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Biomedical subjects

A Das

Publications and source records attributed to A Das.

At least 217 records · Page 12Linked to original sources
PubMed1996

QSAR analysis of membrane permeability to organic compounds.

A general mathematical model involving partition coefficient, molecular weight and hydrogen bonding is used to correlate the structures and permeability of various organic compounds through the toad urinary bladder and human red blood cell (RBC) membranes. Log Per (permeability) is correlated with log Po/w (partition coefficient in olive oil/water, or ether/water), log MW (molecular weight) and Hb (hydrogen bonds). Log Po/w is the most important factor among three parameters examined. While increased MW always has a negative effect on the permeability, increased Hb can have either a slightly positive or a slightly negative effect depending on the solvent and membrane systems used. Systematic comparison of the QSAR's (quantitative structure activity relationship) of different biological membranes may serve as a useful guide in drug targeting to different tissues and cell types.

Alcohols↗
PubMed1996

Clinical presentation of intracranial metastases.

Intracranial metastases are the single most costly neurologic ailment. This article provides the clinician with detailed statements of the patterns of their appearance and tumors of origin. Most common causative cancers are of lung, breast, or melanoma origin. Aggressive therapies carry with them the risk of nervous system dissemination of rare tumors, remote complications of these cancers and the morbidity of therapy.

Adult↗
PubMed1995

Interaction between the phage HK022 Nun protein and the nut RNA of phage lambda.

The nun gene product of prophage HK022 excludes phage lambda infection by blocking the expression of genes downstream from the lambda nut sequence. The Nun protein functions both by competing with lambda N transcription-antitermination protein and by actively inducing transcription termination on the lambda chromosome. We demonstrate that Nun binds directly to a stem-loop structure within nut RNA, boxB, which is also the target for the N antiterminator. The two proteins show comparable affinities for boxB and they compete with each other. Their interactions with boxB are similar, as shown by RNase protection experiments, NMR spectroscopy, and analysis of boxB mutants. Each protein binds the 5' strand of the boxB stem and the adjacent loop. The stem does not melt upon the binding of Nun or N, as the 3' strand remains sensitive to a double-strand-specific RNase. The binding of RNA partially protects Nun from proteolysis and changes its NMR spectra. Evidently, although Nun and N bind to the same surface of boxB RNA, their respective complexes interact differently with RNA polymerase, inducing transcription termination or antitermination, respectively.

Bacteriophage lambda↗
PubMed1995

Mutational analysis of a conserved motif of Agrobacterium tumefaciens VirD2.

The VirD2 polypeptide from Agrobacterium tumefaciens, in the presence of VirD1, introduces a site- and strand-specific nick at the T-DNA borders. A similar reaction at the origin of transfer (oriT) of plasmids is essential for plasmid transfer by bacterial conjugation. A comparison of protein sequences of VirD2 and its functional homologs in bacterial conjugation and in rolling circle replication revealed that they share a conserved 14 residue segment, HxDxxx(P/u)HuHuuux [residues 126-139 of VirD2; Ilyina, T.V. and Koonin, E.V. (1992) Nucleic Acids Res. 20, 3279-3285]. A mutational approach was used to test the role of these residues in the endonuclease activity of VirD2. The results demonstrated that the two invariant histidine residues (H133 and H135) are essential for activity. Mutations at three sites, histidine 126, aspartic acid 128 and aspartic acid 130, that are conserved in a subfamily of the plasmid mobilization proteins, led to the loss of VirD2 activity. Aspartic acid at position 130, could be substituted with glutamic acid and to a much lesser extent, with tyrosine. In contrast, another conserved residue, asparagine 139, tolerated many different amino acid substitutions. The non-conserved residues, arginine 129, proline 132 and leucine 134, were also found to be important for function. Isolation of null mutations that map throughout this conserved domain confirm the hypothesis that this region is essential for function.

Agrobacterium tumefaciens↗
PubMed1995

Long-range horizontal connections and their role in cortical reorganization revealed by optical recording of cat primary visual cortex.

The cortical 'point spread' (PS) is the area of cortex activated by a minimal visual stimulus. Here we use the PS to explore the functional role of lateral connectivity in normal cat primary visual cortex (V1) and its involvement in topographic reorganization of cortex following retinal lesions. We compared the distributions of PSs measured with optical recording, which reflects both spiking and subthreshold activity, with those measured with extracellular electrodes, which reveal spiking activity alone. The spiking PS represented only 5% of the area of activation shown in the optical PS, indicating that the remaining 95% was probably generated by subthreshold activation. The orientation dependence of the pattern of the subthreshold activation and its close match with orientation columns suggests that long-range horizontal connections radiating from the locus of spiking activity were responsible for the observed activation. The spike PS showed anisotropies and inhomogeneities that were related to the pattern of orientation columns and indicated distortions in the representation of visual space on the cortical surface. In the reorganized cortex the spike PS expanded, approximating the extent of the optical PS seen in normal cortex, and suggesting that reorganization was mediated by an unmasking of normally subthreshold activation to suprathreshold levels. The orientation map of the reorganized cortex showed a close match to that obtained before placing the lesion, despite the large shift in topography, supporting the idea that intrinsic horizontal connections were responsible for the remapping.

Action Potentials↗
PubMed1995

Intrinsic transcript cleavage activity of RNA polymerase.

The GreA and GreB transcript cleavage factors of Escherichia coli suppress elongation arrest and may have a proofreading role in transcription. With the use of E. coli greA-greB- mutant, RNA polymerase is demonstrated to possess substantial intrinsic transcript cleavage activity. Mildly alkaline pH mimics the effect of the Gre proteins by inducing transcript cleavage in ternary complexes and antagonizing elongation arrest through a cleavage-and-restart reaction. Thus, transcript cleavage constitutes the second enzymological activity of RNA polymerase along with polymerization/pyrophosphorolysis of RNA, whereas the Gre proteins merely enhance this intrinsic property.

Bacterial Proteins↗
PubMed1995

Interleukin-1-induced leukocyte extravasation across rat mesenteric microvessels is mediated by platelet-activating factor.

Although our understanding of the molecular interactions that mediate the adhesion of leukocytes to venular endothelial cells has greatly expanded, very little is known about the mechanisms that mediate the passage of leukocytes across the vessel wall in vivo. The aim of the present study was to investigate the role of endogenously formed platelet-activating factor (PAF) in the process of leukocyte extravasation induced by interleukin-1 (IL-1). To determine at which stage of emigration PAF was involved, we studied the behavior of leukocytes within rat mesenteric microvessels by intravital microscopy. Rats were injected intraperitoneally with saline, recombinant rat IL-1 beta (IL-1 beta), or the peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) 4 hours before the exteriorization of the mesenteric tissue. In animals treated with IL-1 beta there was a significant increase in the number of rolling and adherent leukocytes within venules (20- to 40-micron diameter) and in the number of extravasated leukocytes in the tissue. Pretreatment of rats with the PAF receptor antagonist UK-74,505 had no effect on the leukocyte responses of rolling and adhesion, but significantly inhibited the migration of the leukocytes across the vessel wall induced by IL-1 beta (76% inhibition). A structurally unrelated PAF antagonist, WEB-2170, produced the same effect (64% inhibition). However, in contrast, UK-74,505 had no effect on the leukocyte extravasation induced by FMLP, indicating selectivity for the response elicited by certain mediators. These results provide the first line of direct evidence for the involvement of endogenously formed PAF in the process of leukocyte extravasation induced by IL-1 in vivo.

Animals↗
PubMed1995

Bipartite function of a small RNA hairpin in transcription antitermination in bacteriophage lambda.

Transcription of downstream genes in the early operons of phage lambda requires a promoter-proximal element known as nut. This site acts in cis in the form of RNA to assemble a transcription antitermination complex which is composed of lambda N protein and at least four host factors. The nut-site RNA contains a small stem-loop structure called boxB. Here, we show that boxB RNA binds to N protein with high affinity and specificity. While N binding is confined to the 5' subdomain of the stem-loop, specific N recognition relies on both an intact stem-loop structure and two critical nucleotides in the pentamer loop. Substitutions of these nucleotides affect both N binding and antitermination. Remarkably, substitutions of other loop nucleotides also diminish antitermination in vivo, yet they have no detectable effect on N binding in vitro. These 3' loop mutants fail to support antitermination in a minimal system with RNA polymerase (RNAP), N, and the host factor NusA. Furthermore, the ability of NusA to stimulate the formation of the RNAP-boxB-N complex is diminished with these mutants. Hence, we suggest that boxB RNA performs two critical functions in antitermination. First, boxB binds to N and secures it near RNAP to enhance their interaction, presumably by increasing the local concentration of N. Second, boxB cooperates with NusA, most likely to bring N and RNAP in close contact and transform RNAP to the termination-resistant state.

Bacterial Proteins↗
PubMed1995

Dexamethasone inhibits ozone-induced gene expression of macrophage inflammatory protein-2 in rat lung.

To address the potential role of the chemokine macrophage inflammatory protein-2 (MIP-2) in airway inflammation, we examined whether MIP-2 may play a role in ozone-induced neutrophilic inflammation of airways and its modulation by dexamethasone in rat lung. Following ozone exposure, MIP-2 mRNA expression in the lung peaked at 2 h after exposure and slowly declined thereafter. Dexamethasone suppressed ozone-induced MIP-2 mRNA expression and neutrophil accumulation in the lung. We suggest that the MIP-2 mRNA induction may switch on the neutrophilic influx observed in this model of lung inflammation. Furthermore, the MIP-2 expression is regulated by dexamethasone which may represent one of the mechanisms by which glucocorticoids exert their potent anti-inflammatory properties.

Animals↗
PubMed1995

Replication of the broad-host-range plasmid RK2: isolation and characterization of a spontaneous deletion mutant that can replicate in Agrobacterium tumefaciens but not in Escherichia coli.

Two spontaneous deletions of a derivative of the broad-host-range plasmid RK2 were isolated from Agrobacterium tumefaciens. The two deletions have lost 56 and 505 bp, respectively, near the origin of replication (oriV). Of the eight 17-bp repeats present in the RK2 oriV, the smaller deletion has lost the first two while the larger one has lost the first three. The deletions led to a significant increase (3- to 7-fold) in plasmid copy number in A. tumefaciens, indicating their importance in copy number control. While the smaller deletion could replicate in Escherichia coli, the larger one could not. The role of the oriV sequences in the replication of pRK2 in A. tumefaciens and in E. coli is discussed.

Agrobacterium tumefaciens↗
PubMed1995

Species-specific 18S rRNA gene amplification for the detection of P. falciparum and P. vivax malaria parasites.

Based on the sequence diversity of the Plasmodium 18S ribosomal RNA (rRNA), we designed oligonucleotide primers for polymerase chain reaction (PCR) to yield different size fragments for P. falciparum and P. vivax. The primers for the PCR procedure were chosen such that the 5' primer was Plasmodium-conserved while the 3' primers were species-specific. Using primer cocktails and cloned plasmid DNAs containing the 18S rRNA genes or parasite genomic DNA as targets, we show that the PCR procedure yields 1.4-kb and 0.5-kb DNA fragments for P. falciparum and P. vivax, respectively. Limited field testing of this procedure demonstrated the utility of a ribosomal gene based species-specific malaria diagnosis.

Animals↗
PubMed1995

Effect of aspirin on gallbladder motility in patients with gallstone disease. A randomized, double-blind, placebo-controlled trial of two dosage schedules.

Patients with gallstone disease have impaired gallbladder motility. Prostaglandins are thought to be important mediators of gallbladder hypomotility. We assessed the effect of aspirin, a prostaglandin inhibitor on gallbladder resting volume and ejection fraction according to a double-blind study protocol in 20 healthy volunteers and 30 patients with gallstone disease. Healthy volunteers had a higher ejection fraction compared to patients with gallstone disease (73.9 +/- 0.9% vs 60.4 +/- 1.0%, P < 0.05). Aspirin in a dose of 350 mg/day for two weeks did not alter gallbladder motility in the healthy volunteers. Thirty patients with gallstone disease were randomized into three treatment groups: group I (placebo), group II (aspirin 350 mg/day), and group III (aspirin 1400 mg/day). After two weeks of treatment, gallbladder ejection fraction was improved in group II (74.0 +/- 1.7% vs 62.0 +/- 1.7%, P < 0.01) and group III (69.8 +/- 3.8% vs 61.2 +/- 1.3%, P < 0.01) but not in group I (60.4 +/- 2.6% vs 59.0 +/- 1.9%, P = NS). The higher dose of aspirin did not induce a greater increase in gallbladder emptying. It is concluded that impaired gallbladder motility in patients with gallstone disease is corrected by short-term oral aspirin even in low dosage. This may be clinically useful in secondary prophylaxis after nonsurgical therapy for gallstone disease.

Adult↗
PubMed1995

The preterm prediction study: significance of vaginal infections. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: Our purpose was to evaluate the association of bacterial vaginosis, trichomonas vaginitis, and monilial vaginitis with spontaneous preterm birth at < 35 weeks 0 days. STUDY DESIGN: A total of 2929 women at 10 centers were studied at 24 and 28 weeks' gestation by Gram stain of vaginal smear, wet mount, and 10% potassium hydroxide preparations to detect vaginal infections. RESULTS: The rates of detected infection at 24 and 28 weeks, respectively, were bacterial vaginosis 23.4% and 19.4%, trichomonas 3.3% and 2.7%, and monilia 21.1% and 19.5%. The occurrence of bacterial vaginosis at 28 weeks was associated with an increased risk of spontaneous preterm birth, odds ratio 1.84 (95% confidence interval 1.15 to 2.95, p < 0.01). Detection of Trichomonas vaginalis (by wet mount) or monilia (by potassium hydroxide preparation) had no significant associations with preterm birth. CONCLUSION: The presence of bacterial vaginosis at 28 weeks' gestation is associated with an increased risk of spontaneous preterm birth.

Adult↗