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Z Vranes

Publications and source records attributed to Z Vranes.

7 recordsLinked to original sources
PubMed1995

Multiple genetic alterations in malignant metastatic insulinomas.

Proto-oncogenes, growth factors/receptors, and tumour suppressor genes were analysed in malignant metastatic insulinomas. Normal pancreas showed only a moderate immunoreaction for c-myc proto-oncogene and a strong reaction for insulin. Benign insulinomas were slightly or moderately positive for transforming growth factor alpha (TGF alpha), weakly positive for epidermal growth factor receptor (EGF-R), and strongly positive for c-myc and insulin. In malignant insulinomas, besides a strong immunoreaction for c-myc and TGF alpha, activation of c-K-ras and overexpression of p53 protein were found. Insulin reaction was moderate or strong. Three out of six malignant insulinomas displayed a c-K-ras point mutation at codon 12. All mutations were guanine to cytosine transversion, resulting in amino acid substitution, glycine to arginine. Mutations were present in metastatic insulinomas only. Patients with mutated c-K-ras oncogene had overexpression of p53 protein as well as c-myc and TGF alpha overexpression. Our results support the view that malignant progression is a consequence of more than one genetic lesion and suggest that activation of myc, TGF alpha an ras genes plays a role in a multistep process of tumour progression, perhaps serving as an initiating event.

Aged↗
PubMed1991

Immunological disturbances in anaesthetic personnel chronically exposed to high occupational concentrations of nitrous oxide and halothane.

Immunological changes in anaesthetic personnel exposed to occupational concentrations of holothane and nitrous oxide 10-60 times greater than the advised maximum were studied during routine work and after 3-4 weeks holiday. Red cell count, haemoglobin concentration and haematocrit decreased during exposure although not significantly, in comparison with a control group, but all had increased significantly after the holidays. Other changes were altered neutrophils and lymphocyte counts. Basophils disappeared from the blood during the exposure. Monocytes were not affected during the exposure, but increased after its cessation. Percentages of CD2 and CD4 lymphocytes increased significantly, but numbers of cells in T lymphocyte subpopulations (total, helper and cytotoxic/suppressor lymphocytes) were not significantly altered. B lymphocytes were most strongly affected: they decreased during working periods and did not recover after holidays. Natural killer (NK) cells, on the other hand, decreased significantly during exposure, but fully recovered during holidays. After stimulation with mitogens, phytohaemaglutin, concanavalin A, and pokeweed, lymphocytes from exposed personnel incorporated significantly more 3H-thymidine than those from control subjects, but stimulation indices did not differ. The natural killer-cell activity, serum Ig concentrations and phagocytosis by granulocytes were not altered.

Adult↗
PubMed1990

Natural killer (NKH-1+) cell number and activity in health and disease.

The proportion of lymphocytes bearing the NKH-1 membrane marker (a natural killer-cell marker) was determined by flow cytometric analysis of the peripheral blood of 40 healthy individuals, 45 patients with multiple sclerosis and 19 with other neurological diseases. Natural killer (NK) cell activity was determined in parallel. It was shown that NKH-1-positive cells were more abundant in the lymphocytic than the mononuclear cell window on the flow-cytometric granularity versus cell size two-parameter display. NK-cell concentration did not correlate with NK-activity in any of the three groups of individuals studied. However, when the data for the three groups were compounded (i.e. when the number of samples analysed exceeded 100) significant correlations were disclosed. No correlation was found between age and NKH-1-positive cell number or activity in any of the three groups of subjects. High variability of the number and activity of natural killer cells in different individuals, and imprecision of phenotyping of the entire pool of NK-cells by means of a single marker, appeared to be responsible for poor correlations of NK-cell number and activity as observed in the study.

Adult↗
PubMed1989

Natural killer cell number and activity in multiple sclerosis.

Natural killer (NK) cell percentage among cells appearing in lymphocytic flow-cytometric gate, and their concentration per unit volume of peripheral blood, as well as NK-cell in vitro activity, were determined in 45 patients with multiple sclerosis (MS, 34 with definite and 11 with probable diagnosis). Two age- and sex-matched control groups consisted of 27 healthy individuals and 19 individuals with other neurological diseases, respectively. NK cells were identified on the basis of their reaction with monoclonal antibody NKH-1, and NK-activity on the basis of their spontaneous killing of K-562 erythroleukemia target cells with mononuclear cells from peripheral blood. MS patients were analyzed in regard to the phase (active, stable inactive, stable progressive) and course (remittent, remittent-progressive, progressive) of the disease. In general, MS patients tended to have both lower number and activity of natural killer cells than either of the two control groups. A statistically significant decrease was found for the concentration of NKH-1+ cells in the blood of all MS patients, for the number of lymphocytes in the blood of patients with remittent course of the disease, and for the number of NKH-1+ cells in the blood of patients with progressive course of the disease. It appeared that more profound defects were associated with the progression of the disease; NK-cell number always appeared more affected than NK-cell activity. In MS patients, NK-cell activity correlated significantly with NK-cell percentages among lymphocytes but poorly with the concentration of NKH-1+ cells in the blood. In healthy controls, neither of the two correlations was significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Detection of oligoclonal IgG bands in unconcentrated CSF in multiple sclerosis and other neurological diseases by isoelectric focusing on ultrathin-layer polyacrylamide gel immunofixation and silver staining.

Isoelectric focusing of proteins (IEF) in ultrathin-layer polyacrylamide gel (0.4 mm, PAG), followed by direct immunofixation with monospecific antiserum and silver staining, is a highly specific, sensitive and simple method for the demonstration of oligoclonal IgG in unconcentrated cerebrospinal fluid (CSF) samples (5-10 microliters). For the present method, the optimal concentrations of IgG in CSF samples are about 0.025-0.030 g/l, corresponding to the applied amount of 125-150 mg. In our testing of this method, oligoclonal IgG bands in CSF specimens were clearly demonstrated in 52 (96%) of 54 patients with clinically established definite diagnosis of multiple sclerosis (MS), in 4 (40%) of 10 patients with infectious diseases of the CNS, and in 9 patients (25%) of 38 with other neurological diseases. Abnormal patterns were also demonstrated in the serum of patients with MS (43%). Intrathecally synthesized IgG was mathematically calculated in 43 (80%) out of 54 patients with MS. This method appears to be a useful alternative for the demonstration of oligoclonal IgG bands in the unconcentrated CSF, especially when questionable or negative results arise by routine electrophoretic technique for oligoclonal bands detection.

Humans↗
PubMedDate not supplied

Molecular genetics of malignant insulinoma.

Malignant insulinoma is an rare form of cancer with poor prognosis and a reported 5-year survival of 35%. Relatively little is known about the etiology of this disease or of the oncogenes and tumor suppressor genes that participate in its genesis and progression. To address this issue, several protooncogenes, including K-ras, N-ras, erbB-2, erbB-3,c-myc, c-fos, c-jun were examined. Also analyzed was the expression of the growth factors TGF-alpha, EGF, and insulin as well as the EGF receptor (EGF-R), p53 and the putative anti-metastasis gene nm23-H1. These were examined in malignant insulinomas, benign insulinomas, pancreatic B cell hyperplasias and in normal endocrine pancreas. Normal endocrine pancreas showed moderate immunoreaction for c-myc and a strong reaction for insulin. All other parameters were negative. Benign pancreatic B cell hyperplasias were slightly or moderately positive for N-ras and TGF-alpha, and were weakly positive for EGF-R. They were strongly positive for c-myc and insulin. In malignant insulinomas there was strong immunoreaction for c-myc, TGF-alpha, N-ras, K-ras and p53. Insulin reaction was moderate or strong. Molecular genetic studies have been performed for the presence of activating point mutations in codon 12 of the c-K-ras oncogene. Mutations were detected using primer-mediated, mutant-enriched, polymerase chain reaction-restriction fragment length polymorphism analysis and were further characterized by allele-specific oligonucleotide hybridization. Four out of six patients with malignant insulinoma and two out of eight patients with benign insulinoma harbored K-ras point mutations at codon 12. All patients with mutated K-ras oncogene also had elevated levels of p53 protein as well as c-myc and TGF-alpha. In one extremely malignant case we found concomitant mutation at codon 12 of K-ras and codon 61 of the N-ras gene. Our data are consistent with the idea that malignant progression is accompanied by the progressive accumulation of multiple genetic lesions and suggest that activation of myc, TGF-alpha and ras genes may be early events in the development of insulinoma.

Adult↗