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Biomedical subjects

S Jain

Publications and source records attributed to S Jain.

At least 253 records · Page 14Linked to original sources

Joubert syndrome: an affected female with bilateral colobomata.

Joubert syndrome is an autosomal recessive disease characterised by hypoplasia or agenesis of the cerebellar vermis, a syndrome of episodic apnoea-hyperpnoea, rhythmic protrusion of the tongue, abnormal eye movements, hypotonia, ataxia, and psychomotor retardation. Extracerebral malformations include multicystic kidney disease, congenital hepatic fibrosis, sacral dermoid cyst and polydactyly. We report the clinical and pathological findings of a 15-year-old girl with Joubert syndrome diagnosed at autopsy. This patient had bilateral colobomata, which has not been previously described in females with Joubert syndrome.

Abnormalities, Multiple↗

Evaluation of oxidative stress before and after haemodialysis in chronic renal failure.

OBJECTIVE: To evaluate the oxidative stress before and after haemodialysis in chronic renal failure patients. METHODS: A prospective study comprising of 22 patients of CRF who have to receive their first haemodialysis. All patients were subjected to standard four hours haemodialysis. The parameters of oxidative stress i.e. erythrocyte malonaldehyde (MDA), reduced glutathione (GSH) and superoxide dismutase (SOD) were measured before and after haemodialysis. RESULTS: The value of mean erythrocyte MDA (9.40 +/- 3.36 mumol/L) and SOD (617 +/- 64.33 units/ml) were significantly higher in patients of CRF before haemodialysis than in controls (p < 0.001). The mean GSH levels were significantly lower (451 +/- 63.91 micrograms/ml) in patients than in controls before haemodialysis (p < 0.001). After haemodialysis MDA levels further increased (12.27 +/- 4.38 mumol/L), SOD levels decreased (458 +/- 69.58 EU/ml) and GSH levels further decreased (396 +/- 41.41 micrograms/ml) (p < 0.001). CONCLUSIONS: There was an evidence of oxidative stress in patients of CRF before haemodialysis which increased further after haemodialysis, the mechanisms of which is not delineated. The procedural factors may be contributing in the increased oxidative stress after haemodialysis.

Adult↗

Transgenic strategies for genetic improvement of Basmati rice.

Transgenic approach offers an attractive alternative to conventional techniques for the genetic improvement of Basmati rice because they enable the introduction of one or more genes into a leading cultivar without affecting its genetic background. During the last ten years, a rapid progress has been made towards the development of transformation methods in rice. Several transformation methods including Agrobacterium, biolistic, and DNA uptake by protoplasts, have been employed to produce transgenic rice. An array of useful genes is now available and many of these have already been transferred in rice to improve the resistance against biotic and abiotic stresses. In Basmati rice, a beginning has already been made regarding the development of tissue culture protocols, transformation methods and production of useful transgenic plants. The application and future prospects of transformation technology to engineer the resistance against insect pests (stem borer, leaf folder, brown plant hopper, gall midge), fungal diseases (blast, bakanae/foot, rot), bacterial diseases (bacterial leaf blight, sheath blight), abiotic stresses (salinity and drought) and improved nutritional quality (accumulation of provitamin A and essential amino acids in endosperm) in Basmati rice, have been addressed.

Breeding↗

Stress induced neuron degeneration and protective effects of Semecarpus anacardium Linn. and Withania somnifera Dunn. in hippocampus of albino rats: an ultrastructural study.

Effects of herbal formulations were studied on hippocampal neuron cell bodies. Study was carried out in adult Swiss albino rats. Experimental rats (E) were divided into three groups. Group E1 rats were given immobilization stress for 14 hr/day for 30 days. Rats in E2 and E3 group were given daily single dose (40 mg/kg/body wt.) of alcoholic extract of S. anacardium and W. somnifera. After 1 hr giving the plant extract, the rats were subjected to stress. Treatment continued for 14 hr for 30 days. Control rats were kept in complete nonstress condition. Ultrastructural characteristics of neuron cell bodies in hippocampal sublayer (CA1-CA4 and Dg) was studied in rats of E1, E2 and E3 groups and compared with control. Results of the present study demonstrated, that both CA2 and Dg, 85% of neuron cell bodies exhibited degenerating characteristics, (which includes karyorrhexis, membrane blebbing, chromatin condensation, chromatin fragmentation and intracellular spacing). Interestingly, after the treatment with S. ancardium cells demonstrating degenerating characteristics was significantly reduced (80%) as compared to treatment with W. somnifera. Study suggests that probably both the herbal drugs have cytoprotective properties.

Animals↗

Foetal amygdalar transplantation facilitates recovery of retention deficit in CeA lesioned rats.

Neural tissue transplant has come off age as a valuable technique for studying normal development and regeneration. Bilateral lesions of the central nucleus of amygdala (CeA) produce complete retention and acquisition deficit in inhibitory avoidance paradigms. The present study reports recovery of retention deficit in active avoidance task (AA) after amygdalar tissue transplantation in CeA lesioned rats. In a group of adult wistar rats, bilateral lesions of the CeA were produced electrolytically. In a separate group of rats foetal amygdalar tissue was transplanted at the CeA lesioned site 2 days after producing lesion. All the rats were trained on AA task before and after 5 days of lesion. In bilaterally CeA lesioned rats, the percentage of avoidance (% avoidance) decreased significantly (P < 0.05) from 85 +/- 18% prelesion to 15.5 +/- 35% postlesion. However, no change in the % avoidance was observed after amygdalar tissue transplantation. The results indicate that the transplanted rats are capable of retaining the learnt information in contrast to the lesion alone group of rats.

Amygdala↗

Effect of tonic pain on schedule specific feeding behaviour.

Food deprivation produces analgesia. This response is reversed i.e. pain sensitivity is lowered, when the food deprived rats are fed. In the present study the effect of chronic pain on the motivation to get food, in food deprived rats, was observed. In ten rats the effect of formalin and morphine plus formalin on the motivation to get food was studied. Injection of formalin significantly (P < 0.01) decreased the number of lever presses from 450 +/- 30 to 225 +/- 25. However, after injecting morphine the effect was reversed. The present study shows reduced internal drive to procure food by the food deprived animals, when they were under chronic pain. The effect was blocked by morphine, suggesting the role of opioids in modulating the motivation for getting food.

Animals↗

Pachygyria/hypogenitalism: A monogenic syndrome.

We describe the clinical and neuroimaging findings of two severely retarded boys born to consanguineous parents. This appears to be a monogenic condition of abnormal neuronal migration associated with hypogenitalism. Reports of other monogenic syndromes of neuronal migration abnormalities are reviewed.

Cell Movement↗

Amplification and overexpression of peroxisome proliferator-activated receptor binding protein (PBP/PPARBP) gene in breast cancer.

Peroxisome proliferator-activated receptor binding protein (PBP), a nuclear receptor coactivator, interacts with estrogen receptor alpha (ERalpha) in the absence of estrogen. This interaction was enhanced in the presence of estrogen but was reduced in the presence of antiestrogen, tamoxifen. Transfection of PBP in CV-1 cells resulted in enhancement of estrogen-dependent transcription, indicating that PBP serves as a coactivator in ER signaling. To examine whether overexpression of PBP plays a role in breast cancer because of its coactivator function in ER signaling, we determined the levels of PBP expression in breast tumors. High levels of PBP expression were detected in approximately 50% of primary breast cancers and breast cancer cell lines by ribonuclease protection analysis, in situ hybridization, and immunoperoxidase staining. Fluorescence in situ hybridization of human chromosomes revealed that the PBP gene is located on chromosome 17q12, a region that is amplified in some breast cancers. We found PBP gene amplification in approximately 24% (6/25) of breast tumors and approximately 30% (2/6) of breast cancer cell lines, implying that PBP gene overexpression can occur independent of gene amplification. This gene comprises 17 exons that, together, span >37 kilobases. The 5'-flanking region of 2.5 kilobase pairs inserted into a luciferase reporter vector revealed that the promoter activity in CV-1 cells increased by deletion of nucleotides from -2,500 to -273. The -273 to +1 region, which exhibited high promoter activity, contains a typical CCAT box and multiple cis-elements such as C/EBPbeta, YY1, c-Ets-1, AP1, AP2, and NFkappaB binding sites. These observations, in particular PBP gene amplification, suggest that PBP, by its ability to function as ERalpha coactivator, might play a role in mammary epithelial differentiation and in breast carcinogenesis.

Base Sequence↗

Active site residues of human beta-glucuronidase. Evidence for Glu(540) as the nucleophile and Glu(451) as the acid-base residue.

Human beta-glucuronidase (hGUSB) is a member of family 2 glycosylhydrolases that cleaves beta-D-glucuronic acid residues from the nonreducing termini of glycosaminoglycans. Amino acid sequence and structural homology of hGUSB and Escherichia coli beta-galactosidase active sites led us to propose that residues Glu(451), Glu(540), and Tyr(504) in hGUSB are involved in catalysis, Glu(451) being the acid-base residue and Glu(540) the nucleophile. To test this hypothesis, we introduced mutations in these residues and determined their effects on enzymes expressed in COS cells and GUSB-deficient fibroblasts. The extremely low activity in cells expressing Glu(451), Glu(540), and Tyr(504) hGUSBs supported their roles in catalysis. For kinetic analysis, wild type and mutant enzymes were produced in baculovirus and purified to homogeneity by affinity chromatography. The k(cat)/K(m) values (mM(-1).s(-1)) of the E540A, E451A, and Y504A enzymes were 34,000-, 9100-, and 830-fold lower than that of wild type hGUSB, respectively. High concentrations of azide stimulated the activity of the E451A mutant enzyme, supporting the role of Glu(451) as the acid-base catalyst. We conclude that, like their homologues in E. coli beta-galactosidase, Glu(540) is the nucleophilic residue, Glu(451) the acid-base catalyst, and Tyr(504) is also important for catalysis, although its role is unclear. All three residues are located in the active site cavity previously determined by structural analysis of hGUSB.

Animals↗

Molecular basis of feline beta-glucuronidase deficiency: an animal model of mucopolysaccharidosis VII.

A family of domestic cats was found that exhibited clinical and biochemical abnormalities consistent with mucopolysaccharidosis VII, an autosomal recessive lysosomal storage disorder caused by beta-glucuronidase deficiency. beta-Glucuronidase activity was undetectable in affected cat fibroblasts and restored by retroviral gene transfer of rat beta-glucuronidase cDNA. beta-Glucuronidase mRNA was normal in affected cat testis by Northern blot analysis. Normal feline beta-glucuronidase cDNA was cloned and characterized, and amplified from affected cat fibroblasts by reverse transcription coupled polymerase chain reaction. There was a G-to-A transition in the affected cat cDNA that predicted an E351K substitution, destroyed a BssSI site, and eliminated GUSB enzymatic activity in expression studies. Multiple species comparison and the crystal structure of human beta-glucuronidase indicated that E351 is a highly conserved residue most likely essential in maintenance of the enzyme's conformation. BssSI digestion of polymerase chain reaction products amplified from genomic DNA indicated that affected cats were homozygous and cats with half-normal beta-glucuronidase activity were heterozygous for the missense mutation. Carriers identified in this manner produced affected kittens in prospective breedings, and a feline MPS VII breeding colony has been established.

Amino Acid Sequence↗

Analysis, expression and prevalence of the Mycobacterium tuberculosis homolog of bacterial virulence regulating proteins.

We have previously reported the identification of a gene from Mycobacterium tuberculosis, H37Rv, which on the basis of its nucleotide sequence encoded a protein product of 38 kDa. This 38-Kda mycobacterial protein designated as VirS exhibits homology with the VirF protein of Shigella, the VirFy protein of Yersinia and the Cfad, Rns and FapR proteins from various enterotoxigenic Escherichia coli strains. In this communication, we show the close sequence and structural similarities of the VirS protein with VirF, VirFy, Cfad, Rns and FapR and describe the results of our studies on the characterization of the virS gene promoter and its expression in E. coli and mycobacteria. virS was present exclusively in the species belonging to the M. tuberculosis complex as revealed by Southern blot and PCR analysis. Our findings suggest the involvement of virS in the regulation of pathogenesis of M. tuberculosis.

Amino Acid Sequence↗

Correlation of acetylator phenotype with peripheral, autonomic and central neuropathy in Northern Indian non-insulin-dependent diabetes mellitus patients.

OBJECTIVES: Genetic susceptibility to diabetic neuropathy has been suspected and tentatively explored; however, diabetic autonomic and central neuropathies are poorly investigated areas. Previous trials correlating types of diabetes and diabetic neuropathy with acetylator dimorphisms have not been conclusive. The present study was designed to test peripheral neuropathy, autonomic neuropathy and integrity of central conduction pathways in patients of non-insulin-dependent diabetes mellitus (NIDDM), and to correlate the findings with the acetylator phenotype. METHODS: Twenty-six patients of NIDDM with stable glycaemic control and 11 age- and sex-matched control subjects were recruited, clinically examined and investigated with glycaemic and lipid profile, renal function tests, nerve conduction studies (sensory and motor), auditory brain stem evoked responses (ABERs) and somatosensory evoked potentials (SEPs). Acetylator status of the subjects was determined by sulphadimidine test. RESULTS: Out of 26 NIDDM patients, eight (30.7%; group 1A) were slow acetylators and 18 (69.3%; group 1B) were fast acetylators. The distribution of slow and rapid acetylators in both the groups was similar. Glycaemic and lipid profiles and 24-h urinary albumin excretion in groups 1A and 1B were also similar. Motor nerve conduction velocity, latency of F wave, sensory nerve conduction and amplitudes of sensory nerve action potentials were not different between fast and slow acetylator NIDDM patients. On testing for ABERs, there were no statistically significant differences in peak latencies of waves I, III and V; interpeak latencies (IPLs) I-III, III-V and I-V; amplitude of waves I, III and V on both sides between NIDDM patients and controls. However, peak latencies of wave III (P < 0.01), wave V (P < 0.005), IPLs I-III and I-V (P < 0.005), IPLs III-V (P < 0.05), and amplitudes of wave I (P < 0.05) and wave V (P < 0.05) on the left side were significantly different in slow acetylator NIDDM patients. Increase on the right side for the same group was statistically significant for IPLs I-III and I-V (P < 0.05). SEPs showed no statistically significant difference between NIDDM patients and controls, and slow and fast acetylator NIDDM patients. CONCLUSIONS: No significant association of acetylator status with peripheral neuropathy in NIDDM subjects was observed in the present study. However, central neural conduction, primarily tested by ABERs, was significantly delayed in slow acetylators compared with fast acetylator NIDDM patients. Hence, there may be a predisposition to neuropathy in this group of patients, and such a predisposition may be better detected by studying central rather than peripheral nervous conduction pathways in NIDDM patients.

Adult↗

Effect of estradiol and selected antiestrogens on pro- and antioxidant pathways in mammalian uterus.

In this study, we examined the effect of 17 beta-estradiol and selected antiestrogens on uterine NADPH-oxidase activity, superoxide dismutase (SOD) activity, hydride (H.-), dienyl radical and O2 -radical generation, and membrane fluidity. NADPH oxidase activity was positively modulated in estradiol-treated animals and negatively regulated in animals that received injections of AF-45, RU-39411, tamoxifen, or ICI-182780. The SOD activity was markedly reduced in estradiol-treated animals when compared with the control animals. A positive modulation of SOD activity was observed upon treatment with AF45, RU39411, tamoxifen, and ICI 182780, though the potency varied among the individual test compounds. We observed detectable H(.-)-radical generation as evidenced from MNP H.- adduct formation in the uterine cell preparations from untreated control animals. Estradiol produced a tremendous augmentation in the superoxide radical profiles in uterine cell preparations compared to the control levels. All the other compounds that were tested significantly lowered the superoxide levels in the test set-up. AF-45, RU-39411, tamoxifen, and ICI-182780 induced varying orders of suppression of H(.-)-radical generation in the test subjects. There was a significant enhancement in membrane fluidity, hydride radical levels, and dienyl radical generation in the estradiol-treated group. All the antiestrogens did not exhibit a similar action on these parameters. RU-39411 exhibited antiestrogen-like activity in modulating hydride levels and membrane fluidity, whereas it stimulated dienyl radical generation. Thus our tests showed that the selected antiestrogens failed to show estrogen-like activity in these assays. It appears that estradiol exerts feedback control over pro- and antioxidant pathways and that markers of oxidative status could be used as a measure to evaluate the antiestrogenic activity of estradiol agonists/antagonists.

Animals↗

Chocolate cysts from ovarian follicles.

OBJECTIVE: To study the development of chocolate cysts by serial transvaginal ultrasonographic tracking of ovarian follicles. DESIGN: Retrospective study. SETTING: Department of Obstetrics and Gynaecology, Sunderland Royal Hospital, Sunderland, United Kingdom. PATIENT(S): We reviewed case notes of all patients who underwent laparoscopy for diathermy to endometriosis/ovarian diathermy/aspiration of ovarian cysts from 1989 to 1998. Twelve women with histories of infertility and proven chocolate cysts with documented ultrasonographic findings were included in the study. INTERVENTION(S): Serial ultrasonographic tracking of ovarian follicles in the cycle leading to the development of the chocolate cysts, followed by ultrasonographic tracking of cysts for 3 months and laparoscopy. MAIN OUTCOME MEASURE(S): Development and formation of chocolate cysts. RESULT(S): The diagnosis of chocolate cysts was confirmed laparoscopically in all patients and histopathologically in four. Ultrasound confirmed that they had all developed from follicles. CONCLUSION(S): Chocolate cysts can develop from ovarian follicles.

Adult↗