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Biomedical subjects

S Graham

Publications and source records attributed to S Graham.

At least 217 records · Page 12Linked to original sources

Immunoaffinity purification of a 72K early antigen of human cytomegalovirus: analysis of humoral and cell-mediated immunity to the purified polypeptide.

An early antigen of human cytomegalovirus (HCMV) was purified from infected cells as a 72K polypeptide by immunoaffinity chromatography using a monoclonal antibody. It was located in both nucleus and cytoplasm, and was non-glycosylated and undetectable on the surface of infected cells. Known seropositive subjects had antibody against the purified protein and it elicited proliferative T cell responses in 10 of 16 subjects. Five of 14 T cell lines established in response to the purified protein were predominantly CD8+ and of these two showed major histocompatibility complex-restricted cytotoxicity against HCMV-infected cells. This provides further evidence that antigens expressed at early times may be targets for the immune response during persistent HCMV infection.

Antibody Formation↗

Hypotheses regarding caloric intake in cancer development.

The epidemiologic evidence on fats as related to cancer has until recently been equivocal. Some studies showed an inhibitory effect, some showed no effect, and a few showed a reduction in risk. More recently, however, epidemiologic inquiries have suggested that fats may be associated with increased risk of cancer of the breast, prostate, cervix, colon, rectum, larynx, and lung. The relationship is not a simple one. There is evidence that a high level of total calories ingested, regardless of whether the source is fats, carbohydrates, or proteins, increases risk. Still other studies suggest that calorie expenditure may be the important fact. Thus, obesity, derived from whatever source, may be etiologically related to some cancers. Fats being a potentially important contributor to obesity over the long term, may in this way increase risk.

Diet Surveys↗

Development of the surgically produced singleton mouse fetus.

All but one mouse embryo were removed from uteri on Day 8 of gestation and delivered via cesarean section on Day 18. Singletons were compared on various developmental indices to similarly delivered controls permitted to reside in uteri containing the normal complement of fetuses. The former were heavier at birth and weaning, had smaller ano-genital distance ratios (ano-genital distance/delivery weight), and displayed walking, gripping, eye-opening, and vaginal-opening earlier than controls. Singletons also exhibited greater durations and frequencies of various prenatal activities relative to controls when observed on Day 17 of gestation. Singleton status did not advance the onset of prenatal activity.

Animals↗

Human natural killer cell lysis of virus-infected cells. Relationship to expression of the transferrin receptor.

Natural killer (NK) cells lyse tumor and virus-infected cells yet the nature of the target structure they recognize is unknown. A normal host cell glycoprotein, the transferrin receptor (TfR), has been proposed as a target structure on tumor cells. We therefore investigated whether changes in the number or physiological recycling of the TfR, consequent on virus infection, were related to the differential susceptibility of virus-infected cells to NK lysis. There was a direct correlation between TfR expression, susceptibility to NK lysis and ability to act as cold target competitors, for human fibroblasts infected with RNA and DNA viruses (cytomegalovirus, herpes simplex, polio, vaccinia and Semliki Forest virus). The NK lysis of human cytomegalovirus-infected fibroblasts was studied in more detail. NK lysis was increased coincident with human cytomegalovirus early antigen expression and this susceptibility to lysis was associated with increased total and recycling TfR but only a slight increase in surface TfR expression. In addition, susceptibility of uninfected human fibroblasts to NK lysis directly correlated with TfR number. However, we were unable to inhibit NK lysis by either excess iron-saturated Tf or affinity-purified TfR. We conclude that there is a direct correlation between total TfR expression and susceptibility to NK lysis of human virus-infected cells; however, the NK target structure on virus-infected cells is probably not the TfR itself.

Cytomegalovirus↗

The expression of ano-genital distance data in the mouse.

Ano-genital distance (AGD) obtained from male and female mice at birth correlated significantly with body weight. Body length did not correlate significantly with AGD in females. Although it did so in the males, the coefficient accounted for less than half of the variance relative to that obtained by correlating AGD with weight. It is suggested that transformed AGD scores (AGD/body weight) rather than raw AGD data be analyzed when AGD is used to determine whether an independent variable that may affect body weight influences the prenatal hormone milieu.

Anal Canal↗

Singleton female mouse fetuses are subsequently unresponsive to the aggression-activating property of testosterone.

Eight-day pregnant mice were surgically prepared so that they carried a single fetus which was delivered by cesarean section on Day 18, one day prior to term. Other animals were permitted to carry their entire complement of fetuses which also were delivered surgically. Their position within a uterine horn relative to one another was noted. Adult ovariectomized testosterone-treated females that had been situated in utero contiguous to no male fetuses attacked an olfactory bulbectomized adult stimulus male. In contrast, females that resided singly in the uterus were unresponsive to the hormone; they displayed no aggressive behavior. Masculinization, therefore, appears to occur in utero in the absence of contiguity to male fetuses.

Aggression↗

Dietary vitamin A and cancer--a multisite case-control study.

The relationship between an index of dietary vitamin A and cancer risk at 25 sites was assessed in retrospective case-control studies. Common control groups for males and females were used in all analyses. Relative risk estimates were derived from multiple logistic regression analyses that controlled for age, alcohol consumption, and smoking exposure. We found that among males, dietary vitamin A is associated with lower risk for cancers of the tongue, floor and other mouth, pharynx, larynx, esophagus, and lung but higher risk for Hodgkin's disease and leukemia. Among females, we found that dietary vitamin A had less effect on risk generally but was associated with lower risk for bladder cancer. These findings are consistent with previous research that showed dietary vitamin A to be associated with decreased risk of squamous epithelial cancers. The association of dietary vitamin A and increased risk of Hodgkin's disease and leukemia among males in addition to the disparity in effect of dietary vitamin A on risk between males and females are areas worthy of further research.

Adult↗

The Chiari osteotomy. A review of 58 cases.

Fifty-eight Chiari osteotomies performed in 51 patients were reviewed retrospectively. The indications for surgery were painful subluxation, instability, or poor acetabular coverage. The average age at surgery was 16 years (range, 7-45), and the average follow-up period was 40 months. The majority of the patients had congenital hip dislocation, but also included were patients with cerebral palsy, Legg-Calvé-Perthes disease, polio, infection, coxa vara, and epiphyseal dysplasia. Supplemental bone grafts were applied as needed. The functional results were unrelated to age, with 26 excellent, 28 good, and four poorly functional hips. After operation, 39 out of 41 had total pain relief, 41 out of 58 had a normal acetabular index, and 54 out of 58 had a normal center-edge angle. Trendelenburg gaits were unchanged by the Chiari osteotomy, but trochanteric transfer improved the gait in few cases.

Acetabulum↗

Lactation and breast cancer. Evidence for a negative association in premenopausal women.

The authors report a case-control study of breast cancer based on an analysis of data collected by interview between the years 1957-1965 from women residing in the communities of Buffalo and Kenmore, New York. Prior reproductive factors, including a detailed lactation history, were examined for 453 white females with breast cancer and 1,365 white females without breast cancer who were selected randomly from the population of Buffalo and Kenmore. There is evidence of a negative association between length of nursing and breast cancer risk in premenopausal women which is not seen in the postmenopausal women. This apparent "protective" effect of lactation persists after statistical control for the potential confounding factors of age, parity, age at first pregnancy, age at menarche, and education. Cases are more likely than controls to have reported unsuccessful lactations due to "insufficient milk." The findings of this study, in conjunction with the authors' review of previously published studies that have examined prior lactation as related to breast cancer risk, suggest that there may be an independent negative association between nursing and subsequent breast cancer risk in premenopausal women. Whether this means that breast feeding is protective or that some women who are unsuccessful at lactation are at increased risk for subsequent breast cancer is not clear. A detailed reanalysis of existing data and more careful attention to detailed prior breast function/dysfunction in future studies are recommended.

Adolescent↗

Assessing nutrient intake with an abbreviated dietary interview.

There is considerable interest in developing a means of assessing dietary intake of specific nutrients with minimal time and expense in epidemiologic studies. Using data from 1,682 individuals who were interviewed using an extensive food frequency dietary history, the authors examined the question of how many foods might be minimally required in order to estimate specific nutrient intakes for epidemiologic purposes. Nutrient indices were constructed for vitamins A and C, dietary fiber, fat, protein, and total calories based on 128 foods included in the interview. They found that a large fraction of the variability of nutrient intake in this population could be explained by a small number of foods. An abbreviated dietary history ascertaining the intake of as few as 15-20 food items may be all that is required in order to test the association between disease outcome and the intake of a single nutrient.

Age Factors↗

Allergy-related diseases and cancer: an inverse association.

This paper presents the results of a retrospective study that examines the association of cancer with a history of asthma, hay fever, hives, and other allergy-related diseases. This study is based on interview data collected from 13,665 cancer cases and 4,079 nonneoplastic controls who were admitted to Roswell Park Memorial Institute from 1957 to 1965. Although there is a general tendency for the age- and cigarette smoking-adjusted odds ratios associated with a history of asthma and hay fever to be less than 1, for both males and females, there is stronger evidence for a decreased risk of cancer associated with a history of hives and other allergy-related diseases. Decreased risks associated with a history of hives and other allergies are seen in males for oral cancer, cancers of the lung, larynx, digestive system, urinary system, and cancers of all sites combined and in females for cancers of the digestive system, reproductive system, in particular, cancer of the cervix, and cancers of all sites combined. None of the few odds ratios over 1 associated with a history of any allergy-related condition are statistically significant (alpha = 0.05). These findings suggest that individuals with allergy-related disorders may be at decreased risk of cancer, although reasons for cautious interpretation of the findings are emphasized. Prospective studies of carefully defined allergic disease cohorts are needed.

Asthma↗

Lifetime occupational exercise and colon cancer.

The authors used data on patients aged 30-79 years admitted to the Roswell Park Memorial Institute in Buffalo, New York, 1957-1965, to compare the amount of lifetime occupational physical activity for 210 white male patients with cancer of the colon and 276 white male patients with cancer of the rectum to the lifetime occupational physical exercise of 1,431 patients with nonneoplastic nondigestive diseases. The authors found that risk of cancer of the colon increased with increasing amount and proportion of time in jobs involving only sedentary or light work. This relationship was not found for rectal cancer. These findings corroborate those of Garabrant et al. (Am J Epidemiol 1984; 119:1005-14). The strength of the associations presented here and the dose-response relationship indicate that limited physical activity could be an important etiologic factor. More inquiries need to be undertaken to study exercise in relation to other factors, such as diet, in colon cancer risk.

Adult↗

An inquiry into the epidemiology of melanoma.

The authors conducted a study of 404 melanoma patients and 521 control patients of both sexes at Roswell Park Memorial Institute. As have previous investigators, they found that higher risk attaches to upper socioeconomic status, as measured by occupation and education, lightness of complexion and hair, and amount of blue in the admixture of eye color. The authors also found a higher risk among individuals who reacted to sun exposure by burning, blistering, or freckling rather than by tanning. A particular concern was to measure risk associated with exposure to the sun. As have two other investigators, they found that risk decreased with increasing exposure, suggesting either that individuals continually exposed to the sun have less risk because of tanning, or that susceptibles purposely avoid sun exposure, or both. The fact that melanoma occurs with greater frequency on sites exposed to the sun suggests that sun exposure plays a part. These studies showed a dose-response increase in risk (odds ratios of up to 4 for males and over 6 for females) with increases in number of traits possessed, such as light complexion, and burning or freckling in response to sun exposure. This is consistent with the authors' earlier finding of a strong familial aggregation of melanoma.

Adult↗