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Biomedical subjects

H Kok

Publications and source records attributed to H Kok.

7 recordsLinked to original sources

Cardiovascular risk at age 53 years in relation to the menopause transition and use of hormone replacement therapy: a prospective British birth cohort study.

OBJECTIVES: To investigate cardiovascular risk factors and changes in risk factor levels in relation to menopausal stage, hysterectomy status and hormone replacement therapy use in a cohort of women aged 53 years with prospective data on smoking, lifetime socio-economic circumstances, and blood pressure and obesity at age 43 years. DESIGN: A prospective study. SETTING: England, Scotland and Wales. POPULATION: A cohort of women from the Medical Research Council Survey of Health and Development. METHODS: A total of 1303 women, aged 53 years, from a UK birth cohort study with measures of cardiovascular risk factors were classified by five menopausal status groups (premenopause, perimenopause, postmenopause, hysterectomy and hormone replacement therapy user). Body mass index, glycosolated haemoglobin, blood pressure, high density lipoprotein, low density lipoprotein and total cholesterol measurements were taken, and analysed within the groups taking confounding variables into account. Changes in body mass index and blood pressure measurement in the same women obtained when 43 years of age were also compared. MAIN OUTCOME MEASURES: Body mass index, glycosolated haemoglobin, blood pressure, high density lipoprotein, low density lipoprotein and total cholesterol. RESULTS: At 53 years, body mass index, waist circumference, total and low density lipoprotein cholesterol, and glycosolated haemoglobin (HbA1c) varied by menopausal status group, but blood pressure did not. Levels of total cholesterol and HbA1c increased across the natural menopause transition, before and after adjustment for body mass index, smoking and lifetime socio-economic circumstances. After adjustment for confounders, levels of risk factors for hysterectomised women were similar to those of naturally postmenopausal women. Women on hormone replacement therapy had lower levels of total and low density lipoprotein cholesterol, HbA1c, and were less obese than postmenopausal women. The lower obesity levels were partly due to these women already being less obese at age 43 years. CONCLUSIONS: This study showed that naturally postmenopausal or hysterectomised women had higher levels of metabolic risk factors compared with premenopausal or perimenopausal women of the same age. The long term stability of these differences and their translation into variations in incidence of cardiovascular disease remain to be seen. The lower levels of metabolic risk factors for women on hormone replacement therapy may protect against future cardiovascular disease or may be overwhelmed by other adverse, and as yet unknown, effects of hormone replacement therapy.

Blood Pressure↗

Consensus strategy to quantitate malignant cells in myeloma patients is validated in a multicenter study. Belgium-Dutch Hematology-Oncology Group.

Recently the Belgium-Dutch Hematology-Oncology group initiated a multicenter study to evaluate whether myeloma patients treated with intensive chemotherapy benefit from additional peripheral stem cell transplantation. To determine treatment response accurately, we decided to quantitate malignant cells. To test a consensus quantitation strategy, 5 centers independently determined the immunoglobulin heavy chain sequences of patient tumor cells and developed allele-specific oligonucleotides (ASO) and ASO-polymerase chain reaction (PCR). We compared the reproducibility of real-time quantitation with quantitation using limiting dilutions. We distributed DNA samples with a 4-log range of tumor cell concentrations and found average quantitation values deviating 74% and 42% from the input values with real-time PCR (1 center) and limiting dilutions (4 centers), respectively. Within single centers we found an average variation coefficient of 0.74, with limiting dilutions not significantly different from the average 0.82 center-to-center variation coefficient. Within a single center, real-time quantitation proved more reproducible (average variation coefficient, 0.36). Quantification was confirmed in 3 patients during treatment in the protocol. This report shows that real-time PCR or limiting dilution assays can be used for quantitation in a single multicenter trial. We present a consensus strategy that allows an accurate comparison of quantitation data generated in independent centers.

Base Sequence↗

Long-term bone marrow cultured stromal cells regulate myeloma tumour growth in vitro: studies with primary tumour cells and LTBMC-dependent cell lines.

Long-term bone marrow cultured stromal cells (LTBMC) produce IL-6 after contact with tumour cells from multiple myeloma patients. We found that LTBMC could substitute for exogenous IL-6 in the stimulation of bone marrow plasma cells from myeloma patients with active disease in short-term cultures. In addition, tumour cells of some patients with inactive disease, which were unresponsive to exogenous IL-6, were induced to IL-6-dependent growth after LTBMC co-culture. To study the role of LTBMC in myeloma tumour growth in vitro, plasma cell lines UM-2 and UM-3 were selected. UM-2 and UM-3 grew in contact with LTBMC and proliferation was blocked by antibodies against IL-6, IL-6 receptor (IL-6R, gp80, CD126) or the common signal transducing unit, gp130 (CD130). Culture with IL-6 alone or combined with GM-CSF resulted in cell death via apoptosis. The combination of IL-6 with soluble gp80, however, maintained in vitro proliferation of UM-2 and UM-3 cells. These data imply that LTBMC regulate myeloma growth in vitro via production of IL-6, possibly via induction of a functional IL-6 receptor on the tumour cells.

Base Sequence↗

A screening for BRCA1 mutations in breast and breast-ovarian cancer families from the Stockholm region.

To identify BRCA1 germ-line mutations in the breast and breast-ovarian cancer families in the Stockholm region, a total of 127 families were screened. DNA from 174 patients from these families were studied using various mutation screening techniques, followed by direct DNA sequencing. Mutations were identified in 7 of 20 families with breast and ovarian cancer and in one family with ovarian cancer only, whereas only 1 family of 106 with breast cancer showed a mutation. Thus, germ-line mutations in BRCA1 were found in one-third of the families with both breast and ovarian cancer, but in only 1% of the breast cancer families. The low frequency of germ-line mutations in the site-specific breast cancer families means that other genes are likely to segregate in these families.

Breast Neoplasms↗

Migration patterns in Hungary: a life course approach.

"This paper discusses the consequences of the ongoing transformation for migration in Hungary. We investigate migration flows towards the Hungarian capital, provincial capitals, towns and rural areas, using a life-course approach. A main aspect within this question is whether there are substantial differences in the migration patterns between the different settlement types. We present answers to questions [about] how the migration patterns changed in the period 1970-1994 and what changes in the kind of triggers resulting [in] moves occurred. The analysis is focused on different settlement types in Hungary: the capital Budapest, 18 provincial capitals, the towns and the rural communities."

Demography↗