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Biomedical subjects

S Sudha

Publications and source records attributed to S Sudha.

35 records · Page 2Linked to original sources
PubMed1999

flex, an X-linked female-lethal mutation in Drosophila melanogaster controls the expression of Sex-lethal.

The Sex-lethal (Sxl) gene is required in Drosophila females for sexual differentiation of the soma, for gem cell differentiation and dosage compensation. We have isolated three new alleles of female-lethal-on-X (flex), an X-linked female-lethal mutation and have characterized its function in sex determination. SXL protein is missing in flex/flex embryos, however transcription from both Sxl(Pe), the early Sxl promoter and Sxl(Pm), the late maintenance promoter, is normal in flex homozygotes. In flex/flex embryos, Sxl mRNA is spliced in the male mode. Analysis of flex germline clones shows that it also functions in oogenesis, but in contrast to Sxl mutants that show an early arrest tumorous phenotype, flex mutant egg chambers develop to stage 10. In flex ovarian clones, Sxl RNA is also spliced in the male form. Hence, flex is a sex-specific regulator of Sxl functioning in both the soma and the germline. Genetic interaction studies show that flex does not enhance female lethality of Sxl loss-of-function alleles but it rescues the male-specific lethality of both of the gain-of-function Sxl mutations, Sxl(M1 )and Sxl(M4.) In contrast to mutations in splicing regulators of Sxl, the female lethality of flex is not rescued by either Sxl(M1 )or Sxl(M4). Based on these observations, we propose that flex regulates Sxl at a post-splicing stage and regulates either its translation or the stability of the SXL protein.

Acetylation↗
PubMed1998

Role of monoamine oxidase type A and B on the dopamine metabolism in discrete regions of the primate brain.

The role of monoamine oxidase (MAO) type A and B on the metabolism of dopamine (DA) in discrete regions of the monkey brain was studied. Monkeys were administered (-)-deprenyl (0.25 mg/kg) or clorgyline (1.0 mg/kg) or deprenyl and clorgyline together by intramuscular injections for 8 days. Levels of DA and its metabolites, dihydroxy phenylacetic acid (DOPAC) and homovanillic acid (HVA) were estimated in frontal cortex (FC), motor cortex (MC), occipital cortex (OC), entorhinal cortex (EC), hippocampus (HI), hypothalamus (HY), caudate nucleus (CN), globus pallidus (GP) and substantia nigra (SN). (-)-Deprenyl administration significantly increased DA levels in FC, HY, CN, GP and SN (39-87%). This was accompanied by a reduction in the levels of DOPAC (37-66%) and HVA (27-79%). Clorgyline administration resulted in MAO-A inhibition by more than 87% but failed to increase DA levels in any of the brain regions studied. Combined treatment of (-)-deprenyl and clorgyline inhibited both types of MAO by more than 90% and DA levels were increased (57-245%) in all brain regions studied with a corresponding decrease in the DOPAC (49-83%) and HVA (54-88%) levels. Our results suggest that DA is metabolized preferentially, if not exclusively by MAO-B in some regions of the monkey brain.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Effects of ethanol ingestion on insulin binding to rat Leydig cells.

Effects of ethanol treatment and its withdrawal on insulin binding to isolated rat Leydig cells were studied. Mature rats were given ethanol by gastric intubation for 30 days at a dose of 3.0 g/kg body weight, twice daily, as a 25% (v/v) aqueous solution and treatment was withdrawn for the subsequent 30 days in an another group. Ethanol treatment markedly increased serum insulin and reduced the 125I-insulin binding to Leydig cells and the activities of Leydig cellular steroidogenic enzymes such as 3 beta-HSD and 17 beta-HSD. Withdrawal of ethanol treatment restored these changed values to their normal levels. The results suggest the possible involvement of subnormal insulin actions, as that of LH, in the ethanol-induced impairment of Leydig cellular steroidogenesis and the resulting hypoandrogenization associated with alcohol abuse.

Animals↗
PubMed1998

Ethnicity, gender, and depressive symptoms in older workers.

We used data from a prospective investigation of full-time workers aged 58 to 64 years and residing in a North Carolina metropolitan area at baseline to examine a causal model for depressive symptomatology among White men, White women, African American men and African American women. We found significant group differences. (1) White men were more vulnerable to social network losses than White women; (2) Work stressors had long-term effects on African American men whose levels of depressive symptoms were also elevated by poor health and retirement; and (3) The influence of income was more dominant among African Americans and its effect was greater for African American women.

Black or African American↗
PubMed1998

Elder-proxy agreement concerning the functional status and medical history of the older person: the impact of caregiver burden and depressive symptomatology.

OBJECTIVES: To examine the influence of caregiver burden and depressive symptomatology on elder-proxy response concordance regarding the older person's functional status and medical history. DESIGN: Cross-sectional study via telephone interviews. SETTING: Community-dwelling older people and caregivers in North Carolina. PARTICIPANTS: 340 matched pairs of frail persons aged 65 and older and their respective caregivers. MEASUREMENTS: Multidimensional Functional Assessment: The OARS methodology RESULTS: Percent agreement on the ADL items ranged from 97.6% on personal hygiene to 99.7% for toileting, with moderate kappa coefficients. IADL percent agreement ranged from 71.5 to 93.7%, with fair to moderate kappa coefficients. Agreement among the medical history items ranged from 76.3 to 98.5% (kappa = .138-.831). Response bias for the IADL composite measure is influenced marginally by caregiver burden (F[259] = 1.751, P = .098). Five of the individual IADL bias items are influenced significantly by burden, such that an increase in burden results in a greater likelihood that the caregiver will overstate disability compared with the rating by the older person. Response bias on the ADL scale was increased among persons who experienced more caregiver burden (OR = 1.096, 95% CI = 1.000, 1.192) and those who spent more hours providing care (OR = 1.012, 95% CI = 1.001, 1.024). Additionally, black caregivers were more likely than white caregivers to disagree with the older people on the ADL scale (OR = 2.73, 95% CI = 1.642, 3.809). A composite of the medical history items is influenced by the relationship of the caregiver to the older person; bias is more likely among adult children ((F[227] = 1.56, P = .081). CONCLUSION: Elder-proxy concordance is highest among ADL items, followed by medical history items and IADL items. Caregiver depressive symptomotology had no significant impact on elder-proxy response concordance on any of the three outcomes of interest: IADL and medical history bias and ADL disagreement. However, caregiver burden was marginally predictive of bias on the total ADL and IADL scales. Additionally, increased burden was significantly predictive of bias on five of the seven individual items of the IADL scale, suggesting that the more burden a caregiver feels, the greater likelihood that s/he will overstate the older person's disability compared with self-report. These findings suggest that clinicians and researchers who use proxy reports to determine treatment regimens and complete data collection efforts may do so with confidence on ADL individual items and medical history items when the older person's frailty is marginal. However, caregiver burden may result in misleading representation of the older person's functional status, specifically in regard to IADL items.

Activities of Daily Living↗
PubMed1997

Ionization, partitioning, and dynamics of tryptophan octyl ester: implications for membrane-bound tryptophan residues.

The presence of tryptophan residues as intrinsic fluorophores in most proteins makes them an obvious choice for fluorescence spectroscopic analyses of such proteins. Membrane proteins have been reported to have a significantly higher tryptophan content than soluble proteins. The role of tryptophan residues in the structure and function of membrane proteins has attracted a lot of attention. Tryptophan residues in membrane proteins and peptides are believed to be distributed asymmetrically toward the interfacial region. Tryptophan octyl ester (TOE) is an important model for membrane-bound tryptophan residues. We have characterized this molecule as a fluorescent membrane probe in terms of its ionization, partitioning, and motional characteristics in unilamellar vesicles of dioleoylphosphatidylcholine. The ionization property of this molecule in model membranes has been studied by utilizing its pH-dependent fluorescence characteristics. Analysis of pH-dependent fluorescence intensity and emission maximum shows that deprotonation of the alpha-amino group of TOE occurs with an apparent pKa of approximately 7.5 in the membrane. The fluorescence lifetime of membrane-bound TOE also shows pH dependence. The fluorescence lifetimes of TOE have been interpreted by using the rotamer model for the fluorescence decay of tryptophan. Membrane/water partition coefficients of TOE were measured in both its protonated and deprotonated forms. No appreciable difference was found in its partitioning behavior with ionization. Analysis of fluorescence polarization of TOE as a function of pH showed that there is a decrease in polarization with increasing pH, implying more rotational freedom on deprotonation. This is further supported by pH-dependent red edge excitation shift and the apparent rotational correlation time of membrane-bound TOE. TOE should prove useful in monitoring the organization and dynamics of tryptophan residues incorporated into membranes.

Fluorescent Dyes↗
PubMed1997

Identification of actin as an estradiol 17-beta-stimulated protein in the human placenta.

Addition of estradiol 17-beta to first trimester human placental minces resulted in an increased synthesis of a protein of apparent molecular weight 45 kDa. The specific involvement of estrogen in the stimulation of this protein was established by demonstrating a reduction in the level of this protein by the addition of CGS 16949 A, an inhibitor of aromatase, a key enzyme in the biosynthesis of estradiol 17-beta and ICI 182,780, an estrogen receptor antagonist. The protein was purified to homogeneity and N-terminal sequencing of two of the internal peptides obtained by enzymatic digestion of the protein, as well as the absence of a free N-terminal indicated that it could be actin. This was confirmed by Western blotting using commercially available actin antiserum. The role of estradiol 17-beta in the stimulation of actin synthesis in human placenta was also established by monitoring the quantitative inhibition of DNase I by actin.

Actins↗
PubMed1997

Attitudes of the critically ill toward prolonging life: the role of social support.

Desires to prolong life were investigated in a hospitalized sample of 212 persons over age 50 whose illnesses were severe and who had an average life expectancy of six to twelve months. The importance of social support was emphasized in defining the context in which the stressors of unfinished business and fear of death prompted desires to prolong life. Interactions existed in predicting desires for prolonging life based on ethnicity and whether respondents did or did not have sustained family contact. Family contact and salience increased the desire to live longer for African Americans, but not for Whites.

Aged↗
PubMed1996

Phenobarbital in the anticonvulsant dose range does not impair learning and memory or alter brain AChE activity or monoamine levels.

The learning and memory in adult, male Wistar rats were assessed using the T-maze and passive avoidance tests after chronic administration of phenobarbital (PB) at 5, 15, 30, 60, or 75 mg/kg intraperitoneally (IP) for 21 days. The PB levels in plasma, the acetylcholine esterase (AChE) activity in the motor cortex, pyriform cortex, olfactory bulb, striatum, septum, and hippocampus and the levels of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) levels in the hippocampus were measured. There was no significant change in learning and memory, AChE activity, or monoamine levels at plasma PB levels of 1.5, 6.0, 9.0, and 25 micrograms/ml (corresponding to doses of 5, 15, 30, or 60 mg/kg PB, respectively). However, at a plasma level of 55 micrograms/ml (75 mg/kg), PB caused impairment in learning and memory. It was associated with an increase in AChE activity and 5-HT levels in the hippocampus. The results indicate that chronic PB administration may not be linked to impaired learning and memory functions at doses used in anticonvulsant therapy.

Acetylcholinesterase↗
PubMed1995

Stress-induced changes in regional monoamine metabolism and behavior in rats.

Groups of adult, male, Sprague-Dawley rats were subjected to either restraint at room temperature or cold restraint at 4 +/- 1 degree C for 2 h. Spontaneous motility, measured immediately after the stress, was decreased and defecation scores were increased in the cold restraint group but not in the restraint group. The rats were then sacrificed and prefrontal cortex, nucleus accumbens, and striatum dissected out. The levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) were measured in these areas by high performance liquid chromatography (HPLC) with electrochemical detection. DA levels were decreased in the prefrontal cortex (-68%), nucleus accumbens (-40%), and striatum (-76%) of the cold restraint group when compared to the controls. DA levels were decreased only in the prefrontal cortex of the restraint rats (-31%) when compared to the controls. The cold restraint group also had increased levels of DOPAC in the prefrontal cortex (+66%) and nucleus accumbens (+65%) and increased levels of HVA in the prefrontal cortex (+43%) when compared to the control group. Our results therefore indicate that cold restraint activates DA metabolism in the prefrontal cortex, nucleus accumbens, and striatum while restraint activates DA metabolism in the prefrontal cortex alone. Thus, cold restraint may be a more potent stressor than restraint alone.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Chronic phenytoin induced impairment of learning and memory with associated changes in brain acetylcholine esterase activity and monoamine levels.

Groups of adult, male, Wistar rats were administered phenytoin (DPH) at 5, 12.5, 25, 50, or 75 mg/kg i.p. for 21 days. The learning and memory of these rats were assessed using the T-maze and passive avoidance tests. The plasma DPH levels, acetylcholine esterase (AChE) activity in different brain regions, and the levels of monoamines in the hippocampus were measured. The results indicate that DPH below the therapeutic plasma level did not significantly impair learning and memory. Correspondingly, no changes were noted in the brain 5-HT or AChE activity. However, DPH, at therapeutic plasma concentrations (i.e., 10.5 micrograms/ml in the dosage range of 50 and 75 mg/kg, respectively), significantly impaired learning and memory in rats. The impaired learning and memory functions were associated with increased 5-HT levels and decreased AChE activity in the hippocampus. With a dose of 75 mg/kg DPH, there was a reduction in the AChE activity in the striatum, in addition to hippocampus. It is conjectured that the neurochemical changes brought about by DPH at therapeutic plasma levels may account for the impairment of learning, memory, and cognitive functions in epilepsy.

Acetylcholinesterase↗
PubMed1995

Changes in learning and memory, acetylcholinesterase activity and monoamines in brain after chronic carbamazepine administration in rats.

Groups of adult male Wistar rats were administered carbamazepine (CBZ) in doses of 5, 10, 20, 40 or 80 mg/kg/day intraperitoneally (i.p.) for 21 days. The learning and memory of the rats were assessed by the T-maze and passive avoidance tests. The CBZ plasma levels, the activity of acetylcholinesterase (AChE) in different brain regions, and the levels of monoamines in the hippocampus were also measured. None of the administered doses of CBZ impaired learning and memory. Rats with CBZ plasma levels of 2.5 and 4.5 micrograms/ml corresponding to the doses of 20 and 40 mg/kg, learned significantly better than controls. AChE activity was decreased in hippocampus and pyriform cortex (19%) in these groups. Simultaneously, an increase in the serotonin (5-HT) (36%) and dopamine (137%) levels in the hippocampus was noted in the 20-mg/kg CBZ group. 5-Hydroxyindole acetic acid (5-HIAA) and homovanillic acid (HVA) levels were increased at 10-, 20-, and 40-mg/kg CBZ doses. However, a dose of 80-mg/kg caused no change in learning performance as compared with that of controls. Correspondingly, no changes were evident in the AChE activity or monoamine levels. We postulated that the decreased AChE activity caused by CBZ in the therapeutic range may lead to increased ACh levels in brain, thus producing improvement in learning and memory. The increased turnover of 5-HT and dopamine (DA) in the hippocampus may play a role in long-term potentiation and improvement in memory.

Acetylcholinesterase↗
PubMed1995

Preliminary study of androgen, thyroid & adrenal status in alcoholic men during deaddiction.

To evaluate the status of the testes, thyroid, and adrenals in male alcoholics during the period of voluntary abstinence and therapy, chronic male drinkers undergoing a 4 wk inpatient deaddiction programme in a social hospital were recruited. Levels of a few serum and urinary hormones/metabolites viz., serum testosterone, total triiodothyronine (T3) and thyroxine (T4) and urinary total 17-ketosteroids (17-KS), estrone, estradiol, and 17-hydroxy corticosteroids (17-OHCS) were assessed in alcoholics thrice during the treatment programme at hospital i.e., on the zero (day of admission), 10th, and 20th day and compared to those of non-alcoholic controls. Alcoholics registered elevated serum total T3, and reduced total T4 and testosterone levels at admission, which persisted even after 20 days of the rehabilitative programme. Markedly high urinary levels of total 17-KS, estrone, and 17-OHCS were observed on zero day of admission. Urinary estrone and 17-OHCS, unlike total 17-KS, showed a trend to return to the normal range during the 20 days period. Urinary estradiol levels, however, recorded no significant alteration. The results of this preliminary study are suggestive of alcohol-induced perturbations on the functional integrity of the testes, thyroid, and adrenal in male alcohol addicts, wherein 20 days period of total alcohol abstinence and rehabilitative programme failed to reverse alcohol-induced hypoandrogenization and altered thyroidal status, but only partially restored certain biochemical events associated with the excretion of steroid metabolites.

17-Hydroxycorticosteroids↗
PubMed1994

Genotoxicity evaluation of pyrazinamide in mice.

Pyrazinamide, an antituberculosis drug, was investigated for genotoxicity in mice, an in vivo rodent system. Three doses (125, 250 and 500 mg/kg bw corresponding to 5, 10 and 20 times the therapeutic dose respectively) were tested. The mitotic index and the frequency of chromosomal aberrations were analysed at three sample times (3, 6 and 24 h) after a single intraperitoneal treatment. The frequency of sperm shape abnormalities was also examined. The mitotic index showed a decrease in drug-treated animals compared with that recorded in the control set. The cells with chromosomal aberrations ranged from 4% to 8%. The maximum frequency of aberrations was found at the 3-h sample time. The frequency of sperm shape abnormalities showed a dose-related increase. These observations suggest pyrazinamide to be a weak genotoxicant at the doses tested.

Animals↗
PubMed1993

Behavioral consequences of predictable vs. unpredictable shocks in rats.

Adult, male, Sprague-Dawley rats were given either predictable or unpredictable footshocks coupled with predictable or unpredictable warning stimuli in a factorially designed experiment. The effect of footshocks on different parameters of motility was studied immediately, 1 h and 24 h later. Footshock-induced stress caused increases in the motility of rats, and this increase persisted for 24 h. Of the parameters studied, distance travelled and time spent in ambulatory behavior were significantly affected, but there was no difference between the predictably and unpredictably shocked animals in the pattern or time course of stress-induced locomotion changes. The defecation scores recorded in footshocked rats were lower than in controls in both the predictably and unpredictably shocked groups, but there was no difference between the predictably and unpredictably shocked groups. Lack of differences in motility and defecation between the two groups limits the usefulness of these parameters in behavioral experiments based on predictability of noxious stimuli.

Animals↗