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Biomedical subjects

S Joshi

Publications and source records attributed to S Joshi.

At least 127 records · Page 7Linked to original sources
PubMed1997

Intra-arterial nitrovasodilators do not increase cerebral blood flow in angiographically normal territories of arteriovenous malformation patients.

BACKGROUND AND PURPOSE: The mechanism of adaptation to chronic cerebral hypotension in normal brain adjacent to cerebral arteriovenous malformations (AVMs) is unknown. To clarify these mechanisms, we performed cerebral blood flow (CBF) studies in structurally and functionally normal vascular territories during 53 distal cerebral angiographic procedures in 37 patients with AVMs. METHODS: CBF was measured using the superselective intra-arterial 133Xe method before and after a 3-minute infusion of either verapamil (1 mg.min-1, n = 23), acetylcholine (1.33 micrograms.kg-1.min-1, n = 7), nitroprusside (0.5 microgram.kg-1.min-1, n = 16) or nitroglycerin (0.5 microgram.kg-1.min-1, n = 7). RESULTS: Mean +/- SD systemic (76 +/- 13 mm Hg) and distal cerebral arterial (55 +/- 16 mm Hg; range, 20 to 97 mm Hg) pressures were not different among groups. Verapamil increased CBF (45 +/- 12 to 65 +/- 21 mL.100 g-1.min-1, P < .001). There was no effect of acetylcholine (no change [46 +/- 9 to 46 +/- 9 mL.100 g-1.min-1], NS) or nitroglycerin (36 +/- 14 to 36 +/- 13 mL.100 g-1.min-1, NS). Nitroprusside decreased CBF (40 +/- 12 to 31 +/- 11 mL.100 g-1.min-1, P < .001). The percent change in CBF after drug administration was proportional to cerebral arterial pressure for verapamil only (r = .57, P = .0051). CONCLUSIONS: When infused intra-arterially in clinically relevant doses in both hypotensive and normotensive normal vascular territories remote from an AVM nidus, calcium channel blockade caused vasodilation, but there was an absence of response to nitric oxide-mediated vasodilators. These data suggest that (1) the nitric oxide pathway probably is not involved in the adaptation to chronic cerebral hypotension in AVM patients and (2) if our findings in vessels remote from or contralateral to the AVM are applicable to vessels of patients with other forms of cerebrovascular disease, clinically relevant doses of intra-arterial nitrovasodilators may not be useful in the manipulation of cerebrovascular resistance.

Acetylcholine↗
PubMed1997

Statistical methods in computational anatomy.

This paper reviews recent developments by the Washington/Brown groups for the study of anatomical shape in the emerging new discipline of computational anatomy. Parametric representations of anatomical variation for computational anatomy are reviewed, restricted to the assumption of small deformations. The generation of covariance operators for probabilistic measures of anatomical variation on coordinatized submanifolds is formulated as an empirical procedure. Populations of brains are mapped to common coordinate systems, from which template coordinate systems are constructed which are closest to the population of anatomies in a minimum distance sense. Variation of several one-, two- and three-dimensional manifolds, i.e. sulci, surfaces and brain volumes are examined via Gaussian measures with mean and covariances estimated directly from maps of templates to targets. Methods are presented for estimating the covariances of vector fields from a family of empirically generated maps, posed as generalized spectrum estimation indexed over the submanifolds. Covariance estimation is made parametric, analogous to autoregressive modelling, by introducing small deformation linear operators for constraining the spectrum of the fields.

Algorithms↗
PubMed1997

Gamma radiation induced leukemia in ICRC strain of mice: a murine model closely simulating human disease for experimental chemotherapy.

We report here a murine model of transplantable lymphoblastic leukemia closely simulating human disease in albino mice of ICRC strain. Both male and female mice of this strain developed leukemia with high incidence (approximately 70%) following whole body exposure to 60Co Gamma Rays (Dose: 1.5 Gray/Week x4). The latent period for development of leukemia was six months. In the leukemic mice there is marked leucocytosis with presence of lymphoblasts in peripheral blood. These blasts infiltrate various organs like liver, spleen, kidney, lymph nodes, testes and brain, Neoplastic cells are T lymphoblasts expressing weak Thy 1.2 membrane antigen and found sensitive to anticancer drugs. Salient features of the murine model are described.

Animals↗
PubMed1997

Topical aspirin provides protection against galactosemic cataract.

Effect of twice daily administration of aspirin eyedrops on the onset and progression of cataract induced by 30% galactose diet was studied. On the 30th day of galactose feeding while all control group rats showed complete stage IV opacity, those receiving aspirin eyedrops showed only mild cataractous changes of stage I. In vitro studies showed that addition of aspirin to the medium significantly decreased dulcitol formation (p < 0.01) and maintained glutathione levels (p < 0.02). Intraocular penetration studies using isolated goat cornea showed excellent penetration by salicylate indicating feasibility of topical administration. The results of the present study demonstrate that topical aspirin possesses significant anticataract activity in galactosemic cataract.

Administration, Topical↗
PubMed1996

Synthesis and HIV inhibition activity of 2',3'-dideoxy-3'-C-hydroxymethyl nucleosides.

A series if 2',3'-dideoxy-3'-C-hydroxymethyl purine nucleosides were prepared based on the photochemical ring expansion of a chiral cyclobutanone precursor, (2S)-trans-2,3-bis[(benzoyloxy)methyl]cyclobutanone, in the presence of a 6-substituted purine. Both alpha- and beta-anomers are produced in this transformation. Deprotection was effected by reaction of the photoadducts with saturated methanolic ammonia. Nine purine nucleosides were tested for their inhibitory effect of HIV IIIB virus on H9 cells. The 6-hexyloxy and adenine derivatives 4e,c, respectively, appeared to be most effective at inhibiting viral reproduction with 4c comparable in activity to ddI and AZT.

Anti-HIV Agents↗
PubMed1996

Oligomycin sensitivity conferring protein of mitochondrial ATP synthase: deletions in the N-terminal end cause defects in interactions with F1, while deletions in the C-terminal end cause defects in interactions with F0.

The structure/function relationships of oligomycin sensitivity conferring protein (OSCP) of bovine mitochondrial ATP synthase were studied by nested deletion mutagenesis, followed by analyses of the resultant OSCPs for their ability to restore partial reactions of ATP synthesis in OSCP-depleted F1-F0 complexes. Our results indicate that, from the N-terminus of OSCP, up to 13 amino acid residues could be deleted without any effect on OSCP coupling activity. However, deletion of 16 or more residues led to a slow decline in the ability of resultant mutant forms to restore ATP synthesis. Compared to the wild-type form of OSCP, deletion mutant ND-28 (deletion of residues 1-28) is 50% as active in its ability to reconstitute ATP-Pi exchange activity. Detailed analyses of mutant ND-28 revealed that it was able to bind to the membrane segment (F0) of ATP synthase and restore oligomycin-sensitive ATPase activity in OSCP-depleted F1-F0 complexes. However, it did not bind to soluble segment F1, nor did it confer cold stability to either soluble F1 or reconstituted F1-F0 complex. On the other hand, studies on nested deletions on the C-terminal end indicate that three residues could be deleted without compromising the energy-coupling activity of OSCP. However, truncations of five or more residues caused an impairment in the ability of resultant mutant forms to restore ATP-Pi exchange activity in OSCP-depleted complexes. Mutant CD-10 (deletion of amino acids 181-190) was completely ineffective as a coupling factor. Detailed analyses of this mutant revealed that the subunit was able to bind to soluble F1 segment and confer cold stability to the enzyme but was neither able to associate with the membrane segment (F0) nor able to reconstitute high oligomycin sensitivity in depleted F1-F0 complexes. We take these data to suggest that the N-terminal end of OSCP corresponding to residues G16-N28 is essential for binding of the coupling factor to soluble F1 but not for coupling the energy of proton translocation to the synthesis of ATP; on the other hand, the carboxyl-terminal end of OSCP containing amino acids K181-M186 is important for F0-OSCP interactions as well as for the coupling of the energy of delta microH+ during the synthesis of ATP. These results suggest a model for OSCP in which the N-terminus is associated with the F1 segment and the C-terminus is associated with the F0 segment, while the central part of the polypeptide forms three or more helices constituting the stalk in the intact F1F0 enzyme.

Adenosine Triphosphatases↗
PubMed1996

Fusion with an RNA binding domain to confer target RNA specificity to an RNase: design and engineering of Tat-RNase H that specifically recognizes and cleaves HIV-1 RNA in vitro.

A target RNA/DNA-specific nuclease could be constructed if a specific RNA/DNA binding domain allowing target RNA/DNA recognition was fused to a (deoxy)ribonucleolytic domain allowing target RNA/ DNA cleavage. The design and construction of such a chimeric enzyme could be of value for both basic research involving structure-function relationships and applied research requiring inactivation of harmful RNA/DNA molecules of cellular or pathogenic origin. The feasibility of this designer nuclease approach for inactivating specific RNA/DNA molecules was assessed using human immunodeficiency virus type-1 (HIV-1) RNA as a model. Trans-activator of transcription (Tat) protein is one of the key regulatory proteins encoded by HIV-1. It binds to the trans-activation-responsive (TAR) RNA element located within the 5' non-coding region of HIV-1 RNAs. The TAR RNA binding domain of this protein was fused to the ribonuclease (RNase) H domain of HIV-1 reverse transcriptase (RT). RNase H by itself lacks an RNA binding domain. The chimeric Tat-RNase H protein was shown to specifically recognize and cleave HIV-1 TAR RNA in vitro. Cleavage was abolished by mutations in the Tat binding region within the TAR RNA, indicating that it is specific to HIV-1 TAR RNA.

Base Sequence↗
PubMed1996

Identification of guanine nucleotide binding regulatory proteins in bovine tracheal smooth muscle.

The identity of G-proteins in airway smooth muscle is not well elucidated. In the present study, by immunoblotting using AS/7 antibody specific for Gi alpha-1/2, EC/2 antibody specific for Gi alpha-3 and RM/1 antibody specific for Gs alpha, we identified, respectively, Mr 39, 41, 46 and 52 KDa, Mr 41 and 43 KDa, and Mr 43 and 46 KDa polypeptides of conventional (heterotrimeric) G-proteins in purified membranes of bovine tracheal smooth muscle. The identity of the Mr 41, 43 and 52 KDa Gi alpha, and the Mr 43 and 46 Gs alpha was also confirmed by ADP-ribosylation with pertussis and cholera toxins, respectively. In addition, the common antibody (AG/1) for both Gi alpha and Gs alpha revealed the presence of all the above polypeptides, except the Mr 52 KDa band. By nitrocellulose blot overlay with [35S]s alpha GTP gamma S, we also detected seven low molecular weight GTP-binding proteins of Mr 18-30 KDa in the bovine tracheal smooth muscle. Photoaffinity crosslinking of [alpha-32P]GTP demonstrated the presence of high molecular GTP-binding proteins of Mr 55, 75 and 110 KDa. It is concluded that plasma membranes of bovine tracheal smooth muscle contain various types of conventional, low molecular weight and high molecular weight G-proteins. This warrantes further attention to elucidate the functional roles of G-proteins in airway smooth muscle.

Adenosine Diphosphate Ribose↗
PubMed1996

G-proteins in guinea pig airway smooth muscle: identification and functional involvement.

In airway smooth muscle, G-proteins have not been identified directly as yet. This study was an attempt to detect various types of conventional Gi- and Gs-proteins in purified membranes of guinea pig airway smooth muscle and to assess the involvement of the G-proteins in agonist-induced contractile response of the smooth muscle. Immunoblotting using AS/7 antibody which recognizes Gi-1/2 demonstrated the presence of polypeptides of M(r) 34, 41 and 75 kDa. Polypeptides of M(r) 43, 46 and 48 kDa were identified with RM/1 antibody that detects Gs-type G-proteins. The AG/1 antibody that recognizes alpha-subunits common to all Gi- and Gs-proteins detected two polypeptides of M(r) 41 and 75 kDa. Heterotrimeric structure of the G-proteins was confirmed by the identification of a single dense beta-subunit band at M(r) 39 kDa with SW/1 antibody. Pertussis toxin (PT) ADP-ribosylated three Gi alpha polypeptides of M(r) 41, 43, and 62 kDa. On the other hand, cholera toxin (CT) catalysed the ADP-ribosylation of two Gs alpha polypeptides of M(r) 46 and 62 kDa. Both PT and CT attenuated the maximum contractile responses of the airway smooth muscle to the muscarinic agonist, methacholine. Pretreatment of the tissues with the sulphydryl alkylating G-protein inhibitor, N-ethylmaleimide, also inhibited the maximum contractions to methacholine. These data suggest that plasma membranes of guinea pig airway smooth muscle contain a variety of conventional, including Gs and Gi, and other types of G-proteins, and at least a portion of the proteins present may be involved in mediating the contractile responses of the smooth muscle to an agonist such as methacholine.

Animals↗
PubMed1996

Anti-inflammatory activity of topical nimesulide gel in various experimental models.

OBJECTIVE AND DESIGN: The anti-inflammatory activity of topically applied nimesulide gel was compared in different experimental models with that of diclofenac and piroxicam gels. MATERIAL: Wistar albino rats of either sex were used. TREATMENT: In acute models, 50 mg of nimesulide or diclofenac were applied to right hind paws 1 h (carrageenan) or immediately before (formalin) irritant injection (sub-plantar). In adjuvant arthritis, 50 mg of nimesulide, diclofenac or piroxicam were applied daily to injected paws for 14 days. METHODS: Paw volume was measured by plethysmograph. Statistical significance was tested with Student's t-test. RESULTS: In the carrageenan paw odema, topical nimesulide gel exhibited similar anti-inflammatory activity to diclofenac gel, and was more effective than diclofenac gel in formalin-paw odema. In both acute (18 h) and chronic (14 d) phases of adjuvant arthritis, nimesulide gel was more effective than diclofenac or piroxicam gels. CONCLUSION: Topical nimesulide gel possesses higher anti-inflammatory activity than that of diclofenac or piroxicam gels.

Administration, Topical↗
PubMed1996

Molecular biology of human immunodeficiency virus type-1.

Tremendous progress has been made in our understanding of the multiplication and pathogenesis of the human immunodeficiency virus, the causative agent of acquired immunodeficiency syndrome (AIDS). To block virus multiplication several targets in the life cycle of the virus have already been identified for which antiviral drugs can be developed and gene therapy can be envisaged as a possible treatment or cure of AIDS. The combination of several therapies might be needed for effective treatment. Prevention of HIV infections through effective vaccines still awaits novel, unconventional strategies.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Comparative analysis of five highly conserved target sites within the HIV-1 RNA for their susceptibility to hammerhead ribozyme-mediated cleavage in vitro and in vivo.

Moloney murine leukemia virus (MMLV)-derived pUCMoTiN-based retroviral vectors were engineered to allow constitutive and Tat (trans-activator of transcription)-inducible expression of five hammerhead ribozymes targeted against highly conserved sequences within the group antigen (Gag), protease (Pro), reverse transcriptase (RT), tat, and envelope (Env) coding regions of human immunodeficiency virus type-1 (HIV-1) RNA. Amphotropic retroviral vector particles were used to infect a human CD4+ lymphocyte-derived MT4 cell line. The pool of stable MT4 transductants expressing these ribozymes were each tested for their susceptibility to HIV-1 infection. RzTat conferred no protection to MT4 cells. RZGag and RzRT completely inhibited virus multiplication for 6 days. RzPro and RzEnv conferred the best protection, as they completely inhibited virus production for 12 and 15 days, respectively. No correlation was found between the degree of HIV-1 resistance conferred and the ability of these ribozymes to cleave their target RNA in vitro. From RzPro-expressing HIV-1-infected cells following virus escape, RzPro and target RNA sequences were amplified and checked for cleavage in vitro. The ribozyme expressed in these cells was shown to cleave the corresponding target RNA. Thus, a mutation in the ribozyme or target RNA does not seem to be the mechanism underlying virus escape.

Base Sequence↗
PubMed1996

Superselective intraarterial papaverine administration: effect on regional cerebral blood flow in patients with arteriovenous malformations.

In this study the authors determined the effect of papaverine on regional cerebral blood flow (rCBF) in the angiographically normal arteriolar beds of patients with arteriovenous malformations (AVMs) who underwent transfemoral superselective angiography. Middle cerebral artery (MCA) branch vessels were catheterized during 10 procedures performed in nine patients. The mean (+/- standard deviation) largest AVM diameter was 4.4 +/- 1 cm. Regional CBF was measured by recording the washout of a bolus of xenon-133 injected through the microcatheter. In a dose-ranging study. rCBF and MCA pressure in two patients were repeatedly measured after 3-minute infusions of papaverine at 0.07, 0.7, and 7 mg/minute. In a single-dose study, an additional eight patients received only the highest dose of papaverine administered over a 3-minute period. In the dose-ranging study, CBF increased from baseline in a dose-dependent fashion. In the single-dose study, papaverine increased in rCBF 103%, from 48 +/- 11 to 95 +/- 23 ml/100 g/minute at an MCA pressure of 55 +/- 23 mm Hg. Increase in rCBF was linearly related (y = 2.2x - 17, r2 = 0.84; p = 0.001) to baseline MCA pressure (range 22-84 mm Hg). Papaverine increases rCBF in a direct proportion to baseline MCA pressure, even at low baseline pressures. Selective infusion of vasodilators should be investigated in acute cerebral hypotension to facilitate either primary or collateral recruitment of CBF by aiding spontaneous autoregulatory vasodilation. In addition, rCBF monitoring may be useful in determining the most effective intraarterial dose of papaverine while minimizing complications due to hyperemia.

Adult↗
PubMed1995

Epithelial hyperplasia of imaginal discs induced by mutations in Drosophila tumor suppressor genes: growth and pattern formation in genetic mosaics.

Lethal mutations in the giant discs (lgd) and fat (ft) tumor suppressor genes of Drosophila cause epithelial hyperplasia in all imaginal discs. By contrast, mutations in the vestigial (vg) gene adversely affect cell viability in the wing imaginal discs and consequently cause loss of pattern in the adult wings. However, combining homozygous lgd or ft mutations with homozygous vg1 increases the size of the wing imaginal discs and partially restores the bristle pattern in the wings of pharate adults. Comparable pattern restoration in vg1 wings is also induced by a newly isolated weak hypomorphic lgd3 allele. Further, mosaic analysis revealed that whereas lgd clones generated by the Minute technique display abnormal differentiation, those induced in a homozygous vg1 background exhibit autonomous restoration of wing pattern. These results suggest that pattern restoration in vg1 wings can serve as an assay for hyperplasia induced by mutations in Drosophila tumor suppressor genes.

Animals↗
PubMed1995

Digestibility of dietary fiber components in vegetarian men.

Digestibility of fiber components namely neutral detergent fiber (total content of cellwall) cellulose, hemicellulose and lignin are estimated in 14 healthy vegetarian men during adlibitum feeding and at 3 energy levels namely 2526, 2868 and 3290 kcals/day. Values of digestibility for adlibitum experiments were 34.17 +/- 2.3 for neutral detergent fiber (NDF), 30.1 +/- 3.9 for cellulose and 53.4 +/- 3.0 for hemicellulose and 8.1 +/- 2.6 for lignin. There was a considerable variability in digestibility of fiber components between individuals.

Adolescent↗