Chromosome and chromosomal progression of human gliomas in vivo, in vitro and in athymic nude mice.
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Biomedical subjects
Publications and source records attributed to J Mark.
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By banding methods the chromosomes were studied in 20 cultured benign mixed salivary gland tumors. The results were considered together with the findings in 61 previously studied adenomas. About 55% of the 81 adenomas had a normal stemline. A total of 39 abnormal stemlines were found in the remaining 36 cases. The abnormal stemlines could be divided into four groups: 1) A large group with chromosome 8 involvement, mostly translocations of segments distal to 8q12; 2) A small group with chromosome 12 involvement, usually translocations of segments distal to 12q13-15;3) A small group with translocations and/or deletions affecting a distal segment of either the short or the long arm of chromosome 3; 4) A heterogeneous and small group with deviations related to those seen in variant cells in cases with normal stemlines. Comparisons with the known localization of proto-oncogenes revealed that almost 60% of the abnormal stemlines showed anomalies which could fit with oncogene activation. Future mapping studies of proto-oncogenes, as well as studies of combined actions of proto-oncogenes, different viral genes and some poorly understood oncogenic factors, will no doubt, enable a more complete characterization of the roles played by oncogenes in the genesis and progression of mixed tumors.
The presence of an efficient high affinity uptake system for L-CSA has been demonstrated in cultured neuronal and glial cells of various types. In neurons and most glial cells L-CSA uptake is inhibited by acidic amino acids, L-glutamate and L-aspartate and requires sodium ions; however the sodium dependence varies from one cell type to the other. The characteristics of the uptake system change during cell maturation, especially in astroblasts. The predominance of CSA uptake in glial cells as compared to neurons, the similarity of the kinetic parameters and of the structural specificity of L-glutamate uptake suggest that both excitatory amino acids are transported by a common system. In view of accumulating evidence, the present results are in agreement with a role of CSA as a neurotransmitter and as a precursor for taurine biosynthesis in the central nervous system.
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Four permanent cell lines derived from malignant human gliomas were karyotyped using Giemsa-trypsin banding. D-65 MG had a stemline with 44 chromosomes, including 11 markers: 1p+, 2q-, 3p-, 3q+, 4p-, 9q-, 11q+, 15q-, 17p+, 21p+, 22q-. The net effect after accounting for fragments in markers was: +8, -10, -16 -X. D-32 MG had chromosome counts 90-91 without a distinct stem karyotype. Modal cells contained from 3 to 5 copies of the normal autosomes and 5 markers: 1q-, 3q-, 7q-, 13q-, 18q-. D-32 MGCl2 had a complex karyotype containing 78-82 chromosomes. There was no stemline, and modal cells varied from one another primarily in their set of marker chromosomes. A total of 23 markers were seen in this line, 17 of which were present in most modal cells. They were partially characterized as: 1q+, 1q+, 2q-, 5q+, 7p-, 7q-, 8p+, 8p+, 9p+, 12p+, 14q-, 16q+, 19q+, 19q+, a small submetacentric chromosome of undetermined origin and two small isochromosomes, i(Dp or Gp) and i(17p or 18p). A-172 MG had a modal peak of 77 chromosomes within which no two cells were exactly alike. Ten markers seen in modal cells were: 1p-, 4p+, 6p+, 6p+, 6q-, 7p-, 9p-q+, 13q+ 14p+, 22q+. There were no normal copies of chromosomes #1, #6, #9, #14. These four glioma-derived cell lines possess unique karyotypes, but each displays some combination of the numerical and structural deviations generally associated with established glioma lines.
Using the G-banding technique the chromosomal patterns in 10 in vitro-cultured human mixed salivary gland tumours were studied. When surveying the results from the present 10 adenomas together with previous results from 31 adenomas, the following characteristic features were found. Mixed tumours probably always originate with a normal diploid stemline. This stemline type was also found to predominate during progression. However, about 41% of the tumours showed abnormal stemlines characterized by highly specific, usually structural, clonal aberrations. The deviations in these abnormal stemlines seemed to preferentially affect certain chromosome types, viz. Nos. 8 and 12. This non-random pattern of deviations - not found earlier in either benign or malignant tumour types in man - indicates that certain regions of, especially, chromosomes 8 and 12 are selectively affected in mixed tumours. Among other things, changes of gene dosage and/or oncogene activation are mentioned as factors possibly influencing the characteristics of this non-random pattern.
Using in vitro methods, the G-banding pattern in a highly differentiated adenocarcinoma of the parotid gland is described. Results from two consecutive preparations of the carcinoma indicated that it had originated with a normal diploid stemline and, subsequently, during progression had developed an aneuploid stemline deviating from the normal only by loss of the Y chromosome. From this hypodiploid stemline some clones and variant cells had been generated, all of them characterized by numerical deviations, particularly various trisomies. Important cytogenetic similarities were found between the present adenocarcinoma and other types of salivary gland neoplasms, in particular pleomorphic adenomas.
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Among 61 human pleomorphic adenomas subjected to chromosomal study by banding methods, two rare cases were detected, one having a dicentric marker chromosome and the other a ring chromosome included in the stemline karyotype. Excepting meningiomas, such marker types have previously only been observed in different types of malignant neoplasms. However, as in meningiomas, the occurrence of dicentrics or rings has no implications as regards the question of malignancy. Both our mixed tumours showed structural changes affecting one chromosome No. 8. These findings, along with similar observations in other pleomorphic adenomas, are discussed in relation to recently advanced hypotheses about the role of oncogenes and changes of gene dosage in the genesis and/or development of mixed tumours.
One hundred female patients were allocated randomly to receive either no analgesic supplementation to methohexitone, nitrous oxide in oxygen anaesthesia, or supplements of fentanyl 1.5 micrograms kg-1 or alfentanil 8, 12 or 16 micrograms kg-1. No differences were seen in the time to recover consciousness, regain orientation or manipulate shapes into a box. Analgesic supplementation resulted in a decrease in the requirement for methohexitone, and improved operating conditions. Some patients in each group who received fentanyl or alfentanil became apnoeic for more than 30 s duration. The duration of apnoea increased with larger doses of alfentanil.
The value of veralipride in menopausal disorders is no longer questionable and has been documented by a number of studies. The purpose of this paper is to study the clinical effectiveness and to look for the biological consequences of three months therapy with veralipride. To achieve this, a thorough biological study (hematology, glucids, lipids, hepatic and renal function) was done in 21 patients with a menopausal syndrome before and after taking veralipride for three months. Clinical effectiveness was excellent with 80% satisfactory results. No signs of intolerance or adverse side-effects were seen. We recorded no significant changes in biological parameters. No disturbances of renal or hepatic function were detected, either in individual assessments or in the overall statistical analysis of the study group. Because it is well tolerated, effective, and devoid of adverse metabolic side-effects, we conclude that veralipride is the best non-hormonal treatment for menopausal disorders presently available.
The uptake of L-glutamine in neuronal and glial cultures derived from rat cerebral hemispheres was found to be mediated by a low affinity-high capacity mechanism which was concentrative in both cell types; the calculated Km and Vmax were twice as high in glial than in neuronal cultures. In contrast L-glutamate was taken up by a high affinity system which was particularly efficient and concentrative in the glial cells. Different transport mechanisms for L-glutamine appeared to operate in the two cell types: L-glutamine uptake in neurons was sodium-dependent, specifically inhibited by L-glutamine but not affected by high potassium concentrations in the external medium; on the other hand, glial glutamine transport was decreased when potassium concentration increased, was sodium-independent and significantly inhibited by 3 structurally related amino acids. No significant contribution of homoexchange could be detected in either cell type. After [14C]glutamine preincubation, the radioactivity released into the superfusion medium by neuronal cells was increased in the presence of a high potassium concentration; no such effect could be seen in the case of glial cultures. A regulatory mechanism is suggested where astrocyte depolarization and repolarization would channel a flux of glutamine toward the neurons, subsequent to a glutamate flux in the opposite direction.
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A female, aged 32, with facial birthmarks and suffering migraine headaches and a slight hemiparesis was examined with isotope scanning, CT and angiography. She was found to have a massive, unilateral angiodysplasia, transforming the right cerebral hemisphere into an expanding vascular sponge-like structure. There was a family history of red facial birthmarks. The patient and her father were analysed cytogenetically by estimating the frequency of chromosome aberrations and sister chromatid exchanges (SCE). The frequency of gaps and breaks was normal compared to healthy controls, but the patient showed a significantly higher level of spontaneous SCE's. The patient and her father also had a higher than normal number of SCE's after addition of mitomycin C (MMC) to the blood culture. Numerical and structural chromosome deviations markedly exceeded normal in both, possibly representing a genetic imbalance in this syndrome.
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A correlative, histologic and cytologic study of seven cases of alveolar rhabdomyosarcoma and chromosome analysis using the G-banding technique (in case 1) is presented. The histologic pattern was characterized by pseudo-alveolar structures, separated by fibrous septa. Primitive, dark, round cells predominated, but differentiated rhabdomyoblasts were found in all cases, and so were multi-nucleated giant cells. Unequivocal cross striation was seen in two cases. Cytologically, the tumors were highly cellular and small, undifferentiated tumor cells predominated. Large polymorphous, sometimes multi-nucleated, cells often with an elongated cytoplasm and eccentric nucleus were observed in all cases. The cell-types found could be well correlated to those identified in the histologic sections. The cytogenetic study revealed a karyotype profile, showing three 2q markers and only one chromosome type No. 13. The observations are different from the karyotype profile of embryonal rhabdomyosarcoma. However, further studies are necessary to elucidate this question.
We report a turbidimetric procedure, using commercially available reagents, for the determination of plasma fibronectin with an unmodified centrifugal analyser. Fixed-time kinetic readings at 340 nm were taken at 60 and 720 s. A wide range of concentration (up to 1000 mg/l) can be measured. Precision and accuracy were quite acceptable. Correlation with radial immunodiffusion was satisfactory. This automated procedure, simple and rapid, allows extensive studies of fibronectin in various diseases.
A New cell line, U-706, established from an uncommon human glioma (possibly giant-cell glioblastoma) is reported in this communication. The tumor gave rise to two permanent sublines, one attached (U-706M) and one non-attached (U-706S) cell line. The growth characteristics, chromosome banding pattern, electronmicroscopic picture and cell surface characteristics of the two sublines are described.