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Biomedical subjects

A Swain

Publications and source records attributed to A Swain.

At least 19 recordsLinked to original sources

Physical status of newborns and neonatal outcome.

OBJECTIVE: To determine the extent to which physical status at birth is associated with neonatal mortality and the causes of mortality vis-a-vis size at birth and gestational age. METHOD: 11,223 consecutive live births completing 26 weeks of gestation and weighing > or = 500 gm were included in the study. Birth weight and chest circumference were recorded as per WHO guidelines. Gestational age was calculated on the basis of L.M.P. and the new Ballard's score. Deaths occurring in the hospital within 28 days were recorded. Percentile values of gestational age specific birth weights were calculated separately for singletons and multiple births. Percentage of SGA was calculated with reference to WHO recommended values. Birth weight-gestational age-specific mortality rates were calculated at 2 wk and 500 gm intervals. RESULT: Low-birth-weight babies constituted 39.8% of the total, much in excess of WHO recommended figure of 15%. 76% deaths occurred among LBW babies and 56.2% among preterms. Mortality showed remarkable decline as the birth weight increased to 2,000 gm. The lowest mortality was among singletons weighing 2,500-3,000 gm and of 38-40 weeks gestation. Prevalence of SGA at 40 and 42 weeks were 73.7% and 83.6% respectively. But, if SGA babies not categorised as LBW were excluded, the values came down to 32% and 36% respectively. 36% of all deaths occurred during the first 24 hrs of birth; asphyxia and related causes contributing to 50% of it. CONCLUSION: Cut-off value of 2,000 gm instead of 2,500 gm for birth weight may be preferable in countries where most LBW babies are SGAs. Simultaneously, deaths in non-LBW babies due to perinatal causes contribute sgnificantly to total neonatal mortality and need due attention through sensitising obstetricians in essential newbom care and timely Intervention.

Birth Weight↗

Up-regulation of WNT-4 signaling and dosage-sensitive sex reversal in humans.

Wnt-4, a member of the Wnt family of locally acting secreted growth factors, is the first signaling molecule shown to influence the sex-determination cascade. In mice, a targeted deletion of Wnt-4 causes the masculinization of XX pups. Therefore, WNT-4, the human homologue of murine Wnt-4, is a strong candidate gene for sex-reversal phenotypes in humans. In this article, we show that, in testicular Sertoli and Leydig cells, Wnt-4 up-regulates Dax1, a gene known to antagonize the testis-determining factor, Sry. Furthermore, we elucidate a possible mechanism for human XY sex reversal associated with a 1p31-p35 duplication including WNT-4. Overexpression of WNT-4 leads to up-regulation of DAX1, which results in an XY female phenotype. Thus, WNT-4, a novel sex-determining gene, and DAX1 play a concerted role in both the control of female development and the prevention of testes formation. These observations suggest that mammalian sex determination is sensitive to dosage, at multiple steps in its pathway.

Amino Acid Sequence↗

Another cause for bilateral haemorrhagic otorrhoea following trauma.

Bleeding from the external auditory meatus (haemorrhagic otorrhoea) following head trauma is usually attributed to a basal skull fracture. However, it may also result from unsuspected facial trauma. We describe a case that highlights an usual but important differential diagnosis for bilateral haemorrhagic otorrhoea.

Adult↗

Comorbidity in a clinical sample of substance abusers.

The sample consisted of 125 male inpatients admitted to one of two substance abuse treatment centers in Iowa. They were diagnosed by means of the Diagnostic Interview Schedule Screening Interview-Quick-DIS version, the Structural Interview for DSM-III-R Personality Disorder (PD), revised, and the Substance Abuse Reporting System. The most frequently diagnosed comorbid Axis I conditions were anxiety and mood disorders, while the most frequently observed Axis II disorders were in Cluster B, borderline PD, and antisocial PD followed by Cluster C, avoidant PD, passive-aggressive PD and obsessive-compulsive PD; and then Cluster A; schizoid PD. Subjects diagnosed with Borderline PD showed the highest rate of comorbid psychopathology, including Axis I disorders of generalized anxiety disorder, major depression, cocaine dependence, and inhalant dependence. The most likely comorbid diagnosis for antisocial PD subjects was bipolar disorder. The schizoid PD and the NoPD groups were less likely to meet criteria for other Axis I disorders. A high rate of comorbid Axis II pathology was also found. Polysubstance dependent subjects were more likely to be diagnosed with anxiety disorder or bipolar disorder than were those who were not polysubstance dependent or were dependent only on alcohol. Polysubstance dependent men were at highest risk for Axis II disorders: 56% of them met criteria for a Cluster B PD, with borderline PD and histrionic PD most frequent.

Alcoholism↗

Cross-cultural comparison of clinical samples of Norwegian and Iowan women with substance-related disorders.

The purpose of this study was to compare two clinical samples of women substance abusers, one from Iowa and one from Norway, along several dimensions: "substance abuse" history, current "abuse" pattern, parental and spouse drinking history, symptoms of psychological distress, and "vulnerability" to relapse. A higher percentage of women substance abusers from Iowa were divorced and lived alone, were "vulnerable" to relapse, and reported more life problems secondary to their substance use than women from Norway. The Iowa women had used more substances in addition to alcohol than had the Norwegian women. The Norwegian women reported greater intensity of emotional distress than the women from Iowa.

Adolescent↗

Repeated acetaminophen dosing in rats: adaptation of hepatic antioxidant system.

Repeated dosing of acetaminophen (paracetamol) to rats is reported to decrease their sensitivity to its hepatotoxic effects, which are associated with oxidative stress and glutathione depletion. We determined if repeated acetaminophen dosing produced adaptive response of key antioxidant system enzymes. Male rats (Sprague-Dawley, 10 weeks) were given 800, 1200, or 1600 mg/kg/day acetaminophen by oral gavage for 4 days. Liver was assayed for oxidative stress and antioxidant markers: malondialdehyde (MDA), thiobarbituric acid reactive substance (TBARS), total antioxidant status (TAS), glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), glucose-6-phosphate dehydrogenase (G6PD), catalase (CAT), and superoxide dismutase (SOD), and alanine transaminase (ALT) as a marker of hepatocellular injury. Acetaminophen at 1200/1600 mg/kg decreased GSH 26/47%, GPx 21/26%, CAT 35/28%, SOD 21/12%; and TAS 28/18% (correlated with CAT, r=0.91; SOD, r=0.66; GPx, r=0.45). Despite antioxidant deficiencies, and no TBARS change, MDA decreased 26%/33%/37% at 800/1200/1600 mg/kg, which correlated with increased GR (61%/62%/76%, r=0.77) and G6PD (130%/110%/190%, r=0.78). Both MDA (r=0.68) and G6PD (r=0.71) correlated with hepatic ALT, which decreased 27%/43%/48%, respectively. Resistance to acetaminophen hepatotoxicity produced by repeated exposure is partially attributable to upregulation of hepatic G6PD and GR activity as an adaptive and protective response to oxidative stress and glutathione depletion.

Acetaminophen↗

Dax1 antagonizes Sry action in mammalian sex determination.

DAX1, which encodes an unusual member of the nuclear hormone-receptor superfamily, is a gene that may be responsible for a sex-reversal syndrome in humans, referred to as dosage-sensitive sex reversal, in which XY individuals carrying duplications of Xp21, part of the small arm of the X chromosome, develop as females. XY mice carrying extra copies of mouse Dax1 as a transgene show delayed testis development when the gene is expressed at high levels, but do not normally show sex reversal. Complete sex reversal occurs, however, when the transgene is tested against weak alleles of the sex-determining Y-chromosome gene Sry. These results show that DAX1 is largely, if not solely, responsible for dosage-sensitive sex reversal and provide a model for early events in mammalian sex determination, when precise levels and timing of gene expression are critical.

Animals↗

A molecular approach to sex determination in mammals.

Mammalian sex determination occurs in the gonad of the developing embryo. This process is dependent on the Y-chromosome-encoded Sry gene that acts in the somatic cells of the genital ridge. The transient nature of Sry gene expression suggests that it acts as a switch from one cell fate to another. One of the roles of Sry is to initiate the differentiation of Sertoli cells, which are the first cell type of the testis to be formed. Two genes are thought to be important in Sertoli cell differentiation and function, Sox9, an Sry-related gene, and SF-1, a nuclear hormone receptor. Sox9 is expressed in Sertoli cells throughout development of the mouse embryo, and inactivating mutations in this gene in humans give rise to XY females. SF-1 is also expressed in Sertoli cells and is thought to activate the AMH gene--an early marker of these cells. DAX-1, an X-linked member of the nuclear hormone superfamily, is a candidate for a human condition in which duplication of regions of the X chromosome results in XY females. Expression of this gene during mouse development is associated with ovary development and is down-regulated in the differentiating testis. Mutations in DAX-1 in humans have shown that this gene is not necessary for testis development. The properties of the DAX-1 gene suggest that it is important in ovary determination and might therefore be antagonistic to the action of the Sry gene.

Animals↗

Steroidogenic factor 1 plays multiple roles in endocrine development and function.

The nuclear hormone receptor family comprises a group of structurally related transcriptional regulators that mediate the actions of diverse ligands, including steroid hormones, thyroid hormone, vitamin D, and retinoids. The nuclear receptor family also contains members for which activating ligands have not been identified-the orphan nuclear receptors. One of these orphan nuclear receptors, steroidogenic factor 1 (SF-1), has emerged as an essential regulator of steroidogenic cell function within the adrenal cortex and gonads; SF-1 also plays important roles in reproduction at all three levels of the hypothalamic-pituitary-gonadal axis. First identified as a tissue-specific regulator of the transcription of the cytochrome P450 steroid hydroxylases, considerably broader roles for SF-1 were revealed by genetic studies in mice lacking SF-1 due to targeted gene disruption. These SF-1-knockout mice had agenesis of their adrenal glands and gonads, male-to-female sex reversal of their internal and external genitalia, impaired gonadotrope function, and agenesis of the ventromedial hypothalamic nucleus. These studies delineated essential roles of SF-1 in regulating endocrine differentiation and function at multiple levels. Despite these insights into roles of SF-1, the precise mechanisms by which SF-1 exerts its multiple effects remain to be determined. This review highlights experiments that have established SF-1 as a pivotal determinant of endocrine differentiation and function and identifies areas in which additional studies are needed to expand our understanding of SF-1 action.

Animals↗

Mouse Dax1 expression is consistent with a role in sex determination as well as in adrenal and hypothalamus function.

Duplications of a chromosome Xp21 locus DSS (Dosage Sensitive Sex reversal) are associated with male to female sex reversal. An unusual member of the nuclear hormone receptor superfamily, DAX1, maps to the DSS critical region and is responsible for X-linked adrenal hypoplasia congenita. Here we describe the isolation of the mouse Dax1 gene and its pattern of expression during development. Expression was detected in the first stages of gonadal and adrenal differentiation and in the developing hypothalamus. Moreover, Dax1 expression is down-regulated coincident with overt differentiation in the testis, but persists in the developing ovary. Comparison of the predicted protein products of the human and mouse genes show that specific domains are evolving rapidly. Our results suggest a basis for adrenal insufficiency and hypogonadotropic hypogonadism in males affected by adrenal hypoplasia congenita and are consistent with a role for DAX1 in gonadal sex determination.

Adrenal Glands↗

Sox9 expression during gonadal development implies a conserved role for the gene in testis differentiation in mammals and birds.

Heterozygous mutations in SOX9 lead to a human dwarfism syndrome, Campomelic dysplasia. Consistent with a role in sex determination, we find that Sox9 expression closely follows differentiation of Sertoli cells in the mouse testis, in experimental sex reversal when fetal ovaries are grafted to adult kidneys and in the chick where there is no evidence for a Sry gene. Our results imply that Sox9 plays an essential role in sex determination, possibly immediately downstream of Sry in mammals, and that it functions as a critical Sertoli cell differentiation factor, perhaps in all vertebrates.

Amino Acid Sequence↗

Social loafing and identifiability: the mediating role of achievement goal orientations.

The purpose of this investigation was to determine if differences in the tendency to exhibit social loafing is a function of achievement-goal orientation and identifiability. Ninety-six males drawn from 10th-grade physical education classes responded to the Task and Ego Orientation in Sport Questionnaire (Duda, 1992) prior to completing a 30-meter sprint task under three separate conditions: as an individual, in a team with individual performance identified, and in a team with individual performance not identified. Following a median split of the task and ego values reported, subjects were divided into high and low groups for both orientations. Sprint times were compared by means of a 2 x 2 x 3 ANOVA (task x ego x sprint condition) with repeated measures on the third factor. Findings revealed that individuals with a combined low task/high ego orientation were significantly slower in the nonidentifiable team condition than in the other two conditions, whereas high-task/low-ego-oriented individuals demonstrated consistent performance across all three conditions. While confirming that identifiability of performance is an important situational variable, the findings suggest that the dispositional factor of achievement orientation may interact to provide a more detailed explanation of the social loafing phenomenon.

Achievement↗

Reproducibility of blood pressure and heart rate reactivity: a meta-analysis.

Reproducibilities of blood pressure and heart rate (HR) reactivity reported in studies assessing responses to the same laboratory stressors across occasions were reviewed with meta-analytic techniques. Changes in HR had the greatest reproducibility (r = .555), followed by systolic blood pressure (SBP) (.407) and diastolic blood pressure (DBP) (.348). Both SBP and HR response reproducibility was higher at shorter test-retest intervals, whereas DBP values varied unsystematically with length of test-retest interval. Older samples exhibited higher SBP and DBP reproducibility to stressors. SBP and DBP reproducibilities were better for tasks that did not make speech demands. The reliability of reactivity assessment was higher when based on three or more measurements. On the basis of available evidence, the drop in stress reproducibility, as test-retest interval increases, places limits on the viability of BP reactivity as a strong marker or risk factor for coronary heart disease.

Aging↗

Steroidogenic factor 1 and Dax-1 colocalize in multiple cell lineages: potential links in endocrine development.

Mutations of the orphan nuclear receptors, steroidogenic factor 1 (SF-1) and DAX-1, cause complex endocrine phenotypes that include impaired adrenal development and hypogonadotrophic hypogonadism. These similar phenotypes suggest that SF-1 and DAX-1 act in the same pathway(s) of endocrine development. To explore this model, we now compare directly their sites of expression. In mouse embryos, SF-1 expression in the urogenital ridge and brain either preceded or coincided with Dax-1 expression, with coordinate expression thereafter in the adrenal cortex, testis, ovary, hypothalamus, and anterior pituitary. The striking colocalization of SF-1 and Dax-1 supports the model that they are intimately linked in a common pathway of endocrine development. The slightly earlier onset of SF-1 expression and its ability to bind specifically to a conserved sequence in the Dax-1 5'-flanking region suggested that SF-1 may activate Dax-1 expression. However, promoter activity of Dax-1 5'-flanking sequences did not require this potential SF-1-responsive element, and Dax-1 expression was unimpaired in knockout mice lacking SF-1, establishing that SF-1 is not required for Dax-1 gene expression in these settings. Although the precise mechanisms remain to be established and may be multifactorial, our results strongly suggest that these two orphan nuclear receptors interact in a common pathway of endocrine development.

Animals↗