Findings described in this report are for 6,763 white male Seventh-day Adventists who completed a dietary questionnaire in 1960. Between 1960 and 1980 mortality data were collected on cohort members. Overweight men had a significantly higher risk of fatal prostate cancer than men near their desirable weight. The predicted relative risk of fatal prostate cancer was 2.5 for overweight men. Suggestive positive associations were also seen between fatal prostate cancer and the consumption of milk, cheese, eggs, and meat. There was an orderly dose-response between each of the four animal products and risk. The predicted relative risk of fatal prostate cancer was 3.6 for those who heavily consumed all four animal products. The results of this study and others suggest that animal product consumption and obesity may be risk factors for fatal prostate cancer.
The authors studied 2,950 population-based colon cancer cases in males in Los Angeles County, California, that were diagnosed between 1972 and 1981. To determine if colon cancer risk is reduced by physical activity on the job in males aged 20-64 years, the authors first rated each occupation by judging the activity level as high, moderate, or sedentary. Men with sedentary jobs had a colon cancer risk at least 1.6 times that of men whose jobs required a high level of activity. Risk increased in a stepwise manner as activity level decreased. This gradient was consistently seen within each socioeconomic stratum, among whites, blacks, immigrant and native Hispanics, and for each subsection of the colon from the hepatic flexure to the sigmoid. The protective effect of physical activity was very strong in the descending colon and diminished in a gradient both proximally and distally. There was no such relationship between physical activity and risk for rectal cancer. Physical activity may play a major, previously unrecognized role in colon cancer etiology. Such a role is consistent with the known pattern of colon cancer occurrence and with our understanding of colon physiology and colon cancer pathogenesis. In addition to the implications for prevention, understanding the effects of physical activity on colon cancer risk may allow future studies to evaluate more accurately the role played by diet.
The patterns of risk by histologic type of lung cancer were analyzed with the use of data from a large hospital-based case-control study (7,804 cases and 15,207 controls) of lung cancer performed in Western Europe. Relative risks (RR) increased with duration of cigarette use for all histologic types, although the gradients of risk were greater for Kreyberg I cell types, particularly squamous cell carcinoma (SCC), than for adenocarcinoma (AC). Risks also declined more sharply with years since cessation of smoking for all Kreyberg I cell types, in particular for SCC, rather than for AC. After adjustment for duration of use, the RR associated with number of cigarettes smoked per day, frequency and depth of inhalation, and fraction of cigarette consumed were not consistently different by cell type, suggesting that intensity-related measures of cigarette exposure have less effect on cell type than duration-related factors. Among those who never smoked there were marked cell type differences by sex, with a greater proportion of AC compared to SCC for females (45 vs. 25%) than for males (35 vs. 33%). Review of limited work histories indicated that occupational associations also were more strongly related to Kreyberg I than to Kreyberg II tumors.
The authors present a critical review of the literature on the hemorrhagic complications of pituitary adenomas, especially those leading to apoplexy. They emphasize the distinction between pituitary apoplexy, hemorrhages leading to sudden endocrine alterations, and asymptomatic hemorrhages. Moreover, they speculate upon the possible pathophysiology of pituitary apoplexy and its predisposing factors. The clinical presentation, natural history, radiological findings, and differential diagnosis are also discussed. Finally, the historical evolution of the treatment of pituitary apoplexy is reviewed, with emphasis on the surgical treatment.
A population-based case-control study of renal cell carcinoma (495 cases and 697 controls) in the Minneapolis-St. Paul seven-county metropolitan area implicated cigarette smoking as a risk factor with an odds ratio (OR) among men of 1.6 (95% confidence intervals: 1.1-2.4) and among women of 1.9 (1.3-3.0). A statistically significant dose response was observed in both sexes for pack-years of cigarette use. On the basis of calculations of attributable risk, it was estimated that 30% of renal cell cancers among men and 24% among women were due to smoking. High relative adult weight as measured by the body mass index (BMI) was found to be a major risk factor among women but not among men, with those in the highest 5% of the BMI having an OR of 5.9 (1.8-20.4) in comparison to the lowest quartile. This association with excess weight was not seen at age 20, but it became more pronounced with increasing age, suggesting that the primary influence of weight gain is during the late stages of renal carcinogenesis. Excess risks were also related to ethnic background (particularly, German), which may account in part for the elevated incidence of renal cancer in the North Central area of the United States. In addition, positive associations were observed for long-term use of phenacetin-containing analgesics, heavy meat consumption, and heavy tea drinking (females only). An occupational clue was provided by an increased risk for exposure to petroleum, tar, and pitch products. Excesses of certain urologic and cardiovascular diseases were also observed among the cases compared to controls.
Secretory protein-I (SP-I) of parathyroid glands and chromogranin A ( CGA ) of adrenal medullary chromaffin cells are chemically similar if not identical proteins. Both proteins are contained within secretory granules and appear to be cosecreted with granule contents, for example, in the parathyroid with PTH and in the adrenal with epinephrine and dopamine beta-hydroxylase. Antisera to bovine SP-I and porcine CGA , together with antisera to a variety of peptide hormones, were used in an immunofluorescence study of rat tissues in order to determine the probable distribution and cellular localization of these proteins. In addition to their previously demonstrated presence in parathyroid and adrenal cells, the SP-I/ CGA protein family was detected in cells of the thyroid that contained calcitonin and often SRIF but not thyroglobulin; in cells of the anterior pituitary staining for the alpha-subunit of TSH/FSH/LH but not in cells staining for GH, PRL, ACTH, or beta-endorphin; in pancreatic islet cells staining for SRIF and pancreatic polypeptide-related peptides, but not for insulin or glucagon; in the celiac and mesenteric ganglia in cells some of which contained SRIF; and in the gastric antrum in cells containing SRIF, but not gastrin. SP-I/ CGA was not detected in cells of the liver, kidney, parotid gland, or acinar pancreas or in the intermediate or posterior lobes of the pituitary. These results suggest that this protein family enjoys a widespread but highly restricted distribution in many different endocrine-peptide cells of the rat, many that are believed to be of the APUD cell series. The possibility is raised that SP-I/ CGA plays some physiological role in the secretory process or exerts an effect of its own in the periphery after secretion.
We studied the distribution and regulation of aromatase activity in the adult rat brain with a sensitive in vitro assay that measures the amount of 3H2O formed during the conversion of [1 beta-3H]androstenedione to estrone. The rate of aromatase activity in the hypothalamus-preoptic area (HPOA) was linear with time up to 1 h, and with tissue concentrations up to 5 mgeq/200 microliters incubation mixture. The enzyme demonstrated a pH optimum of 7.4 and an apparent Michaelis-Menten constant (Km) of 0.04 microns. We found the greatest amount of aromatase activity in amygdala and HPOA from intact male rats. The hippocampus, midbrain tegmentum, cerebral cortex, cerebellum, and anterior pituitary all contained negligible enzymatic activity. Castration produced a significant decrease in aromatase activity in the HPOA (P less than 0.001), but not in the amygdala or cerebral cortex (P greater than 0.05). The HPOAs of male rats contained significantly greater aromatase activity than the HPOAs of female rats. In females, this enzyme activity did not change during the estrous cycle or after ovariectomy. Administration of testosterone to gonadectomized male and female rats significantly enhanced HPOA aromatase activities (P less than 0.05) to levels approximating those found in HPOA from intact males. Therefore, our results suggest that testosterone, or one of its metabolites, is a major steroidal regulator of HPOA aromatase activity in rats.
Evidence associating malignant melanoma with semiquantitative and questionnaire indicators of past sunlight exposure is presented from a case-control study of 511 patients and 511 matched control subjects in Western Australia. That melanoma is related to sun exposure was supported by associations with actinic skin damage graded by cutaneous microtopography, history of nonmelanotic skin cancer, duration of residence of migrants to Australia, and mean annual hours of bright sunshine received at locations where the subjects had resided. Separate analyses of histogenetic subtypes revealed that Hutchinson's melanotic freckle melanoma had the strongest associations with indicators of sunlight exposure. For superficial spreading melanoma, a specific relationship was observed with age at arrival as against duration of residence in Australia. Migrants arriving before age 10 years appeared to have a risk similar to that of native-born Australians, whereas the estimated incidence in those arriving after age 15 years was around one-quarter of the native-born rate, with arrival at later ages giving no additional advantage. Control subjects arriving in Australia before age 10 years had an increased number of nevi on their arms, suggesting that sun exposure in early life may be a factor in nevus production and, therefore, a determinant of later potential to develop superficial spreading melanoma.
We studied the regulation of aromatase activity in the hypothalamus-preoptic area ( HPOA ) of adult male rats using a sensitive in vitro assay which measures the amount of 3H2O formed by tissue homogenates during the conversion of [1 beta-3H]androstenedione to estrone. After castration, HPOA aromatase activity was decreased by 60% (P less than 0.05), seminal vesicle (SV) and ventral prostate (VP) weights were significantly decreased (P less than 0.05), and serum LH levels were elevated. We found that testosterone (T) or 5 alpha-dihydrotestosterone (DHT) administered in Silastic capsules for 7 days reversed the effects of castration. Testosterone and DHT stimulated HPOA aromatase activity 133% and 92%, respectively (P less than 0.05). Both steroids significantly increased SV and VP wet weights and suppressed serum levels of LH (P less than 0.05). Administration of either estradiol or progesterone did not reverse the effect of castration on HPOA aromatase activity or any other parameter measured. To determine the involvement of androgen receptors in the mechanism by which androgens affect brain aromatase, we administered the nonsteroidal antiandrogen flutamide to intact male rats (15 mg/day for 7 days). There was 42% less HPOA aromatase activity in treated rats than in oil-injected controls (P less than 0.05). Flutamide significantly decreased SV and VP wet weights, while serum LH levels were enhanced (P less than 0.05). Likewise, administration of flutamide to T-implanted castrated males blocked the T-induced increase in HPOA aromatase activity and accessory sexual organ wet weights, and prevented the T-induced suppression of serum LH. Flutamide given alone to castrated rats had no effect. Since both T and DHT stimulated HPOA aromatase activity and since the effects of T are blocked by the concomitant administration of the antiandrogen flutamide, we concluded that the control of HPOA aromatase activity by androgens is receptor mediated.