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Biomedical subjects

L Zech

Publications and source records attributed to L Zech.

At least 37 records · Page 2Linked to original sources

The maintenance, distribution and development of biomedical computer software: an exercise in software engineering.

The growing reliance of biomedical investigations on computer software in almost all facets of their work places considerable emphasis on the need for the integrated management of the software. In order to efficiently develop, distribute, and maintain the software, tools are required which not only automate these tasks but also, wherever possible, 'semi-intelligently', alert their user to irregular situation. We describe an assortment of such tools routinely used in the management of the SAAM/CONSAM biokinetic software and illustrate their application. Furthermore, using these techniques we have presented some comparative performances of numerical integrators and of computer processors.

Computers

An EBV genome carrying pre-B cell leukemia in a homosexual man with characteristic karyotype and impaired EBV-specific immunity.

A Burkitt-like lymphoma/leukemia confined to bone marrow was detected in a human T cell leukemia virus (HTLV)-III/LAV- and Epstein-Barr virus (EBV)-seropositive homosexual man. The tumor cells were EBNA-positive and contained at least 22 EBV genomes per cell. They were totally immunoglobin negative, but showed other markers for B cells detected with monoclonal antibodies. The patient had an impaired cellular immunity to EBV antigens and EBV-infected cells at diagnosis, but these reactions normalized during treatment. Cell clones derived from the bone marrow tumor in vitro also carried EBV and had six different marker chromosomes, including the typical 14q+ chromosome and a t(8 - ;8), which resulted in trisomy for the largest part of 8q. Partial trisomy for 12q was also observed. The patient completed six courses of combination chemotherapy and remains in excellent health after 34 months of follow-up.

Adult

Karyotypic characterization of established cell lines and short-term cultures of human lung cancers.

Karyotypic patterns were analyzed from the four major histopathologic groups of human lung cancer: small cell (SCC), squamous cell (SQC), large cell (LCC), and adenocarcinoma (ADC). The studies were performed on banded chromosomes from direct preparations of pleural fluids (one case of SQC and LCC, respectively) and on cell lines. All metaphases were aneuploid and showed highly rearranged chromosomes, with the exception of the direct preparation of the SQC, which was pseudodiploid. The number of marker chromosomes varied-from tumor to tumor. No consistent aberrations could be detected. Special attention was paid to chromosomes 3p-, which was earlier reported to be a characteristic marker chromosome for SCC. We could confirm the presence of that abnormality in two of our six SCC lines. However, we also found a 3p- in a primary SQC culture, in one LCC cell line, and in one ADC cell line. The breakpoint on 3p was not consistent. In some lines, numerical and structural changes of chromosomes #1, #12, #14, and #22 were also noteworthy, although none of these chromosome abnormalities seemed to be correlated to a certain histopathologic group.

Adenocarcinoma

Del(3)(p13) in B-prolymphocytic leukemia--a new nonrandom chromosomal aberration possibly related to the c-ras oncogene.

Cytogenetic analysis was performed on the leukemic cells from two patients with B-prolymphocytic leukemia. Both patients had del(3)(p13) chromosomal abnormality, as well as other clonal aberrations. Del(3p) was previously reported in one case of B-cell prolymphocytic leukemia, and is known to be a specific aberration in small-cell carcinoma of the lung. In B-cell prolymphocytic leukemia, as in other B-lymphocytic leukemias/lymphomas, the karyotype often involves chromosomes #3, #6, #11, and #12. All of these chromosomes are suggested sites for the c-ras oncogene family.

Aged

Prognostic information from cytogenetic analysis in chronic B-lymphocytic leukemia and leukemic immunocytoma.

Fifty-five patients with a clonal expansion of B lymphocytes in the peripheral blood were studied. According to the Kiel classification, 22 patients had chronic lymphocytic leukemia (CLL), 29 had immunocytoma (IC), two had prolymphocytic leukemia, and one had centrocytic lymphoma; one was not subclassified. Cytogenetic studies after B cell mitogen stimulation showed that six patients had an extra chromosome 12 as the sole abnormality. Another ten patients had an extra chromosome 12 together with other abnormalities. One patient had dup(12). Fifteen patients showed clonal aberrations without +12. Eleven patients showed only normal metaphases, and 12 patients were not evaluated cytogenetically. The cytogenetic subgroup pattern did not distinguish between CLL and IC patients. There was no significant difference between the CLL and IC groups as regards clinical findings and prognosis. However, the cytogenetic typing proved to be of prognostic significance. Increasing numbers of chromosomal aberrations within the cell clone were significantly associated with a poorer prognosis, ie, with impairment of survival (P = .04) and therapy-free survival (P less than 10(-4]. Patients with complex karyotypes (at least clonal aberrations) showed the poorest survival (P = .007). Patients with +12 required treatment earlier than patients with a normal karyotype (P = .01) and patients with karyotypic changes other than +12 (P = .006). These latter differences were even more pronounced when only IC patients were considered (P = .005 and P = .002, respectively). A multivariate analysis revealed that +12 was as strong an indicator of poor survival as advanced Rai or Binet stages and a stronger predictor of therapy-demanding disease.

Adult

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

Transport of very low density lipoprotein triglycerides in varying degrees of obesity and hypertriglyceridemia.

Measurements of transport of triglycerides (TG) in very low density lipoproteins (VLDL) were carried out in 59 patients by injection of radioactive glycerol, determinations of specific activities of VLDL-TG for 48 h thereafter, and treatment of the data by multicompartmental analysis. The patients were divided into three groups: normal weight (89-120% ideal weight), mildly obese (120-135% ideal weight), and markedly obese (135% ideal weight). They had varying levels of VLDL-TG ranging from normal to markedly elevated. In many subjects, there was a positive correlation between concentrations and transport of VLDL indicating that overproduction of VLDL-TG contributed to hypertriglyceridemia. In others, and particularly in several markedly obese subjects, transport rates were greatly increased without significant hypertriglyceridemia, suggesting that they had enhanced capacity to clear TG. In all groups, however, there were patients whose degree of hypertriglyceridemia seemed out of proportion to their transport rates. This finding and the fact that many patients have increased secretion of VLDL-TG without elevated plasma TG suggests that both overproduction of VLDL-TG and insufficient enhancement of clearance contributed to the development of hypertriglyceridemia.The data showed a poor correlation between transport rates determined by our multicompartment analysis and single-exponential analysis used previously by other investigators (r = 0.46); this comparison was not improved by segregating patients according to their degree of obesity. Although two conversion pathways (fast and slow synthetic paths) were required to fit the data, there was no correlation between transport rates and the ratio of the two pathways. Also, despite the known pathway of conversion of VLDL to low density lipoprotein, no correlation was found between VLDL-TG transport rates and estimated low density lipoprotein-cholesterol concentrations.

Biological Transport

Trisomy 8 in the chronic phase of Philadelphia negative chronic myelocytic leukaemia.

An unusual case of Philadelphia negative chronic myelocytic leukaemia and an extra chromosome 8 in all bone marrow cells is described. The abnormality was present at diagnosis of the disease and throughout the chronic phase which lasted for somewhat less than 2 years. The patient died soon after the blastic transformation with no other chromosomal abnormalities.

Aged