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Biomedical subjects

S Graham

Publications and source records attributed to S Graham.

At least 91 records · Page 5Linked to original sources

The production of a macrophage-activating factor from rainbow trout Salmo gairdneri leucocytes.

Rainbow trout head kidney and blood leucocytes are shown to be capable of secreting a soluble macrophage-activating factor (MAF) after stimulation with concanavalin A (Con A). The presence of phorbol myristate acetate (PMA) as a co-stimulant increased the production of MAF. Both respiratory burst activity (nitroblue tetrazolium, NBT, reduction and H2O2 production) and bactericidal activity were enhanced after incubation of resident or elicited macrophages with the MAF-containing supernatants for 48-72 hr. The target culture period before the addition of MAF did not affect their responsiveness, but a continuous presence of MAF was necessary for maximal stimulation.

Aeromonas

A prospective randomized trial of alpha 2B-interferon/gamma-interferon or the combination in advanced metastatic renal cell carcinoma.

Eighty-nine patients with advanced measurable metastatic renal cell carcinoma were entered into a prospective randomized trial comparing alpha-interferon to gamma-interferon and to the combination. The trial was performed in order to confirm the activity of gamma-interferon and assess the potential clinical synergism. Response rates were 5, 10, and 5%, respectively. The low response rate may have been due to the inability to raise the doses of the interferons to higher levels. Clinical synergy at this dose, route, and schedule of administration in renal cell carcinoma does not exist.

Carcinoma, Renal Cell

In vivo effects of zinc deficiency on calmodulin concentrations in selected rat tissues.

Two groups of male Sprague-Dawley rats, one fed zinc-deficient diet, ad libitum, the other, pair-fed with the same diet, but given supplemental zinc in the drinking water (8 mg Zn++/ml) were studied. After ten weeks of diet, rats were exsanguinated and zinc and calmodulin concentrations in brain and testis were measured. Mean zinc concentration in testis was significantly decreased in rats fed zinc-deficient diet without supplemental Zn++, but mean zinc concentration in brain was not different. Similarly, mean calmodulin concentration in testis was decreased in rats fed zinc-deficient diet without supplemental Zn++ whereas mean calmodulin concentration in brain was not different. Distribution studies of zinc and calmodulin showed that both zinc and calmodulin were released more freely into soluble fractions of testis in rats fed zinc-deficient diet without supplemental Zn++. These results indicate, for the first time in in vivo studies, that zinc influences the calmodulin content of testis.

Animals

Detection of propionic acid vapor by rats with lesions of olfactory bulb areas associated with high 2-DG uptake.

This study tested the functional significance of recent 2-deoxyglucose (2-DG) results demonstrating a discrete focus of activity in the olfactory bulb of rats exposed to the vapor of propionic acid. Rats with lesions that destroyed this area of the olfactory bulb performed as well as did sham operated and lesioned controls in detection of amyl acetate, butanol, geraniol, propionic acid, and on a test for propionic acid threshold. Our results demonstrate that an area of the olfactory bulb containing a major focus of metabolic activity induced by exposure to an odor can be removed without producing a deficit in the detection of that odor.

Animals

Characterization of a human malignant mesothelioma cell line (H-MESO-1): a biphasic solid and ascitic tumor model.

Human malignant mesothelioma of the pleura was successfully transplanted s.c. into athymic nude mice and grew as a solid neoplastic mass. Tumor growth resulted in death of the animals between 98 and 161 days after implantation. Minced samples of the growing tumor were propagated as a malignant peritoneal effusion. Animals with malignant ascites died predictably at 32 to 33 days. Light and electron microscopy, and immunocytochemistry demonstrated a similarity of the transplanted solid and fluid malignancies with the human primary mesothelioma. Cytogenetic analysis demonstrated a predominance of cells with a triploid number of identifiable but abnormal human chromosomes. This model, which mimics the clinical behavior of malignant mesothelioma in the human, may be of value in animal trials of chemotherapy and immunotherapy.

Animals

Diet and lung cancer risk: findings from the Western New York Diet Study.

This study compares the diets of 450 lung cancer cases (296 males, 154 females) with those of 902 controls (587 males, 315 females). Cases were lung cancer patients diagnosed between August 1980 and July 1984 in three western New York counties, while controls were selected from the general population of these same counties. Usual diet was estimated by detailed interviews using a modified food frequency method. Case-control comparisons were made for dietary fat, protein, fiber, calories, cholesterol, and vitamins A, C, and E according to quartiles of intake, adjusting for age and pack-years of cigarettes by multiple logistic regression. Risk was lower for males in the lowest quartile of total dietary fat intake compared with those in the highest quartile (relative risk = 0.5), although the overall trend in the association with dietary fat was not statistically significant (p = 0.12). Likewise, there was a weak, but not statistically significant, direct association between dietary cholesterol and lung cancer in men (p = 0.17). The intake of vitamin A from fruits and vegetables (carotene) was much more strongly associated with reduced cancer risk. For males, the relative risks by quartiles (lowest intake to highest intake) were 1.8, 1.8, 1.0, 1.0 (p for trend = 0.001). For females, this relation was considerably weaker, and was not statistically significant. These findings are generally in agreement with those of several previous studies. The risk reduction associated with vitamin A from fruits and vegetables (carotene) was most evident for males, for those with squamous cell cancers, for light or ex-smokers, and for those over 60 years of age.

Adult

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