Balwant Ahluwalia

Blood hormone profiles in prostate cancer patients in high‐risk and low‐risk populations

Epidemiologic data reveal that the incidence rate of prostate gland carcinoma among the black population in the United States (US) is several times higher than among Nigerians. A collaborative study between the two countries was undertaken, and blood hormone (testosterone [T], dihydrotestosterone [DHT], estrone [E1], estradiol [E2], and prolactin [P1]), total acid phosphatase (TP), and prostatic acid phosphatase (PAP) profiles in the two population groups were compared. In the US groups (patients and controls) there were significantly higher levels of T (P < 0.01) and E1 (P < 0.05) compared with the Nigerians. Also, the US patients had significantly higher levels of T (P < 0.05) and E1 (P < 0.01) compared with their matched controls. In the Nigerians T but not E1 levels were significantly lower (P < 0.05) in patients compared with controls. DHT, E2, and PI were not significantly different in patients and controls between and within the populations. Nigerian patients had higher levels (P < 0.001) of TP and PAP compared with US patients. It is concluded that differences in blood hormone profiles in the two population groups are based on factors other than the genetic makeup of the populations.

Variation of Ethinylestradiol Blood Levels Among Healthy Women Using Oral Contraceptives

Data concerning ethinylestradiol (EE) blood levels among 93 healthy women using oral contraceptives are presented. Seventy-two per cent of the observed variation in EE blood levels was unexplainable on the basis of time since ingestion of the last oral contraceptive, day of menstrual cycle, race, age, weight, height, blood pressure, cigarette consumption, alcohol consumption, diurnal variation, or lifetime use of oral contraceptives.

Alcohol modulates cytokine secretion and synthesis in human fetus: an in vivo and in vitro study

It is well recognized that alcohol passes through the placenta and affects the fetal immune system. The underlying mechanism accounting for immune suppression is not clear. Cytokines are recognized as the principal mediators of a variety of immunologic and pathophysiologic events. The study was designed to examine whether alcohol use during pregnancy affects cytokine synthesis and secretion in the human fetus. Fetal (cord blood) and mothers blood were used for the study. Studies were conducted in vivo and in vitro. For the in vivo study, cytokine levels were measured in cord blood in mothers who drank moderate to heavy (chronic) amounts of alcohol during pregnancy. For the in vitro study, cord blood was obtained from mothers who were drug-free throughout pregnancy. Lymphocytes were isolated and stimulated with lipopolysaccharide (LPS; Escherichia coli, 26:B6). The capacity of lymphocytes to synthesize cytokines was examined in the presence of 20, 50, and 100 mM alcohol. Among the cytokines examined were the tumor necrosis factor (TNF alpha) and interleukins (IL-1 alpha and beta and IL-6). The selection of cytokines was based on their presumptive role in the pathophysiology of alcoholism. Cytokines were measured by using a specific immunoassay. When data obtained from moderate alcohol users were compared with those obtained from nonusers, no significant differences were observed in any of the cytokines examined (p>0.05). In chronic alcohol users, levels for all cytokines increased significantly (p<0.001) in both the fetus and the mother. Among the cytokines, IL-1beta, IL-6, and TNFalpha were the predominant cytokines affected by chronic use of alcohol during pregnancy. The order of stimulation was IL-6, IL-1 beta, TNFalpha, and IL-1 alpha in descending order. In the in vitro study, alcohol blunted LPS stimulation of cytokines, and the alcohol-induced decrease in cytokine synthesis was proportional to the level of alcohol in the media, suggesting a direct effect of alcohol on cytokine synthesis. In general, the blunting effect of alcohol on LPS stimulation was more prominent in the fetus compared with that in mother. We conclude that chronic alcohol use during pregnancy stimulated the fetal cytokine synthesis and secretion, and IL-1beta, IL-6, and TNF alpha were the predominant cytokines affected by alcohol. The in vitro data suggest a direct effect of alcohol on cytokine synthesis.

Constitutive expression of the steroid sulfatase gene supports the growth of MCF-7 human breast cancer cells in vitro and in vivo

Many human breast tumors are driven by high intratumor concentrations of 17β-estradiol that appear to be locally synthesized. The role of aromatase is well established, but the possible contribution of the steroid sulfatase (STS), which liberates estrogens from their biologically inactive sulfates, has been inadequately assessed and remains unclear. To evaluate the role of STS further, we transduced estrogen-dependent MCF-7 human breast cancer cells with a retroviral vector directing the constitutive expression of the human STS gene. Gene integration was confirmed by Southern hybridization, production of the appropriately sized messenger RNA by Northern hybridization, and expression of functional protein by metabolism of[ 3H]estrone sulfate to [3H]estrone. Maximum velocity estimates of estrone formation are 64.2 pmol estrone/mg protein·h in STS-transduced cells (STS Clone 20), levels comparable to those seen in some human breast tumors. Lower levels of endogenous activity are seen in MCF-7 cells (13.0 pmo...

Fetal megacystis: differential diagnosis.

The purpose of our retrospective observational series was to determine whether the sonographic characteristics of fetal megacystic bladders can be used to reliably establish the most likely diagnosis in fetuses with this condition. The sonographic records of pregnant patients referred to our institutions over a 10‐year period who were found on initial 2‐dimensional sonography to be carrying fetuses with megacystis were examined for evidence of a keyhole sign, bladder thickness, amniotic fluid index, and fetal sex. When available, 3‐/4‐dimensional sonography, Doppler angiography, tomographic ultrasound imaging, virtual organ computer‐aided analysis, and automatic volume calculation were used as part of the detailed fetal anatomic survey. Twenty fetuses with megacystis were identified. Seventeen were male; 2 were female; and 1 had ambiguous genitalia. All male fetuses with megacystis originally had a diagnosis of prune belly syndrome. The diagnosis for 10 male fetuses with a keyhole sign was changed to megacystis secondary to posterior urethral valves. The fetus with ambiguous genitalia had prune belly syndrome. One of the female fetuses had a diagnosis of urethral atresia, and the diagnosis for the other female fetus was megacystis‐microcolon‐intestinal hypoperistalsis syndrome. In conclusion, in fetuses with megacystic bladders, it is possible to distinguish between cases with prune belly syndrome, posterior urethral valves, urethral atresia, and megacystis‐microcolon‐intestinal hypoperistalsis syndrome by a detailed anatomic survey using 2‐ and 3‐/4‐dimensioinal sonographic techniques.

Evidence of Higher Ethynylestradiol Blood Levels in Human Hypertensive Oral Contraceptive Users

These studies were designed to investigate the differences in blood plasma levels of ethynylestradiol (EE2) in women who developed hypertension while taking combined estrogen and progesterone oral contraceptives (OCs) and in normotensive OC users. Blood samples were collected in heparinized tubes 10 hours after OC ingestion, the plasma was separated, and EE2 was measured by radioimmunoassay. The results showed significantly higher plasma levels of EE2 in the hypertensive OC users as compared with the levels in normotensive OC users (P less than 0.01). In another study, blood samples from hypertensive and normotensive OC users were obtained for 3 consecutive days at fixed intervals following OC ingestion, and plasma levels of EE2 were measured. The results showed consistently higher EE2 blood levels during this 3-day period in the hypertensive subjects (P less than 0.01). It is postulated that the higher blood levels of EE2 in hypertensive OC users result from either decreased metabolism or excretion of synthetic estrogens.

Dexamethasone suppresses sex-hormone binding globulin.

Dexamethasone suppression (DEX-S) for 14 days has been used to determine the probable source of androgen excess. The exact mechanism(s) of DEX-S is still unclear. The authors postulated that dexamethasone (DEX) inhibits either the synthesis or secretion of sex-hormone binding globulin (SHBG). To examine this hypothesis, 14 women with polycystic ovarian disease (PCOD) and 3 volunteers were given DEX for 14 days. The PCOD group included obese and nonobese women (+/- 15% ideal body weight). Plasma determinations by radioimmunoassay of total testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate, luteinizing hormone; follicle-stimulating hormone; cortisol, and SHBG were made. DEX suppressed SHBG levels (P less than 0.01). SHBG levels were significantly lower in the obese than in the nonobese (P less than 0.01). All androgens were suppressed by DEX, with the exception of androstenedione post-DEX levels, which were significantly greater than pre-DEX levels in 6 of 14 subjects (P greater than 0.05). This observation is consistent with DEX suppression of SHBG.

A smaller molecular weight retinol binding protein in rat testis seminiferous tubules

Abstract In the cytosol fraction in rat testis seminiferous tubules a lower molecular weight protein of ∼4,800 daltons that binds retinol with high specificity has been isolated and purified by ammonium sulfate precipitation and on Sephadex column chromatography. The hexane extract of the component gave a characteristic retinol fluorescence spectrum. The amino acid composition was qualitatively similar to the retinol binding protein in the blood with the exception that cystine and cysteine were absent.

Alcohol inhibits cell mitosis in G2-M phase in cell cycle in a human lymphocytes in vitro study

Alcohol abuse is associated with the loss of immunocompetence, which leads to decreasing resistance to infections. No single mechanism can be accountable for the detrimental effects of alcohol on the bodys defense mechanism. We present data demonstrating that, in cultured lymphocytes, 10-40 mM alcohol in the media caused 18-90% decrease in cell mitosis (p < 0.001). There was a linear decrease in cell mitosis upto 40 mM alcohol; at 100 mM cell mitosis virtually ceased. This study aimed to determine in which phase of the cell cycle did alcohol mediate its effects. The results showed that DNA synthesis was not affected with up to 50 mM alcohol, suggesting that G1-S phase in the cell cycle remained unaffected. At 100 mM alcohol, DNA synthesis decreased significantly (p < 0.01). From the results of this study, we conclude that a subpharmacological dose level of alcohol (10 mM) significantly inhibited cell mitosis and the inhibitory effect of alcohol was mediated in the G2-M phase in the cell cycle. The G1-S phase was unaffected.

Amniotic fluid and umbilical artery levels of sex hormones and prostaglandins in human cocaine users

Biochemical evaluation of amniotic fluid contents is often used to monitor fetal secretory and excretory functions. To determine whether cocaine use during pregnancy affects fetal endocrine secretions, amniotic fluid and umbilical artery samples were collected at term, and selected gonadal hormones and prostaglandins were assayed. Gestational age, birth weights, and placental weights were recorded. The data showed that birth weights were significantly decreased (P less than 0.001) in cocaine users, but gestational age and placental weights were unaffected. Amniotic fluid levels of androstenedione and testosterone were decreased (P less than 0.05) in males born to cocaine users; females were not affected. Prostaglandins (PGF2 alpha and PGE2) were significantly increased (P less than 0.01) in cocaine users. In the umbilical artery, follicle-stimulating hormone was increased (P less than 0.01) in males and females, while luteinizing hormone was increased (P less than 0.01) only in males. We conclude that cocaine passes through the placenta and affects the fetal testes-hypophyseal endocrine system.