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Biomedical subjects

J Fishman

Publications and source records attributed to J Fishman.

At least 91 records · Page 5Linked to original sources
PubMed1984

Ewing sarcoma of the hand: literature review and a case report of nonsurgical management.

A case of a 12-year-old girl with Ewing sarcoma of the third metacarpal bone is described. Following an incisional biopsy, radiation therapy and adjuvant chemotherapy were given. The girl is now 34 months postdiagnosis and 25 months off therapy in sustained complete remission and functionally normal right hand. Of the seven previously published cases only two are long-term survivors (one had disarticulation, and the other resection of the fourth and fifth rays).

Adolescent↗
PubMed1984

The early treatment of peritalar dislocation.

Peritalar dislocation is an uncommon injury and was first described after flying accidents. Ten patients are reported who sustained this injury after minor trauma. They were treated by closed reduction and immobilisation of the ankle in a plaster cast for between 10 and 12 weeks, the first 2 weeks being non-weightbearing. No degenerative changes were detectable in the subtalar joints one year after injury. Early reduction and immobilisation may be significant in reducing the incidence of degenerative arthritis in the subtalar joint.

Adolescent↗
PubMed1984

Increased estrogen-16 alpha-hydroxylase activity in women with breast and endometrial cancer.

We have measured the three principal oxidative transformations of estradiol by means of a radiometric procedure in women with breast or endometrial cancer and in age matched controls. No difference between the 17 beta-ol oxidation or 2-hydroxylation of the hormone was observed between the study groups. In contrast, 16 alpha-hydroxylation was strikingly elevated in the women with breast and endometrial cancer relative to the age matched controls. Evidence is presented that this increased activity precedes the clinical evidence of the disease and that it represents a significant risk factor for these estrogen dependent tumors. This risk may be mediated by one of the products of 16 alpha-hydroxylation, 16 alpha-hydroxyestrone, which exhibits unique biological properties.

Aged↗
PubMed1984

Regiospecific transfer of tritium into 3H2O from labeled estrogens by mushroom tyrosinase.

The specificity of mushroom tyrosinase in displacing 3H from estradiol and catechol estrogens labeled at C-1, C-2, C-4 or C-6,7 was investigated under various conditions. [2-3H]E2 Yielded significant amounts of 3H2O, in the presence of NADH, and the rate of 3H loss from the steroid paralleled that of the radioactivity remaining in the aqueous fraction after extraction with organic solvents. NADH had little effect on the release of 3H from [1-3H]E2 or [4-3H]E2 but glutathione was highly active in this respect, with considerable differences being observed between lyophilizable 3H2O and yields of water-soluble products. It is proposed that 3H losses from C-2 of estradiol reflects oxidative displacement of this isotope by tyrosinase while the loss observed from C-1 and C-4 is the result of non-enzymatic conjugation with glutathione after the formation of the catechol estrogen. The difference between lyophilizable 3H2O and the yield of water-soluble products obtained with [1-3H]E2 and [4-3H]E2 provided a measure of the relative amount of conjugation occurring at C-1 and C-4. These findings were confirmed by double label experiments with 3H- and 14C-labeled estrogens and the isolation of the glutathionyl derivatives. The catechol estrogens did not serve as substrates for further hydroxylation by the enzyme even when C-2 was available for this reaction. These experiments give further information about the specificity of tyrosinase in its reaction with aromatic steroids and provide a simple and rapid method for confirming the distribution of 3H at C-2 or C-4 of estradiol.

Basidiomycota↗
PubMed1984

Charcoal-catalyzed transfer of tritium into 3H2O from regiospecifically-labeled 2-hydroxyestradiol in the presence of thiols.

Charcoal was found to catalyze the release of 3H2O from [1-3H]2-hydroxyestradiol-17 beta ([1-3H]2-OHE2) or [4-3H]2-hydroxyestradiol-17 beta ([4-3H]2-OHE2) and this effect was shown to occur in the presence of glutathione or other thiols and to depend on the concentration of free steroid. The radiometric assay for measuring the formation of 3H2O was not affected significantly by subsequent treatment of the incubation mixture with charcoal if the ratio of steroid to tissue (rat brain or liver microsomes) was low and only initial rates of 3H release were measured. 2-Hydroxyestradiol did not show the charcoal effect in the presence of tyrosinase, either when it was generated from its parent estrogen or added to the enzyme. The formation of 3H2O from [4-3H]2-OHE2 in the presence of glutathione was inhibited by ascorbic acid but the addition of dextran or albumin did not protect the catechol estrogen from the charcoal-catalyzed loss of tritium. The reaction with glutathione and charcoal occurred even at 4 degrees C but other adsorbants such as alumina, silica or hydroxylapatite were without effect.

Catalysis↗
PubMed1984

Suppression of the preovulatory luteinizing hormone surge in the rat by 2-hydroxyestrone: relationship to endogenous estradiol levels.

Injection of 100 micrograms 2-hydroxyestrone (2OHE1) at various times on the morning of proestrus into normal 4-day-cycling rats results in abolition of the preovulatory LH surge in a number of animals tested. The greatest response was observed when the administration of 2OHE1 coincided with endogenous estradiol (E2) levels that were close to but not at their maximal proestrous levels. The catechol estrogen failed to abolish the LH surge if given much earlier or after the E2 maximum had already been reached. The effectiveness of 2OHE1 inhibition of the LH surge was greatly increased by the administration of 1 microgram E2 1 h before the catechol estrogen. 2OHE1 did not interfere with LH secretion in response to LHRH administration, indicating that the inhibitory action of the catechol estrogen is exercised at the hypothalamic level. In contrast to its inhibition of the positive feedback, 2OHE1 administered either before or after the injection of E2 to ovariectomized rats had no effect on the negative feedback of the hormone on pituitary LH secretion. The narrow and specific "time window" on proestrus when an injection of 2OHE1 results in the abolition of the preovulatory LH surge and its relation to the endogenous E2 preovulatory secretion suggest that the catechol estrogen interferes with a brief neuronal triggering event obligatory for LHRH release. The evidence also indicates that this action does not involve conventional competition for the E2 receptor.

Animals↗
PubMed1984

Effects of 2-hydroxyestradiol-17 beta, 2-hydroxyestradiol-17 alpha, and 4-hydroxyestrone on the preovulatory luteinizing hormone surge in the rat: agonist and antagonist actions.

Four-day cycling rats equipped with intracardiac catheters were injected with 2-hydroxyestradiol-17 beta (2OHE2-17 beta) at 0800, 0900, 1000, and 1200 h on the morning of proestrus. The administration at 0800 and 0900 h resulted in abolition of the afternoon preovulatory LH surge in virtually all animals. Injections given at 1000 and 1200 h were ineffective in this respect. The isomeric catechol estrogen 4-hydroxyestrone effectively inhibited the LH surge when given at 0900 h, but not if injected at 1000 or 1200 h. In contrast, the nonestrogenic 2-hydroxyestradiol-17 alpha was effective in blocking the LH surge when given at 0900 or 1000 h. Rats treated with 2OHE2-17 beta at 1000 h responded normally to exogenous LHRH administration in the afternoon, indicating that the action of 2OHE2-17 beta is at the hypothalamic level. 2OHE2-17 beta and 4-hydroxyestrone, which are potent estrogens, may act in this instance first as estrogen agonists, advancing the "time window" when their catechol antagonist properties in blocking the LH surge can be functional. The nonuterotropic 2-hydroxyestradiol-17 alpha and 2-hydroxyestrone act solely as catechol estrogens and inhibit the preovulatory LH surge if administered at a time when they be present during this physiological window, which is thought to involve events at the estrogen-catecholaminergic interphase.

Analysis of Variance↗
PubMed1984

Catechol estrogen formation and metabolism in brain tissue: comparison of tritium release from different positions in ring A of the steroid.

Catechol estrogens labeled with 3H at different positions in rings A and B of the steroid were synthesized by chemical or enzymatic methods, and their oxidative transformation by male rat brain microsomes was followed by the transfer of 3H into 3H2O. This reaction was shown to occur more readily with the catechol estrogens than with the parent steroid and was also influenced by the position of the radiolabel. Tritium was displaced less readily from C-1 than from C-2 or C-4 of the aromatic ring. Spermine, which is known to increase cytochrome P-450-mediated hydroxylation reactions, had no effect on the release of 3H from ring A of either estradiol or 2-hydroxyestradiol with rat brain microsomes in contrast to liver. Glutathione and other thiols were able to cause a rapid loss of 3H from labeled catechol estrogens, even in the absence of tissue, but in double label experiments with [4-3H]- and [4-14C]2-hydroxyestradiol, the isotope ratio in the recovered catechol estrogen was unchanged. The results illustrate some of the problems in determining accurately the metabolism of estrogens by measuring 3H2O formation when aromatic hydroxylation is involved and also highlight the possible interaction of the catechol estrogens with cellular nucleophiles such as glutathione.

Animals↗
PubMed1984

The influence of dietary protein and carbohydrate on the principal oxidative biotransformations of estradiol in normal subjects.

Dietary protein, when substituted for carbohydrate or fat, can increase cytochrome P-450-dependent drug oxidation rates in humans. Endogenous estrogens, as well as drugs, are also metabolized by cytochrome P-450 and other enzymes in the hepatic endoplasmic reticulum. Therefore, it was of interest to determine whether variations in diet can alter the major metabolic pathways for estrogens, as assessed by radiometric methods. Eight normal men were fed a high protein diet (44% of calories as protein, and 35% as carbohydrate for 2 weeks), followed by a high carbohydrate diet (70% of calories as carbohydrate and 10% as protein) for an additional 2 weeks. The fat and total energy contents of the two diets were equal. The percent oxidation of [2-3H]estradiol, measured as 3H2O released, which is an in vivo measure of 2-hydroxylation of endogenous estrogen, was greater in all eight men during the high protein dietary period than during the high carbohydrate dietary period (44 +/- 3% and 33 +/- 3%, respectively, means +/- SE, P less than 0.005). In contrast, 16 alpha-hydroxylation of estrogen, as measured using [16 alpha-3H]estradiol, did not change significantly. Our findings demonstrate that dietary components can alter estradiol oxidation in humans and that the 2- and 16 alpha-hydroxylases for estrogen are under separate regulatory control. The influences of specific nutrients on estrogen metabolism may have potential significance for diseases in which these hormones may play a role in clinical expression.

Antipyrine↗
PubMed1984

Trial on control of hypertension by nutritional means: three-year results.

Ability to safely withdraw medication from well-controlled mild hypertensives was tested in a 3-group randomized trial. Group I (Intervention): drugs were stopped 2 months after nutrition counseling began. Counselling continued throughout the remaining years of the trial to achieve: a minimum of 10 lb weight loss if overweight; reduction of sodium intake to 1800 mg/day or less; reduction of alcohol intake to not more than 2 drinks per day. Group II (control group 1): drugs were stopped to see if previous long-term blood pressure control had a carryover effect without diet change. Pressure was monitored frequently in both groups with return to treatment if diastolic blood pressure rose to 90 mmHg or above. Group III (control group 2) remained on drugs for comparison of blood pressure and biochemical variables. In Group I mean weight loss at 3 years was 7 lb (3.18 kg) with 39% losing 10 lb (4.55 kg) or more; sodium intake was reduced by 37%. Blood pressure control without drugs was achieved in 44% of Group I patients. This compares with only 15% in Group II. These findings suggest it may be possible after establishing good blood pressure control, to maintain control in a sizeable proportion with less or no medication, when reduction of weight, sodium, and alcohol is achieved.

Antihypertensive Agents↗
PubMed1983

Novel method of evaluating biological 19-hydroxylation and aromatization of androgens.

[19C3H]Androstenedione of high specific activity has been prepared. In liver incubation the isotope was shown to be stable to biological processes other than 19-hydroxylation. Incubation of the new substrate with human placental microsomes yielded 3H2O, 3HCOOH and estrogens devoid of radioactivity. The formation of 3H2O and 3HCOOH was close to the expected 2:1 ratio indicating that the material can be used to discriminate between 19-hydroxylation which yields 3H2O and aromatization which results in 3HCOOH. Comparison of the formation of 3H2O from [1 beta, 2 beta 3H]androstenedione and of 3HCOOH from [19C3H3]androstenedione in placental microsomal incubation showed that the aromatization of the former was 3.2 times faster indicating an isotope effect of that magnitude for the aromatization of [19C3H] vs [19CH3]androstenediones. The new substrate will be an effective probe and discriminant of both 19-hydroxylation and aromatization of androgens in vivo and in vitro, reactions which have been reported to be dissociated in specific tissues.

Androgens↗
PubMed1983

Naloxone, a specific opioid antagonist, reverses chronic idiopathic constipation.

Two patients with long-standing idiopathic chronic constipation, which responded only to large daily doses of laxatives and additional suppositories and enemas, were treated with the specific opioid antagonist, naloxone, on a single-blind crossover basis. Both patients responded to naloxone treatment, with increased passage of faeces and increased wet and dry faecal weight. Although naloxone is poorly absorbed after oral administration, there was a positive response during oral as well as intravenous treatment, suggesting that the primary effect of naloxone is at specific opiate receptor sites in the myenteric plexus and other neural and endocrine cells of the intestinal wall.

Administration, Oral↗
PubMed1983

Nutrition-endocrine interactions: induction of reciprocal changes in the delta 4-5 alpha-reduction of testosterone and the cytochrome P-450-dependent oxidation of estradiol by dietary macronutrients in man.

The in vivo biotransformations of drugs known to be metabolized by enzymes localized in the endoplasmic reticulum of liver can be greatly altered by diet in humans, as we have shown previously. Steroid hormones also are metabolized extensively by hepatic microsomal enzymes; therefore, we examined the possibility that testosterone and estradiol biotransformations, as assessed with radiolabeled tracer methods, could be influenced by dietary macronutrients. Normal males were fed a high-protein diet for 2 weeks, followed by a high-carbohydrate diet for an additional 2 weeks. The delta 4-5 alpha-reduction of testosterone was considerably diminished, while the cytochrome P-450-dependent hydroxylation of estradiol at the C2 position was substantially enhanced during ingestion of the high-protein diet as compared with the high-carbohydrate diet. These results indicate that dietary macronutrients can significantly alter major metabolic pathways for testosterone and estradiol in man. The mechanism by which reciprocal changes in the delta 4-5 alpha-reduction of testosterone and the cytochrome P-450-mediated oxidation of estradiol are produced by diets is not known. Similar changes in steroid delta 4-5 alpha-reduction and cytochrome P-450-dependent chemical oxidations have been observed in circumstances in which the mixed-function oxidase system in liver is induced by agents such as phenobarbital, hexachlorobenzene, dioxin, and polyhalogenated biphenyls. Thus, the alterations in steroid hormone metabolism produced by dietary macronutrients in man mimic those that can be produced by drugs and environmental chemicals.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1983

Effects of obesity on estradiol metabolism: decreased formation of nonuterotropic metabolites.

Obesity is associated with an increased incidence of reproductive dysfunction and estrogen-linked diseases. In the present study, we have examined the principal oxidative biotransformations of estradiol in 13 obese premenopausal females and 10 obese males compared to those in 9 premenopausal female and 15 male controls. These studies were carried out using a recently devised, sensitive radiometric method which permits the assessment of the total in vivo oxidative metabolism of estradiol at specific sites (i.e. 17 alpha, 16 alpha, or C-2) on the steroid molecule. Our results indicate that obesity (greater than 60% above ideal body weight) is associated with significant decreases in hydroxylation at C-2 in both sexes (P less than 0.001 for females and P less than 0.02 for males) and in oxidation at 17 alpha in premenopausal females (P less than 0.05) compared to that in age-matched, normal weight controls. Analysis of the plasma 3H2O specific activity curves suggested a slight decrease in the rate of 17-oxidation in obese subjects. The extent of hydroxylation at 16 alpha was not significantly affected by obesity. These metabolic alterations documented in obesity could result in a relative hyperestrogenic state, since, unlike the other estrogen metabolites, the 2-hydroxyestrogen compounds display relatively little peripheral estrogenic activity. This metabolic alteration on a prolonged basis might be contributory to the prevalence of certain hormonally related diseases in obese individuals.

Adult↗
PubMed1983

Inhibition of phasic but not tonic pituitary secretion by 2-hydroxyoestrone in the rat: evidence of action as an oestrogen antagonist.

Rats with 4-day oestrous cycles, implanted with intracardiac catheters, were injected with 2-hydroxyoestrone at noon on pro-oestrus and their plasma LH levels monitored at frequent intervals thereafter. A dose of 100 micrograms 2-hydroxyoestrone completely abolished the preovulatory LH rise in four out of ten animals tested, showing no effect in the six others. When an injection of 10 micrograms oestradiol 1 h before the 2-hydroxyoestrone administration was given all the rats showed an absence of the preovulatory LH surge, while it remained intact in the controls treated with oestradiol only. The principal metabolite of 2-hydroxyoestrone, 2-methoxyoestrone, exhibited no influence on the pituitary gonadotrophin release. Repeated injections of 100 micrograms doses of 2-hydroxyoestrone to long-term ovariectomized rats produced no change in plasma LH and prolactin levels. In animals primed with oestradiol benzoate, 2-hydroxyoestrone given 1-2 h after the priming dose blocked the phasic release of the pituitary hormones on the afternoon of the 2 subsequent days. The LH and prolactin surges in the primed animals, however, were not affected when the catechol oestrogen was injected 2 h before their appearance. These results indicate that in the cyclic rat exogenous 2-hydroxyoestrone inhibits the preovulatory LH surge when its administration is coincident with the preovulatory oestradiol rise. In the ovariectomized rat 2-hydroxyoestrone inhibits the oestrogen-dependent priming step but does not affect either the oestrogen-independent expression of the induced surges or the tonic secretion of these pituitary hormones. These results indicate a dissociation of central and peripheral activities in this oestradiol metabolite and suggest that this catechol oestrogen functions as an oestrogen antagonist in neuroendocrine events. Since catechol oestrogens can be formed in the brain these pharmacological responses may reflect physiological mechanisms.

Animals↗
PubMed1983

Abnormal estrogen conjugation in women at risk for familial breast cancer at the periovulatory stage of the menstrual cycle.

The present study was designed to establish whether women with a family history of breast cancer exhibit endocrine abnormalities which could be responsible for their increased risk for the disease. Plasma hormone levels were measured every second day throughout the menstrual cycle in 30 women at risk for familial breast cancer and in an equal number of matched controls. Thirteen of the 14 substances measured exhibited no differences between the two populations, but plasma androsterone sulfate was significantly lower in the high-risk subjects. Thirteen urinary hormones were measured every day throughout the cycle with only the mean estrone and estradiol glucuronide but not estriol glucuronide content being significantly lower in the high-risk subjects. A compensatory increase in the urinary estrogen sulfates was observed. Daily analysis of these differences showed that they were most pronounced in thry day throughout the cycle with only the mean estrone and estradiol glucuronide but not estriol glucuronide content being significantly lower in the high-risk subjects. A compensatory increase in the urinary estrogen sulfates was observed. Daily analysis of these differences showed that they were most pronounced in thry day throughout the cycle with only the mean estrone and estradiol glucuronide but not estriol glucuronide content being significantly lower in the high-risk subjects. A compensatory increase in the urinary estrogen sulfates was observed. Daily analysis of these differences showed that they were most pronounced in the periovulatory period of the cycle. These results suggest that the genetic risk for breast cancer is associated with an abnormality in estrogen conjugation at a specific time of the ovulatory cycle.

Androgens↗