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Biomedical subjects

R Krishnan

Publications and source records attributed to R Krishnan.

At least 55 records · Page 3Linked to original sources
PubMed1999

New onset and remission of suicidal ideation among a depressed adult sample.

BACKGROUND: Previous research has demonstrated that suicidal ideation often predicts suicide completion. METHODS: The present study examined clinical and phenomenological variables associated with the presence, development and remission of suicidal ideation among depressed adults. The sample (n = 81) was derived from subjects enrolled in the Duke Clinical Research Center for the Study of Depression in Late Life. RESULTS: Greater pessimistic thinking at baseline predicted the development of suicidal ideation one year later and the older a person was when he or she first experienced depression, the more likely he or she was to report remission from suicidal ideation one year following onset. LIMITATIONS: Longitudinal analyses were based on relatively small samples. Variables that were not significant in these analyses might be in a larger sample. CONCLUSIONS: The longitudinal design of this study mitigates limitations associated with cross-sectional or retrospective designs and advances our understanding of a clinical profile associated with the development and remission of suicidal thoughts.

Adolescent↗
PubMed1999

Structure-binding studies of the adrenal AT4 receptor: analysis of position two- and three-modified angiotensin IV analogs.

Amino acid substitutions in positions two and three of angiotensin IV (VYIHPF) were carried out to determine which structural features of the side-chains were important for achieving high-affinity binding to bovine adrenal receptors. These studies demonstrated that an activated aromatic ring in the second position side-chain resulted in the highest-affinity binding. Position three required a hydrophobic amino acid to achieve high-affinity binding. Both aliphatic and aromatic side-chains were sufficient to yield high-affinity binding.

Adrenal Glands↗
PubMed1999

A new model of orthotopic penetrating corneal transplantation in the sheep: graft survival, phenotypes of graft-infiltrating cells and local cytokine production.

BACKGROUND: Orthotopic penetrating keratoplasty in the sheep was developed as an outbred preclinical model to allow correlation of the cellular infiltrate during graft rejection with local production of cytokine mRNA. METHODS: Penetrating corneal autografts and allografts were performed in Merino sheep. Graft outcome was followed at the slit-lamp. Corneal infiltrates were examined by immunoperoxidase staining on postmortem specimens. Cytokine mRNA was detected by polymerase chain reaction. RESULTS: Corneal autografts survived indefinitely. Allografts became vascularized and underwent rejection at a median of 20 days postgraft. Both endothelial and epithelial rejection lines were observed. Immunohistochemical staining of rejecting grafts showed up-regulation of major histocompatibility complex class I molecules on corneal graft epithelium, damaged or absent graft endothelium and a marked, predominantly mononuclear cell infiltrate. CD4-positive T cells were observed in the graft within 2 days of the onset of rejection, followed several days later by CD8-positive T cells. Messenger RNA transcripts for interleukin (IL)-2, tumour necrosis factor (TNF)-alpha and IL-10 (but not for interferon (IFN)-gamma or IL-4) were found in autografted corneas. Proportionately, more allografts than autografts contained transcripts for IL-2 and TNF-alpha, and IFN-gamma was detected in three of four allografts. CONCLUSIONS: Corneal graft rejection in the sheep is macroscopically and histologically similar to human corneal graft rejection. Allografts become infiltrated by both CD4- and CD8-positive T cells and local production of pro-inflammatory cytokines occurs during graft rejection.

Animals↗
PubMed1998

Combined anti-vascular cell adhesion molecule-1 and anti-leukocyte function-associated molecule-1 monoclonal antibody therapy does not prolong allograft survival in an ovine model of renal transplantation.

This study investigates the therapeutic efficacy of an anti-vascular cell adhesion molecule (VCAM)-1 monoclonal antibody (mAb), alone or in combination with an anti-leukocyte function-associated-1 mAb, in prolonging allograft survival in an ovine model of renal transplantation. The kinetics of VCAM-1 induction and expression during renal allograft rejection have also been studied. Sheep receiving anti-ovine VCAM-1 antibody demonstrated graft failure at a mean of 8.4 (+/- SD; 0.7) days after transplantation compared with 9.3 (+/- 0.5) days after transplantation for the group given control antibody and 7.7 (+/- 0.3) days after transplantation in the animals given the combined anti-VCAM-1 and anti-leukocyte function-associated-1 mAb therapy. VCAM-1 expression was detected in the allografts at day 1 after transplantation, with peak expression detected by day 5. Tubular expression of VCAM-1 was minimal, with sparse focal staining at the basolateral surfaces. The degree of mononuclear cell infiltrate in the allografts paralleled the progressive increase in VCAM-1 expression after transplantation, and there was no difference in the level of mononuclear cell infiltrate compared with controls.

Animals↗
PubMed1998

Constitutive and barbital-induced expression of the Cyp6a2 allele of a high producer strain of CYP6A2 in the genetic background of a low producer strain.

The levels of one or more cytochrome P450 (CYP) enzymes and the respective mRNAs are found to be higher in insecticide-resistant insects than in susceptible insects. To understand better how insects regulate the levels of CYPs, we examined the expression of the Cyp6a2 gene in various strains of Drosophila melanogaster. We also took a transgenic approach to understand the molecular mechanisms that are involved in strain variation of Cyp6a2 expression. RNA blot analysis showed that the constitutive expression of Cyp6a2 varies from strain to strain; the level of CYP6A2 mRNA is barely detectable in the underproducer ry506 strain, whereas it is very high in the overproducer 91-R and MHIII-D23 strains. The long terminal repeat (LTR) of mobile element 17.6 that is found in the 3' untranslated region (UTR) of the Cyp6a2 gene of some strains does not appear to have any role on the steady-state CYP6A2 mRNA level. We also found that the Cyp6a2 gene is inducible by barbital in 91-R, ry506 as well as 91-C, which carries an LTR insertion. To examine the genetic background of the underproducer ry506 strain with respect to Cyp6a2 expression, we transformed the ry506 strain with the Cyp6a2 allele of the overproducer 91-R strain (Cyp6a2-91 R) and measured the constitutive and barbital-induced expression of the Cyp6a2-91 R transgene in the transformed flies. The Cyp6a2-91 R transgene carrying 129 bp of DNA upstream of the ATG codon did not show any constitutive or barbital-induced expression in the ry506 host genome. However, transgenes with 1331 and 985 bp upstream DNA showed similar levels of constitutive expression that were higher than that of the endogenous Cyp6a2 gene of the ry506 host strain, but lower than the expression of the same gene in the 91-R strain. Both these transgenes, with 1331 and 985 bp upstream DNA, also showed induction with 0.1 M barbital. DNA sequence analysis revealed that in both 91-R and ry506, the upstream DNA between +1 and -985 bp contains a distal and a proximal group of three potential barbie boxes, i.e. cis-elements that are thought to be involved in barbiturate-mediated induction of CYP genes. Except for four bases located near the distal cluster of barbie boxes and two other bases, the base sequence of the upstream DNA is identical in ry506 and 91-R strains. These results suggest that the underproducer ry506 strain has the trans-regulatory factors to support constitutive and induced expression of the Cyp6a2-91 R allele carrying DNA between -129 and -1331 bp regions. Possible reasons for low constitutive expression of the endogenous Cyp6a2 gene and moderate level of expression of the Cyp6a2-91 R allele in the ry506 genetic background are discussed.

Alleles↗
PubMed1998

Highly selective mechanism-based thrombin inhibitors: structures of thrombin and trypsin inhibited with rigid peptidyl aldehydes.

The crystal structures of three highly potent and selective low-molecular weight rigid peptidyl aldehyde inhibitors complexed with thrombin have been determined and refined to R values 0.152-0. 170 at 1.8-2.1 A resolution. Since the selectivity of two of the inhibitors was >1600 with respect to trypsin, the structures of trypsin-inhibited complexes of these inhibitors were also determined (R = 0.142-0.157 at 1.9-2.1 A resolution). The selectivity appears to reside in the inability of a benzenesulfonamide group to bind at the equivalent of the D-enantiomorphic S3 site of thrombin, which may be related to the lack of a 60-insertion loop in trypsin. All the inhibitors have a novel lactam moiety at the P3 position, while the two with greatest trypsin selectivity have a guanidinopiperidyl group at the P1 position that binds in the S1 specificity site. Differences in the binding constants of these inhibitors are correlated with their interactions with thrombin and trypsin. The kinetics of inhibition vary from slow to fast with thrombin and are fast in all cases with trypsin. The kinetics are examined in terms of the slow formation of a stable transition-state complex in a two-step mechanism. The structures of both thrombin and trypsin complexes show similar well-defined transition states in the S1 site and at the electrophilic carbon atom and Ser195OG. The trypsin structures, however, suggest that the first step in a two-step kinetic mechanism may involve formation of a weak transition-state complex, rather than binding dominated by the P2-P4 positions.

Aldehydes↗
PubMed1998

Magnetic resonance imaging signal hypointensity and iron content of putamen nuclei in elderly depressed patients.

We previously introduced a semiquantitative scale for assessment of iron content of putamen nuclei as determined by magnetic resonance imaging (MRI)--the Signal Hypointensity in the Putamen (SHIP) scale. Such hypointensity may be related to putamen nuclei iron content, although this suggestion remains controversial, especially in the elderly. In the present study, we apply the SHIP scale to a sample of 68 elderly depressed patients (diagnosed with DSM-IV major depression using the Diagnostic Interview Schedule and clinical interview) and a group of 28 age-matched non-depressed control subjects. MRI scans were conducted on a single 1.5-T General Electric Signa system with axial acquisitions obtained parallel to the canthomeatal line. Technical parameters were as follows: (1) repetition time (TR) = 500 ms and echo time (TE) = 15 ms for T1-weighted images; (2) TR = 2500 ms and TE = 30 ms for proton-density-weighted images; and (3) TR = 2500 ms and TE = 80 ms for T2-weighted images. Among depressed patients, older age of depression onset and greater severity of depression were associated with increased putamen nuclei iron deposition. When depressed patients were compared with control subjects, the patient group demonstrated greater putamen nuclei iron, but the finding was significant only for the left hemisphere. Our findings support previous neuroimaging studies linking both changes in the basal ganglia and greater left-sided brain pathology to late-life depression.

Age of Onset↗
PubMed1998

Role of nitric oxide in angiotensin IV-induced increases in cerebral blood flow.

The present study investigated the effects of three newly synthesized AngIV analogs (Lysine1-AngIV, Norleucine1-AngIV, and Norleucinal) on cerebral blood flow (CBF) in anesthetized Sprague-Dawley rats utilizing laser-Doppler flowmetry. The results indicate that internal carotid infusions of AngIV, Norleucine1-AngIV, Norleucinal, and Lysine1-AngIV increased CBF above baseline by 25, 32, 33 and 44%, respectively, without changing systemic arterial blood pressure. In a second experiment separate groups of rats were pretreated with nitric oxide (NO) synthase inhibitor, Nw-nitro-L-arginine methyl ester (L-NAME) or saline, followed by AngIV or Norleucinal for the purpose of evaluating the hypothesis that the mechanism of action of these compounds is linked to the release of NO. Pretreatment with saline followed by AngIV and Norleucinal increased CBF by 29 and 39%, respectively, while pretreatment with L-NAME blocked the vasodilatory effects of AngIV and Norleucinal, suggesting that the increment in blood flow induced by these compounds is dependent upon the synthesis and release of NO from vascular endothelial cells.

Angiotensin II↗
PubMed1998

Outbreak of nosocomial Acinetobacter baumannii bacteremia in a high risk ward.

Acinetobacter baumannii is emerging as a major cause of nosocomial infections particularly in high risk patients. Being resistant to adverse environmental conditions, it can stay for prolonged periods in the hospital environment. We report an outbreak in the medical oncology ward where nine patients suspected of bacteraemia were blood culture positive for A. baumannii from the two samples each, one collected through the i.v. cannula and another through the peripheral veneous puncture. The bacteria was also isolated from the environmental sources from the various samples collected. The biotype, antibiogram, cellular protein profiles on SDS-PAGE and the restriction enzyme analysis patterns of the patient isolates and the environmental isolates were similar. This points to the environment as a source of infection. With reinforcement of proper barrier nursing and use of disposable heparine ampoules it was possible to control the outbreak.

Acinetobacter Infections↗
PubMed1998

Acucise endopyelotomy: a successful therapeutic intervention in the treatment of ureteropelvic junction obstruction.

Ureteropelvic junction obstruction is a well-recognized cause of pain and eventual renal failure. This condition may be congenital or it can develop secondary to renal calculi, infection, and instrumentation. Surgical intervention is the definitive therapy, and a number of surgical options are available to treat ureteropelvic junction obstruction. We describe an approach using the Acucise cutting balloon to perform retrograde endopyelotomy. In 12 patients making up 13 renal units, our success rate was 92.3%, at a mean follow-up of 8.4 months (range 2 to 21 months). Complications were minimal. Based on our experience, Acucise endopyelotomy is a successful therapeutic intervention in treating ureteropelvic junction obstruction.

Adolescent↗
PubMed1997

Flow-through amperometric immunosensor: fast 'sandwich' scheme immunoassay.

A flow-through immunosensor based on a high-surface-area carbon immunoelectrode has been developed. Dispersed carbon material serves as a carrier for immobilized antibodies and at the same time as an electrode material. The 'sandwich' scheme of immunoassay has been used. Iodine formed as a result of the enzymatic oxidation of iodide by a peroxidase label has been detected amperometrically. The immunosensor consists of a disposable sensing element (immunocolumn) containing dispersed carbon material with immobilized antibodies which also acts as a working electrode. A current collector connects the working electrode to the measuring device. The electrochemical detection time of the peroxidase-labeled immuno-complex does not exceed several minutes. The overall time of analysis including flowing of analyte, flowing of antigen, washing and detection stages is as low as 22 min. This technique allows fast determination of rabbit IgG (used as a model analyte) with a low detection limit in the picomolar range and also the determination of human IgM in blood plasma with a low detection limit in the nanomolar range.

Animals↗
PubMed1997

Characterization of ovine umbilical vein endothelial cells and their expression of cell adhesion molecules: comparative study with human endothelial cells.

This paper reports the isolation and characterization of sheep umbilical vein endothelial cells (ShUVEC) and examines the kinetics of the expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). In culture, the cells demonstrate the classical endothelial cell phenotype, including the expression of von Willebrand Factor (vWF), the metabolism of acetylated-low density lipoprotein (Ac-LDL) and the typical cobblestone monolayer appearance. Northern analysis of the expression of ICAM-1 and VCAM-1 mRNA by ShUVEC stimulated with either LPS or recombinant ovine (ro)-TNF-alpha or IL-1 beta demonstrated peak RNA expression for both molecules at between 2 and 6 h after stimulation. Maximum VCAM-1 protein expression occurred between 6 and 12 h after stimulation with ro-TNF-alpha, followed by a slight decrease to a plateau extending beyond 48 h. The levels and kinetics of expression of additional cell surface proteins on ShUVEC, including P-selectin (CD62P), beta 1 integrin (CD29) and ovine MHC classes I and II, were found to be almost identical to that observed on human endothelial cells (HUVEC) cultured under similar conditions. Based on the above results, we conclude that the ShUVEC represent the ovine equivalent of HUVEC, both phenotypically and functionally.

Animals↗
PubMed1997

Anti-ovine VCAM-1 monoclonal antibodies inhibit adhesion and proliferation between sheep endothelial and mononuclear cells in vitro.

This paper reports the production and characterization of three monoclonal antibodies (mAb) recognizing ovine vascular cell adhesion molecule-1 (VCAM-1). The mAb were raised against sheep umbilical vein endothelial cells (ShUVEC) and flow cytometric analysis demonstrated that one mAb, QE4G9, was cross-reactive with human VCAM-1 expressed on Chinese hamster ovary cell transfectants. Protein modulation studies on ShUVEC and immunoperoxidase staining of inflamed renal tissue further indicated the reactivity of the other two ovine mAb, QE1F3 and QE2G4, with ovine VCAM-1. The flow cytometric profile of the three mAb on stimulated ShUVEC was identical to that observed with the cross-reactive anti-human VCAM- mAb, HAE2-1. Peak expression occurred between 6-12 h after stimulation, followed by a slight decrease to a plateau extending beyond 48 h. In functional assays, all mAb inhibited adhesion of PMA-activated sheep PBMC to stimulated ShUVEC. In addition, QE4G9 inhibited proliferation of sheep PBMC in the mixed lymphocyte-endothelial cell reaction (MLER) by 56%. The results demonstrate that the three anti-ovine VCAM-1 mAb recognize functional epitopes on sheep vascular endothelial cells. These mAb will be valuable tools in the investigation of VCAM-1 expression in various pathophysiological conditions using sheep models, and in the study of VCAM-1-mediated leucocyte-endothelial cell interactions, both in vitro and in vivo.

Animals↗
PubMed1997

Gastric strongyloidiasis in a Malaysian patient.

Strongyloides stercoralis infection is of low prevalence in Malaysia. We report an unusual case presenting primarily with gastric symptoms. The patient was a 72 years old Chinese male admitted for progressive weight loss and abdominal bloating. Gastroscopic examination revealed mucosal prepyloric elevations in the gastric mucosa. Gastric strongyloidiasis was confirmed by the presence of adult forms, as well as ova and larval rhabditiform stages of the worm in the gastric mucosal crypts. We believe that this is the first histologically documented case of gastric strongyloidiasis in Malaysia.

Aged↗