Search PubMed⌕ Search

Biomedical subjects

N Sehgal

Publications and source records attributed to N Sehgal.

18 recordsLinked to original sources

H2O2 at physiological concentrations modulates Leydig cell function inducing oxidative stress and apoptosis.

H(2)O(2) is one of the active reactive oxygen species secreted by macrophages that are seen closely aligned with Leydig cells in the testicular interstitium. The present study was initiated to investigate the role of H(2)O(2) on Leydig cell function in vitro at physiological concentrations. Significant decrease in both testosterone production (p < 0.05) and 3 beta-hydroxysteroid dehydrogenase activity (p < 0.05) in adult Leydig cells were observed even with H(2)O(2) at low concentrations (30 - 50 microM). H(2)O(2) exposure increased oxidative stress in Leydig cells with the rise in lipid peroxidation and fall in the activities of the antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT) & glutathione-s-transferase (GST). There was also a marginal increase (approximately 8%) in cell apoptosis accompanied by rise in FasL expression and caspase-3 activation. The above findings indicate that H(2)O(2) as a bio-molecule modulates Leydig cell function at or below physiological concentrations through a variety of actions like decrease in steroidogenic enzyme activity and increase in oxidative stress and apoptosis.

3-Hydroxysteroid Dehydrogenases↗

Antiretroviral agents restore Mycobacterium-specific T-cell immune responses and facilitate controlling a fatal tuberculosis-like disease in Macaques coinfected with simian immunodeficiency virus and Mycobacterium bovis BCG.

The contribution of immune reconstitution following antiretroviral treatment to the prevention or treatment of human immunodeficiency virus-related primary or reactivation tuberculosis remains unknown. Macaque models of simian immunodeficiency virus-Mycobacterium bovis BCG (SIV/BCG) coinfection were employed to determine the extent to which anti-Mycobacterium tuberculosis immunity can be restored by antiretroviral therapy. Both SIV-infected macaques with active BCG reinfection and naive animals with simultaneous SIV/BCG coinfection were evaluated. The suppression of SIV replication by antiretroviral treatment resulted in control of the active BCG infection and blocked development of the fatal SIV-related tuberculosis-like disease. The resolution of this disease coincided with the restoration of BCG purified protein derivative (PPD)-specific T-cell immune responses. In contrast, macaques similarly coinfected with SIV/BCG but not receiving antiretroviral therapy had depressed PPD-specific primary and memory T-cell immune responses and died from tuberculosis-like disease. These results provide in vivo evidence that the restoration of anti-mycobacterial immunity by antiretroviral agents can improve the clinical outcome of an AIDS virus-related tuberculosis-like disease.

Adenine↗

Purification of vitellogenin from the plasma of Indian freshwater murrel, Channa punctatus (Bloch) by different methods: a comparative study.

Plasma from estrogenized, [32P] NaH2PO4-injected murrel, Channa punctatus was collected in the presence of proteolytic inhibitors and subjected to different separation procedures singly or in combination, viz., gel filtration chromatography on Ultrogel AcA 34, ion-exchange chromatography on DEAE sephacel, or selective precipitation with dimethylformamide or with Mg2+: EDTA in order to isolate vitellogenin from other plasma proteins. The results show that chromatography on Ultrogel or DEAE sephacel yields intact vitellogenin whereas prior precipitation with DMF or with Mg2+: EDTA results in either co-precipitation of other plasma proteins or in the cleavage of phosvitin-like material from the native vitellogenin molecule.

Animals↗

Internal disc disruption and low back pain.

Internal disc disruption is a common cause of disabling low back pain in a substantial number of young, healthy adults. Crock described this painful entity and reported annular fissures that distort the internal architecture of the disc; Externally the disc appears relatively intact and undeformed. A clinical diagnosis of internal disc disruption, in absence of objective clinical findings, is extremely difficult. The only convincing means to establish the diagnosis is provocation discography. Unfortunately, this procedure is controversial, making the existence of internal disc disruption suspect. Recent studies indicate the existence of a biochemical/ biomechanical model of discogenic pain, which explains the disabling low back pain in some subjects with no objective evidence of nerve-root compromise. However, a reluctance to acknowledge internal disc disruption as a valid clinical entity delays diagnosis and treatment. Failure to identify and treat this entity early and aggressively results in longterm disability, thereby perpetuating the enigma of chronic low back pain.

Journal Article↗

Risk of recurrent seizures after a primary human herpesvirus 6-induced febrile seizure.

OBJECTIVE: To test the hypothesis that children experiencing first febrile seizures caused by human herpesvirus 6 (HHV-6) have an increased risk for recurrent seizures when compared with children experiencing first febrile seizures attributed to other illnesses. DESIGN AND PARTICIPANTS: Descriptive prospective study of 36 HHV-6 culture-positive children and a matched subgroup of 86 HHV-6 culture-negative children, all of whom had their first febrile seizures evaluated in a tertiary care emergency department and were followed for at least 12 months, with an average follow-up of 35.7 months. PRIMARY OUTCOME MEASURE: The recurrence of seizures among HHV-6 culture-positive and HHV-6 culture-negative children with no known previous neurologic deficits. RESULTS: A decreased incidence of recurrent seizures occurred in children whose first febrile seizures were caused by HHV-6. Twenty percent of HHV-6 culture-positive children and 40% of HHV-6 culture-negative children (P < 0.038) experienced a recurrent seizure within 1 year of their first febrile seizure. The mean time to recurrence within 12 months was 8.6 months for children with HHV-6 infection and 3.8 months (P < 0.001) for children without HHV-6 infection. Most recurrent seizures occurred within 12 months of a first febrile seizure for both HHV-6-positive and HHV-6-negative children (88 and 91%). CONCLUSIONS: Children who had their first febrile seizures caused by primary HHV-6 infection did not demonstrate an increased risk for recurrent seizures when compared with children whose first febrile seizures were from other etiologies.

Child, Preschool↗

Beyond Ashworth. Electrophysiologic quantification of spasticity.

Spasticity is a hallmark of upper motor neuron lesion, which is easily identified but is difficult to quantify and treat. The Ashworth scale lacks reliability. Available biomechanical and electrophysiologic studies offer a more reliable measure of spastic hypertonia but have limited clinical utility. A uniformly acceptable, reliable, and practical measure of spasticity continues to elude the clinician. This chapter reviews the basic neuroanatomy and physiology of the stretch reflex and the pathophysiology of the spasticity. Current biomechanical and electrophysiological techniques are used to quantify spasticity.

Afferent Pathways↗

Three-dimensional reconstruction of anomalous beige mouse macrophage lysosomes.

Cells of the beige mouse, the murine counterpart of the Chediak-Higashi Syndrome, contain enlarged anomalous lysosomes. The three-dimensional structure of these lysosomes from peritoneal macrophage was ascertained by study of electron micrographs taken in a series of serial sections combined with computer-assisted analysis. The most common basic structural units identified were biconcave discs and hollow cup/ovoid-shaped structures. Other more bizarre forms were represented by the fusion of these basic lysosomal variants. Anomalous lysosomal forms were found in both beige resident and exudate peritoneal macrophage. A similar study of lysosomes in animals not carrying the beige mutation revealed the presence of smaller but structurally similar forms of the basic lysosomal variants. This latter finding indicates that the presence of lysosomal variants per se in the beige animal is not a finding unique to these animals but rather that their distinctiveness derives from their increased size and propensity to undergo fusion with each other. The usefulness of computer-assisted three-dimensional reconstruction is demonstrated.

Animals↗

Qualitative and quantitative differences between resident peritoneal mononuclear phagocytes of beige and control mice.

A qualitative and quantitative comparison of resident peritoneal macrophages (RPM) from beige (C57BL6Jbg/bg), (bg), and control black (C57BL/6J), (BL), mice has been made. Giant anomalous lysosomes as described for other leukocytes are inconsistently demonstrable. The principal morphological expression of the bg phenotype in RPM is the presence of elongated dumbbell-shaped, horseshoe-shaped, and ring-formed cytoplasmic lysosomes demonstrable by electron microscopy. Detailed analysis indicates that these are probably variations of the same basic structure, a deformed biconcave disc with differences in form resulting from their being cut in various planes of section. Additional structural complexity results from fusion between adjacent lysosomes. Thus the distinctive lysosomes of bg mouse RPM are not totally analogous to those structures described in other cell types. A morphometric analysis of control RPM compared to those from bg animals shows a significant decrease in the lysosomal volume proportion from 5.8% to 5.0% (P less than 0.02) with a corresponding increase in the mitochondrial volume proportion in cells from bg animals (P less than 0.05). There are no differences between bg and controls in regard to cellular profile areas, nuclear profile areas, nuclear volume proportions, and the volume to surface ratios of either the average cell or nucleus. This study represents the first compilation by morphometric methods of total granule content in the bg animal and demonstrates the ability of these techniques to detect significant quantitative changes in cells as structurally complex as mononuclear phagocytes.

Animals↗

Changes in content and cAMP-dependent phosphorylation of specific proteins in granulosa cells of preantral and preovulatory ovarian follicles and in corpora lutea.

The responsiveness of granulosa cells to the gonadotropins and cAMP increases as ovarian follicles mature. To determine if this change in response might be related to either the content or cAMP-dependent phosphorylation of specific proteins, we labeled proteins in 30,000 X g supernatant fractions (cytosol) with [gamma-32P] ATP in the presence or absence of cAMP. Using two-dimensional gel electrophoresis, we observed that granulosa cells of preantral follicles exhibited low amounts of cAMP-dependent phosphorylation of two proteins with apparent molecular weights of 54,000-56,000 and 43,000. Using [32P]8-N3cAMP and photoaffinity labeling procedures, the Mr = 54,000-56,000 protein was identified as RII, the regulatory subunit of type II protein kinase. Polychromatic silver staining, as well as the photoaffinity labeling, revealed that RII exists in three forms, each of which was also labeled by [gamma-32P] ATP. Based on the relative isoelectric points and specific silver staining of highly purified actin and phosphorylated actin, the Mr = 43,000 protein has been provisionally identified as actin. Five proteins (Mr = 37,500, 27,500, 22,500, 19,000, and 15,000), in addition to RII and actin, were phosphorylated in cytosol of granulosa cells from preovulatory follicles. By adding increasing concentrations of exogenous catalytic subunit to the cytosols, we demonstrated that the content, as well as the phosphorylation of these proteins, was increased selectively in granulosa cells of antral follicles. By using hypophysectomized rats, we demonstrated that these five proteins are induced by follitropin (FSH). Because they were not present in cytosols of thecal cells or corpora lutea, they appear to be specific markers for granulosa cells. The content and phosphorylation of RII was also dramatically increased in cytosols of granulosa cells from antral follicles, whereas that of actin remained unchanged. These observations indicate that granulosa cell differentiation involves regulation by FSH of specific proteins which are substrates for cAMP-dependent protein kinase. Thus, FSH and cAMP appear to regulate the intracellular content and phosphorylation of a cAMP response system in granulosa cells. The extent to which RII and the five specific phosphoproteins themselves regulate granulosa cell responsiveness remains to be determined.

Animals↗

Ocular leprosy.

Explore the source record for details and available documents.

Adolescent↗

Epidemiological and clinical patterns of genital lesions.

A 5-year study of 668 patients with genital lesions revealed that teenagers and those in the age group of 20 to 40 are most vunerable. The poor, the uneducated and unmarried persons are at high risk. Chancroid and syphilis are the majority of cases. Inguinal bubo, herpes pregenitalis, condylomata acuminata, erosive balanitis and traumatic ulcers were seen less frequently. Most of the genital lesions had the classic clinical features. The findings of this study suggest that the pattern of genital lesions is showing borderline changes.

Adolescent↗

The disruption of macaque CD4+ T-cell repertoires during the early simian immunodeficiency virus infection.

T-cell receptor (TCR) complementarily determining region 3 (CDR3) spetratyping analysis was employed to assess the ability of an AIDS virus to disrupt CD4 + T-cell repertoires during the primary infection. Rhesus and pig-tailed macaques infected with simian immunodeficiency virus (SIV)mac 251 and SIVsmmFGb, respectively, were evaluated. Following SIV infection, the macaques exhibited an apparent decline of CD4 + peripheral blood lymphocyte (PBL) counts, which was associated with a change in CDR3 profiles from multiple-length distribution to one- or two-length dominance in the selected TCR Vbeta-expressing CD4 + PBL subpopulations. Molecular analysis of the perturbed cell subpopulations suggested that the CD4 + T cells bearing the dominant CDR3 length were clonally expanded. These results indicate that SIV infection can induce a disruption of macaque CD4 + T-cell repertoires during the primary infection. The finding in this study, therefore, suggests that the virus-induced clonal dominance can contribute to the disruption of CD4 + T-cell repertoires.

Animals↗