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L Zech

Publications and source records attributed to L Zech.

At least 19 recordsLinked to original sources
PubMed1992

EMSA: a SAAM service for the estimation of population parameters based on model fits to identically replicated experiments.

This paper presents a new technique for the aggregation of models to produce population parameter estimates based on a set of identically replicated experiments. After describing the theoretical basis for the technique we discuss tactical and strategic issues associated with its implementation in the SAAM software. Finally, we demonstrate its utility in the aggregation of models fitted to four simulated experiments.

Algorithms↗
PubMed1990

del(3p)(p13p21) in renal cell adenoma and del(4p)(p14) in bilateral renal cell carcinoma in two unrelated patients with von Hippel-Lindau disease.

Karyotype analyses of renal cell adenoma in one patient and bilateral renal cell carcinomas (RCC) in another unrelated patient have been performed. Both patients belonged to families with von Hippel-Lindau disease (vHL). In the adenoma, we found a clonal del(3)(p13p21) and a small clone of two cells with an additional del(14)(q13). This result indicates that the same region that is often deleted in RCC may also be deleted in a renal cortical adenoma. This finding may facilitate the localization of a tentative renal cell adenoma/carcinoma tumor suppressor locus. In the tumors from the patient with bilateral carcinomas we found a clonal del(4)(p14) on one side and on the other a del(4)(p14) together with del(14)(q13). In this case, there was no detectable 3p defect in the tumors. This result raises the question whether an alternative/additional locus on chromosome 4p may be involved in the RCC/vHL syndrome. Constitutional karyotypes were in both cases normal.

Adenoma↗
PubMed1990

Gating kinetics of pH-activated membrane fusion of vesicular stomatitis virus with cells: stopped-flow measurements by dequenching of octadecylrhodamine fluorescence.

To identify the initial stages of membrane fusion induced by vesicular stomatitis virus, we performed stopped-flow kinetic measurement with fluorescently labeled virus attached to human erythrocyte ghosts that contained symmetric bilayer distributions of phospholipids. Fusion was monitored spectrofluorometrically using an assay based on mixing of the lipid fluorophore octadecylrhodamine. At 37 degrees C and pH values near the threshold for fusion, a lag phase of 2 s was observed. The lag time decreased steeply as the pH decreased, while the initial rate of fusion showed the reverse functional dependence on pH. The observed rapid fluorescence changes resulted from fusion of virus bound to the target, and the time lags were not due to association-dissociation reactions between virus and target. For a given pH value, the temperature dependence of the lag time was similar to that of the initial rate of fusion. The results were fitted to a multistate model similar to that resulting from ion channel gating kinetics. The model allows testing of hypotheses concerning the role of cooperativity and conformational changes in viral spike glycoprotein-mediated membrane fusion.

Animals↗
PubMed1990

The gene for insulin-like growth factor-binding protein-1 is localized to human chromosomal region 7p14-p12.

Insulin-like growth factors (IGF) I and II are bound to high-affinity binding proteins in the blood circulation and other body fluids. These IGF-binding proteins are expressed at different concentrations in different tissues and are thought to regulate the activity of IGF I and II. Cloned cDNA for IGF-binding protein-1 (IGFBP1) has been used to verify the location of its gene to human chromosome 7 by Southern blotting to DNA from a human-mouse hybrid cell line. Further, by in situ hybridization the gene was regionally localized to 7p14-p12, and a Mendelian-inherited two-allele BglII restriction enzyme length polymorphism was identified, with the most frequent allele occurring in 53% of the chromosomes.

Carrier Proteins↗
PubMed1989

Appearance of a transient inv(14)(q11q32) in a case of B cell chronic lymphocytic leukemia.

The inv(14)(q11q32) has been reported to be a specific chromosome aberration in T-cell chronic lymphocytic leukemia (T-CLL) and different types of T-cell lymphomas. Here, the first case of B-CLL with a clonal inv(14)(q11q32) in a phytohemagglutinin-stimulated bone marrow culture is presented. In a subsequent study 9 months later, tetradecanoyl-o-phorbol-13-acetate stimulated blood and bone marrow cultures revealed a clone with a t(1;11)(p13.2;q23.1) and an aberrant chromosome 17.

Aged↗
PubMed1989

Epstein-Barr virus-transformed pro-B cells are prone to illegitimate recombination between the switch region of the mu chain gene and other chromosomes.

Six independently maintained sublines of FLEB 14, a fetal-liver-derived Epstein-Barr virus-transformed pro-B cell line that has not yet rearranged its immunoglobulin genes, were examined after in vitro propagation during 19-36 months. Two lines showed no immunoglobulin heavy chain gene rearrangement, whereas one allele was rearranged with breakpoints inside the switch region of the mu chain gene in the remaining four. These rearrangements had been generated by the translocation of different chromosome fragments to the immunoglobulin heavy chain gene cluster-carrying 14q32 band in each of the four lines. Previously, a similar rearrangement was found in a fifth subline concurrently with a reciprocal 6;14 translocation. The transposed pieces have been derived from chromosomes 16 and 18 in two of the more recently rearranged lines. Their origins could not be determined in the remaining two lines, but they were different from each other and the other three 14q+ markers. The 14q+ marker-carrying variant has replaced its diploid progenitor suggesting that the translocation has conveyed some in vitro growth advantage on its carrier. This was also supported by the duplication of the 14q+ marker and the loss of its normal chromosome 14 homologue in one subline during serial culturing. The vulnerability of the switch region of the mu chain gene to illegitimate recombination at the pro-B stage and the possible relevance of this finding for the origin of the Burkitt lymphoma-associated 8;14 (immunoglobulin heavy chain gene cluster/MYC) translocation is discussed.

B-Lymphocytes↗
PubMed1989

A resource facility for kinetic analysis: modeling using the SAAM computer programs.

Kinetic analysis and integrated system modeling have contributed significantly to understanding the physiology and pathophysiology of metabolic systems in humans and animals. Many experimental biologists are aware of the usefulness of these techniques and recognize that kinetic modeling requires special expertise. The Resource Facility for Kinetic Analysis (RFKA) provides this expertise through: (1) development and application of modeling technology for biomedical problems, and (2) development of computer-based kinetic modeling methodologies concentrating on the computer program Simulation, Analysis, and Modeling (SAAM) and its conversational version, CONversational SAAM (CONSAM). The RFKA offers consultation to the biomedical community in the use of modeling to analyze kinetic data and trains individuals in using this technology for biomedical research. Early versions of SAAM were widely applied in solving dosimetry problems; many users, however, are not familiar with recent improvements to the software. The purpose of this paper is to acquaint biomedical researchers in the dosimetry field with RFKA, which, together with the joint National Cancer Institute-National Heart, Lung and Blood Institute project, is overseeing SAAM development and applications. In addition, RFKA provides many service activities to the SAAM user community that are relevant to solving dosimetry problems.

Animals↗
PubMed1988

Direct outgrowth of in vivo Epstein-Barr virus (EBV)-infected chronic lymphocytic leukemia (CLL) cells into permanent lines.

In the course of our efforts to characterize the EBV-carrying cells that are responsible for direct growth or the 2-step mechanism, based on virus release from the explanted cells and subsequent transformation of previously uninfected cells, we have encountered an unusual CLL patient who carried a small subpopulation of in vivo EBV-infected leukemia cells. These were predominantly present in the low-density fraction and grew into EBV-carrying lines upon explantation after a relatively short latency period, 3-4 weeks. Cytogenetic examination conclusively proved the leukemic origin of the established CLL lines. They carry a ring chromosome 15 and are trisomic for chromosome 12. The same changes are also found in the majority of the peripheral blood lymphocyte population. Taken together, our results suggest that the EBV-genome and the cytogenetic changes may have contributed to the immortalization of the CLL cells in a complementary or synergistic fashion.

Antigens, Viral↗
PubMed1988

Effect of insulin deficiency on low density lipoprotein metabolism in rabbits.

These studies have been carried out in rabbits with alloxan-induced diabetes in order to see if insulin deficiency affects low density lipoprotein (LDL) catabolism. The results showed that plasma LDL-cholesterol was lower in diabetic rabbits, associated with a fall in the cholesterol to protein ratio of LDL particles. In addition, 125I-LDL disappeared more slowly from plasma of diabetic rabbits, leading to a significant reduction in fractional catabolic rate and a decrease in residence time of 125I-LDL. These data demonstrated that LDL composition and catabolism are greatly altered as a consequence of insulin deficiency.

Animals↗
PubMed1987

Cytogenetic studies on human myeloma cell lines.

Cell lines (U-266, U-1957, U-1996 and U-2030) established from 4 patients with multiple myeloma (MM) were analyzed cytogenetically. The cell lines represent different stages in B-cell differentiation as evidenced by ultrastructural and functional characteristics. The karyotypic pattern in 3 newly established myeloma lines was studied after a few months in culture and compared to the old myeloma cell line U-266, which was examined after 6, 7 and 8 years of continuous cultivation. Frequency of progressive numerical and structural aberrations during long-term cultivation and their correlation with alterations in growth properties were addressed. We describe the presence of a high frequency of both numerical and structural chromosomal abnormalities in the cells of all 4 myeloma lines studied. Chromosomes often associated with structural abnormalities were 1, 3, 6, 12 and 14. A 14q + marker chromosome was detected in 2 of the 4 cell lines. The breakpoints on the chromosomes participating in structural aberrations in myeloma exhibit some correlation to chromosome sites at or close to locations of mapped oncogenes. No translocations of c-myc were found. These data were further supported by Southern blot analysis (unpublished data). The extent of numerical, but not structural, aberrations correlates with the differentiation stage of the myeloma lines in that the 2 mature lines U-266 and U-1957 were both near-diploid. Multiple progressive chromosomal changes have emerged in U-266 during a period of 8 years with development of independence of feeder cells and increased growth rate. However, capacity for production of complete Ig molecules has remained stable.

Aneuploidy↗
PubMed1987

Human c-fos proto-oncogene mapped to chromosome 14, band q24.3-q31. Possibilities for oncogene activation by chromosomal rearrangements in human neoplasms.

The human c-fos proto-oncogene was mapped by in situ hybridization to chromosome 14, band q24.3-q31. As a probe we used 3H-labelled mouse c-fos RNA transcribed in vitro by SP6-RNA-polymerase. Of a total of 40 grains on chromosome 14, 19 (47.5%) were located within the 14q24.3-q31 region (p much less than 0.001). Mechanisms for c-fos to gain transforming ability by a break in a critical part of the gene have recently been described. Thus there are several possibilities for chromosomal aberrations within the 14q24.3-q31 region to be responsible for c-fos deregulation and which may result in neoplastic growth. Such specific aberrations are found in a variety of human neoplasms.

Animals↗
PubMed1987

High density lipoprotein (HDL) metabolism in noninsulin-dependent diabetes mellitus: measurement of HDL turnover using tritiated HDL.

High density lipoprotein (HDL) kinetics were studied by injecting [3H]apoprotein A-I (apoA-I)/HDL into 12 subjects with normal glucose tolerance and 12 patients with noninsulin-dependent diabetes mellitus (NIDDM). The results indicate that the mean fractional catabolic rate (FCR) of apoA-I/HDL was significantly faster [0.63 +/- 0.07 (+/- SEM) vs. 0.39 +/- 0.02 1/day; P less than 0.001] and the apoA-I/HDL synthetic rate greater (29.4 +/- 2.9 vs. 22.9 +/- 1.3 mg/kg X day; P less than 0.02) in patients with NIDDM than in normal subjects. Furthermore, there were statistically significant inverse relationships between apoA-I/HDL FCR and plasma levels of both HDL cholesterol (r = -0.71; P less than 0.001) and apoA-I (r = -0.63; P less than 0.001). In addition, the increase in apoA-I/HDL FCR was directly related to fasting plasma glucose (r = 0.78; P less than 0.001) and insulin (r = 0.76; P less than 0.001) concentrations. These data support the view that the decrease in plasma HDL cholesterol and apoA-I levels commonly found in patients with noninsulin-dependent diabetes is due to an increase in the catabolic rate of apoA-I/HDL secondary to the defects in carbohydrate metabolism present in these patients.

Aged↗
PubMed1987

Role of insulin in regulation of high density lipoprotein metabolism.

The effect of alloxan-induced insulin deficiency on high density lipoprotein (HDL) metabolism was studied in rabbits. Rabbits with alloxan-induced diabetes had significantly higher (P less than 0.001, mean +/- SEM) plasma concentrations of glucose (541 +/- 13 vs. 130 +/- 2 mg/dl), triglyceride (2851 +/- 332 vs. 101 +/- 10 mg/dl), and total plasma cholesterol (228 +/- 55 vs. 42 +/- 4 mg/dl) than did normal control rabbits. However, diabetic rabbits had lower plasma HDL-cholesterol (7.2 +/- 1 vs. 51.3 +/- 1.3 mg/dl, P less than 0.001) and HDL apoA-I (38.3 +/- 6.0 vs. 87.2 +/- 4.3 mg/dl, P less than 0.001) concentrations. HDL kinetics were compared in diabetic and normal rabbits, using either 125I-labeled HDL or HDL labeled with 125I-labeled apoA-I, and it was demonstrated that HDL fractional catabolic rate (FCR) was slower and residence time was longer in the diabetic rabbits when either tracer was used. The slow FCR and the low apoA-I pool size led to reduced apoA-I/HDL synthetic rate in diabetic rabbits (0.97 +/- 0.11 vs. 0.34 +/- 0.07 mg per kg per hr). Thus, the reduced plasma HDL-cholesterol concentrations seen in rabbits with alloxan-induced insulin deficiency was associated with a lower total apoA-I/HDL synthetic rate. Since insulin treatment restored to normal all of the changes in plasma lipoprotein concentration and kinetics seen in diabetic rabbits, it is unlikely that the phenomena observed were secondary to a nonspecific toxic effect of alloxan. These data strongly support the view that insulin plays an important role in regulation of HDL metabolism.

Animals↗
PubMed1987

Establishment and phenotypic characterization of three new human myeloma cell lines (U-1957, U-1958, and U-1996).

Three new human myeloma cell lines (U-1957, U-1958, and U-1996) have been established in vitro. The cell lines are Epstein-Barr virus (EBV) negative, monoclonal, and aneuploid and should thus represent malignant cell populations and not EBV-carrying non-neoplastic B lymphoblastoid cell lines. The myeloma origin of the cell lines is also suggested by their capacity for production of monoclonal complete immunoglobulin (Ig) molecules (U-1957 and U-1958) or IgG light chains (U-1996) of the same type as the myeloma protein in vivo. All the cell lines have morphological features of plasmablasts-plasma cells but appear to represent slightly different stages of B cell differentiation. Thus, the U-1958 has plasma cell morphology, expresses only PCA-1 and OKT-10 but no other B cell antigens, and secretes 1.5 micrograms/mL of IgG/10(6) cells/24 hours. The U-1957 has plasma cell morphology and expresses Fc receptors and the LB-1 antigen in addition to the PCA-1 and OKT-10 antigens. This line produces only minimal amounts of IgG, which appears not to be secreted. The U-1996, finally, is a kappa light chain producer, has a plasmablast morphology, and expresses LB-1 in addition to the PCA-1 and OKT-10 antigens. All three cell lines are chromosomally heterogeneous and contain several markers with a 14q+ abnormality as a common characteristic abnormality. These new myeloma lines have been in continuous culture for approximately 3 years and are instrumental in studies of various aspects of the biology of human myeloma.

Aged↗
PubMed1986

Specific chromosome markers involved with chronic T lymphocyte tumors.

In a series of 12 patients with chronic T cell tumors, 9 showed abnormalities of the long arm of chromosome #14. The most common aberration was an inversion with breakpoints in q11 and q32, which was seen in 7 patients. One patient had a translocation between chromosomes #9 and #14, with breaks in 9q34 and 14q11, and in another patient, the two long arms of chromosome #14 were fused together in q32, forming a dicentric chromosome. The results confirm earlier suggestions that rearrangements of band 14q11 are involved with T cell tumors and may be of importance for the development of the disease. Chromosome #8 aberrations were seen in seven patients, six of whom had an extra 8q in common. Abnormalities of chromosome #7 occurred in five patients, but the breaks were localized in different bands. The significance of the karyotypic changes in our present and previous series of patients is discussed, together with data from other laboratories.

Chromosome Aberrations↗