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Biomedical subjects

M C Pike

Publications and source records attributed to M C Pike.

At least 271 records · Page 15Linked to original sources
PubMed1979

Breast-cancer incidence and mortality rates in different countries in relation to known risk factors and dietary practices.

Breast-cancer incidence and mortality rates in different countries were found to be correlated with height, weight and age at menarche, all of which have been identified as risk factors in cohort or case-control studies of breast cancer. There were, however, correlations with total fat and animal protein consumption per capita even after controlling for the 3 anthropometric variables. This suggests that, while some of the effects of diet on breast-cancer rates may be mediated through effects on these known risk factors, there may be more direct effects as well.

Adult↗
PubMed1979

Phospholipid methylation in macrophages is inhibited by chemotactic factors.

Chemotaxis by human monocytes has been shown to require methylation mediated by S-adenosyl-L-methionine(AdoMet), but the specific transmethylation reaction necessary for this function was not elucidated. In an attempt to define the methylation requirement for chemotaxis, we examined the effect of chemotactic agonists and antagonists on protein carboxy-O-methylation of protein and methylation of phospholipid in guinea pig macrophages. Chemotactic agents tested over a wide dose and time range produced no alteration in carboxy-O-methylation. However, these agents did produce an effect on the methylation of phosphatidylethanolamine by macrophages. AdoMet-mediated phospholipid methylation was inhibited by as much as 73% by chemotactic factors, and there was excellent correlation (r = 0.99) between their concentrations for producing half-maximal chemotactic responses and for inhibiting phospholipid methylation. The inhibition of methylation by chemotactic factors was observed at all incubation times and could not be explained by an increased turnover of membrane phospholipid. Neither the chemotaxis antagonist fPhe-Met nor the nonchemotactic tripeptide Met-Met-Met significantly depressed phospholipid methylation. Immune phagocytosis by macrophages similarly did not alter phospholipid methylation. The chemotactic factors produced no alteration in total macrophage phospholipid synthesis or in the phospholipid methylation in a nonchemotactic cell type. The formation of newly methylated derivatives of phosphatidylethanolamine in macrophages was decreased by a biologically active dose of chemotactic factor. These findings indicate that chemotactic factors are capable of altering the methylation of phosphatidylethanolamine in chemotactically responsive cells. The inhibition of phospholipid methylation by chemotactic factors may be necessary for the translation of a chemotactic signal on the surface of the cell into directional cell movement.

Animals↗
PubMed1979

Risk factors for nodular sclerosis and other types of Hodgkin's disease.

The age-adjusted incidence rates of nodular sclerosis in Los Angeles County from 1972 to 1975 were 58% lower in Mexican-Americans and 42% lower in blacks than in other whites. They were the same for each sex among other whites and the curve of age-specific incidence peaked in young adulthood. The incidence of nodular sclerosis was directly associated with social class. In contrast, the rates for other histological varieties of Hodgkin's disease (lymphocyte predominance, mixed cellularity, lymphocyte depletion) were only 12% lower in Mexican-Americans but 34% lower in blacks. In other whites, the rates were 92% higher in men and increased gradually with age while there were no clear trends with social class. These characteristics support the hypothesis that, at least for purposes of etiology, the nodular sclerosis form of this disease should be considered a distinct entity. Self-administered questionnaire were completed by 218 of the 1972 to 1973 Hodgkin's disease patients and 218 individually matched neighbourhood controls. Significantly high risk ratios for Hodgkin's disease were found for prior appendectomy (risk ratios = 1.9, p = 0.01) and for past amphetamine use (risk ratios = 3.0, p = 0.01). The elevated risk associated with amphetamine use had been found in a previous study.

Adolescent↗
PubMed1979

The hormonal basis of breast cancer.

Both animal experiments and certain well-established breast cancer risk factors suggest that risk to the disease is fundamentally determined by the hormones of the pituitary-gonadal axis. Although international comparisons of urinary estrogens have given support to this ypothesis, case-control studies and international comparisons of plasma estrogens and prolactin have not. Methodological problems and sampling biases probably account for the inconsistency of these investigations. Taking advantage of the known familial increased risk to breast cancer, we conducted comparative studies of teenage daughters of patients with breast cancer, including a group of girls whose mothers had bilateral breast cancer when they were less than 50 years old. The results of these studies revealed that these high-risk girls appear to have elevated levels of estrogens, prolactin, and progesterone.

Adolescent↗
PubMed1978

Resistance of neoplasms to immunological destruction: role of a macrophage chemotaxis inhibitor.

Several tissue culture lines of 6C3HED, a murine lymphoma, were more susceptible to immunologic destruction in vivo than the highly virulent 6C3HED line maintained by serial intramuscular transplantation. The attenuated tissue culture cells were rejected by normal syngeneic recipients, but thymectomized mice were unable to reject attenuated cells. In such mice, the growth rate of attenuated cells was equivalent to the growth rate of virulent cells in normal syngeneic mice. The increased susceptibility of attenuated cells to destruction by syngeneic hosts was shown to correlate with decreased production by the tumor cells of a macrophage chemotaxis inhibitor, and not with altered antigen density. In addition, when inhibitor isolated from virulent cells was administered to mice challenged with attenuated cells, the latter cells became virulent in vivo. When attenuated and virulent cells were administered simultaneously in the same host, the attenuated cells were able to develop into progressively growing tumors. The data suggest that the successful growth of neoplastic cells in normal may require tumor cells to produce factors which subvert the ability of the host to mobilize macrophages rapidly at the tumor site.

Animals↗
PubMed1978

The epidemiology of tropical myositis in the Mengo Districts of Uganda.

In the five-year period 1964-68 1,335 patients were admitted to Mulago Hospital, Kampala, with tropical myositis. The marked increase in the number of admissions during the study period is attributed to a change in the utilization of the hospital rather than to a true increase in the incidence of the disease. There was found to be only slight variation in incidence between different age and sex groups and there was no convincing evidence that immigrants from high altitude areas, where the disease is rare, were at different risk. There was statistically significant month-to-month variation in admission rates but there was no apparent correlation with rainfall, and no marked seasonal variation. During the quinquennium there was a changing pattern of admission rates for patients from different counties, and some evidence of 'space-time' clustering. These findings are compatible with the primary muscle damage being induced by a virus or the presence of aberrant hookworm larvae, but an ingested toxin cannot be excluded. Trauma may also play a role in determining localization of the disease in some cases.

Age Factors↗
PubMed1978

Requirement of S-adenosyl-L-methionine-mediated methylation for human monocyte chemotaxis.

The chemotactic response of motile bacteria requires the methylation of specific proteins by S-adenosyl-L-methionine. To determine whether methylation is required for the chemotaxis of human leukocytes, we studied the effects of inhibition of S-adenosyl-L-methionine-mediated methylation on monocyte chemotactic responsiveness. Methylation was inhibited in monocytes by treating the cells with substances that produced elevations in intracellular S-adenosyl-L-homocysteine, a competitive inhibitor of S-adenosyl-L-methionine methylation. Treatment of isolated monocytes with the adenosine deaminase inhibitor, erythro-9-(2-hydroxy-3-nonyl)adenine, plus exogenous adenosine and L-homocysteine thiolactone increased intracellular S-adenosyl-L-homocysteine levels by as much as 1500-fold. Concomitant with increases in S-adenosyl-L-homocysteine were a decrease in monocyte protein carboxy-O-methylation as well as a marked inhibition of monocyte chemotactic responsiveness. Conditions that almost completely inhibited methylation and chemotaxis did not depress monocyte phagocytosis, indicating that this latter function either is independent of S-adenosyl-L-methionine-mediated methylation or is extremely resistant to inhibition of such reactions by S-adenosyl-L-homocysteine. These studies indicate that S-adenosyl-L-methionine-mediated methylation is required for the chemotaxis of eukaryotic cells and that the chemotactic and phagocytic functions of human monocytes have different requirements for methylation.

Adenosine Deaminase Inhibitors↗
PubMed1977

Contacts between young patients with Hodgkin's disease. A case-control study.

To investigate the possibility that Hodgkin's disease (H.D.) may be transmitted from person to person, a case-control study was conducted among 87 of the 97 H.D. patients diagnosed under the age of 40 years in the period 1962-71, resident at the time of diagnosis in a defined area around Oxford. For each of the 87 H.D. patients a matched control patient was selected with a diagnosis other than that of a chronic or malignant disease. H.D. patients and controls were interviewed to determine their places of schooling and work and attempts were made to link pairs of patients who had attended the same school or work place at the same time. The findings do not support the hypothesis that H.D. patients may pass on the disease to others. Among the H.D. patients, links between 40 pairs were established, compared with 40-75 links expected, based upon the experience of all 174 persons studied. The only finding which was statistically significant (p approximately 0-04) arose when H.D. patients were considered to be "susceptible" from 10 to 5 years before diagnosis and "infective" from diagnosis to 2 years after diagnosis: 7 pairs of links were found against 2-75 expected. However, since 7 postulated periods of susceptibility and 9 postulated periods of infectivity were examined, this one "statistically significant" finding might easily have arisen by chance.

Adolescent↗
PubMed1977

A new procedure for the statistical evaluation of intrauterine contraception.

An improved statistical method for assessing the efficacy of intrauterine contraception is presented. This method, called the log-rank method, is based on a daily life table, which yields the best estimates of the cumulative net termination probabilities. It provides a sensitive chi-square test statistic to detect differences among these probabilities for two or more contraceptive devices. When three or more devices are compared, the chi-square statistic may be partitioned into additive components representing comparisons among groups of devices. The log-rank method also permits adjusting for differences among subgroups by controlling for factors such as parity or age. Although calculations may be performed on a desk calculator, a FORTRAN-IV computer program is made available to interested researchers.

Computers↗
PubMed1977

Disorders of leukocyte chemotaxis.

The rapid accumulation of inflammatory cells at sites of microbial invasion or neoplastic transformation is a central event in immunologically-mediated host defense. The availability of methodology to accurately quantify leukocyte migration in vitro has allowed the disclosure of previously unrecognized clinical disorders, namely leukocyte dysmotility syndromes. Although this area of clinical investigation is in its infancy, one can identify several processes associated with abnormal leukocyte accumulation. Abnormalities of immune recognition, chemotactic factor production, cellular motility or inhibitors of chemotaxis have been identified in different human diseases. In the upcoming years, pharmacological intervention directed at correcting specific causes of leukocyte dysmotility may well enhance our ability to treat certain infectious, inflammatory, and neoplastic diseases.

Antibody Formation↗
PubMed1977

Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples.

Part I of this report appeared in the previous issue (Br. J. Cancer (1976) 34,585), and discussed the design of randomized clinical trials. Part II now describes efficient methods of analysis of randomized clinical trials in which we wish to compare the duration of survival (or the time until some other untoward event first occurs) among different groups of patients. It is intended to enable physicians without statistical training either to analyse such data themselves using life tables, the logrank test and retrospective stratification, or, when such analyses are presented, to appreciate them more critically, but the discussion may also be of interest to statisticians who have not yet specialized in clinical trial analyses.

Drug Evaluation↗
PubMed1977

Further studies of space-time clustering of Burkitt's lymphoma in Uganda.

All hospital-treated cases of Burkitt's lymphoma (BL), with onset of symptoms in the period 1963-68 and resident in the Lango and Acholi districts of Uganda, were identified. The average annual incidence of BL in the 6-year period was 1-87 X 10(-5), similar to that in the adjacent West Nile district. Contrary to findings in other areas of Uganda, there was no evidence of seasonal variation in the onset of cases, nor of space-time clustering, nor of a decline in the incidence of BL in the study period. An inverse relationship was noted between the median age at onset of BL and the incidence of the disease in different areas of Uganda, a finding consistent with intense malarial infection being a precipitating factor for BL. The variable observations with respect to space-time clustering of BL and seasonal variation in incidence in different areas remains unexplained, but it is suggested that a closer study of the patterns of malarial infection in these areas may help to account for the findings.

Age Factors↗
PubMed1977

Specific receptor sites for chemotactic peptides on human polymorphonuclear leukocytes.

Synthetic N-formylmethionyl peptides are chemotactic attractants for human polymorphonuclear leukocytes. The well-defined structure-activity relationship of these peptides in eliciting a chemotactic response suggests that the interaction of the peptides with a specific cellular binding site may initiate chemotaxis. By using tritiated N-formylmethionyl-leucyl-phenylalanine (fMet-Leu-[3H]Phe), a potent chemotactic peptide with high specific radioactivity, we have directly identified binding sites on human polymorphonuclear leukocytes. Binding of fMet-Leu-[3H]Phe to polymorphonuclear leukocytes is rapid (t1/2 less than 2 min) and reversible. The equilibrium dissociation constant (KD) for the interaction of fMet-Leu-[3H-A1Phe with the binding site is 12-14 nM at 37 degrees. The number of binding sites is approximately 2000 per cell. The specificity of the binding sites for a series of N-formylmethionyl peptides exactly reflects the specificity of the chemotactic response to the peptides in that they compete for the binding sites and initiate chemotaxis with the same order of potency (fMet-Leu-Phe greater than fMet-Met-Met greater than fMet-Phe greater than fMet-Leu greater than fMet),fPhe-Met is a competitive antagonist of the chemotactic activity of N-formylmethionyl peptides and has a calculated KD of 6x10-5 M. FPhe-Met also half-maximally inhibits binding of fMet-Leu[3H]Phe binding was the highest in polymorphonuclear leukocytes. No binding of fMet-Leu-[3H]Phe to human erythrocytes could be detected. These data indicate that fMet-Leu-[3H]Phe can be used to identify binding sites for chemotactic peptides on human polymorphonuclear leukocytes. It is likely that these binding sites initiate the specific response of motile cells to N-formylmethionyl peptides.

Binding Sites↗