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Biomedical subjects

R J Moore

Publications and source records attributed to R J Moore.

At least 127 records · Page 7Linked to original sources

Protection of Fasciola hepatica against flukicidal action of the amine of diamphenethide in vitro.

A variety of compounds structurally related to serotonin and dopamine were tested for their ability to protect adult liver flukes against the flukicidal effect in vitro of an active metabolite of diamphenethide (diamphenethide-amine). The most effective was dopamine. The protective effect of dopamine was also assessed by analysis of the metabolite and adenine nucleotide levels and excretory products of flukes exposed to diamphenethide-amine in vitro. Most notably, dopamine appeared to depress considerably the large elevation of internal malate which is a characteristic effect of diamphenethide-amine on liver flukes.

Acetanilides↗

Ventricular tachyarrhythmias in regional myocardial hyperkalemia: efficacy of three antiarrhythmic agents.

Potassium chloride infusion into the left anterior descending coronary artery induces a sequence of events analogous to those occurring during acute transmural ischemia. These include ST elevation, intramural conduction delay, ventricular techyarrhythmias and fibrillation. The influence of antiarrhythmic agents in an intact anesthetized canine model have not previously been tested. We have evaluated the efficacy of lidocaine, procaine amide and practolol in animals during regional hyperkalemia. In the untreated, only 9% survided a 20 minute observation period. All three treatment groups exhibited a reduced incidence of tachycardia and 74% survived the test period. In each treatment group this was associated with a further prolongation of intramural conduction time in the affected wall. This antiarrhythmic efficacy, thought possibly to be due to transformation of unidirectional to bidirectional block, supports the view that modulation of transcellular potassium activity contributes to the control of ischemic arrhythmias.

Animals↗

Recurrent urinary calculi associated with toluene sniffing.

A young man who presented initially with a ureteral stone was found to have toluene-induced renal tubular acidosis. Persistent toluene sniffing resulted in recurrent calculi and life-threatening hypokalemic paralysis. The pathophysiology, classification and treatment of renal tubular acidosis are discussed.

Acidosis, Renal Tubular↗

Use of enhanced computerized tomography to evaluate osmotic blood-brain barrier disruption.

Enhanced computerized tomography (CT) is a noninvasive means of monitoring blood-brain barrier (BBB) disruption. In the present study this technique was used to monitor the degree, distribution, extent, and reversibility of osmotic BBB disruption. With a canine model, the timing of administration of iodinated contrast agent was shown to be crucial to optimize enhancement by CT of the disrupted BBB. Meglumine iothalamate given intravenously resulted in excellent enhancement on CT scan. Intracarotid infusion of this contrast agent was less satisfactory. Under similar conditions, enhancement due to metrizamide was less marked and more transient than that observed with meglumine iothalamate. Systemically administered methotrexate after osmotic BBB disruption resulted in increased brain levels in areas that closely correlated with CT scan enhancement. These results suggest that the CT scan provides an excellent noninvasive monitor of both BBB disruption and the delivery of chemotherapeutic agents to the brain. (Neurosurgery 6: 49--56, 1980)

Animals↗

Regulation of cytoplasmic dihydrotestosterone binding in dog prostate by 17 beta-estradiol.

17 beta-estradiol enchances androgen-induced prostate growth in the castrate dog to a degree comparable to that seen in spontaneous prostatic hypertrophy. To investigate the mechanism of this synergism, cytosol androgen binding was measured by a density gradient technique in prostates of control and 17 beta-estradiol-treated castrate dogs. [3H]Dihydrotestosterone was bound principally to a moiety that averaged 8.6S in size. Approximately twofold enhancement of this binding by 17 beta-estradiol was demonstrable after 1 wk of treatment with 750 microgram/wk and after 3 wk with 75 microgram/wk. Under conditions in which binding in the 8S region was demonstrable with dihydrotestosterone and testosterone no binding of 3 alpha-androstanediol or progesterone was detectable. Thus, enhancement by 17 beta-estradiol of a prostate cytosol androgen-binding protein occurs under circumstances in which 17 beta-estradiol enhances androgen-mediated prostatic growth.

Animals↗

Concentration of dihydrotestosterone and 3 alpha-androstanediol in naturally occurring and androgen-induced prostatic hyperplasia in the dog.

Previous studies have suggested that dihydrotestosterone accumulation in the prostate may be involved in the pathogenesis of prostatic hyperplasia in man and dog. However, the fact that the administration of 10 mg dihydrotestosterone/d to castrated, mongrel dogs (0.5 mg/kg body wt) causes little growth in the prostate, whereas identical doses of 3alpha- androstanediol regularly induce prostatic hyperplasia (> 14 g weight) has raised the possibility that the dihydrotestosterone accumulation may be the result rather than the cause of the pathology. To investigate the mechanism of this phenomenon, we measured the levels of dihydrotestosterone and 3alpha-androstanediol in prostates from 75 dogs. In both naturally occurring and 3alpha-androstanediol-induced prostatic hyperplasia, the levels of dihydrotestosterone were high (>5 ng/g), whereas in immature glands and glands from dihydrotestosterone-treated animals, levels were similar (2.1 and 2.6 ng/g, respectively). 3alpha-Androstanediol levels were no different in animals treated with dihydrotestosterone or 3alpha-androstanediol.Therefore, because exogenous 3alpha-androstanediol is a better precursor of prostatic dihydrotestosterone than exogenous dihydrotestosterone itself, the effects of treatment with larger doses (2.5 mg/kg per d) of dihydrotestosterone and 3alpha-androstanediol for 12 wk were examined. In these amounts, dihydrotestosterone was as effective as 3alpha-androstanediol in inducing the development of prostatic hyperplasia and in elevating prostatic dihydrotestosterone concentration. Because dihydrotestosterone accumulates in spontaneous prostatic hyperplasia, because the administration of sufficient amounts of dihydrotestosterone to the castrated dog can induce the development of prostatic hyperplasia, and because 3alpha-androstanediol induces the development of hyperplasia via conversion to dihydrotestosterone, we conclude that accumulation of dihydrotestosterone is the cause of canine prostatic hyperplasia.

Androstenediols↗

Studies on the mechanism of 3 alpha-androstanediol-induced growth of the dog prostate.

The conditions under which dihydrotestosterone and 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-androstanediol) induce prostatic growth in the castrate dog have been investigated in animals in which the initial size of the prostate was either normal or large. When androgen replacement was commenced immediately after castration of dogs with preexisting prostatic hypertrophy, dihydrotestosterone was as effective as 3 alpha-androstanediol in maintaining prostate weight. Under all other conditions examined (replacement commenced immediately after castration in dogs with small prostates or 2 weeks after castration in dogs with large prostates), 3 alpha-androstanediol but not dihydrotestosterone induced significant prostatic growth. The maximal effect of 3 alpha-androstanediol in inducing prostatic growth was observed in 12 weeks. The administration of 17 beta-estradiol enhanced the growth-promoting action of 3 alpha-androstanediol, but did not affect the action of dihydrotestosterone or influence 3 alpha-hydroxysteroid dehydrogenase activity in prostate. Thus, the synergistic effect of 17 beta-estradiol and 3 alpha-androstanediol seems to be independent of any effect on the interconversion of the two androgens. The activity of the 3 alpha-hydroxysteroid dehydrogenase in dog prostate was high under all conditions of accelerated prostatic growth and appeared to be under androgenic control.

3-Hydroxysteroid Dehydrogenases↗

Clinical, endocrinological, and enzymatic characterization of two patients with 5 alpha-reductase deficiency: evidence that a single enzyme is responsible for the 5 alpha-reduction of cortisol and testosterone.

Two siblings with 46,XY male pseudohermapthroditism were demonstrated to have the phenotype characteristic of 5 alpha-reductase deficiency, namely normal testes and male Wolffian duct derivatives (epididymis, vas deferens, and seminal vesicle) terminating in a blind-ending vagina. Clitoromegaly was present at birth and increased further at the time of expected puberty. The diagnosis of 5 alpha-reductase deficiency was confirmed by demonstration of male levels of testosterone and testosterone precursors before and after hCG administration, elevated plasma testosterone to dihydrotestosterone and urinary etiocholanolone to androsterone ratios, and by in vitro studies indicating 5 alpha-reductase enzyme deficiency in the epididymis of one patient. Studies of control and mutant epididymal microsomes indicated that a single enzyme is responsible in the normal person for the 5 alpha-reduction of testosterone and cortisol (and probably other delta 4-3-ketosteroids as well) and that 5 alpha-reductase activity is undetectable for all substrates examined in the mutant. This finding explains why the formation of 5 alpha-reduced glucocorticoids is also defective in the disorder.

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

Studies of gonadotropin-gonadal dynamics in patients with androgen insensitivity.

Four patients with androgen insensitivity had plasma LH and FSH measured at 20-min intervals for 24 h and at 15- to 30-min intervals for 3 h after the injection of LRH. Twenty-four-hour mean testosterone (T), estradiol, and androstenedione (delta 4) levels were also measured. Patients with androgen insensitivity had significantly elevated LH levels (P less than 0.05) and an increase in the number of LH secretory episodes (P less than 0.001) compared to normal subjects. The amplitude of the LH secretory episodes, expressed as the absolute increment, was significantly higher than normal controls (P less than 0.005). The LH response to LRH (absolute increment) was twice that of normal, but was not significantly different from normal subjects. The 24-h mean FSH levels were normal in three of the patients and elevated in one. This patient had the mildest degree of androgen insensitivity on clinical exam and the greatest degree of testicular atrophy. The 24-h mean T, estradiol, and delta 4 levels were higher than normal, but only the delta 4 was significantly increased (P less than 0.05). To determine if the elevated LH levels were in response to a decrease in the free T level, we measured T-binding capacity (TBG), TBG was higher than normal controls but was not significantly different, suggesting that elevated LH levels were probably in response to a decrease in T action at the hypothalamic-pituitary level. This was further supported by the inability of prolonged dihydrotestosterone administration to affect LH secretion in one of the patients with the Reifenstein syndrome.

Adolescent↗

Sex-role self-concepts of homosexual men and their attitudes toward both women and male homosexuality.

A nonclinical sample of 88 homosexual males responded to a questionnaire that assessed their sex-role self-concept and their attitudes toward both women and male homosexuality. Results indicated that in terms of socially valued masculine and feminine characteristics, the majority of homosexual males viewed themselves as predominantly androgynous. These respondents also favored equality between the sexes, reflecting positive attitudes toward women. Similarly, those homosexual men who supported equality between the sexes also held more positive attitudes toward male homosexuality.

Adult↗

Steroid 5alpha-reductase in cultured human fibroblasts. Biochemical and genetic evidence for two distinct enzyme activities.

Various properties of the steroid 5alpha-reductase have been examined in cell-free extracts of skin and of fibroblasts cultured from genital and nongenital skin from control subjects and from patients with several forms of male pseudohermaphroditism. When 20alpha-hydroxy-4-[1,2-3H] pregnen-3-one was used as substrate, two 5alpha-reductase activities could be demonstrated in intact skin and cultured fibroblasts. The major activity, previously described for microsomes from human prepuce and extracts of cultured foreskin fibroblasts, is characterized by a narrow pH optimum near 5.5 and is limited to fibroblasts derived from genital skin. A second activity, not limited by the site of biopsy, has been demonstrated over a higher and broader range of pH (from 7 to 9); this enzyme activity is found in both genital and nongenital skin and in fibroblasts cultured from all skin regions. Whereas there is wide variability in the activity at pH 5.5 in genital skin fibroblasts, the activity at pH 7 to 9 is similar in fibroblasts derived from all anatomical sites. The two activities exhibit different kinetics with respect to steroid substrate and are also dissimilar in their subcellular distributions. Other properties, such as coenzyme requirement, steroid substrate specificity, and instability with increasing temperature, appear to be similar.

Cells, Cultured↗

Methaqualone (Mandrax) abuse, urine testing, and identification: clinical correlation between a new mass urinalysis test and a military drug abuse program.

A urine test presently based on thin-layer chromatography screening and gas-liquid chromatography (GLC) confirmation has been a practical way of detecting methaqualone use in individuals. A more practical test is the radioimmuno assay for screening and GLC for confirmation. It appears that the drug methaqualone can be easily detected in the urine up to 72 hr after the last dosage. Individuals evaluated after being identified through the urine testing procedure readily admit to the use of illegal drugs and are most cooperative in giving drug abuse data, whether it is Mandrax, hashish, herion, or alcohol. The majority evaluated in this study were not in any program for drug abuse although all but one admitted to frequent drug abuse. The finding has been generally true of the other urinalysis test for drugs of abuse as the majority of the soldiers in the rehabilitation program have been identified by urinalysis over the past year. Because of the uncertainty of surveys on how prevalent was Mandrax use (anywhere from 5 to 90%, depending on who was consulted), a random selection of urines was done in September/November 1973. A total of 7,545 urine samples were tested those 2 months and the results were 2.9 and 3.9% positive respectively. Since that time and through June 1974 approximately 250 urine samples a week were tested for Mandrax based on a special request by the commander who suspected an individual of abusing Mandrax, and approximately 20 to 30% of the samples were positive. During June and July all randomly collected urines were tested and the results on a daily basis were from 1.5 to 3.5%. Since July 1974 no urines have been collected or tested. The follow-up indicates that of this number practically all are clinically confirmed as drug abusers and are entered into the Army's Drug Rehabilitation Program.

Adolescent↗

Diminished 5alpha-reductase activity in extracts of fibroblasts cultured from patients with familial incomplete male pseudohermaphroditism, type 2.

The activity of 5alpha-reductase, the enzyme that converts testosterone to dihydrotestosterone, has been assessed in cell-free extracts of fibroblasts grown from foreskin, labia majora, scrotum, and nongenital skin from control subjects, from patients with developmental defects of the urogenital system, drom two subjects with the type 2 form of familial incomplete male pseudohermaphroditism and from individuals with other forms of hereditary male pseudohermaphoditism. Enzyme activity was shown to be maximal in the pH range of 5 to 6. Substrate specificity studies indicated that the enzyme so assayed is the 5alpha-reductase previously characterized in human foreskin. The activity of the enzyme was low in normal fibroblasts grown from nongenital skin and high in most fibroblasts grown from genital skin. 5alpha-Reductase activity in extracts of foreskin fibroblasts from two subjects with the type 2 disorder was undetectable at pH 5.5. Activity in comparable fibroblast extracts from most patients with other forms of hereditary male pseudohermaphroditism was easily measurable.

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