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Biomedical subjects

L Hellman

Publications and source records attributed to L Hellman.

At least 73 records · Page 4Linked to original sources
PubMed1982

Structure and evolution of the heavy chain from rat immunoglobulin E.

The nucleotide sequence of the rat epsilon-chain mRNA has been determined by sequencing cloned cDNA copies of the mRNA. The established sequence covers the coding region, the 3'-non coding region and most of the 5' non-coding region. A comparison with the nucleotide sequence of the human epsilon-chain constant region reveals that C3 and C4 are the most highly conserved domains. The rat epsilon-chain contains a C-terminal decapeptide which is not present in the human counterpart.

Amino Acid Sequence↗
PubMed1982

Abnormal levels of plasma hormones in men with prostate cancer: evidence toward a "two-disease" theory.

The 24-hr mean plasma concentrations of 13 hormones or hormone metabolites (cortisol, testosterone, dihydrotestosterone, dehydroisoandrosterone, dehydroisoandrosterone sulfate, androsterone, androsterone sulfate, estrone, thyroxine, triiodothyronine, LH, FSH, and prolactin) were measured in 16 rigorously screened patients (aged 55-80) with stage C or D prostate cancer and 36 normal men. Nine of the hormones showed no abnormalities in the patients but four (testosterone, dihydrotestosterone, cortisol, and estrone) showed abnormalities. Testosterone and dihydrotestosterone, which, respectively, decreased with age and showed no change with age in the normal men, rose sharply with age in the patients. The patients' curves crossed the normal curves at about age 65; patients 65 or above showed normal values while patients under age 65 showed significantly subnormal levels of both hormones: testosterone averaged 282 ng/dl in patients vs 434 ng/dl in controls (P less than 0.0001) and dihydrotestosterone averaged 70 ng/dl in patients vs 99 ng/dl in controls (P less than 0.01). Cortisol, which was age invariant in the normal men, fell sharply with age in the patients; patients under 65 had significantly elevated levels (10.1 vs 6.9 micrograms/dl; P less than 0.0001), while patients 65 or older had normal levels. Estrone levels were age invariant in both patients and controls, but the mean level in patients was markedly elevated (81 vs 47 pg/ml in controls; P less than 0.001). The cortisol/testosterone ratio almost completely separated prostate cancer patients under 65 from normal men, but did not discriminate patients 65 or older from normal. The findings indicate that prostate cancer patients under 65 differ markedly in their endogenous hormonal pattern from patients 65 or older. This leads us to propose a "two-disease" theory of prostate cancer, with possible differences in genetic factors and prognosis.

Age Factors↗
PubMed1982

Characterization and molecular cloning of the mRNA for the heavy (epsilon) chain of rat immunoglobulin E.

We report a study of the mRNA for the heavy (epsilon) chain of rat IgE. Cytoplasmic RNA was prepared from the two rat immunocytomas IR2 and IR162 and fractionated by sucrose gradient centrifugation. An enriched fraction containing approximately 5% mRNA for the epsilon chain was obtained in this way. When translated in vitro, it produced a 59,000-dalton polypeptide, which in the presence of a membrane fraction yielded a 90,000-dalton polypeptide, presumably through posttranslational modification. Both polypeptides were precipitated by rabbit antisera that were monospecific for rat epsilon chains. The epsilon chain mRNA was estimated to be approximately 2200 nucleotides long and constitutes a minute fraction in the total mRNA both in the IR2 and the IR162 tumors, unlike the mRNA for light chains. Double-stranded cDNA copies prepared frm the RNA fraction, which was enriched for epsilon chain mRNA, were inserted into the Pst I cleavage site of the pBR322 vector. Twenty clones with inserts exceeding 1000 base pairs were used for selection of mRNA from the IR2 tumor. By in vitro translation of the selected mRNA, one clone was identified that yielded a polypeptide with the same size as the unprocessed epsilon chain. The nucleotide sequence was determined for part of the inserted cDNA in this candidate clone and was found to be homologous to a sequence in the constant region (C) of the human epsilon chain. In this communication we report a sequence from the C epsilon 3 domain of the rat IgE. When compared to the corresponding sequence of human IgE, 55% of the amino acids in the rat sequence were found to be conserved.

Amino Acid Sequence↗
PubMed1982

Plasma testosterone and sleep: relationship to sleep stage variables.

A study was performed to determine whether the pattern of secretion of testosterone (T) during the night bears a systematic relationship to the cyclically recurring periods of rapid eye movement (REM) and non-REM (NREM) sleep. In four healthy male volunteers, 10-20 min sampling of plasma for T was carried out through a long indwelling catheter in conjunction with all-night polysmonography. Analysis of plasma T, comparing the samples drawn during the REM and NREM stages, did not reveal a significant difference in the mean concentration of T between the two sleep stages or among specified time segments of the NREM-REM cycles. A more exacting approach to exploring for a correlation of the secretory pattern with the sleep-stage cycle was then undertaken. This method used the NREM-REM cycle as the independent variable in the analysis. We were able to demonstrate that the positions of the peaks and troughs of T concentration in each REM-NREM cycle are discriminable when examined in relation to the time of REM sleep onset in each cycle. The tendency for peaks in T concentration to be associated with repetitive inaugurations of REM sleep is coordinate with a pattern of serial "upswing" in T concentrations that occurs in the period from 30 to 10 min before the transition from NREM to REM sleep. Accordingly, it proved possible to demonstrate certain signs of interaction between the activity of the pituitary-gonadal system and the mechanisms that regulate central nervous system state in sleep. The more traditional parameter of comparison (mean concentration of hormone in REM and NREM sleep) did not detect the association.

Adult↗
PubMed1981

Selective elevation of plasma free cholesterol concentration by administration of estrogen in the presence of total biliary obstruction.

On the basis of clinical observations suggesting interactive effects of biliary obstruction and estrogen therapy on plasma cholesterol levels, a prospective study of the effect of ethinyl estradiol on plasma lipid levels was carried out in a patient with total biliary obstruction. A daily dose of 50 micrograms of ethinyl estradiol raised the plasma free cholesterol concentration from 265 mg/dl to 550 mg/dl over a period o 3 weeks; there was no change in plasma ester cholesterol concentration. Withdrawal of the estrogen was followed by a fall to baseline of the free cholesterol concentration over a 45-day period; once again there was no change in ester cholesterol. Plasma phospholipid concentration rose and fell in direct proportion to the changes in free cholesterol; plasma triglyceride concentration was unaffected by the estrogen. To account for the results of this study, it is suggested that the already elevated plasma levels of lipoprotein-X in biliary obstruction are further elevated by estrogen administration.

Aged↗
PubMed1979

Effect of flutamide on estradiol metabolism.

The effect of flutamide, a potent nonsteroidal antiandrogen, on the metabolism of iv tracers of [3H]estradiol was studied in five patients with advanced prostate cancer. The drug produced no change in the percentage of the injected radioactivity recovered in urine or in the glucuronide or nonglucuronide conjugate fractions. Of the five individual metabolites that were quantitated, estrone, estradiol, and estriol were unaffected by flutamide, but the drug caused striking decreases in conversion of estradiol to 2-hydroxyestrone (4.0% vs. 7.4%) (P less than 0.005) and 2-methoxyestrone (1.1% vs. 2.6%; P less than 0.05); every one of the patients showed a marked fall in recovery of both of these compounds. This depression of the formation of 2-oxygenated metabolites is reminiscent of the findings in liver disease; the same abnormality occurs regularly in cirrhosis and frequently in extrahepatic biliary obstruction. Taken together with our previous studies of the effects of flutamide on testosterone and cortisol metabolism, this study demonstrates that flutamide produces multiple functional, reversible, cirrhosis-like disturbances of steroid metabolism. Because these disturbances are universal in the patients studied regardless of whether they had clinical responses to flutamide, we doubt that the steroid metabolic changes play a role in the therapeutic effect of the drug.

Anilides↗
PubMed1979

Plasma cortisol profiles in Cushing's syndrome.

Plasma cortisol profiles were studied by the frequent sampling method in 5 patients with Cushing's disease (CD), 7 patients with Cushing's syndrome due to adrenocortical adenoma (AA), and one patient with bronchogenic carcinoma. Plasma ACTH was measured by radioimmunoassay at 10 min intervals in 2 of the subjects. In CD, there was distinct episodic secretion of cortisol and ACTH; the coefficients of variation about the mean plasma cortisol concentration ranged from 24 to 27%; plasma ACTH ranged from zero to 455 pg/ml with a mean of 94 pg/ml. In AA, the tumour secreted cortisol at a constant rate with little fluctuation; the coefficients of variation of plasma cortisol concentration ranged from 8 to 14%; plasma concentrations of ACTH were always near zero. In the patient with bronchogenic carcinoma, the coefficient of variation of cortisol was 14%. These results were apparent even in profiles of plasma cortisol concentrations measured over only a 6 h period. It is concluded that characteristics of plasma cortisol and ACTH secretory patterns are helpful in differentiating Cushing's syndrome of differing aetiology.

Adenoma↗
PubMed1978

Absorption of sodium from hypertonic sodium phosphate enema solutions.

Absorption of sodium from hypertonic sodium phosphate enema solutions has been studied in 11 patients by means of labeling the contained sodium with added 24Na and determining the radioactivity of body fluids after administration of the enemas. The sodium absorption thus estimated is a maximal figure and may represent an overestimate, since radioactivity can enter the body fluids by ion exchange without net transport of sodium. An average of 5.5 per cent of the instilled radioactivity was absorbed, corresponding to not more than 228 mg sodium. Absorption of such a quantity of sodium does not appear to represent a source of concern in the management of salt-restricted patients.

Adult↗
PubMed1978

Weight and circadian luteinizing hormone secretory pattern in anorexia nervosa.

In previous studies we had established that emaciated women with active primary anorexia nervosa (AN) had immature 24-hr luteinizing hormone (LH) secretory patterns. In this study, we have examined the circadian LH patterns of eight women with AN who had partially or fully recovered their ideal weights. Three of the women were studied before and after weight gain and five women were studied only after the appearance of binge-eating and consequent weight gain (by history). Our findings are: (1) The adult (mature) circadian LH secretory pattern was not present in women who had partially or totally achieved ideal weight but who otherwise remained symptomatic; (2) those women who showed both weight gain and normalization of LH pattern were also symptomatically improved in other respects; (3) the degree of immaturity of pattern did not correlate reliably with the duration of illness, the degree of fatness, or the extent of deficit from ideal weight; (4) the mode of illness onset and the type of secretory pattern were not related; and (5) the return of menses did not show a simple relationship to weight, fatness, or maturity of LH pattern.

Adolescent↗
PubMed1978

Effect of flutamide on cortisol metabolism.

The effect of flutamide on cortisol metabolism was studied in eight patients with prostate cancer. Flutamide markedly decreased the formation of 3 alpha, 17,21-trihydroxypregnane-11,20-dione (THF), and the 11-oxy-17-ketosteroid metabolites by 72%, 50%, and 46% respectively; however, 3 alpha, 11 beta, 17,21-tetrahydroxy-5 alpha- pregnan-20-one was increased by 46%. The 24-h mean plasma cortisol concentration was not altered. The cortisol production rate decreased by an average of 53% (from 32.7 to 15.5 mg/24 h). The effect of the drug on plasma cortisol kinetics was studied in three patients. This showed that flutamide increased the t1/2 (from 80 to 108 min) but decreased the distribution volume (from 17.8 to 13.8 liters) and the MCR (from 222 to 130 liters/24 h). The changes in THE and THF formation and in the t1/2 and MCR of [C]cortisol are similar to the effects observed in patients with intrahepatic cholestasis. It is suggested that in the case of flutamide these changes were also due to a cholestasis-producing effect of the drug on the liver. As the clinical response to the drug did not correlate with the cortisol metabolic changes, its therapeutic effect was probably not mediated by its effects on cortisol metabolism.

Aged↗
PubMed1978

Twenty-four-hour plasma prolactin patterns in prepubertal and adolescent boys.

The concentration of PRL was measured every 20 min for 24 h in six prepubertal and three adolescent boys. In both groups, PRL secretory episodes occurred throughout the 24-h period. In all subjects, the mean concentration of PRL was significantly higher during sleep than during wakefulness; the mean concentration during the entire 24-h period, during sleep or during wakefulness, was not different between the prepubertal subjects and the adolescents. These data suggest the absence of an ontogenetic change for PRL secretion in boys. During acute sleep-wake reversal, two of three pubertal boys showed significantly higher PRL during daytime sleep than during nocturnal wakefulness. This suggest that PRL release in adolescent boys is linked with sleep, rather than with clock time.

Adolescent↗
PubMed1977

Virilizing adrenal cortical carcinoma.

A 43-year-old man with a 36-year history of virilization due to an adrenal carcinoma is presented. The initial presentation at age 7 with precocious puberty and epiphyseal bone fusion suggested increased androgen effect at a very early age. The patient's 36-year course before his death suggested either a very slow growing adrenal carcinoma or untreated congenital adrenal hyperplasia that progressed to an adrenal carcinoma. Endocrine evaluation showed markedly increased DHEA and DHEA-sulfate levels. These were associated with elevated plasma and urinary estradiol levels and suppressed LH and FSH plasma concentrations. The 24-hour mean levels of cortisol and testosterone were normal. Studies of the circadian periodicity of cortisol showed a disturbed temporal pattern but a normal 24-hour mean concentration that correlated with a normal cortisol production rate. The 24-hour LH secretory pattern showed a decrease in the normal episodic fluctuation of this hormone over the 24-hour period.

Adrenal Cortex Neoplasms↗
PubMed1977

Studies of the diurnal pattern of plasma corticosteroids and gonadotropins in two cases of feminizing adrenal carcinoma: measurements of estrogen and corticosteroid production.

Two adult men with feminizing adrenal cortical carcinoma had measurements of their 24-h plasma corticosteroid and gonadotropin patterns as well as 24-h mean hormone levels of estradiol, estetrol, 11-desoxycortisol, DHEA-S, DHEA and testosterone. Cortisol, 11-desoxycortisol and estrogen production rates were also measured. The 24-h corticosteroid patterns showed preservation of the normal 24-h episodic and circadian patterns, albeit at higher levels. The cortisol production rates were markedly elevated despite only moderate elevation of the 24-h mean cortisol level. There were elevated plasma 11-desoxycortisol levels and a markedly elevated 11-desoxycortisol production rate in one patient and THS excretion in the other. The plasma estradiol levels, urinary excretion and production rates were markedly elevated. In addition, there was a decrease in the specific activity of estriol compared with estrone and estradiol as well as measurable levels of estetrol in both patients. These latter observations coupled with the urinary immunoassayable hCG in one patient suggest that these tumors may be functioning like trophoblastic tissue. The possibility that estetrol may serve as an additional marker for tumors of trophoblastic origin is of additional interest.

Adrenal Cortex Hormones↗
PubMed1977

The effect of 7beta, 17alpha-dimethyltestosterone (calusteron) on testosterone metabolism in women with advanced breast cancer.

Calusterone (7beta, 17alpha-dimethyltestosterone) is a 17-alkylated, orally active androgenic steroid used in the treatment of breast cancer. The effect of this steroid on the metabolism of 14C-testosterone and the excretion of endogenous urinary androgen metabolites has been studied in four patients with breast cancer. Total glucuronide metabolites of the tracer decreased significantly, the andorsterone/etiocholanolone ratio rose by a factor of 2-4, and there was increased formation of uncharacterized polar metabolites. There was no significant change in either the sum of the excretion of endogenous androgen metabolites or the androsterone/etiocholanolone ratio. The changes resemble those we have seen in cirrhosis of the liver. It is concluded that the effects of Calusterone on testosterone metabolism, like its effects on cortisol or estradiol metabolism, represent nonspecific effects of an orally administered 17-alkylated steroid on hepatic structure and function, and probably bear no relationship to its therapeutic effect in breast cancer.

Androsterone↗
PubMed1977

The metabolism and 24-hour plasma concentrations of androsterone in man.

A radioimmunoassya for free androsterone permitting facile analysis of plasma taken at 20 min intervals over 24 h has revealed a curve of varying concentrations which formed a pattern similar to curves of cortisol and dehydroisoandrosterone, boht bein primary adrenal secretory products and the latter being the major precursor of androsterone. The mean of the average 24 h concentrationof androsterone in men was 55 +/- 14 ng/dl (n = 8). Such temporally related behavior requires rapid production and removal of both 17-ketosteroids, processes which have been confirmed by tracer studies where it has been shown that in a two compartment system, androsterone has a t1/2 of 25 +/- 9 min for the fast component and metabolic clearance rate of 4050 +/- 1315 L per day (n = 10). The data are in accord with an approximate production rate of androsterone which is consistent with values reported for its urinary excretion.

Androsterone↗