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Biomedical subjects

A Agarwal

Publications and source records attributed to A Agarwal.

At least 325 records · Page 18Linked to original sources
PubMed1994

Relationship of sperm parameters with levels of reactive oxygen species in semen specimens.

The levels of reactive oxygen species were compared in semen specimens from suspected subfertile men and from normal volunteers, and correlated with other semen parameters. Reactive oxygen species formation was measured in semen samples that had no white blood cells by a chemiluminescence assay with a Luminometer. The relationship of seminal reactive oxygen species to several sperm parameters was evaluated. A total of 84 specimens from 69 suspected subfertile men and 15 normal volunteers was tested for reactive oxygen species production. Comparison of reactive oxygen species levels in white blood cell-negative patient and donor specimens showed significantly higher values (p < 0.005) in the patient group. Similarly, levels in patient and donor specimens with normal sperm motility were significantly lower (p < 0.005) than those in specimens showing poor motility. The seminal reactive oxygen species levels of white blood cell-negative patients with abnormal morphology were significantly higher (p < 0.005) than those in white blood cell-negative patients with normal morphology. Our results show that seminal reactive oxygen species levels in suspected subfertile men are significantly higher than in normal men, and that the presence of excess reactive oxygen species in semen is positively correlated with low sperm concentration, poor motility and poor morphology. In conclusion, the evaluation of reactive oxygen species levels in cases of idiopathic male infertility could serve as an important marker of sperm dysfunction.

Humans↗
PubMed1994

Analysis of a novel cyclic Amp inducible prespore gene in Dictyostelium discoideum: evidence for different patterns of cAMP regulation.

The D7 cDNA clone hybridizes to a 2.8 kb mRNA which first appears at the mound stage of development in the cellular slime mold Dictyostelium discoideum. This gene which is cyclic AMP (cAMP) inducible and is expressed specifically in the prespore cells contains an open reading frame interrupted by only one intron. The predicted amino acid sequence indicates a novel prespore protein which differs from all of the previously described prespore proteins in that it contains no internal repeats and does not share any homology with any of the other prespore genes. The amino acid sequence predicts a protein of 850 amino acids with a molecular weight of 95,343 daltons and an isoelectric point of 4.25. The protein is very rich in glutamine (13.8%), asparagine (10.6%) and glutamic acid (10.4%) with one potential glycosylation site and 28 possible sites for phosphorylation. The amino terminus is hydrophobic with characteristics of a signal sequence while the entire carboxyl half of the protein is notable for its hydrophilicity. Comparison of cAMP regulation of the D7 gene with the regulation of two other cAMP regulated prespore genes, the PL3(SP87) gene and the Psa(D19), reveals some striking differences. Disaggregation in the presence of cAMP results in transient degradation of mRNA for all three genes. The transcription rate for the D7 and PsA(D19) genes remains relatively unaffected by disaggregation but there is a rapid although transient decline in the transcription rate of the PL3(SP87) gene. Although the accumulation of all three mRNAs is first detectable at mound stage, transcription of the D7 and PsA(D19) genes is detected earlier in development, at rippling aggregate stage several hours prior to the earliest time when transcription of the PL3(SP87) gene is detected. Analysis of the promoter region of the D7 gene reveals three CA like boxes flanked by direct repeats as well as four G rich regions that may serve as regulatory elements.

Amino Acid Sequence↗
PubMed1994

Tuftsin-bearing liposomes as rifampin vehicles in treatment of tuberculosis in mice.

The antitubercular activity of rifampin was considerably increased when it was encapsulated in egg phosphatidylcholine liposomes. A further increase in the activity was observed when the macrophage activator tetrapeptide tuftsin was grafted on the surface of the drug-loaded liposomes. Intermittent treatments (twice weekly) with these preparations were significantly more effective than the continuous treatments. Rifampin delivered twice weekly for 2 weeks in tuftsin-bearing liposomes was at least 2,000 times more effective than the free drug in lowering the load of lung bacilli in infected animals. However, pretreatment with drug-free tuftsin-bearing liposomes did not render the pretreated animals resistant to the Mycobacterium tuberculosis infections, neither did it appreciably increase the chemotherapeutic efficacy of the liposomized rifampin. These results clearly demonstrate that liposome targeting to macrophages could considerably increase the antitubercular activity of liposomized drugs such as rifampin. Also, it shows that immunoprophylactic treatment with macrophage activators such as tuftsin does not afford any advantage in treatment of tuberculosis infections, presumably because of inactivation of the primed macrophages by the mycobacterial sulfatides.

Amino Acid Sequence↗
PubMed1994

Modified Levinson's test in rapid diagnosis of tuberculous meningitis.

Modified Levinson's precipitation test was done in 64 cases of TBM, 54 cases of TBM with inconsistent CSF finding, and 32 cases of pyogenic meningitis. The test was positive in 93.7% cases of TBM (sensitivity, 93.7%), 85.5% cases of TBM with doubtful diagnosis and in 9.4% cases of pyogenic meningitis (specificity 90.6%) compared to 79.7%, 72.2% and 18.8% in original Levinson's test, respectively. With CSF examination only 66% cases of TBM could be diagnosed while with modified Levinson's test and CSF analysis 89% cases could be diagnosed (p < 0.001). So modified Levinson's test for diagnosis of TBM is better than Levinson's test (p < 0.05) with an added advantage of time saving.

Antitubercular Agents↗
PubMed1993

Synthesis, cloning and expression of a synthetic gene for high potential iron protein from Chromatium vinosum.

A synthetic gene encoding the peptide sequence for the low molecular weight (M(r) approximately 9600 Da) high-potential iron protein (HiPIP) from the photosynthetic bacterium Chromatium vinosum has been constructed by shotgun ligation of twelve complimentary oligonucleotides varying in size from 42-mers to 48-mers. After cloning the gene into a pET-21d(+) vector, expression of holoprotein in yields of 35 mg/liter of culture was obtained following induction with isopropyl-beta-D-thiogalactoside (IPTG). The recombinant protein was characterized by electronic absorption, 1H NMR, electrochemistry, N-terminal sequencing and amino acid analysis. This is the first example of the expression of a high potential ferredoxin containing a fully constituted [Fe4S4] cluster.

Amino Acid Sequence↗
PubMed1993

Three-dimensional quantitative structure-activity relationships of 5-HT receptor binding data for tetrahydropyridinylindole derivatives: a comparison of the Hansch and CoMFA methods.

A series of new derivatives of 3-(1,2,5,6-tetrahydropyridin-4-yl)indole (4-THPI) has been synthesized, and their dissociation constants at the 5-HT1A and 5-HT2 serotonin (5-HT) receptor subtypes have been determined. The new data were combined with similar binding data on a related set of THPI analogs reported previously (Taylor et al. Mol. Pharmacol. 1988, 34, 42-53) and used to develop 3-dimensional quantitative structure-activity relationships (3-D QSARs) for these compounds at the 5-HT1A and 5-HT2 receptor sites, by the method of comparative molecular field analysis (CoMFA). Since the previous study included several conventional QSARs obtained by Hansch analysis, and the new compounds in some cases fall within the congeneric series used in those analyses, we were able to make a direct comparison of the predictive capabilities of CoMFA and Hansch analysis using identical training and test data sets. The overall quality of actual predictions of activity by both methods appears to be about the same, as assessed by the root mean square (rms) residuals between actual and predicted pKi values. On the one hand, the compounds most poorly predicted by the Hansch analysis were 34, 35, and 37, while compounds 30-33 were relative poorly predicted by CoMFA. However, a clear advantage of CoMFA is the ability to include diversely substituted or noncongeneric analogs that must be omitted from conventional QSAR analysis. Using the entire data set of 45 THPI analogs reported here, pKi predictions for six additional compounds having 5-heteroarylindole substituents gave rms residuals of 0.46 and 0.36 for the 5-HT1A and 5-HT2 models, respectively; this is close to the experimental error of the binding data. The significance of the CoMFA field graphs in terms of molecular features required for activity and selectivity at these 5-HT receptor subtypes is discussed.

Animals↗
PubMed1993

Involvement of p72syk, a protein-tyrosine kinase, in Fc gamma receptor signaling.

Previous studies have demonstrated that multichain immune recognition receptors, such as the T-cell receptor, signal their occupancy by inducing tyrosine phosphorylation of cellular protein substrates. Type I and II receptors for the Fc portion of IgG are single-chain immune recognition receptors having external, transmembrane, and cytoplasmic domains. In the present study, we have investigated the possibility that, upon engagement, Fc gamma receptors induce protein-tyrosine phosphorylation. Our findings reveal increased phosphorylation of a number of proteins on tyrosine residues after cross-linking of either high (Fc gamma RI) or low (Fc gamma RII) affinity receptors expressed on HL60 cells. Engagement of Fc gamma RII induced rapid tyrosine phosphorylation that decayed to basal levels by 40 min. In contrast, phosphorylation induced by Fc gamma RI cross-linking was more delayed, peaking at 5-10 min, and returning to basal levels by 60 min. Kinase assays of cellular proteins immunoprecipitated from lysates of activated cells by antibody to phosphotyrosine revealed phosphorylation of a 72-kDa molecule that was not present in lysates of resting cells. This phosphoprotein was identified as p72syk by immunoprecipitation with antibodies directed against two different regions of the syk gene product. Immunoprecipitation with antibodies against p72syk followed by immunoblotting with anti-phosphotyrosine antibodies revealed an activation-dependent tyrosine phosphorylation of p72syk. Thus, our present findings demonstrate induction of protein-tyrosine phosphorylation following engagement of monomeric immune recognition receptors and identify p72syk as a tyrosine kinase substrate involved in signaling by Fc gamma RI and Fc gamma RII.

Cell Line↗
PubMed1993

Sequence homology between bacteriorhodopsin and G-protein coupled receptors: exon shuffling or evolution by duplication?

Bacteriorhodopsin (BR) is a membrane protein of known structure, widely used for the homology modeling of G-protein-coupled receptors (GPCR). The observation of apparently transposed sequence similarities between some of the helical domains of BR and GPCR has led to the suggestion that exon shuffling may have occurred in the later evolution of GPCR, which would necessitate a different folding pattern for the seven transmembrane helices of GPCR. An alternate hypothesis is that duplication occurred in the evolution of an ancestral gene, such that helices 5-7 originated as duplicates of helices 1-3, leading to intragenic as well as intergenic similarities between helices 1-3 and 5-7 of BR and various GPCR. Analyses of GPCR and BR sequences suggest that such a duplication may have occurred; symmetry within the BR structure is also consistent with homology between these two regions. The hypothesis of evolution by duplication is consistent with the conventional, unshuffled homology model, which is also supported by the obvious conservation of the retinal binding Lys moiety on helix 7 in both BR and the mammalian opsins.

Amino Acid Sequence↗
PubMed1993

Ischaemic central retinal vein occlusion in the young.

Little is known about the behaviour of central retinal vein occlusion (CRVO) in the young. We studied the course and visual outcome in 25 patients with CRVO aged less than 40 years with special reference to the association with underlying systemic disorders. Eight patients had ischaemic CRVO while 17 had non-ischaemic CRVO. Systemic disorders associated with ischaemic CRVO included end-stage renal disease in 3, and hypercholesterolaemia, beta-thalassaemia and hypertension in 1 each. All patients with ischaemic CRVO had unusually severe disease and a rapid downhill course. Management included panretinal photocoagulation in 7 eyes, trabeculectomy with 5-fluorouracil in 3 eyes and cyclocryopexy in 2 eyes. Despite this 3 eyes became phthisical and the final visual acuity in all eyes ranged from no light perception to 6/60. Three patients with end-stage renal disease died within 15 months of diagnosis of venous occlusion.

Adult↗
PubMed1993

Hereditary nephritis (Alport's syndrome)--clinical profile and inheritance in 28 kindreds.

Sixty-three patients, (52 males and 11 females) from 28 kindreds of hereditary nephritis (Alport's syndrome) were identified over a 14-year period from 1977 to 1991. Group I included 51 patients with (a) positive family history of haematuria with or without chronic renal failure, (b) characteristic GBM changes on electron-microscopy, (c) characteristic ocular signs, and (d) high-frequency sensorineural deafness. Group II included 12 patients with a negative family history. All of them had evidence of renal disease with characteristic ocular signs and deafness and four had characteristic GBM changes on electron-microscopy. The main clinical features were haematuria in 96.8%, deafness in 82.5%, and diminished visual acuity in 66.7% of affected subjects. Hypertension was present in 71.4% patients. Pure tone audiometry revealed high-frequency sensorineural deafness in 96.8%. Ocular examination showed bilateral anterior lenticonus in 37.8%, retinal flecks in 22.2%, cataract in 20%, and keratoconus in 6.7% patients. Proteinuria (> 2.0 g/24 h) was detected in 31.8%. Sixteen (57.1%) of the 28 index patients (all males) were diagnosed for the first time when they presented with end-stage renal disease. Serum creatinine in the overall group ranged from 0.9 to 18.7 mg/dl(7.81 +/- 5.37 mg/dl). Adequate renal tissue was obtained by biopsy in 14 patients. Light-microscopy revealed focal segmental glomerulosclerosis in five, mesangial proliferation in four, chronic interstitial nephritis in three, and mesangiocapillary and crescentic glomerulonephritis in one each. Electron-microscopy showed characteristic changes in the GBM in seven specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗