-B activity in neurogenic muscular atrophies.

Creatine kinase isoenzymes were determined in skeletal muscle biopsy specimens of 34 patients suffering from neurogenic muscular atrophies. The findings were compared: (1) with those of 38 control muscle samples and (2) with those in 41 muscular dystrophies and other myopathic conditions. The measurements were made by electrophoretic separation and elution of the isoenzymes and by immunoinhibition assay. The results showed that the total and specific CK activity were significantly decreased (P less than 0.005) in neurogenic atrophies in contrast to myopathic conditions where no differences from control levels were observed. This decrease was due to a decrease of the CK-M subunit activity, while the CK-B subunit was elevated. The muscle CK-MB activity was considerably elevated in muscular dystrophies (P less than 0.02) and myositis (P less than 0.001), but it was also slightly elevated in neurogenic conditions. The similarity of the muscle CK isoenzyme pattern in neurogenic atrophies and myotonic dystrophy was noted. These findings could possibly reflect considerable difference in the regeneration process of neurogenic atrophies and muscular dystrophies.

Biopsy↗

Evidence for seasonal variation in polymyositis.

Fifty-one cases of polymyositis/dermatomyositis were reviewed in order to investigate seasonal distribution in the onset of the disease. The time (month, season) of first admission of the 51 patients was evaluated as well as the time of initial symptoms onset in 26 cases with duration of the disease which was less than 1 year. In both groups a concentration of cases was found for the months of March, April and May. This concentration was statistically significant (p less than 0.003 and p less than 0.007, respectively). These findings suggest that environmental factors could be involved in the etiology of the disease.

Adolescent↗

Nucleo-cytoplasmic ratio in ageing skeletal muscle.

In order to investigate possible changes in the nucleo-cytoplasmic ratio of the muscle fibres during ageing, samples of quadriceps femoris from 15 normal individuals whose age ranged from 17 to 82 years were studied (autopsy material). The mean lesser diameter and the number and size of the muscle fibre nuclei were calculated using a planimetric technique. It was found that nucleo-cytoplasmic ratio increased significantly after the age of 60 years. This was due to a decrease in the mean fibre size whilst the number and the size of myonuclei remained unchanged. The resemblance of this finding to denervation atrophy changes is noted.

Adolescent↗

Delusional depression: further evidence for genetic contribution.

To quantify the contribution of genetic factors in the pathogenesis of delusional depression, the incidence of major depression in the first degree relatives of 77 delusional, 76 nondelusional depressive patients, and 153 age- and sex-matched controls was calculated in a case-control study. The morbid risk for psychiatric disorders, including major depression and bipolar I disorder, did not distinguish the two proband groups. The segregation analysis showed that the model of multifactorial inheritance fits best to our results. Heritability was estimated on the basis of a threshold model for multifactorial inheritance, and a high contribution of genetic factors for both subgroups was found.

Adult↗

Serum creatine kinase B levels in diseases of the central nervous system.

The creatine kinase B (CK-B) subunit was determined by our own highly sensitive solid-phase direct immunoassay in three neurological diseases which represent models of central nervous system (CNS) involvement: idiopathic epilepsy (18 patients), a disease characterised by a transient neuronal hyperactivity; Parkinson's disease (17 patients), a degenerative disorder of the CNS, and multiple sclerosis (21 patients), which represents a model of demyelination of the CNS. A group of 50 controls was also studied. The results showed that in patients with epilepsy and multiple sclerosis the CK-B activity was considerably lower than in the controls (p less than 0.01 and p less than 0.005, respectively), while no differences were found between the controls and the patients with Parkinson's disease. It is suggested that the low CK-B activity observed might be due to the medication taken or to the disease process itself. The present findings have to be considered as an indication for further CK isoenzyme studies in systematic disorders of the nervous system.

Creatine Kinase↗

Serum creatine kinase B subunit levels in neurogenic atrophies.

This study is an attempt to determine the creatine kinase B (CK-B) subunit levels in neurogenic atrophies. A group of 69 patients was studied and the results were compared with those in a group of 32 patients with muscle disease. The results showed that the CK-B levels are considerably higher in patients with amyotrophic lateral sclerosis (P less than 0.001) and peroneal muscular atrophy (P less than 0.001). Further studies in the various subgroups of neurogenic atrophies showed that, regardless of the nosological entity, the CK-B activity is considerably higher: (1) in the "widespread" as opposed to "limited" forms (P less than 0.001); (2) in the "chronic" than in the "acute" neurogenic atrophies (P less than 0.001); and (3) in the "active" as opposed to "residual" forms (P less than 0.02). It is suggested that the increase of CK-B in neurogenic atrophies is a strong indication of an active regeneration process in the denervated muscle.

Creatine Kinase↗