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Biomedical subjects

P Baum

Publications and source records attributed to P Baum.

At least 19 recordsLinked to original sources
PubMed1995

Femorotibial bypass for claudication: do results justify an aggressive approach?

PURPOSE: The role of infrainguinal arterial reconstructive surgery for claudication is controversial. We reviewed the results of femorotibial bypass procedures performed in a select group of patients with disabling claudication in an attempt to define a role for this aggressive approach. METHODS: Data were retrieved from the vascular registry, and hospital records were obtained for all patients undergoing femorotibial reconstruction for disabling claudication during the past 16 years at Brigham and Women's Hospital. Follow-up interviews were obtained to assess overall health, walking impairment, functional status, and patient satisfaction. RESULTS: During a 16-year period a total of 57 tibial reconstructions were performed in 53 patients for claudication (5% of all infrainguinal vein reconstructions). Autogenous vein conduit was used in all cases, most of which (70%) involved the greater saphenous vein in situ. Distal anastamoses were to the tibioperoneal trunk (12%), anterior tibial (18%), posterior tibial (47%), and peroneal (23%) arteries. Major complications occurred in 9%, and no perioperative deaths occurred. Overall 5-year survival was 54% +/- 15%, and no major amputations were performed. Cumulative primary and secondary graft patency at 5 years were 81% +/- 6% and 86% +/- 5%, respectively. Patency rates were significantly better than those achieved in a concurrent series of tibial bypasses for limb salvage and were equivalent to those achieved with femoropopliteal bypass for claudication. Interviewed patients reported improved walking distance, reduced claudication, and a high degree of overall satisfaction with their operation. CONCLUSION: Results obtained with femorotibial bypass performed for claudication were superior to those obtained for limb salvage and were equivalent to those obtained with femoropopliteal bypass for claudication. The results obtained in this highly selected cohort suggest that patients at low risk with significant functional impairment from claudication, available autogenous vein, and suitable tibial outflow to the ischemic muscular bed can be offered revascularization with the expectation of durable long-term results.

Adult↗
PubMed1995

Peripheral arterial-vascular disease in women: prevalence, prognosis, and treatment.

Lower extremity atherosclerosis results in significant morbidity in women, particularly in women following the menopause. Up to 25% of women aged 55 to 74 years are affected by this disease. When noninvasive testing is used to determine the prevalence of lower extremity atherosclerosis, and men in this age group are equally represented. Cigarette smoking, diabetes mellitus, and menopause are risk factors for atherosclerosis of particular interest in women. The prevalence of cigarette smoking is rising rapidly among women, and diabetes appears to be a greater risk factor for atherosclerosis in women than in men. Risk factor reduction, in addition to an exercise program, are important parts of the treatment program for stable claudication. In both men and women with more severe symptoms, an ankle/branchial index (ABI) of less than 0.3 is associated with more severe symptoms, an ankle/brachial index (ABI) of less than 0.3 is associated with a poor prognosis. Men and women fare equally well following revascularization for severe peripheral atherosclerosis. However, there are some data to suggest that women may be offered peripheral revascularization at a lower rate.

Age Factors↗
PubMed1994

Genomic organization and chromosomal localization of mouse Eplg2, a gene encoding a binding protein for the receptor tyrosine kinase elk.

The human gene EPLG2 (Eph ligand-2) encodes a potential ligand for the receptor tyrosine kinase elk. High sequence conservation between the human and the rat cDNAs and developmentally regulated expression of the rat gene suggest that the protein encoded by EPLG2 plays an important role in mammalian development. To facilitate analysis of the physiological role of the protein, we have cloned and characterized a 24-kb region of mouse genomic DNA containing the mouse homologue of EPLG2 (Eplg2), including 5'- and 3'-flanking sequences. Restriction mapping, coupled with Southern blot hybridization and sequencing, was used to determine the structural organization of the gene. The Eplg2 genomic locus spans a region of approximately 12 kb, encoding five exons and four introns. The first intron comprises approximately 8.5 kb of the entire 12-kb genomic sequence. Eplg2 was mapped to the mouse X chromosome by interspecific backcross analysis and is tightly linked to the androgen receptor (Ar) locus.

Amino Acid Sequence↗
PubMed1994

Molecular characterization of a family of ligands for eph-related tyrosine kinase receptors.

A family of tyrosine kinase receptors related to the product of the eph gene has been described recently. One of these receptors, elk, has been shown to be expressed only in brain and testes. Using a direct expression cloning technique, a ligand for the elk receptor has been isolated by screening a human placenta cDNA library with a fusion protein containing the extracellular domain of the receptor. This isolated cDNA encodes a transmembrane protein. While the sequence of the ligand cDNA is unique, it is related to a previously described sequence known as B61. Northern blot analysis of human tissue mRNA showed that the elk ligand's mRNA is 3.5 kb long and is found in placenta, heart, lung, liver, skeletal muscle, kidney and pancreas. Southern blot analysis showed that the gene is highly conserved in a wide variety of species. Both elk ligand and B61 mRNAs are inducible by tumour necrosis factor in human umbilical vein endothelial cells. In addition, both proteins show promiscuity in binding to the elk and the related hek receptors. Since these two ligand sequences are similar, and since elk and hek are members of a larger family of eph-related receptor molecules, we refer to these ligands as LERKs (ligands for eph-related kinases).

Amino Acid Sequence↗
PubMed1994

LERK-2, a binding protein for the receptor-tyrosine kinase ELK, is evolutionarily conserved and expressed in a developmentally regulated pattern.

We have isolated and characterized cDNA clones that encode the rat homologue of a binding protein, LERK-2, for the receptor tyrosine kinase, elk. The cDNAs contain an open reading frame of 1527 nucleotides capable of encoding a protein 345 amino acid residues in length. The nucleotide sequence of the present clones is > 90% identical to the previously identified human LERK-2 cDNA, and the predicted proteins encoded by the rat and human clones are identical at 95% of amino acid residues. Recombinant proteins expressed from the rat cDNAs bind to elk with high affinity, similar to recombinant human LERK-2 and an endogenously-expressed rat elk-binding protein. Expression of the rat LERK-2 mRNA was detected in embryonic brain, kidney, lung, skeletal muscle, thymus, liver, and heart, and diminished in the early post-natal period. Significant LERK-2 mRNA expression in the young adult rat was restricted to the lung, kidney, heart and testes.

Amino Acid Sequence↗
PubMed1992

Requirement for ESP1 in the nuclear division of Saccharomyces cerevisiae.

Mutations in the ESP1 gene of Saccharomyces cerevisiae disrupt normal cell-cycle control and cause many cells in a mutant population to accumulate extra spindle pole bodies. To determine the stage at which the esp1 gene product becomes essential for normal cell-cycle progression, synchronous cultures of ESP1 mutant cells were exposed to the nonpermissive temperature for various periods of time. The mutant cells retained viability until the onset of mitosis, when their viability dropped markedly. Examination of these cells by fluorescence and electron microscopy showed the first detectable defect to be a structural failure in the spindle. Additionally, flow cytometric analysis of DNA content demonstrated that massive chromosome missegregation accompanied this failure of spindle function. Cytokinesis occurred despite the aberrant nuclear division, which often resulted in segregation of both spindle poles to the same cell. At later times, the missegregated spindle pole bodies entered a new cycle of duplication, thereby leading to the accumulation of extra spindle pole bodies within a single nucleus. The DNA sequence predicts a protein product similar to those of two other genes that are also required for nuclear division: the cut1 gene of Schizosaccharomyces pombe and the bimB gene of Aspergillus nidulans.

Amino Acid Sequence↗
PubMed1991

MPS1 and MPS2: novel yeast genes defining distinct steps of spindle pole body duplication.

It is crucial to the eucaryotic cell cycle that the centrosome undergo precise duplication to generate the two poles of the mitotic spindle. In the budding yeast Saccharomyces cerevisiae, centrosomal functions are provided by the spindle pole body (SPB), which is duplicated at the time of bud emergence in G1 of the cell cycle. Genetic control of this process has previously been revealed by the characterization of mutants in CDC31 and KAR1, which prevent SPB duplication and lead to formation of a monopolar spindle. Newly isolated mutations described here (mps1 and mps2, for monopolar spindle) similarly cause monopolar mitosis but their underlying effects on SPB duplication are unique. The MPS1 gene is found by electron microscopy to be essential for proper formation of the site at which the new SPB normally arises adjacent to the existing one. By contrast, a mutation in MPS2 permits duplication to proceed, but the newly formed SPB is structurally defective and unable to serve as a functional spindle pole. Distinct temporal requirements for the CDC31, MPS1, and MPS2 gene functions during the SPB duplication cycle further demonstrate the individual roles of these genes in the morphogenetic pathway.

Cell Cycle↗
PubMed1988

A yeast gene essential for regulation of spindle pole duplication.

In eucaryotic cells, duplication of spindle poles must be coordinated with other cell cycle functions. We report here the identification in Saccharomyces cerevisiae of a temperature-sensitive lethal mutation, esp1, that deregulates spindle pole duplication. Mutant cells transferred to the nonpermissive temperature became unable to continue DNA synthesis and cell division but displayed repeated duplication of their spindle pole bodies. Although entry into this state after transient challenge by the nonpermissive temperature was largely lethal, rare survivors were recovered and found to have become increased in ploidy. If the mutant cells were held in G0 or G1 during exposure to the elevated temperature, they remained viable and maintained normal numbers of spindle poles. These results suggest dual regulation of spindle pole duplication, including a mechanism that promotes duplication as cells enter the division cycle and a negative regulatory mechanism, controlled by ESP1, that limits duplication to a single occurrence in each cell division cycle. Tetrad analysis has revealed that ESP1 resides at a previously undescribed locus on the right arm of chromosome VII.

Cell Cycle↗
PubMed1986

Yeast gene required for spindle pole body duplication: homology of its product with Ca2+-binding proteins.

Saccharomyces cerevisiae strains bearing temperature-sensitive alleles of the cell division cycle gene CDC31 are specifically defective in duplication of the spindle pole body, the microtubule-organizing center of yeast. To define the function encoded by CDC31 more fully, we have isolated genomic clones of the gene by selection for complementation of a temperature-sensitive allele. The locus from which the clone was derived was marked by integration of a nutritional marker and found by meiotic mapping to cosegregate with CDC31. The polypeptide sequence of the open reading frame in the CDC31 gene was determined and compared with the sequences of other known proteins. This revealed significant homology with the calmodulins and other members of the Ca2+-binding protein family. On the basis of comparison with these related proteins, it is evident that the CDC31 gene product has at least two binding sites for Ca2+ and is also homologous with other regions of the calmodulin sequence. We propose that Ca2+ fluxes within the yeast cell play a key role in spindle pole body duplication and consequently in the organization of the microtubule arrays.

Amino Acid Sequence↗
PubMed1984

Cardiovascular effects of intracerebroventricular injection of vasopressin in unanaesthetized normotensive and DOCA-salt hypertensive rats.

The mean arterial pressure (MAP) and heart rate (HR) responses to intracerebroventricular (i.c.v.) administration of arginine vasopressin (AVP) in unanaesthetized normotensive control and DOCA-salt hypertensive rats were studied. Intracerebroventricular administration of AVP (0.25-1000 ng) to control rats produced dose-dependent long-lasting increases in MAP (5-45 mmHg) and HR (35-110 beats/min). Peripheral treatment of rats with an antipressor AVP antagonist had no effect on i.c.v. AVP-induced increases in MAP and HR, whereas the responses were blocked by i.c.v. administration of the antagonist. Peripheral administration of phentolamine and propranolol also completely blocked the changes in MAP and HR. DOCA-salt hypertensive rats showed significantly greater increases in MAP and HR in response to i.c.v. AVP and a tenfold lower threshold for stimulation. The results demonstrate that AVP acting on central neural structures can produce increases in MAP and HR by stimulating sympathetic outflow. Increased sensitivity and responsiveness to i.c.v. AVP in hypertensive rats suggest a potential mechanism of action of AVP in hypertension.

Animals↗
PubMed1978

Identification of tubulin from the yeast Saccharomyces cerevisiae.

A tubulin-like protein was identified in the lower eukaryote Saccharomyces cerevisiae. The following criteria were used: (i) copolymerization of the 35S-labeled yeast protein with porcine brain tubulin; (ii) immunoprecipitation of the 35S-labeled yeast protein with antiflagellar tubulin antibody; (iii) the presence of the yeast protein as a constituent of isolated yeast nuclei; and (iv) splitting of the yeast protein in a gel electrophoretic system containing sodium dodecyl sulfate that resolved the alpha- and beta-tubulin chains from other sources. This protein did not appear to have significant affinity for the plant alkaloid, Colcemid.

Cell Nucleus↗