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Biomedical subjects

L Zech

Publications and source records attributed to L Zech.

At least 55 records · Page 3Linked to original sources

Extra chromosome 12 and prognosis in chronic lymphocytic leukaemia.

Peripheral blood lymphocytes from 22 consecutive patients with chronic lymphocytic leukaemia were stimulated with the polyclonal B-cell mitogens lipopolysaccharide from E. coli (LPS) and Epstein-Barr virus (EBV). Stimulation was successful for chromosome analysis in 14 patients. Eleven patients had chromosomal aberrations and 7 of these had an extra chromosome 12. In 2 patients an extra chromosome 12 was the only abnormality, while additional aberrations were found in 5 patients. 3 patients had complex aberrations involving deletion of chromosome 6. 1 of these patients also had a translocation between chromosomes 12 and 14. 1 patient had a translocation between chromosomes 11 and 14. In 3 patients no aberrations were detected. The time elapsing between diagnosis and appearance of clinical symptoms which were indications for treatment was significantly shorter in patients with an extra chromosome 12 than in these without this abnormality. Thus, it appears that an extra chromosome 12 is associated with a more rapid course of the disease, and may therefore be of importance for the predition of prognosis.

Adult↗

Establishment and characterization of two neoplastic cell lines (U-1285 and U-1568) derived from small cell carcinoma of the lung.

Two human cell lines have been established in vitro from patients with small cell carcinoma of the lung (SCC). The U-1285 line was derived from the classical small cell type of SCC while the U-1568 originated from a larger cell variant. The cell lines grow as suspension cultures and have been passaged continuously in vitro for 3 years (U-1285) and 2 years (U-1568), respectively. The malignant nature of the lines is suggested by their infinite growth potential, their capacity to form colonies in agarose and their aneuploidy. Both cell lines contain cytoplasmic electron dense particles indistinguishable from classical neurosecretory granules but only in U-1568 has hormone production (human chorion gonadotropin (alpha-HCG)) been proven. The U-1568 line produces carcino-embryonic antigen (CEA) while both U-1285 and U-1568 produce alpha-feto-protein (AFP). Chromosome analysis reveal aneuploidy of both lines. Among structural aberrations, involvement of chromosome 14 in U-1285 and chromosomes 1, 7 and 12 in U-1568 is interesting since alterations of these chromosomes have been described previously in other malignant conditions.

Carcinoma, Small Cell↗

Establishment and characterization of a continuous lung squamous cell carcinoma cell line (U-1752).

A continuous cell line, U-1752, was established from a lung tumor originally diagnosed as a small cell carcinoma. The cell line has been in continuous in vitro passage for 29 months. The epithelial, rather than small cell nature of the U-1752 cells was demonstrated by the presence of desmosomes, prominent tonofilament bundles, by the reactivity with an anti-keratin antiserum and by the expression of cell surface receptors for epidermal growth factor (EGF). The U-1752 cells grow as monolayer cultures and have a population doubling time of around 36 hours at optimal growth in 20% calf serum. The most important neoplastic features of U-1752 were its aneuploidy, its capacity for colony formation in agarose and its tumorigenic potential subcutaneously in nude mice.

Adult↗

Influence of nicotinic acid on metabolism of cholesterol and triglycerides in man.

The mechanisms for the hypolipidemic action of nicotinic acid were examined in 12 patients with hyperlipidemia. Most patients were studied in the hospital on a metabolic ward. The first month was a control period followed by 1 month on nicotinic acid. During treatment with nicotinic acid, the triglycerides (TG) decreased in total plasma by an average of 52% and in very low density lipoproteins (VLDL) by 36%. Transport rates of VLDL-TG were determined by multicompartmental analysis following injection of [3H]glycerol as a precursor. Nicotinic acid decreased transport (synthesis) of VLDL-TG by an average of 21%. Kinetic modeling of the VLDL-TG data suggested that the TG reduction was due to a decrease in TG content of VLDL and hence a reduction in lipoprotein size more than number. For the whole group, plasma cholesterol fell during nicotinic acid therapy by a mean of 22%. The drug produced no detectable changes in fecal excretions of cholesterol (neutral steroids) or bile acids. However, it induced a small but significant increment in hepatic secretion of biliary cholesterol that might have led to a net loss of cholesterol from the body even though this loss could not be detected by sterol balance. Despite this increase in outputs of biliary cholesterol, there was not a significant increase in molar % cholesterol or in % saturation of gallbladder bile. Therefore, it is doubtful that nicotinic acid enhances the risk for cholesterol gallstones.

Absorption↗

Prostaglandin E1 binding and adenylate cyclase activation in normal and transformed fibroblasts.

The binding of [3H]prostaglandin E1 to membranes of clones of normal rat kidney fibroblasts (NRK cells) has been measured. Cell lines that responded to prostaglandin E1, such as NRK and NRK transformed with Schmitt-Ruppin strain of Rous sarcoma virus (SR-NRK cells), have a high affinity prostaglandin E1 binding site. Murine-sarcoma-virus-transformed lines of NRK cells are unresponsive to prostaglandin E1 and have reduced prostaglandin E1 binding Exposure of cells to prostaglandin E1 results both in decreased prostaglandin E1 responsiveness and reduced prostaglandin E1 binding. Activation of adenylate cyclase is correlated to binding of prostaglandin E1 to receptors in both NRK and SR-NRK cell membranes. Mathematical models suggest that GTP decreases the affinity of hormone for its receptor while increasing the catalytic efficiency of adenylate cyclase, and that aggregates of occupied receptors may play an important role in the activation of adenylate cyclase.

Adenylyl Cyclases↗

2 translocations, t(11;14) and t(1;6), in a patient with plasma cell leukaemia and 2 populations of plasma cells.

2 translocations, t(11;14) and t(1;6), were found in 24 out of 46 metaphases in bone marrow cells from an untreated patient with plasma cell leukaemia. The predominating cell population produced only kappa chains while a minute population produced IgG kappa. All serum Ig's were low and only minimal amounts of monoclonal IgG kappa were found in the serum and very small amounts of kappa light chains in the urine. Analyses of ours and 2 other reported patients indicated the possibility that the location of breakpoints on the chromosomes may be of etiologic importance for the type of light chain and perhaps for the class of heavy chain.

Aged↗

Chromosome aberrations and sister chromatid exchanges in Swedish paint industry workers.

Workers in the Swedish paint industry exposed to a mixture of organic solvents, mainly containing xylene or toluene, were investigated for genotoxic effects. No difference in the frequency of sister chromatid exchanges (SCE), 0.192 and 0.193 per chromosome, respectively, was noted in the peripheral lymphocytes of the exposed group of 17 workers and their matched reference group. No correlation was found between xylene or toluene exposure and SCE frequency nor between total solvent exposure and SCE frequency. The frequency of chromosome aberrations was also investigated for the five most exposed workers and their matched referents, and no difference was found. There was no correlation between SCE and chromosome breaks.

Adult↗

Nonrandom chromosomal aberrations in chronic lymphocytic leukemia revealed by polyclonal B-cell-mitogen stimulation.

Peripheral blood lymphocytes from 11 patients with chronic lymphocytic leukemia were stimulated by Epstein-Barr virus (EBV), lipopolysaccharide from Escherichia (LPS), and phytohemagglutinin (PHA). Chromosome analysis with the Q-banding technique after 5 days incubation revealed an extra chromosome 12 in 5 of the patients and a translocation between chromosome 11 and chromosome 14 in 1. Two patients had a deletion of chromosome 6, and only 3 patients had a normal karyotype. In most patients, the abnormalities were found in the majority of metaphases after stimulation with EBV, LPS, or both mitogens, while PHA revealed a normal karyotype, with the exception of a total of 4 metaphases in 3 patients. An extra chromosome 12 appears to be specifically associated with chronic lymphocytic leukemia. The frequency of chromosomal abnormalities in this disease appears to be much higher than has previously been thought.

B-Lymphocytes↗

Studied of very low density lipoprotein triglyceride metabolism in an obese population with low plasma lipids: lack of influence of body weight or plasma insulin.

Pima Indians have a high prevalence of hyperinsulinemia, obesity, and diabetes, but they have low plasma cholesterol levels, reduced low density lipoprotein synthesis, and little arteriosclerotic heart disease. To investigate lipoprotein metabolism further in this group, very low density lipoprotein (VLDL) metabolism was studied, using [3H]glycerol as an endogenous precursor of triglyceride (TG) synthesis, in 15 obese Pima nondiabetic males and compared to that of 10 obese and 13 normal weight, normolipidemic, nondiabetic Caucasian males. The resultant kinetic data were analyzed using a multicompartmental model which includes two pathways for VLDL-TG synthesis and a process of stepwise delipidation for VLDL catabolism. As compared to obese Caucasians, the obese Pimas had a lower rate of VLDL-TG synthesis, and a lower proportion of slow pathway for synthesis. The fractional catabolic rate in the Pimas was higher than in either Caucasian group, a larger proportion of VLDL-TG was delipidized at each step, and particle residence time was shorter. When the relation between VLDL-TG metabolism and plasma insulin was examined, plasma insulin levels in the Pima were not correlated with VLDL-TG synthetic rates, catabolic rates, or plasma pools. On the other hand VLDL-TG synthetic rates were correlated with plasma free fatty acid levels. Thus, in this population with low plasma lipids and reduced arteriosclerotic heart disease, VLDL-TG synthesis is low, VLDL-TG catabolism is accelerated, and VLDL pools appear to be insensitive to the influence of body weight and hyperinsulinemia.

Adolescent↗

Sister chromatid exchanges and chromosome aberrations in children after treatment for malignant lymphoma.

Sister chromatid exchanges and chromosomal aberrations were investigated in lymphocytes from 11 children with malignant lymphoma after cessation of treatment. Chemotherapy combined with radiation was administered, terminating between 4 months and 13 years before chromosome analyses were performed. The frequency of sister chromatid exchanges per chromosome was the same, 0.20, in the patients and a matched control group, although there was a significant heterogeneity between individuals. The number of cells with chromosome abnormalities increased from 2.9% in control children to 4.8% in treated patients, a nonsignificant increase. Only translocations showed a significant increase.

Adolescent↗

Simultaneous staining of sister chromatid exchanges and Q-bands in human chromosomes after treatment with methyl methane sulphonate, quinacrine mustard, and quinacrine.

Human peripheral lymphocyte chromosomes were stained simultaneously for sister chromatid exchanges (SCEs) and Q-banding. No effect of treatment with MMS, QM, and Q on the distribution of SCEs in chromosomes was found compared with controls. The SCEs were distributed between chromosomes roughly according to metaphase length, with the shorter chromosomes underrepresented. The majority of SCEs were located to pale bands, while a few occurred in bright bands and at interfaces between pale and bright bands. A greater frequency than expected of SCEs had occurred at identical sites in homologous chromosomes. This frequency was significantly increased after treatment with MMS.

Chromosome Banding↗

Growth of diploid, Epstein-Barr virus-carrying human lymphoblastoid cell lines heterotransplanted into nude mice under immunologically privileged conditions.

Human Epstein-Barr virus-carrying lymphoid cell lines which have been classified on the basis of studies on clonality and morphological, chromosomal and functional parameters as lymphoblastoid cell lines (LCL) of presumed non-neoplastic origin were inoculated intracerebrally into nude mice. All eighteen of them grew, killing the host mice within 7 to 25 days, except for 2 which grew more slowly. At autopsy, the brain of the nudes was found to be invaded by infiltrating lymphomas. Sixteen of these lymphomas, when recultured in vitro, gave rise to cell lines with growth properties and morphology indistinguishable from those of the inoculated LCL. Chromosomal examinations showed that 3/7 cell lines injected, which grew as lymphomas in the brain, were still normal diploid on reexplantation whereas the remaining four had become aneuploid. Four lines derived from intracerebral lymphomas (2 diploid, 1 aneuploid and 1 untested) were inoculated subcutaneously into adult nude mice. None of them grew. When the corresponding four original LCL lines were inoculated subcutaneously into newborn nude mice, they grew rapidly, but failed to do so in newborn normal mice or intracerebrally in adult normal mice. One such line, U-1450, was treated with anti-lymphocyte serum (ALS). Small nodules developed at the site of inoculation. From one nodule a cell line was cultured, 1450 ALSAD. It was morphologically indistinguishable from the line of origin. The lines obtained from nude mice inoculated with polyclonal LCL seem to have a restricted clonal representation, but were not monoclonal, as evidenced by analyses of their pattern of immunoglobulin synthesis.

Aneuploidy↗

Isochromosome 17 in a patient with a myeloproliferative disorders terminating in eosinophilic leukemia.

A patient is described, who for more than two years had a myeloproliferative disorder which terminated in eosinophilic leukemia. Chromosome analysis revealed an isochromosome 17 in all metaphases of bone marrow cells. This abnormality has now been found in two out of six patients with eosinophilic leukemia investigated by banding techniques, and may therefore have etiologic importance. Chromosome analysis in the hypereosinophilic syndrome has practical value for differentiating malignant and non-malignant disease.

Aged↗