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Biomedical subjects

M C Pike

Publications and source records attributed to M C Pike.

At least 145 records · Page 8Linked to original sources
PubMed1990

Chemoattractants stimulate phosphatidylinositol-4-phosphate kinase in human polymorphonuclear leukocytes.

Chemoattractant receptor-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) by phospholipase C is instrumental for leukocyte activation. Previous studies have demonstrated that chemoattractant treatment of intact polymorphonuclear leukocytes (PMN) causes a transient decrease in PIP2 due to phospholipase C activation, followed by an increase in cellular PIP2 levels. The present study determined whether chemoattractants altered the activities of the two enzymes responsible for the synthesis of PIP2, phosphatidylinositol kinase, and phosphatidylinositol-4-phosphate (PIP) kinase. Incubation of intact PMN with the N-formylated peptide chemoattractant formyl-methionyl-leucyl-phenylalanine at 37 degrees C caused a rapid (3 min), 2-fold stimulation of PIP kinase activity isolated from a particulate membrane fraction. The increase in PIP kinase was dose-dependent for a variety of N-formylated chemoattractants as well as leukotriene B4. Lineweaver-Burk analysis showed that the Vmax of PIP kinase was increased 2-fold by formyl-methionyl-leucyl-phenylalanine, without a significant change in the apparent Km of the enzyme for ATP. Phosphatidylinositol kinase was, however, not altered by any chemoattractants tested. Nonchemotactic activators of the oxidative burst in leukocytes such as phorbol myristate acetate and ionophore A23187 did not significantly alter PIP kinase, suggesting a specificity for chemotactic agents. These findings demonstrate direct, chemoattractant-induced stimulation of PMN PIP kinase which may serve to replenish the important phospholipid, PIP2, in the membrane following its hydrolysis by phospholipase C.

1-Phosphatidylinositol 4-Kinase↗
PubMed1990

Serum hormone levels in pre-menopausal Chinese women in Shanghai and white women in Los Angeles: results from two breast cancer case-control studies.

To assess whether risk of breast cancer in young women is associated with differences in luteal-phase hormone production and to attempt to explain differences in risk of breast cancer of young Shanghai Chinese and Los Angeles white women, two concurrent case-control studies of serum hormone concentrations were conducted. Both studies were carefully controlled for the possible confounding effects of age, weight, height, pregnancy history, and day of the menstrual cycle, by individually matching cases and controls on these factors. Case eligibility was limited to women with localized breast cancer. Sixteen of 39 Shanghai breast-cancer cases were sampled prior to the histologic diagnosis of their disease. The remaining 23 Shanghai cases and all 42 Los Angeles cases were diagnosed, and treated by surgery only, at least six months prior to hormonal evaluation. All subjects were sampled on day 22 of the menstrual cycle. Overall, cases had 13.5% higher serum estradiol concentrations (p = 0.038) with a case-to-control excess of 16.6% in Shanghai subjects (p = 0.089) and 10.8% in Los Angeles subjects (p = 0.23). There were no appreciable differences in amounts of sex-hormone binding globulin between cases and controls. Cases had lower progesterone levels than controls, but the situation was reversed when the analysis was restricted to subjects with evidence of ovulation. Los Angeles controls had 20.6% greater estradiol concentrations than Shanghai controls (p = 0.036); adjustment for body weight accounted for only 25.7% of this difference.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

The relationship of free fatty acids with the binding of oestradiol to SHBG and to albumin in women.

Free fatty acid concentration, sex hormone binding globulin (SHBG) concentration, % free oestradiol and % SHBG-bound oestradiol were measured in fasting and non-fasting serum samples from 48 women. Free fatty acids were 128% higher (P less than 0.001) and % SHBG-bound oestradiol was 11% lower (P = 0.001) in fasting than non-fasting samples, but these changes were not significantly correlated (r = -0.16, P = 0.287). Mean SHBG concentration and % free oestradiol did not differ significantly between fasting and non-fasting samples. Between subject correlations were calculated for measurements from 30 premenopausal women: % free oestradiol was inversely correlated with SHBG and free fatty acids and positively correlated with Quetelet's Index; % SHBG-bound oestradiol was positively correlated with SHBG but was not consistently or significantly related to free fatty acids or Quetelet's Index. It was concluded that physiological increases in free fatty acid concentrations do not increase % free oestradiol and that free fatty acids are less important than SHBG concentration and perhaps other variables in determining differences between individuals in oestradiol binding to SHBG.

Adult↗
PubMed1990

Reproductive factors and colon cancers.

In Los Angeles County, the age-adjusted incidence rate of colon cancer in men is almost 30% higher than that in women; however, in the descending and sigmoid colon, age-specific incidence rates for women are higher than those for men before age 55. Since menstrual and/or reproductive factors may be involved in producing this crossover in age-specific rates, they were examined in a population-based case-control study involving 327 white women with adenocarcinoma of the colon and age-, race- and neighbourhood-matched controls. After adjustment for other factors associated with colon cancer in this study (family history of large bowel cancer, total fat intake, calcium, weight and activity level), ever having been pregnant was protective (RR = 0.56, 95% CI = 0.33-0.97). For one to two pregnancies, the RR was 0.76 (CI = 0.42-1.37); for three or more pregnancies, the RR was 0.45 (CI = 0.25-0.81). However, the relationship between the number of pregnancies and colon cancer risk was actually U-shaped, with risk decreasing with successive pregnancies up to four and then increasing with additional pregnancies. The U-shaped relationship was present for incomplete as well as for full-term pregnancies and was more striking for cancers occurring in the distal (descending and sigmoid) than proximal (caecum to splenic flexure) colon. Risk was not related to age at menarche or use of exogenous oestrogens, but delayed natural menopause was weakly protective in the proximal but not distal colon. The crossover in incidence rates in the distal colon can be completely accounted for by the pregnancy effect. The U-shape of the pregnancy curve suggests the possibility of competing factors, some protective, especially after one or several pregnancies, and others conferring increasing risk with successive pregnancies, regardless of the pregnancy outcome.

Adenocarcinoma↗
PubMed1990

Serum oestrogen levels in postmenopausal women: comparison of American whites and Japanese in Japan.

Serum oestrone (E1), oestradiol (E2) and sex hormone binding globulin (SHBG) levels were studied in postmenopausal Japanese women in Japan (n = 91) and postmenopausal American white women (n = 38). The Japanese women were deliberately chosen to be from a rural agricultural area in order to get samples which represent as closely as possible the traditional Japanese 'lifestyle' that gave rise to the low rates of breast cancer in Japan. E1 levels were 47%, and E2 levels 36%, greater in the American women; these differences were only reduced to 43% and 27% after adjustment for the lower weight of the Japanese. These results were all statistically highly significant. There was little difference in SHBG levels between the Japanese and the American women. These results for E1 and E2 could be an important part of the explanation why Japanese and American breast cancer rates continue to diverge further after the menopause.

Aged↗
PubMed1990

Sex hormones in women in rural China and in Britain.

Plasma concentrations of certain hormones linked to breast cancer risk were measured in age-pooled samples from 3,250 rural Chinese women in 65 counties, and 300 British women, all aged 35-64. In age-groups 35-44, 45-54 and 55-64 respectively, mean oestradiol concentrations were 36% (P = 0.043), 90% (P less than 0.001) and 171% (P = 0.001) higher in the British than in the Chinese women, and mean testosterone concentrations were 48% (P less than 0.001), 68% (P less than 0.001) and 53% (P = 0.001) higher in the British than in the Chinese women. The difference in testosterone concentrations between the two countries appeared to be due largely to the lower average body weight in the Chinese women. Sex hormone binding globulin did not differ significantly between the two countries in age groups 35-44 and 45-54, but was 15% (P = 0.002) lower in the British than in the Chinese women at ages 55-64. Prolactin concentrations did not differ significantly between the two countries in any age group.

Adult↗
PubMed1990

Hormone levels in older women: a study of post-menopausal breast cancer patients and healthy population controls.

Hormone concentrations in blood and total 12 h urine values were compared between 40 post-menopausal women with breast cancer and 40 control women in a study which carefully controlled for the possible confounding effects of age, weight and pregnancy history by individually matching cases and controls on these factors. Breast cancer cases had received only surgical treatment for their localised disease, which was diagnosed from 1 to 9 years before hormonal evaluation. Cases had 15% higher serum oestradiol levels (P = 0.02), 40% more urinary oestradiol (P = 0.03) and 44% more urinary oestriol (P = 0.04) than control women. Cases also had higher levels of serum and urinary oestrone, but these differences were not statistically significant. The percentages of serum oestradiol not bound to albumin or sex-hormone binding globulin did not differ between cases and controls, nor were there statistically significant differences in the serum levels of prolactin, sex-hormone binding globulin or dehydroepiandrosterone sulphate. These results provide further support for the hypothesis that breast cancer risk is determined in part by post-menopausal serum oestrogen concentration.

Aged↗
PubMed1990

Long term effects of a first pregnancy on serum concentrations of dehydroepiandrosterone sulfate and dehydroepiandrosterone.

A previous paper in this journal reported that first pregnancy was followed by a marked decrease in dehydro-epiandrosterone sulfate (DHAS) and dehydroepiandrosterone (DHA) levels. We report here confirmatory observations from cross-sectional measurements in 460 women. In premenopausal subjects (n = 306), the mean DHAS level was 21% lower (P = 0.005) and the mean DHA level was 32% lower (P less than 0.001) in parous than in nulliparous women. Neither DHAS nor DHA was related to parity in postmenopausal women (n = 154).

Adult↗
PubMed1990

The question of estrogen replacement therapy in patients with a prior diagnosis of breast cancer.

While there is a general belief that hormone replacement therapy increases the risk of recurrence of breast cancer, there is in fact no hard data to prove this notion. Indirect evidence is provided, however, from observations on the effect of obesity on risk of breast cancer recurrence. This is because obesity is associated in postmenopausal women with increased circulating estrogen levels and obesity is also associated with lower sex hormone binding globulin levels so that the levels of non-SHBG bound estradiol are further increased.

Breast Neoplasms↗
PubMed1990

Reducing cancer risk in women through lifestyle-mediated changes in hormone levels.

The major hormone-associated cancers of women, viz. breast, endometrium, and ovary, account for some 40% of all female cancers in the U. S. Variable expression of estrogens and progestins account for major differences in the incidence of breast and endometrial cancer. Identified differences in premenopausal ovarian hormone expression and the known effects of post-menopausal weight on estrogen metabolism now permit an essentially complete hormonal explanation of the epidemiology of endometrial cancer. Recent confirmation of decreased ovarian steroid levels in certain Oriental women now permits a hormonal explanation of the four- to sixfold differences in breast cancer rates between Japanese and U.S. women, and a complete hormonal explanation of the epidemiology of breast cancer is almost at hand. A delay of 2 years in the age at menarche plus a low postmenopausal weight are predicted to lead to a more than 50% lifelong reduction in both breast cancer and endometrial cancer. A 2-year delay in menarche is predicted to lead to an 18% reduction in ovarian cancer. The lifestyle basis of variable premenopausal ovarian hormone expression is poorly understood and should be the focus of a major research effort. Profound effects on estrogen and progestin expression and on cancer rates are obtained from use of hormonal contraceptives and menopausal hormone replacement therapy; it appears possible to use this knowledge to construct a LHRHA-plus-estrogen contraceptive regimen that should produce a major lifelong reduction in current U.S. breast cancer rates (32% reduction from 5 years use; 55% from 10 years use). The proposed regimen should also cause a major lifelong reduction in ovarian cancer rates (40% reduction from 5 years use; 66% from 10 years use). Addition of a progestin-containing IUCD to such a regimen should also cause a major lifelong reduction in endometrial cancer rates (55% reduction from 5 years use; 82% reduction from 10 years use).

Breast Neoplasms↗
PubMed1989

Laminin promotes the oxidative burst in human neutrophils via increased chemoattractant receptor expression.

The extracellular matrix component, laminin, enhances the chemotactic responsiveness of polymorphonuclear leukocytes (PMN) in vitro, and low doses of chemoattractant substances augment the expression of PMN cell surface receptors for laminin. This study determined whether laminin acts in concert with chemoattractants to activate PMN. Laminin (5 to 100 micrograms/ml) stimulated lysozyme release and superoxide production in response to the chemoattractant, FMLP by as much as 69%. These results could be explained by changes in cell surface chemoattractant receptor expression in that incubation of normal PMN with laminin (5 to 75 micrograms/ml) increased the binding of 19 nM FML[3H]P by 35 to 80%. This corresponded to as much as a 2.5-fold increase in the number of chemoattractant receptors/cells which had a lower average affinity. Laminin did not change the number or affinity of FML[3H]P receptors present on organelle-depleted PMN cytoplasts, and the laminin-induced increase in FML[3H]P receptors expressed on PMN from a patient with a specific granule deficiency was only 11 to 21% of that seen in normal PMN. These findings suggest that chemoattractants augment the expression of laminin receptors which mediate PMN attachment to basement membranes, followed by laminin-induced increases in the expression of cryptic chemoattractant receptors contained in intracellular granules, with resultant augmentation of the oxidative burst.

Adult↗
PubMed1989

The relationships of SHBG with current and previous use of oral contraceptives and oestrogen replacement therapy.

Sex hormone binding globulin (SHBG) concentration was measured in serum samples from 2077 premenopausal and 901 naturally postmenopausal women who had no history of disease or of recent drug use likely to affect SHBG. Current users of oral contraceptives (OCs) and of oestrogen replacement therapy had higher mean SHBG values than non-current users. Both premenopausal and postmenopausal women who had previously used OCs had a lower mean SHBG concentration than never users of OCs. Previous use of oestrogen replacement therapy was not related to SHBG.

Adult↗