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Biomedical subjects

M van Vliet

Publications and source records attributed to M van Vliet.

43 records · Page 3Linked to original sources

Allelotype of human breast carcinoma: a second major site for loss of heterozygosity is on chromosome 6q.

Loss of heterozygosity (LOH), which is detected with polymorphic DNA markers by comparing constitutional and tumor genotypes, has been observed at a number of different chromosome arms in primary breast tumors. These include 1p, 1q, 3p, 11p, 13q, 17p and 18q. We present here the results of a screening of all non-acrocentric chromosome arms, including those of the X chromosome, with at least one polymorphic marker per arm, in a total of 86 breast carcinomas. This dataset, termed an allelotype, indicates that in addition to the chromosome regions listed above, allelic loss may be observed in more than 30% of informative cases on 6q, 8q, 9q, 15q, and 16q. Multiple LOH involving at least two different chromosomes in a single tumor was observed in approximately 75% of the investigated tumors, and revealed complex chromosome involvement. Six different combinations of concurrent LOH at two different chromosome arms were found to be significantly correlated (r greater than 0.45; P less than 0.01). Tumors showing LOH at 3p or 17p were preferentially aneuploid, while LOH at 6q and 17q was inversely correlated with the number of positive lymph nodes and age respectively.

Alleles↗

Somatic genetic changes on chromosome 18 in breast carcinomas: is the DCC gene involved?

Recently, a gene has been isolated from the long arm of chromosome 18 which was shown to be frequently deleted in colorectal carcinomas and hence designated the DCC gene (Fearon et al., 1990). To explore the possible involvement of this gene in breast cancer, we have used 5 polymorphic DNA markers (one for 18p, and four for 18q) to examine the status of chromosome 18 in 49 primary breast carcinomas by comparing the genotypes of lymphocyte and tumour DNA samples. Imbalance of alleles, resulting in allelic loss of duplication, was observed in 17 cases (38% of informative cases). In 13 of these, this imbalance included the locus D18S8 located within the DCC gene region. In the remaining 4 cases this locus was not involved, with the affected chromosome region mapping proximally of D18S8 in 3 cases, and distally in 1 case. These results indicate that chromosome 18 is rearranged in breast cancer more frequently than is expected on the basis of cytogenetic data alone, and warrant a closer inspection of the DCC gene in this tumour.

Alleles↗

Effects of neuraminidase treatment on CFUs properties and CFUs numbers.

Incubation of bone marrow cells with Vibrio cholerae neuraminidase decreases the number of CFUs to a minimum of 25% of control numbers. It is shown that this decrease in CFUs numbers is not due to cytotoxic effects of neuraminidase but to a decrease in the spleen seeding efficiency of colony forming cells. Neuraminidase acts in two ways. It removes negatively charged neuraminic acids from membrane glycoproteins and glycolipids and it can adsorb to the cell surface. It is investigated which of the two enzyme effects is responsible for the decrease in CFUs numbers. Inhibition of the enzyme reaction by EDTA prevents to a great extent the decrease in CFUs numbers, while tests with mouse spleen cells and human erythrocytes show that EDTA has no or a positive effect on the adsorption of neuraminidase to the cell surface. This indicates that the neuraminidase induced decrease in CFUs numbers is caused by the enzymatic removal of neuraminic acids rather than by the adsorption of the enzyme to the cell surface.

Adsorption↗

Electrophoretic mobility properties of murine hemopoietic cells in different stages of development.

In vivo spleen colony forming cells (CFUs) and three developmental stages of in vitro granulocyte/macrophage colony forming cells (GM CFUc 1, 2 & 3) are characterized by their surface charge density using the free-flow electrophoresis technique. CFUs have a somewhat higher electrophoretic mobility than have GM CFUc. GM CFUc 1, 2 & 3 appear to be identical in their mobility properties. Treatment with neuraminidase-by which negatively charged N-acetylneuraminic acid (NANA or sialic acid) groups are cleaved from membrane glycoproteins-changes the electrophoretic mobility of the various hemopoietic cells differentially. Neuraminidase treatment strongly reduces the electrophoretic mobility of CFUs and GM CFUc 1, has a moderate effect on the mobility of GM CFUc 2 and causes a relatively small reduction in the mobility of GM CFUc 3. It is suggested that the number of neuraminidase susceptible NANA groups on the cell surface decreases during early hemopoietic cell development.

Animals↗

Immune responses to experimental stress: effects of mental effort and uncontrollability.

OBJECTIVE: Two important determinants of physiological stress responses have been identified, uncontrollability of the stressor and amount of effort involved in coping with the stressor. In the present experiment, we tried to identify the specific contributions of effort and uncontrollability to immune system responses to stress. METHODS: In a 2 x 2 design, effort and uncontrollability were manipulated independently of each other. Subjects participated in one of four experimental conditions, and their endocrine, immune, and sympathetic nervous system responses to the task were assessed. RESULTS: Effort had a stimulating effect on enumerative immunological parameters (CD8 and CD16+ cells) and on natural killer cell activity. The effect occurred immediately after the stressor and was transient. Regression models indicated that this effort effect may have been mediated by activation of the sympathetic nervous system. Uncontrollability influenced in vitro production of the cytokine interleukin-6, leading to decreased production 15 and 30 minutes after the stressor. Uncontrollability also led to an increased level of cortisol, but no evidence was found that the decrease in cytokine production was mediated by cortisol release. CONCLUSION: The results suggest that two major stressor characteristics, effort and uncontrollability, may have differential effects on the immune system.

Adaptation, Psychological↗

A new liquid homogeneous assay for HDL cholesterol determination evaluated in seven laboratories in Europe and the United States.

We evaluated a new liquid homogeneous assay for the direct measurement of high density lipoprotein cholesterol (HDL-C Plus) in seven laboratories. The assay includes two reagents which can be readily used in most available clinical chemistry analyzers. The total CVs of the new method were below 4.6% and the bias in relation to the designated comparison method was below 3.9%. The total error ranged between 4 to 7%. HDL-C values determined by this method were in good agreement with those obtained by the old homogeneous assay using lyophilized reagents, and other homogeneous and precipitation assays (0.944 < r < 0.996). The assay was linear up to at least 3.89 mmol/l HDL-C. Hemoglobin did not interfere, whereas in icteric samples slight deviations were observed. Lipemia up to 11.3 to 22.6 mmol/l triglycerides did not interfere with this homogeneous HDL-C assay. In samples of patients with paraproteinemia, discrepant results were seen. This liquid homogeneous HDL-C assay was easy to handle and produced similar results in all laboratories participating in this study. This method will enable clinical laboratories to reliably measure HDL-C for risk assessment of coronary heart disease.

Artifacts↗