Hypogonadotropic hypogonadism associated with retinitis pigmentosa in a female sibship: evidence for gonadotropin deficiency.
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Biomedical subjects
Publications and source records attributed to B J Davidson.
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to examine the possible effects of aging on circulating steroid hormones in postmenopausal women, blood samples were drawn from 155 women, aged 34 to 83 years, with spontaneous ovarian failure. The C-21 steroids, pregnenolone and 17-hydroxypregnenolone; the delta 4 progestins, progesterone and 17-hydroxyprogesterone; and cortisol did not change with age and were similar in concentration to the levels measured during the follicular phase of premenopausal women. The delta 5 androgens, dehydropiandrosterone and dehydroepiandrosterone sulfate, declined significantly (P less than .001) with age, whereas no change was noted in the delta 4 androgens, androstenedione and testosterone. The levels of estradiol (E2) and estrone (E1) were strongly correlated with percent ideal weight but did not change with age. The authors conclude that 1) The production of progestins does not change with age in normal adult women, other than that resulting from the loss of secretion associated with ovarian corpus luteum function. 2) The decline of delta 5 androgens without corresponding changes in their precursors suggests an age-related change of adrenal 17,20 desmolase activity. 3) The levels of E2 and E1 reflect an effect of body size but not of age on peripheral aromatization of precursor androgens.
A woman with bilateral hyperplasia of ovarian hilar cells, stromal lipidic cells (hyperthecosis), and unilateral adenoma of Leydig cells is described. Her clinical course was characterized by long-standing virilism with a recent exacerbation suggesting growth of a tumor from the hyperplastic stromal lipidic cells. Evidence for this hypothesis included similar light and electron microscopic features of the hyperplastic and neoplastic cells and identical patterns of secretion of steroid hormones. Comparison of the in vivo steroid biosynthesis of the hyperplastic lipidic cells with that of testicular Leydig cells showed several similarities. These included 1) secretion of 5 and delta 4 steroids; 2) greater secretion of the delta 4 hormones, progesterone and 17-hydroxyprogesterone, than of the delta 5 steroids, pregnenolone and 17-hydroxypregnenolone; 3) prominent secretion of testosterone but not androstenedione; and 4) limited secretion of estrogens, with estradiol as the principal estrogen. These findings support prior microscopic evidence that ovarian lipidic cells and testicular Leydig cells represent cells of common function and, likely, common origin.
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Thirty-five consecutive patients with adenocarcinoma of the endometrium and an equal number of control subjects matched to the cancer patients for age and percentage of ideal weight were studied prospectively. In the cancer patients, the mean +/- SE serum androstenedione, testosterone, estrone (E1) and estradiol (E2) levels were 503 +/- 34 pg/ml, 224 +/- 22 pg/ml, 38.7 +/- 3.6 pg/ml, and 14.5 +/- 0.9 pg/ml, respectively. Similar concentrations were found in the control subjects. Body weight and percentage of ideal weight showed highly significant correlations (P less than 0.001) with E1 and E2 but not with the androgen concentrations in either group. The heavier patients had higher E1 and E2 levels. Age and years since menopause did not correlate with any of the hormonal levels. The cancer patients with overt diabetes tended to be more obese and have higher estrogen levels than did the nondiabetic subjects. Those with a history of prior estrogen usage were more slender and had lower endogenous estrogens than the nonusers. Twenty-three of the cancer patients (66%) had a presumed risk factor(s) for the development of this tumor, that is, excess body weight, high endogenous estrogen levels, or a history of prior estrogen usage. These data support the concept that conditions which lead to continued, unopposed estrogen stimulation may be associated with malignant transformation of the endometrium.
Although all postmenopausal women are relatively estrogen-deficient, osteoporosis develops in only some of them. This could be related to a greater-than-normal degree of postmenopausal failure in sex hormone production or to a decrease in biologic effect at target tissue sites. We compared the concentration of sex steroids in serum and the concentration of cytosolic estrogen receptors in one target tissue (obtained by biopsy of the uterine cervix) in 18 women with postmenopausal osteoporosis and in 18 age-matched postmenopausal control subjects. Serum androstenedione and estrone were not significantly lower and serum estradiol was only marginally lower in the osteoporotic patients. Estrogen-receptor concentration in cervical tissue from both postmenopausal groups was not significantly different. We concluded that abnormalities of residual postmenopausal production of sex steroids and binding of sex steroids to cervical target tissue are not the major factors accounting for the decreased bone mass in women with postmenopausal osteoporosis.
The effect in vivo of the plasma proteins in human serum on the transport of [3H]testosterone (T), [3H]-dihydrotestosterone (DHT), and [3H]estradiol (E2) through the brain capillary wall, i.e., the blood-brain barrier, was studied in anesthetized rats using a tissue-sampling-single-injection technique, In the absence of plasma proteins, approximately 90% of plasma T, DHT, or E2 was transported into brain on a single pass after a bolus carotid injection of labeled hormone. Serum was obtained from 57 patients in seven different clinical conditions: pregnancy, oral contraceptive use, thin and obese postmenopausal, follicular phase female, hirsutism, and normal male; the level (mean +/- SD) of sex hormone-binding globulin (SHBG) varied from 17 +/- 5 nM (hirsutism) to 323 +/- 83 nM (pregnancy). When the carotid injection solution was made 67% serum, the amount of T, DHT, or E2 transported into brain was inhibited in proportion to the concentration of SHBG. Among the patient groups, an overall linear inverse correlation between the mean SHBG level and the mean extraction of unidirectional influx of testosterone (r = 0.99) and estradiol (r = 0.98) was observed. These studies indicate that a) the undirectional clearance by brain of both testosterone and estradiol is inversely related to the SHBG level and b) the fraction of hormone transported into brain greatly exceeds the free (dialyzable) moiety and is essentially equal to the albumin-bound fraction of plasma testosterone or estradiol.
Detection of a visual signal requires information to reach a system capable of eliciting arbitrary responses required by the experimenter. Detection latencies are reduced when subjects receive a cue that indicates where in the visual field the signal will occur. This shift in efficiency appears to be due to an alignment (orienting) of the central attentional system with the pathways to be activated by the visual input. It would also be possible to describe these results as being due to a reduced criterion at the expected target position. However, this description ignores important constraints about the way in which expectancy improves performance. First, when subjects are cued on each trial, they show stronger expectancy effects than when a probable position is held constant for a block, indicating the active nature of the expectancy. Second, while information on spatial position improves performance, information on the form of the stimulus does not. Third, expectancy may lead to improvements in latency without a reduction in accuracy. Fourth, there appears to be little ability to lower the criterion at two positions that are not spatially contiguous. A framework involving the employment of a limited-capacity attentional mechanism seems to capture these constraints better than the more general language of criterion setting. Using this framework, we find that attention shifts are not closely related to the saccadic eye movement system. For luminance detection the retina appears to be equipotential with respect to attention shifts, since costs to unexpected stimuli are similar whether foveal or peripheral. These results appear to provide an important model system for the study of the relationship between attention and the structure of the visual system.
Four tachistoscopic forced-choice recognition experiments explored the flexibility of processes underlying word perception. Stimuli were words, orthographically regular but unfamiliar pseudowords, and orthographically irregular nonsense strings. In the first two experiments, subjects knew that several different kinds of stimuli would occur in each block of trials and that one kind would occur much more often than the others. No matter which stimulus subjects expected to see most often, accuracy on words and pseudowords differed little, and both were identified considerably better than nonsense. In the third and fourth experiments, subjects were led to believe that only on stimulus type would occur but were surreptitiously shown another type on a small number of trials. Words were again identified more accurately than nonsense, and the size of the effect was independent of expectations. However, when either words or nonsense strings were expected exclusively, pseudoword accuracy did not differ from nonsense accuracy. Only when subjects knew that pseudowords would occur did they identify pseudowords more accurately than nonsense. This dissociation between word and pseudoword identification indicates the operation of two independent encoding mechanisms during tachistoscopic recognition, a stimulus-specific or logogenlike system sensitive to particular familiar strings and an orthographic mechanism sensitive to generally applicable constraints on letter sequencing. The stimulus-specific mechanism appears to be utilized automatically, but use of the orthographic mechanism is under strategic control. As shown in the first two experiments, however, rather extraordinary measures were required to demonstrate the flexibility of the orthographic processes used in this task.
BACKGROUND: Amplification of the cyclin D1 (CCND1) gene, which encodes a cell cycle regulating protein, has been described in several solid tumors including head and neck squamous cell carcinoma (HNSCC). While correlations between CCND1 amplification and tumor behavior have been suggested, no investigation has focused on risk factor exposure as a potential cause of CCND1 alteration. METHODS: Southern blotting was used to identify CCND1 amplification in 57 previously untreated HNSCC tumor specimens Tissue from 27 cases was analyzed for CCND1 mRNA expression by Northern biot analysis. RESULTS: In 13/57 (23%) cases, a 2-5 fold amplification of CCND1 was found. CCND1 mRNA expression was higher in amplified than in non-amplified tumors and supported an association between CCND1 amplification and increased expression of CCND1 mRNA. No correlation was found between CCND1 amplification or CCND1 expression and clinical or pathological parameters. However, analysis of risk factor exposure revealed that patients with greater tobacco exposure were more likely to have tumors with CCND1 amplification (p = .037). Also, tobacco exposure was correlated with CCND1 expression in tumors. CONCLUSION: Tobacco exposure is a well-known risk factor for HNSCC. CCND1 amplification and alterations in expression may be causally related to tobacco carcinogen exposure and lead to a loss of cell cycle regulation.
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