Levels of follicle-stimulating hormone, luteinizing hormone and prolactin were evaluated in 52 cases of postpill amenorrhea at the Institute of Post Graduate Medical Education and Research, Calcutta, India. All 52 patients had experienced amenorrhea for one year since discontinuation of oral contraceptive therapy. The incidence of postpill amenorrhea was much higher in patients with histories of oligomenorrhea or irregular menstrual periods. No relationship was seen between the number of cycles of pills used and the incidence of postpill amenorrhea. The ratio of luteinizing hormone to follicle-stimulating hormone in all cases exceeded unity, indicating that postpill amenorrhea is a type of functional secondary amenorrhea.

Amenorrhea↗

PubMedDate not supplied

Correlation of concentrations of estriol-3-sulfate with those of potassium and sodium in human breast cyst fluid.

Estriol-3-sulfate (E3-3S) was assayed in 92 specimens of human breast cyst fluid (BCF) obtained by needle aspiration from women with fibrocystic disease. The concentrations of K+ and Na+ were determined in the same samples. The median concentration of E3-3S in the fluids from premenopausal women under 51 years of age (69 cases) was 4.4 ng/mL. Based on the K+ levels the samples were divided into two groups, above 50 mM (Type I) and below 50 mM (Type II). Correlations were made between the concentrations of the estrogen conjugate and the univalent ions. In the premenopausal women, Type I cysts were associated with above median E3-3S and Type II cysts with below median E3-3S (P less than 0.01). A K+/Na+ ratio of more than one was also related to elevated E3-3S (P less than 0.025). The BCF obtained from postmenopausal women and women older than 50 years tended to be low in E3-3S (median 1.64 ng/mL) and high in K+ but there were too few cases to permit statistical comparisons to be made. Since fibrocystic disease constitutes a risk factor for the development of breast cancer, it will be of interest to determine retrospectively whether any of the above subsets of BCF may be useful in identifying a patient at such risk.

Adult↗

PubMedDate not supplied

Human-specific insertion/deletion polymorphisms in Indian populations and their possible evolutionary implications.

DNA samples from 396 unrelated individuals belonging to 14 ethnic populations of India, inhabiting various geographical locations and occupying various positions in the socio-cultural hierarchy, were analysed in respect of 8 human-specific polymorphic insertion/deletion loci. All loci, except Alu CD4, were found to be highly polymorphic in all populations. The levels of average heterozygosities were found to be very high in all populations and, in most populations, also higher than those predicted by the island model of population structure. The coefficient of gene differentiation among Indian populations was found to be higher than populations in most other global regions, except Africa. These results are discussed in the light of two possible scenarios of evolution of Indian populations in the broader context of human evolution.

Alleles↗

PubMedDate not supplied

Alterations of the P16 gene in uterine cervical carcinoma from Indian patients.

In our analysis, alterations in the P16 tumor suppressor gene were seen in 33% (15/46) of sampled uterine cervical lesions. Among the alterations, mutations in P16 were detected in 15% (7/46) of the samples. One mutation occurred at intron 1/exon 2 splice junction. All the other mutations were in exon 2 with three of them as silent mutations. The promoter hypermethylation and homozygous deletion of P16 gene were detected in 6.5% (3/46) and 8.7% (4/46) of the samples respectively. Loss of heterozygosity and microsatellite size alterations at the P16 locus were seen in 17% (8/46) of the samples. HPV16/18 infection was detected in 76% (35/46) of the samples. But no association was found between P16 alterations and HPV infection. Thus, it seems that P16 inactivation may be associated with the development of some uterine cervical carcinoma.

Adult↗

PubMedDate not supplied

Trophoblastic cell lines generated from tumour necrosis factor receptor-deficient mice reveal specific functions for the two tumour necrosis factor receptors.

In mice and humans, expression of the tumour necrosis factor receptor-1 (TNF-R1) gene in placental trophoblast cells is constitutive whereas expression of the TNF-R2 gene is developmentally programmed. In order to study the individual functions of TNF-R1 and -R2 in this lineage, cell lines were generated from placental explants of homozygous matings of gestation day 10 outbred mice (Swiss-Webster), TNF-R1-deficient (TNF-R1-/-) and TNF-R2-/- transgenic mice as well as the background strain for the TNF-R2-/- mice (WT, C57BL/6x129). All of the cells exhibited trophoblast markers; they contained cytokeratin intermediate filaments, expressed alkaline phosphatase activity and displayed transferrin receptors, but were negative for vimentin filaments and the macrophage marker, F4/80. Analysis of DNA by polymerase chain reaction demonstrated the expected TNF-R genotype in each line. In experiments testing the effects of recombinant mouse TNF-alpha (rmTNF-alpha) on viability and proliferation of the cell lines, rmTNF-alpha modestly but dose-dependently inhibited the growth of WT and TNF-R2-/- cells while having no effect on TNF-R1-/- cells. Actinomycin D-treated WT and, to a lesser extent, TNF-R2-/- cells, were more sensitive to growth inhibition than untreated cells whereas TNF-R1-/- cell responses remained unchanged. These data indicated that rmTNF-alpha inhibits growth of trophoblastic cells through TNF-R1 and that newly synthesized protein(s) provide partial protection against toxicity. In contrast to the receptor species-specific effects on cell growth exerted by rmTNF-alpha, both TNF-R mediated inhibition of alkaline phosphatase activity. Collectively, the observations support the postulate that receptor expression is the key factor which determines the nature and extent of TNF-alpha effects on trophoblast cell growth and function.

Alkaline Phosphatase↗

PubMedDate not supplied

Placental morphogenesis in pregnancies with Down's syndrome might provide a clue to pre-eclampsia.

Insufficient perfusion of placenta in pre-eclampsia is commonly associated with oxidative stress leading to increased superoxide formation and reduced invasion of uterine spiral arteries by differentiated migratory cytotrophoblasts. The superoxide dismutase (SOD) level, responsible for eliminating toxic superoxides, drops significantly in pre-eclampsia. On the contrary, the SOD synthesis increases dramatically, compared to that of normal placenta, in pregnancies with trisomy 21 (T21) fetus. However, despite a low level of placental hypoplasia, the overall perfusion of T21 placentae is comparable to that of normal pregnancy. In the light of recent reports on alternative modes of SOD function and factors regulating pathways of cytotrophoblast differentiation, here we have attempted to reconcile the two seemingly disparate pregnancy conditions and suggest that trisomy 21 pregnancies might provide new insight into our understanding of placental morphogenesis in pre-eclampsia.

Adult↗

PubMedDate not supplied

Immunoglobulin (Gm and Km) allotypes in nine endogamous groups of West Bengal, India.

Blood samples from 898 individuals of nine endogamous groups of West Bengal, India were typed for determining the haplotypic structure in the gamma-light chain (Gm) and kappa-light chain (Km) of immunoglobulin (IgG). The Gm haplotype frequencies detected by Glm (1), Glm (2) and G3m (5) markers suggest that in this eastern state of India there is considerable variation of frequencies of the typical Mongoloid haplotype Gm1,5, which shows a high incidence in Rajbanshi, Rabha, Garo and Lodha groups. On the contrary, this haplotype is probably absent in the high caste groups, Rarhi Brahmin and Vaidya, and is relatively infrequent in Jalia Kaibarta, a scheduled caste of the south-western part of the state. The Km1 allele is also high in frequency among Rajbanshi, Rabha, Garo and Munda in comparison with Rarhi Brahmin and Vaidya, suggesting the former four groups' strong Mongoloid affiliation. This survey signifies that there is considerable variation in the extent of Mongoloid admixture in Bengali populations. Such admixture is not restricted in specific social class either. It further demonstrates that heterogeneity of the genetic structure of Bengali populations do not correspond to the present social ranking on the basis of caste hierarchy.

Asian People↗

PubMedDate not supplied

Serum estradiol-binding profiles in postmenopausal women undergoing three common estrogen replacement therapies: associations with sex hormone-binding globulin, estradiol, and estrone levels.

OBJECTIVE: To compare the effects of three commonly prescribed estrogen replacement therapies-oral conjugated equine estrogens (CEE; n = 37), oral micronized estradiol (ME; n = 25), and transdermal estradiol (TE; n = 24)-on the binding characteristics of plasma estradiol as related to the concentrations of blood sex hormone-binding globulin (SHBG), estradiol, and estrone. DESIGN: Menopausal volunteers, opting for estrogen replacement therapy, gave blood at 0, 2, and 4 months. SHBG was assayed by automated immunoabsorbent technology. Estradiol and estrone were determined by quantitative gas chromatography/mass spectrometry. After tritiated estradiol was added to serum, the percentage of estradiol not bound to protein was determined by ultrafiltration and the percentage of estradiol bound to SHBG was measured by a method exploiting that this protein, even when bound to estradiol, binds avidly to Concanavalin A-Agarose. RESULTS: In each study, 2- and 4-month data were similar. Increases in SHBG concentrations were 100% (p < 0.001), 45% (p < 0.001), and 12% (nonsignificant) for subjects who were receiving CEE, ME, and TE regimens, respectively. Decreases in the percentage of estradiol not bound to protein and increases in the percentage of estradiol bound to SHBG correlated with changes in the concentrations of this protein mediated by the therapies. The order for increases in estradiol was ME-TE >> CEE, whereas for estrone, the order was ME > CEE >> TE, divergent from the SHBG responses. CONCLUSIONS: The diverse responses observed can be explained by differences in the estrogen load delivered to target tissues as controlled by the intermediary circulation and metabolism of the hormones introduced in these regimens.

Adult↗

PubMedDate not supplied

Netherton syndrome presenting as congenital psoriasis.

A white boy had erythroderma and dense scale at birth. By 3 months the scale had localized to scalp, diaper area, and acral surfaces. Two biopsy specimens were read as psoriasiform dermatitis at 1 and 3 months. It was not until he was 10 months of age, when terminal hairs grew with nodose irregularities (trichorrhexis invaginatum), that the correct diagnosis of Netherton syndrome was made.

Biopsy↗

PubMedDate not supplied

Bifunctional role of protein tyrosine kinases in late preconditioning against myocardial stunning in conscious rabbits.

Although protein tyrosine kinases (PTKs) have been implicated in late preconditioning (PC) against infarction, their role in late PC against stunning is unknown. Furthermore, it is unknown whether PTK signaling is necessary only to trigger late PC on day 1 or also to mediate it on day 2. Thus, conscious rabbits underwent a sequence of six 4-minute coronary occlusion/4-minute reperfusion cycles for 3 consecutive days (days 1, 2, and 3). In the control group (group I, n=7), the recovery of systolic wall thickening after the 6 occlusion/reperfusion cycles was markedly improved on days 2 and 3 compared with day 1, indicating the development of late PC against stunning. Administration of the PTK inhibitor lavendustin-A (LD-A, 1 mg/kg IV) before the first occlusion on day 1 (group II, n=7) completely prevented the late PC effect against stunning on day 2. Late PC against stunning was also abrogated when LD-A was given before the first occlusion on day 2 (group III, n=7); however, in these rabbits, the late PC effect became apparent on day 3, indicating that LD-A itself did not have any delayed deleterious actions on myocardial stunning. In group V (n=5), the sequence of 6 occlusion/reperfusion cycles resulted in a robust increase in the activity of inducible NO synthase (iNOS [assessed as Ca(2+)-independent L-citrulline formation]) and nitrite+nitrate (NO(x)) tissue levels 24 hours later (on day 2), with no concomitant change in Ca(2+)-dependent NO synthase (endothelial NO synthase and/or neuronal NO synthase) activity. Similar results were obtained on day 3 (group VIII, n=6), indicating sustained upregulation of iNOS. Administration of LD-A either on day 1 (group VI, n=5) or on day 2 (group VII, n=6) abrogated the increase in iNOS activity and NO(x) levels on day 2. LD-A had no effect on iNOS activity or NO(x) levels in the absence of PC (group X, n=5). This study demonstrates that in conscious rabbits, PTK activity is necessary not only to trigger late PC against stunning on day 1 but also to mediate the protection on day 2. This investigation also provides the first direct evidence that cardiac iNOS activity is upregulated during the late phase of ischemic PC in rabbits. Furthermore, the data indicate that PTK signaling is essential for the augmentation of iNOS activity and that PTKs modulate this enzyme at two distinct levels: at an early stage on day 1 and at a late stage on day 2. This bifunctional role of PTKs in late PC has broad implications for the signaling mechanisms that underlie the response of the heart to ischemic stress and, possibly, other stresses.

Animals↗