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Biomedical subjects

M C Pike

Publications and source records attributed to M C Pike.

At least 253 records · Page 14Linked to original sources
PubMed1981

Transmethylation reactions are required for initial morphologic and biochemical responses of human monocytes to chemoattractants.

Transmethylation reactions mediated by S-adenosyl-L-methionine are required for the chemotaxis of mononuclear leukocytes. It is not yet known, however, whether methylation reactions participate in the initial transduction of the chemotactic signals that lead to the alterations in cellular morphology required for chemotaxis and/or whether they are necessary for the subsequent biochemical events needed for sustained directed migration. We therefore investigated the effects of inhibiting methylation on 2 early responses induced by chemoattractant-receptor occupancy in human monocytes; the rapid morphologic alteration from round to a triangular, motile cell configuration (polarization) and the release of [3H]-arachidonic acid from membrane phospholipids. Both of these initial responses to 3 types of chemoattractants were severely depressed in monocytes treated with the methylation inhibitors, erythro-9-[2-hydroxy-3-nonyl]adenine (EHNA) plus adenosine and L-homocysteine or by 3-deazaadenosine plus L-homocysteine. These findings indicate that methylation reactions are required for the transduction of signals after chemotactic factor receptor occupancy in monocytes, which lead to a motile cellular configuration and release of arachidonic acid from membrane phospholipids. Activation of phospholipases with destruction of cell-associated phosphatidylinositol appears to account for the major source of arachidonic acid released by monocytes exposed to chemoattractants. This pathway for arachidonic acid release requires a transmethylation reaction since it is blocked by inhibitors of methylation.

Adenine↗
PubMed1981

The role of transmethylation reactions in regulating the binding of BCG-activated murine macrophages to neoplastic target cells.

The ability of BCG-activated macrophages from C57BL/6J mice to lyse neoplastic targets was depressed by inhibitors of methyltransferase reactions (10(-4) M adenosine, 10(-5) M EHNA, and 10(-4) M L-homocysteine or 10(-5) M DZA). Binding of P815 mastocytoma targets to BCG-activated macrophages, which has been shown to be a necessary event in cytolysis of those targets, was also inhibited by adenosine, EHNA, and L-homocysteine or by DZA at the above concentrations. Inhibition of binding was obtained when macrophages were pretreated with the inhibitors, whereas pretreatment of targets with the inhibitors did not alter binding. The inhibitors were not toxic to the macrophages, as judged by morphology and viability of the macrophage cultures as well as by ability of macrophages to bind antibody-coated P815 targets or to secrete plasminogen activator. The inhibitors, at concentrations that inhibited cytolysis and binding, also depressed one type of S-adenosyl-L-methionine-mediated methylation reaction (protein carboxy-O-methylation) in BCG macrophages. The data suggest that transmethylation reactions are essential for the ability of BCG activated murine macrophages to bind and, hence, to destroy P815 tumor cells.

Animals↗
PubMed1981

Estimation of the proportional hazard in two-treatment-group clinical trials.

Two easily-computed approximate methods of obtaining an estimate of the ratio of the hazard rates for two treatments in survival analysis are compared, by simulation, with the partial maximum likelihood (CML) estimator which assumes the Cox model with no covariates. The two methods studied are the Mantel-Haenszel estimator, and the O/E method which employs the ratio of the 'relative death rates' for the two treatments. Uncensored and censored cases are examined for both continuous and tied data with the assumption of either an underlying exponential distribution or a Weibull distribution with shape parameter 2. The O/E method is biased but, within the range of values of the ratio of the hazard rates of interest in clinical trials, it is more efficient in terms of mean square error than either CML or the Mantel-Haenszel method for all but the largest trials. The Mantel-Haenszel method is minimally biased, gives answers very close to those obtained using CML, and may be used to provide satisfactory approximate confidence intervals.

Clinical Trials as Topic↗
PubMed1980

N-Formylmethionyl peptide receptors on equine leukocytes initiate secretion but not chemotaxis.

The chemotaxis of leukocytes appears to be initiated by the binding of chemotactic factors to the surface of these cells. N-Formylated peptides induce chemotaxis and lysosomal enzyme secretion of leukocytes; because these peptides are available in a purified radiolabeled form, they have been useful in the characterization of receptors for chemotactic factors. Equine polymorphonuclear leukocytes secrete lysosomal enzymes but do not exhibit chemotaxis in respone to the N-formylated peptides, even though they have a high-affinity cell surface receptor for these agents. The specificity of the equine receptor resembles the specificity of the receptor on chemotactically responsive leukocytes from other species. Equine polymorphonuclear leukocytes may thus be an excellent model for the study of the events that lead to a biological response following receptor occupancy.

Animals↗
PubMed1980

Development of specific receptors for N-formylated chemotactic peptides in a human monocyte cell line stimulated with lymphokines.

A human monocyte-like cell line, U937, when grown in continuous culture, does not secrete lysosomal enzymes or migrate towards chemotactic factors. When the cells are stimulated by lymphokines, however, they develop the ability both to migrate directionally and to secrete enzymes in response to several types of chemoattractants. The development, by stimulated cells, of chemotactic and secretory responses to one class of chemoattractants, the N- formylated peptides, is accompanied by the appearance on the cells of specific binding sites for these substances. Using tritiated N-formyl- methionyl-leueyl-phenylalanine (fMet-Leu-[(3)H]Phe) as a ligand, it was determined that unstimulated U937 cells possess no detectable binding sites. However, after stimulation with lymphocyte culture supernates for 24, 48, and 72 h, they developed 4,505 (+/-) 1,138, 22,150(+/-) 4,030, and 37,200 (+/-) 8,000 sites/cell, respectively. The dissociation constants for the interaction of fMet-Leu-[SH]Phe with the binding sites were approximately the same regardless of stimulation time and ranged between 15 and 30 nM. The binding of fMet-Leu-[(3)H]Phe by stimulated U937 cells was rapid and readily reversed by the addition of a large excess of unlabeled peptide. The affinity of a series of N-formylated peptides for binding to U937 cells exactly reflected the potency of the peptides in inducing lysosomal enzyme secretion and chemotaxis. The availability of a continuous human monocytic cell line that can be induced to express receptors for N-formylated peptides will provide a useful tool not only for the characterization of such receptors but also for the delineation of regulatory mechanisms involved in cellular differentiation and the chemotactic response.

Binding Sites↗
PubMed1980

Influence of cytoskeletal assembly on phosphatidylcholine synthesis in intact phagocytic cells.

Interactions of the plasma membrane with the cytoskeleton are required for diverse cellular functions such as adhesion, division, secretion, endocytosis and chemotaxis. We therefore investigated whether the reversible assembly of microtubules and/or microfilaments in leukocytes affected the synthesis of a key membrane component, phosphatidylcholine. The effects of a variety of antitubuin and antimicrofilament agents on phosphatidylcholine synthesis via the methylation of phosphatidyl-ethanolamine and its formation through CDP-choline were studied. The antitubulins inhibited the incorporation of 3H-methyl groups into phosphatidylethanolamine in guinea pig macrophages and polymorphonuclear leukocytes by as much as 64%, while cytochalasin B, an antimicrofilament agent, had no effect. In contrast, the incorporation of methyl-3H-choline into phosphatidylcholine was stimulated in these cells by as much as 2 fold by the anti-tubulins. The synthesis of phosphatidylcholine in a nonphagocytic cell type, splenic lymphocytes, was not altered in the presence of the antitubulin agents. Changes in the state of polymerization of cellular tubulin pools associated with certain specialized functions of cells may, through effects on phosphatidylcholine synthesis, alter local membrane composition, microviscosity, or the interaction of membrane proteins with their environment.

Animals↗
PubMed1980

Bias and efficiency in logistic analyses of stratified case-control studies.

Two approaches to the estimation of the parameters in the logistic model applied to the analysis of stratum matched case-control studies are compared. It is shown that the "unconditional likelihood method' gives estimates of odds ratios which may be severely exaggerated if the stratum sizes are not large; however, if stratum sizes are not small the "conditional likelihood method' is computationally prohibitive. The use of small stratum sizes (e.g., 1-to-1 matching) leads to some loss of efficiency if the matching is irrelevant but it is shown that the loss is small for odds ratios up to at least 3. There would seem to be strong arguments for the routine use of matched designs as the reduction in confounding bias produced by such matching may be considerable whereas there is only a small loss in efficiency compared with unmatched designs.

Humans↗
PubMed1980

Changing ratio of breast cancer incidence rates with age of black females compared with white females in the United States.

Age-standardized breast cancer rates were approximately 30% lower in U.S. black women compared to white women. This observation concealed the fact that black women under age 40 years had a higher incidence of breast cancer than did white women, whereas white women over 40 years had a higher incidence. The known risk factors for breast cancer development (early age at menarche, late age at first full-term delivery, and a late age of menopause) differed in black and white populations, which might explain this difference in breast cancer incidence between blacks and whites at different ages.

Adolescent↗
PubMed1980

Case-control study of intracranial meningiomas in women in Los Angeles County, California.

A case-control study was conducted among women in Los Angeles County to investigate possible causes of intracranial meningiomas. Questionnaires sought information from patients and from a neighbor of each one on characteristics and past experiences that might be associated with the development of this disease. Information was obtained on 188 matched patient-neighbor pairs. Three primary factors appeared to be associated with meningioma occurrence: 1) a history of head trauma (odds ratio = 2.0, P = 0.01), 2) consumption of certain cured meats (odds ratio = 2.8, P less than 0.01), and 3) exposure to medical and dental diagnostic X-rays to the head. For diagnostic X-rays, the strongest association was with early exposure (less than 20 yr old) to full-mouth dental X-ray series (odds ratio = 4.0, P less than 0.01).

Age Factors↗
PubMed1979

"Incessant ovulation" and ovarian cancer.

A case-control study of 150 ovarian cancer patients under the age of 50 and individually matched controls was done to study the influence of fertility and oral contraceptive use on the risk of ovarian cancer. The risk decreased with increasing numbers of live births, with increasing numbers of incomplete pregnancies, and with the use of oral contraceptives. These three factors can be amalgamated into a single index of protection--"protected time"--by considering them all as periods of anovulation. The complement of protected time--viz., "ovulatory age", the period between menarche and diagnosis of ovarian cancer (or cessation of menses) minus "protected time"--was strongly related to risk of ovarian cancer. Other factors found to be associated with increased ovarian cancer risk were obesity, cervical polyps, and gallbladder disease. Women who had an "immediate" intolerance to oral contraceptive use had a fourfold increased risk of ovarian cancer. 7 patients, but no controls, could recall a family history of ovarian cancer.

Abortion, Spontaneous↗
PubMed1979

Risk factors for cancer of the testis in young men.

An individual matched case-control study of testis cancer in 131 men under age 40 was conducted to investigate antecedent risk factors including events during prenatal life. Ten patients were born with an undescended testis compared to only two controls (p less equal to 0.02), a previously reported risk factor. Two new risk factors were uncovered: six patients-mothers received hormones during the index pregnancy compared to only one control-mother, and eight patient-mothers and two control-mothers reported excessive nausea as a complication of the index pregnancy. A hypothesis linking these three factors is presented: viz, that a major risk factor for testis cancer is a relative excess of certain hormones (in particular estrogen) at the time of differentiation of the testes.

Adolescent↗