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Biomedical subjects

D Kahn

Publications and source records attributed to D Kahn.

At least 55 records · Page 3Linked to original sources
PubMed2001

Nucleotide sequence and predicted functions of the entire Sinorhizobium meliloti pSymA megaplasmid.

The symbiotic nitrogen-fixing soil bacterium Sinorhizobium meliloti contains three replicons: pSymA, pSymB, and the chromosome. We report here the complete 1,354,226-nt sequence of pSymA. In addition to a large fraction of the genes known to be specifically involved in symbiosis, pSymA contains genes likely to be involved in nitrogen and carbon metabolism, transport, stress, and resistance responses, and other functions that give S. meliloti an advantage in its specialized niche.

Agrobacterium tumefaciens↗
PubMed2001

The composite genome of the legume symbiont Sinorhizobium meliloti.

The scarcity of usable nitrogen frequently limits plant growth. A tight metabolic association with rhizobial bacteria allows legumes to obtain nitrogen compounds by bacterial reduction of dinitrogen (N2) to ammonium (NH4+). We present here the annotated DNA sequence of the alpha-proteobacterium Sinorhizobium meliloti, the symbiont of alfalfa. The tripartite 6.7-megabase (Mb) genome comprises a 3.65-Mb chromosome, and 1.35-Mb pSymA and 1.68-Mb pSymB megaplasmids. Genome sequence analysis indicates that all three elements contribute, in varying degrees, to symbiosis and reveals how this genome may have emerged during evolution. The genome sequence will be useful in understanding the dynamics of interkingdom associations and of life in soil environments.

Bacterial Adhesion↗
PubMed2001

The InterPro database, an integrated documentation resource for protein families, domains and functional sites.

Signature databases are vital tools for identifying distant relationships in novel sequences and hence for inferring protein function. InterPro is an integrated documentation resource for protein families, domains and functional sites, which amalgamates the efforts of the PROSITE, PRINTS, Pfam and ProDom database projects. Each InterPro entry includes a functional description, annotation, literature references and links back to the relevant member database(s). Release 2.0 of InterPro (October 2000) contains over 3000 entries, representing families, domains, repeats and sites of post-translational modification encoded by a total of 6804 different regular expressions, profiles, fingerprints and Hidden Markov Models. Each InterPro entry lists all the matches against SWISS-PROT and TrEMBL (more than 1,000,000 hits from 462,500 proteins in SWISS-PROT and TrEMBL). The database is accessible for text- and sequence-based searches at http://www.ebi.ac.uk/interpro/. Questions can be emailed to interhelp@ebi.ac.uk.

Databases, Factual↗
PubMed2001

Microsporidiosis in the graft of a renal transplant recipient.

Microsporidia are intracellular protozoa that are emerging as significant opportunistic infections in AIDS patients. Although there are numerous published reports of intestinal and disseminated infections in patients with AIDS, there have been only two previous reports in transplantation medicine, both on intestinal microsporidiosis. We report here the first documented case of extra-intestinal microsporidiosis in a transplant recipient. A 39-year-old renal transplant recipient presented with a pyrexia and deteriorating graft function. Light microscopic examination of a renal allograft biopsy revealed numerous microsporidian spores within the renal tubular epithelium. Transmission electron microscopy confirmed the presence of an Encephalitozoon infection and was highly suggestive of Encephalitozoon intestinalis. Therapy with albendazole was extremely effective and resulted in recovery of renal function. Although a rare cause of renal allograft dysfunction, microsporidiosis is curable. It may be underdiagnosed, and should be considered in the differential diagnosis of transplant recipients presenting with opportunistic infections.

Adult↗
PubMed2001

New members of the Drosophila Myc transcription factor subfamily revealed by a genome-wide examination for basic helix-loop-helix genes.

The basic helix-loop-helix (bHLH) proteins represent an evolutionary conserved class of transcription factors that are known to play important roles in cell determination and differentiation during animal embryonic development. Following an exhaustive search of the complete Drosophila genome sequence using a PSI-BLAST strategy, we identified 19 new genes, bringing the total number of bHLH-encoding genes in the Drosophila genome to 56. These new genes belong to various subfamilies of bHLH transcription factors, such as the Daughterless, Hairy-Enhancer of split, bHLH-PAS or bHLHZip subfamilies. The embryonic expression pattern of each of these new genes has been analyzed by in situ hybridization. By looking for closely structurally related motifs, we found two genes that represent likely orthologues of vertebrate Mnt and Mlx. Together with previous reports, our data suggest that, similar to networks involved in neurogenesis and myogenesis, the network of Myc-related genes has been globally conserved throughout evolution.

Algorithms↗
PubMed2001

Impact of Celsior solution on hepatocellular, reperfusion and endothelial cell injury after liver transplantation.

BACKGROUND: Initially, preservation solutions were developed to maintain cell function of the transplanted organs. However, recently developed preservation solutions also contain a variety of substances to reduce the reperfusion injury. AIM: To study the effect of three different preservation solutions on the liver cell injury, endothelial cell function and reperfusion injury after liver transplantation. MATERIAL AND METHODS: Large White X Landrace pigs of either sex were subjected to orthotopic liver transplantation. Donor livers were flushed and stored in University of Wisconsin Solution, Eurocollins Solution or Celsior Solution for 3 hours. Blood samples were taken at various times post transplantation for assessment of aspartate aminotransferase, hyaluronic acid, malondialdehyde and Vitamin A levels. RESULTS: Serum aspartate aminotransferase levels were lower in the livers preserved in the Wisconsin solution. Plasma malondialdehyde levels were lower and serum Vitamin A levels were higher in the livers preserved in Celsior solution. Serum hyaluronic acid levels increased after liver transplantation but were similar with all three solutions. CONCLUSIONS: There was less hepato-cellular injury in the livers preserved in Wisconsin solution and less reperfusion injury with the Celsior solution. The endothelial cell injury was similar with all three solutions.

Animals↗
PubMed2001

Effect of early arterialization of the porcine liver allograft on reperfusion injury, hepatocellular injury, and endothelial cell dysfunction.

The conventional technique of liver transplantation involves the initial perfusion of the graft with portal blood. However, recent evidence suggests that initial arterialization of the graft may be better. The aim of this study is to evaluate the timing of arterialization on reperfusion injury, hepatocellular injury, and endothelial cell function after liver transplantation. Large white X Landrace pigs (n = 24) were subjected to orthotopic liver transplantation. The animals were randomly assigned to 4 groups, ranging from late arterialization (60 minutes after portal reperfusion) to early rearterialization (20 minutes before portal reperfusion). Aspartate aminotransferase levels continued to increase 4 hours posttransplantation in group 1 (late arterialization), but remained stable after 1 hour posttransplantation in group 4 (early rearterialization). Levels of malondialdehyde doubled in all groups after portal reperfusion with the exception of group 4, in which the liver received arterial blood before portal reperfusion. Vitamin A levels decreased in all groups after revascularization, but the decrease was more pronounced and prolonged in groups 1 and 2 (late arterialization) compared with groups 3 and 4 (early rearterialization). Hyaluronic acid levels continued to increase in all groups until 1 hour posttransplantation except in group 4, in which the level decreased from 20 minutes posttransplantation. Results of this study show that early rearterialization is associated with less hepatocellular damage, less reperfusion injury, and improved liver endothelial cell function. In conclusion, our results indicate that early rearterialization of the graft is beneficial to the transplanted liver.

Animals↗
PubMed2001

Samarium-153-EDTMP in the treatment of refractory rheumatoid arthritis.

We examined the preliminary safety and efficacy of intravenous samarium-153-EDTMP (Sm-153) in the treatment of refractory rheumatoid arthritis (RA). In an open-label sequential group comparison of 0.5, 1.0, and 2.0 mCi/kg, Sm-153 was administered as a single intravenous infusion to 24 patients with refractory disease. Across treatment doses, the frequency of American College of Rheumatology (ACR) 20% responses was 25%, 29%, 25%, and 33% at 2, 4, 8, and 12 weeks, respectively. Expected significant declines in absolute neutrophil count, hemoglobin, and platelet counts were observed with nadirs seen between 2-4 weeks. Sm-153, at doses of 0.5 and 1.0 mCi/kg, is well tolerated but minimally effective in the treatment of refractory RA as measured using ACR response criteria.

Adolescent↗
PubMed2001

Ethical considerations in research with bereaved families.

This article describes a research project aimed at delivering an intervention to bereaved family members living in the community. The issues covered are access to subjects, recruitment and retention of subjects, and random assignment to control and experimental groups.

Bereavement↗
PubMed2001

Evaluation of various corrections to the standardized uptake value for diagnosis of pulmonary malignancy.

OBJECTIVE: Standard uptake values (SUVs) are widely used for quantifying the uptake of 18F-fluorodeoxyglucose (18F-FDG) in tumours. The objective of this study was to evaluate the accuracy of SUVs for malignancy in lung nodules/masses and to analyse the effects of tumour size, blood glucose levels and different body weight corrections on SUV. METHODS: One hundred and twenty-seven patients with suspicious lung lesions imaged with 18F-FDG positron emission tomography (PET) were studied retrospectively. Pathology results were used to establish lesion diagnosis in all cases. SUVs based on maximum pixel values were obtained by placing regions of interest around the focus of abnormal 18F-FDG uptake in the lungs. The SUVs were calculated using the following normalizations: body weight (BW), lean body weight (LBW), scaled body surface area (BSA), blood glucose level (Glu) and tumour size (Tsize). Receivers operating characteristic (ROC) curves were generated to compare the accuracy of different methods of SUV calculation. RESULTS: The areas under the ROC curves for SUV(BW), SUV(BW+Glu), SUV(LBW), SUV(LBW+Glu), SUV(BSA), SUV(BSA+Glu) and SUV(BW+Tsize) were 0.915, 0.912, 0.911, 0.912, 0.916, 0.909 and 0.864, respectively. CONCLUSION: The accuracy of SUV analysis for malignancy in lung nodules/masses is not improved by correction for blood glucose or tumour size or by normalizing for body surface area or lean body weight instead of body weight.

Fluorodeoxyglucose F18↗
PubMed2001

glnD and mviN are genes of an essential operon in Sinorhizobium meliloti.

To evaluate the role of uridylyl-transferase, the Sinorhizobium meliloti glnD gene was isolated by heterologous complementation in Azotobacter vinelandii. The glnD gene is cotranscribed with a gene homologous to Salmonella mviN. glnD1::Omega or mviN1::Omega mutants could not be isolated by a powerful sucrose counterselection procedure unless a complementing cosmid was provided, indicating that glnD and mviN are members of an indispensable operon in S. meliloti.

Bacterial Proteins↗
PubMed2001

Significance of the portal vein helix.

BACKGROUND: The portal venous system plays a major role in a variety of disease processes. Although the anatomy, histology and physiology of the portal vein have been extensively studied over the last century, very little attention has been given to its unique helical structure. Previous documentation of the helical structure has been based on microscopic, macroscopic and radiological appearances. MATERIALS AND METHODS: A more refined method than the above was used to image the portal vein helix. Resin casts of the portal venous system were performed in 6 rats, 1 baboon and 1 human. RESULTS: All species had a clearly demonstrated helical structure of the portal vein situated above the splenic vein. CONCLUSION: The unique structure of the portal vein and its subsequent helical flow has been neglected in medical research. The significance of the activated portal helix and its effect on the blood flow into the liver needs further investigation.

Animals↗
PubMed2000

Lysine-73 is involved in the acylation and deacylation of beta-lactamase.

Lysine 73 is a conserved active-site residue in the class A beta-lactamases, as well as other members of the serine penicillin-sensitive enzyme family; its role in catalysis remains controversial and uncertain. Mutation of Lys73 to alanine in the beta-lactamase from Bacillus licheniformis resulted in a substantial reduction in both turnover rate (k(cat)) and catalytic efficiency (k(cat)/K(m)), and a very significant shift in pK(1) to higher pH in the bell-shaped pH-rate profiles (k(cat)/K(m)) for several penicillin and cephalosporin substrates. The increase in pK(1) is consistent with the removal of the positive ammonium group of the lysine from the proximity of Glu166, to which the acid limb has been ascribed. The alkaline limb of the k(cat)/K(m) vs profiles is not shifted appreciably, as might have been expected if this limb reflected the ionization of Lys73 in the wild-type enzyme. The k(cat)/K(m) at the pH optimum for the mutant was down about 200-fold for penicillins and around 10(4) for cephalosporins, compared to the wild-type, suggesting significant differences in the mechanisms for catalysis of penicillins compared to cephalosporins. Burst kinetics were observed with several substrates assayed with K73A beta-lactamase, indicating an underlying branched-pathway kinetic scheme, and rate-limiting deacylation. FTIR analysis was used to determine whether acylation or deacylation was rate-limiting. In general, acylation was the rate-limiting step for cephalosporin substrates, whereas deacylation was rate-limiting for penicillin substrates. The results indicate that Lys73 plays an important role in both the acylation and deacylation steps of the catalytic mechanism. The effects of this mutation (K73A) indicate that Lys73 does not function as a general base in the catalytic mechanism of beta-lactamase. The existence of bell-shaped pH-rate profiles for the K73A variant suggests that Lys73 is not directly responsible for either limb in such plots. It is likely that both Glu166 and Lys73 are important to each other in terms of maintaining the optimum electrostatic environment for fully efficient catalytic activity to occur.

Acylation↗
PubMed2000

ProDom and ProDom-CG: tools for protein domain analysis and whole genome comparisons.

ProDom contains all protein domain families automatically generated from the SWISS-PROT and TrEMBL sequence databases (http://www. toulouse.inra.fr/prodom.html ). ProDom-CG results from a similar domain analysis as applied to completed genomes (http://www.toulouse. inra.fr/prodomCG.html ). Recent improvements to the ProDom database and its server include: scaling up to include sequences from TrEMBL, addition of Pfam-A entries to the set of expert validated families, assignment of stable accession numbers, consistency indicators for domain families, domain arrangements of sub-families and links to Pfam-A.

Computer Graphics↗