Biomedical subjects
Publications and source records attributed to J Levin.
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Rabbit endogenous pyrogens occurred in two forms. One was an apparently single protein with a pI of 7.3; the other was a family of proteins with pI values of 4.5 to 5.0. We selected two of the latter, with pI values of 4.6 and 4.72, as representative of the group and compared them with the pI 7.3 pyrogen. Antisera raised in three goats completely neutralized the pyrogenic activity of the pI 7.3 pyrogen. Larger doses of these antisera did not block the pyrogenic activity of either of the pI 4.5 to 5.0 pyrogens. The pI 7.3 pyrogen contained a free --SH group which was essential to its biological activity. It was inactivated by 100 mM N-ethylmaleimide or 200 mM iodoacetamide, bound to Thiol-Sepharose columns, and could be eluted from them with mercaptoethanol. Neither of the pI 4.5 to 5.0 pyrogens was inactivated by N-ethylmaleimide or iodoacetamide, and neither bound to Thiol-Sepharose. Both endogenous pyrogens gave negative results in the Limulus lysate test for bacterial endotoxins. These results suggest that the pI 7.3 and pI 4.5 to 5.0 endogenous pyrogens are not closely related to each other and are consistent with the idea that they may not be related at all. Alternative hypotheses are discussed.
Various haematological, ferrokinetic and iron absorption measurements were carried out on 15 patients with chronic renal failure who were undergoing regular haemodialysis. There was no evidence that the rate of iron absorption was impaired significantly by the depressed erythropoietic activity present in these patients. In contrast, there was a significant inverse correlation between the rate of iron absorption and the serum ferritin concentration, which has been shown to be an index of the size of the iron stores. This relationship, which was shown with both small (3 mg) and large (50 mg) doses of ferrous iron, was no different from that previously noted in subjects with normal renal function. These results suggest that iron deficiency in patients with chronic renal failure undergoing regular haemodialysis can be adequately prevented or treated with oral iron therapy, since the absorptive mechanism for iron appears to be normal.
The intercorrelation matrix between the scales of the California Psychological Inventory, given in the manual, was factor analyzed. Three factors were extracted and rotated by varimax. The matrix was rescaled, first normalizing the rows, then standardizing the columns to a mean sum of squares of one. Unity was used as a cut-off point for determination of salient loadings. The first two factors were similar to the results reported in a previous Study by Nichols and Schnell. The third factor was interpreted as an independence-dependence dimension.
Galactorrhea is a recognized sequel of chest injury, but serum PRL levels in these patients have not been systematically documented. Therefore, we examined the PRL responses over 5 days in patients undergoing either mastectomy (10 patients) or thoracotomy (10) and in seven patients undergoing elective laparotomy (controls). Basal serum PRL levels were normal in every subject. There were no consistent or significant alterations in PRL levels after laparotomy or thoracotomy. After mastectomy, PRL levels rose from a mean preoperative level of 7.1 +/- 1.3 to 16.0 +/- 3.3 ng/ml (P < 0.01) on the first postoperative day. Mean levels continued to rise to 35.6 +/- 6.6 ng/ml (P < 0.005) on day 5; levels were supranormal in eight subjects. Hyperprolactinemia persisted in the four subjects evaluated 4 weeks postoperatively and in one of five patients evaluated at 6 months. In a retrospective study, serum PRL levels were measured months to years after thoracotomy (31 patients) and mastectomy (53 patients) and compared to levels in 41 normal female controls. Mean serum PRL levels were 8.4 +/- 1.3 ng/ml in the control group, 13.1 +/- 0.9 ng/ml in the thoracotomy group (P < 0.005), and 20.6 +/- 3.1 ng/ml in the mastectomy group (P < 0.001). One thoracotomy patient and 18 mastectomy patients (34%) had supranormal PRL levels. It is concluded that mastectomy acutely stimulates PRL secretion in most subjects, and levels may remain elevated for months, perhaps for years, in a proportion of patients. Both the acute and chronic hyperprolactinemic states are probably the result of neurogenic PRL release mediated via the suckling reflex.
The plasma concentration of cortisol is elevated in many patients with anorexia nervosa. It has remained unclear whether this elevation of plasma cortisol level is due only to a slowing of the rate of cortisol metabolism or whether there is, as well, an increase in adrenal secretory activity in anorexia nervosa. We studied adrenocortical activity in 9 female patients and one male patient with anorexia nervosa before and during recovery. The 24-h mean level of plasma cortisol and the rate of urinary free cortisol excretion decreased during recovery, from 11.4 to 7.4 micrograms/dl and from 225 to 116 micrograms/day, respectively (P less than 0.005 and P less than 0.10, paired t test). These changes were associated with a significant decline in the rate of cortisol production from 24.3 to 17.9 mg/day as measured by radioisotope dilution (P less than 0.005). These results suggest that adrenal secretory activity is increased in anorexia nervosa and that the elevation of plasma cortisol level observed in this syndrome reflects not only a slowing of cortisol metabolism but also a rise in cortisol production.
The 24-hr mean plasma concentrations of dehydroisoandrosterone (DHA) and dehydroisoandrosterone sulfate were measured in 11 women with primary operable breast cancer, ages 31 to 78 years, and in 37 normal women, ages 21 to 75 years. In contrast to the marked and progressive decline of DHA and dehydroisoandrosterone sulfate concentration with age in the normal women, the concentrations of both steroids were age invariant in the cancer patients. The premenopausal patients had subnormal plasma DHA and dehydroisoandrosterone sulfate levels, while the post menopausal patients had supranormal levels. Since the plasma DHA/androsterone ratio was normal in the premenopausal patients and significantly elevated in the postmenopausal patients, it is postulated that the subnormal plasma adrenal androgen levels in the premenopausal patients were due principally to diminished production of these steroids, while the elevated plasma levels in the postmenopausal patients were due principally to slowed metabolic removal. Reports in the literature that DHA inhibits the development of breast cancer in mice suggest that the subnormal plasma DHA levels in premenopausal breast cancer may have clinical significance.
24-hour mean plasma levels of T3 and T4 were compared in 29 rigorously selected breast cancer patients (all stages) and 27 healthy women, and 8 A.M. "spot" plasma T4 levels were compared in 43 consecutive unselected breast cancer patients (all stages), 22 women with other-than-breast cancer, 21 women with miscellaneous non-cancerous illnesses, and the same 27 healthy women. The 24-hour T3 levels were the same in the breast cancer patients and healthy controls, but the 24-hour T4 levels were significantly higher in the cancer patients (7.7 vs 5.8 micrograms/dl, p less than 0.001); equal elevations were present in all stages of cancer. Spot T4 levels were likewise significantly higher in the breast cancer patients than in the healthy controls (8.8 vs 7.3 micrograms/dl, p less than 0.005). The women with other-than-breast cancer and the women with miscellaneous non-cancerous illnesses also showed significant elevations of spot T4 levels, indistinguishable from those of the breast cancer patients. It is concluded that breast cancer patients as a group show significant hyperthyroxinemia and that this finding may represent a second nonspecific abnormality of thyroid hormones in disease, hypotriiodothyroninemia (low-T3 syndrome) being the first.
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Microdensitometric measurement of the DNA content of individual megakaryocytes was performed using megakaryocyte colonies obtained following culture, in soft agar, of hematopoietic cells from C57BL/6J mice. Two types of colonies were detected. After 7 days of culture, the big cell type contained 16 /+- 2.3 acetylcholinesterase (AChE) positive cells/colony, with a mean ploidy level of 16.8 /+- 0.8/cell and the ploidy distribution characteristic of recognizable megakaryocytes in bone marrow. The heterogeneous type contained 44 /+- 9.6 cells/colony (some of which were AChE negative), with a mean ploidy level of 6.8 /+- 0.7/cell. The ploidy distribution of heterogeneous colonies differed markedly from big cell colonies, with preponderance of 2N and 4N cells. Colony-forming cells, obtained 4-5 days after induction of acute thrombocytopenia, gave big cell colonies with a marked increase in DNA content. Mean ploidy level increased to 21.5 /%- 1.8/cell; the frequency of 32N cells increased from 17% to 30% and 64N cells from 0% to 6%. This is the pattern of change observed in bone marrow, in vivo, 24 to 48 hr after induction of acute thrombocytopenia. The number of cells/colony did not increase. In contrast, acute thrombocytopenia did not alter the ploidy of heterogeneous colonies. The different responses to the stimulus of acute thrombocytopenia suggest that there are at least two types of Meg-CFC. The delayed appearance of altered Meg-CFC that produced big cell colonies indicates that the pool of stem cells, from which committed megakaryocyte precursors are derived, may respond indirectly to the stimulus of platelet depletion.
One hundred and fifty-one patients with hyperthyroidism were treated with varying doses of radio-iodine (131I), and the results were analysed 1 year later. Of the patients with Graves' disease who received the lowest 131I doses (mean 2,8 mCi) 39% had persistent thyrotoxicosis and 25% were hypothyroid 12 months after therapy. Moderate doses of 131I (mean 5,9 mCi) reduced the rate of persistent disease to 19% and increased the rate of hypothyroidism by only 4% (P less than 0,05). When 131I dosages were calculated according to thyroid weight (microCi/g), patients who received the lowest doses (mean 115 microCi/g) again had significant rates of both persistent hyperthyroidism (38%) and hypothyroidism (24%). These data indicate that very low doses of 131I in the treatment of Graves's disease may result in a high incidence of persistent disease, but do not necessarily result in a very low incidence of early hypothyroidism. Low-dose 131I regimens are unsuitable for treatment of thyrotoxicosis unless very good facilities for patient follow-up are available.
Cytoplasmic oestradiol receptors and peroxidase from 170 tumours from patients with breast cancer were assayed. The results were analysed in terms of racial groups and menopausal status. It was found that 68% of the receptor-positive tumours were peroxidase-positive, while 59% of the receptor-negative tumours were peroxidase-positive. When results were analysed in terms of racial groups 68% of tumours from White patients were peroxidase-positive and receptor-positive, while only 48% of receptor-negative tumours in this group were peroxidase-positive. This contrasts with the finding of 57% receptor-positive/peroxidase-positive tumours as opposed to 70% receptor-negative/peroxidase-positive tumours in Black patients.
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Absolute cortisol production was estimated from the urinary excretion of tetrahydro metabolites of cortisol in 74 healthy women varying in weight from 12% below to 218% above desirable weight, and in 37 healthy men varying in weight from 3% below to 139% above desirable weight, and was measured by isotope dilution (after 14C tracers) in 26 of the women and 23 of the men. The relationship of both parameters to urinary creatinine excretion (as a measure of lean body mass) and to percent deviation from desirable weight (relative weight) was determined. Both absolute cortisol production and urinary creatinine excretion showed a significant positive linear correlation with relative weight in the men and women, but cortisol production/g urinary creatinine excretion (by isotope dilution or by tetrahydro metabolite excretion) was weight-invariant in both sexes. The geometric mean of cortisol production/g creatinine was 12.9 mg/g in men and 14.5 mg/g in women; the difference was not statistically significant. The geometric mean of tetrahydro metabolite excretion/g creatinine was 3.7 mg/g in men and 3.8 mg/g in women; the difference was not statistically significant. The average ratio of cortisol production to tetrahydro metabolite excretion was 3.5 in men and 3.8 in women, values not significantly different from one another and closely confirming our previously reported value of 3.6, based on the conversion of cortisol tracers to radioactive urinary tetrahydro metabolites. It is concluded that there is no functionally significant elevation of cortisol production in obese men or women: the increase in absolute production is solely a consequence of greater lean body mass, and the production/U lean body mass is weight-invariant. It appears desirable to make any comparisons of one group of patients with another in terms of cortisol production/g urinary creatinine in order to eliminate body size and obesity as confounding factors, so that disease-related differences may emerge clearly.
Flutamide (4'-nitro-3'-trifluoromethylisobutyranilide) has a pronounced effect on the delta 4-3-ketosteroid 5-reductases of cortisol in man. The urinary metabolites isolated following 4-14C-cortisol administration to men with prostatic cancer treated with flutamide indicate decreased activity of the 5 beta-reductase with increased activity of 5 alpha-reductase. The alternate pathway of cortisol metabolism to the cortols and cortolones via Reichstein's substances epi E and Epi U is enhanced.
Thirty women with breast masses were evaluated psychologically and endocrinologically ten years ago while they were awaiting breast biopsy (3). Eight of these women proved to have benign fibrocystic disease and 22 had breast cancer. A significant (p < 0.05) positive correlation was found between extent of failure of psychological "defenses" and cortisol metabolite excretion rate in these 30 women. On follow-up, 12 women had died (11 with cancer and one who had had benign disease); 7 women were lost to follow-up. Of the remaining 11, one refused to participate, leaving 10 women for follow-up study (7 who had had mastectomy for breast cancer and 3 with benign breast lesions). They were reevaluated using the same assessment techniques as 10 years before. The psychological parameters and cortisol metabolite excretion rates did not show a significant change over the span of ten years. These data support the hypothesis that these psychological parameters and cortisol metabolite excretion rates reflect relatively abiding characteristics and are not as much affected by a "psychosocial threat" as previous research has suggested.
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