PubMed Health⌕ Search

Biomedical subjects

B Rosenzweig

Publications and source records attributed to B Rosenzweig.

At least 19 recordsLinked to original sources

Fatty acid production in Schizochytrium sp.: Involvement of a polyunsaturated fatty acid synthase and a type I fatty acid synthase.

Schizochytrium sp. is a marine microalga that has been developed as a commercial source for docosahexaenoic acid (DHA, C22:6 (omega-3), enriched biomass, and oil. Previous work suggested that the DHA, as well as docosapentaenoic acid (DPA, C22:5 omega-6), that accumulate in Schizochytrium are products of a multi-subunit polyunsaturated fatty acid (PUFA) synthase (1). Here we show data to support this view and also provide information on other aspects of fatty acid synthesis in this organism. Three genes encoding subunits of the PUFA synthase were isolated from genomic DNA and expressed in E. coli along with an essential accessory gene encoding a phosphopantetheinyl transferase (PPTase). The resulting transformants accumulated both DHA and DPA. The ratio of DHA to DPA was approximately the same as that observed in Schizochytrium. Treatment of Schizochytrium cells with certain levels of cerulenin resulted in inhibition of 14C acetate incorporation into short chain fatty acids without affecting labeling of PUFAs, indicating distinct biosynthetic pathways. A single large gene encoding the presumed short chain fatty acid synthase (FAS) was cloned and sequenced. Based on sequence homology and domain organization, the Schizochytrium FAS resembles a fusion of fungal FAS beta and alpha subunits.

Amino Acid Sequence↗

Chromosomal localization of three human genes encoding bone morphogenetic protein receptors.

Bone morphogenetic proteins (BMPs) are members of the TGF-beta superfamily that play a pivotal role in bone formation during embryogenesis and fracture repair. BMP signaling occurs via hetero-oligomeric serine/threonine kinase complexes of BMP type I (BMPR-IA or BMPR-IB) and type II receptors (BMPR-II). BMPR-IA and IB are closely related receptors, with sequence differences conserved between different species, suggesting that they serve distinct functions. Here we report the cDNA cloning of human BMPR1B and the chromosomal localization of all three BMPR genes. Using somatic cell hybrid and FISH analyses, the BMPR1A, BMPR1B, and BMPR2 genes were assigned to 10q23, 4q22-24, and 2q33-34, respectively. A processed BMPR1A pseudogene was mapped to 6q23.

Bone Morphogenetic Protein Receptors↗

Identification and characterization of a pro-tumor necrosis factor-alpha-processing enzyme from the ADAM family of zinc metalloproteases.

Tumor necrosis factor-alpha (TNF) is initially expressed as a 26-kDa membrane-bound precusor protein (pro-TNF) that is shed proteolytically from the cell surface, releasing soluble 17-kDa TNF. We have identified human ADAM 10 (HuAD10) from THP-1 membrane extracts as a metalloprotease that specifically clips a peptide substrate spanning the authentic cleavage site between Ala76 and Val77 in pro-TNF. To confirm that HuAD10 has TNF processing activity, we cloned, expressed, and purified an active, truncated form of HuAD10. Characterization of recombinant HuAD10 (rHuAD10) suggests that this enzyme has many of the properties (i.e. substrate specificity, metalloprotease activity, cellular location) expected for a physiologically relevant TNF-processing enzyme.

ADAM Proteins↗

Molecular cloning and characterization of a novel p38 mitogen-activated protein kinase.

The p38 mitogen-activated protein kinases (MAPK) are activated by cellular stresses and play an important role in regulating gene expression. We have isolated a cDNA encoding a novel protein kinase that has significant homology (57% amino acid identity) to human p38alpha/CSBP. The novel kinase, p38delta, has a nucleotide sequence encoding a protein of 365 amino acids with a putative TGY dual phosphorylation motif. Dot-blot analysis of p38delta mRNA in 50 human tissues revealed a distribution profile of p38delta that differs from p38alpha. p38delta is highly expressed in salivary gland, pituitary gland, and adrenal gland, whereas p38alpha is highly expressed in placenta, cerebellum, bone marrow, thyroid gland, peripheral leukocytes, liver, and spleen. Like p38alpha, p38delta is activated by cellular stress and proinflammatory cytokines. p38delta phosphorylates ATF-2 and PHAS-I, but not MAPK-activated protein kinase-2 and -3, known in vivo and in vitro substrates of p38alpha. We also observed that p38delta was strongly activated by MKK3 and MKK6, while p38alpha was preferentially activated by MKK6. Other experiments showed that a potent p38alpha kinase inhibitor AMG 2372 minimally inhibited the kinase activity of p38delta. Taken together, these data indicate that p38delta is a new member of the p38 MAPK family and that p38delta likely has functions distinct from that of p38alpha.

Amino Acid Sequence↗

Noninvasive tracking of coronary atherosclerosis by electron beam computed tomography: rationale and design of the Felodipine Atherosclerosis Prevention Study (FAPS).

The Felodipine Atherosclerosis Prevention Study is designed to evaluate the efficacy of the calcium antagonist felodipine ER and combined felodipine/simvastatin therapy on retarding the progression of atherosclerosis, estimated by serial changes in coronary calcium evaluated by noninvasive electron beam computed tomography. Subjects include 180 men and women aged 40 to 69 and 50 to 69 years, respectively, with moderate type IIa dyslipidemia, with either cardiovascular disease or risk factors. All subjects receive simvastatin lipid-lowering therapy, and are randomized either to felodipine or placebo for a treatment period of 2 years. Monitoring of blood chemistry, measures of lipids and apolipoproteins, blood pressure, evaluation of symptoms, and interim clinical event monitoring are done at routine follow-up visits. Baseline and 2-year follow-up electron beam computed tomography, measuring changes in total calcium score, area, and mass, evaluate the effects of intervention on the progression of calcified atherosclerosis. The results from the Felodipine Atherosclerosis Prevention Study will provide valuable information about the effect of felodipine alone and in combination with simvastatin on progression of calcified atherosclerosis evaluated noninvasively.

Aged↗

Glial cell-line derived neurotrophic factor (GDNF) mRNA upregulation in striatum and cortical areas after pilocarpine-induced status epilepticus in rats.

Glial cell-line derived neurotrophic factor (GDNF) has recently been cloned and shown to have trophic effects on dopaminergic nigral neurons. However, GDNF mRNA has not been detected in striatum or other forebrain areas of adult rat. Using limbic motor status epilepticus induced by pilocarpine to activate neurons in motor and limbic areas, we now demonstrate GDNF mRNA signals in the striatum, hippocampus and cortex using in situ hybridisation. The finding of GDNF mRNA in the stimulated striatum opens the possibility that GDNF may be a target-derived, trophic factor in the nigro-striatal system. This expression of GDNF mRNA may be linked to excitatory cortical input. Increases in GDNF mRNA after status epilepticus in hippocampus and neocortex indicate additional roles for GDNF.

Animals↗

Randomized double-blind trial of terodiline in the treatment of urge incontinence in women.

OBJECTIVE: To evaluate the effects of terodiline in women with urge incontinence. METHODS: After a 2-week run-in period, 93 women with urinary frequency and urge incontinence were randomized to either placebo or terodiline, 25 mg twice daily, in a double-blind study for 4 weeks. Symptoms were evaluated using daily frequency-volume charts to record voiding frequency, number of incontinent episodes, absorbent pad use, and quality of life. RESULTS: The terodiline group showed a 70% decrease in the mean (+/- standard deviation) number of incontinent episodes per week (15.8 +/- 24, decreasing to 4.9 +/- 11.9; P < .01), which persisted throughout the study period. The placebo group achieved a 9% reduction in the mean number of incontinent episodes (13.0 +/- 11.3, decreasing to 11.9 +/- 16; P < .05) only in the final week of treatment. Side effects, especially anticholinergic side effects, were more common in the terodiline group, but resulted in only one dropout. Both the treated and placebo groups improved in daytime frequency and quality-of-life indices. CONCLUSION: Terodiline is well tolerated and effective in reducing urge incontinent episodes in women.

Butylamines↗

The role of von Willebrand factor in pre-eclampsia.

The von Willebrand factor (vWF) has gained considerable interest in recent years as a marker of endothelial cell activation or insult and by virtue of its interactions with platelets and vessel walls. Altered patterns of vWF multimers were found to occur frequently in patients with thrombotic thrombocytopenic purpura in the acute and chronic stages. This disorder shares some clinical and laboratory findings with pre-eclampsia, including thrombocytopenia. Recent studies have also suggested that abnormalities of endothelial cell metabolism play a central role in the pathophysiology of pre-eclampsia. In order to determine if vWF could be instrumental in the disease process and the thrombocytopenia of pre-eclampsia we analyzed the ante- and postpartum structural and functional distribution of vWF. This data was correlated with hematological parameters such as platelet counts and the clinical severity of the disease. We found no consistent changes of vWF in association with thrombocytopenia or clinical severity. However, functional vWF was lower in postpartum samples of severely affected pre-eclamptics as compared to normal controls. This finding may reflect endothelial cell exhaustion after stimulation or cellular injury. Elevated titers of fibrin split products and thrombocytopenia were evident in severe pre-eclampsia, as seen in DIC, despite factor VIII coagulant levels within the normal range. Our data is consistent with the hypothesis of endothelial cell dysfunction in pre-eclampsia. However, the mechanism of thrombocytopenia in this disorder does not appear to be related to alterations in the structure or biological function of vWF.

Adult↗

Wild-type and mutant actin genes in Caenorhabditis elegans.

We have sequenced the four actin genes of Caenorhabditis elegans. These four genes encode typical invertebrate actins and are highly homologous, differing from each other by, at most, three amino acid residues. As a first step toward an understanding of the developmental regulation of this gene set we have also sequenced mutant actin genes. The mutant genes were cloned from two independent revertants of a single dominant actin mutant. For both revertants, reversion was accompanied by an actin gene rearrangement. The accumulation of actin mRNA during development in these two revertants is different from that of wild-type animals. We present here a correlation between actin gene structure and expression in wild-type and mutant animals. The results, suggest that co-ordinate regulation of actin genes is not essential for wild-type muscle function. In addition, it appears that changes in the 3' region of at least one of the actin mRNA may affect its steady-state regulation during development.

Actins↗

Organization and expression of the COX6 genetic locus in Saccharomyces cerevisiae: multiple mRNAs with different 3' termini are transcribed from COX6 and regulated differentially.

COX6 and its surrounding genetic locus have been characterized for the yeast Saccharomyces cerevisiae. Flanking genes are found closely spaced upstream and downstream of COX6. The upstream gene and COX6 are transcribed from opposite strands and are separated by no more than 300 bp. COX6 is transcribed into three different size classes of mRNA (1000b, 830b, and 700b) differing in length in their 3' untranslated regions. All three classes of mRNAs are found on polysomes and, hence, are most likely translated. The different COX6 mRNAs vary in abundance during growth in rich media and are affected differentially as cells are shifted into media containing high or low glucose concentrations. The largest mRNA is much more susceptible to glucose repression/derepression than are the two smaller mRNAs, whereas the smallest RNA is preferentially accumulated during growth in rich media. These findings demonstrate that COX6 mRNAs with different 3'-termini are either synthesized differentially or differ in stability and suggest the existence of a complex system regulating COX6 expression.

Amino Acid Sequence↗

Sequence comparisons of developmentally regulated collagen genes of Caenorhabditis elegans.

Collagen genes col-6, col-7 (partial), col-8, col-14 and col-19 from the nematode Caenorhabditis elegans were sequenced, and compared to the previously sequenced genes col-1 and col-2. The genes are between 1.0 and 1.2 kb in length, and each includes one or two short introns. The presumptive promoter regions contain sequences similar to the eukaryotic TATA promoter element. Two distinct, conserved sequences were found in the presumptive promoter regions of, respectively, the dauer larva-specific genes col-2 and col-6, and the primarily adult-specific genes col-7 and col-19. The domain structures of the collagen polypeptides are similar: each polypeptide contains two triple-helix forming (Gly-X-Y)n domains, one of 30-33 amino acids (aa), and the other of 127-132 aa. The latter domain is interrupted by one to three short (2-8 aa) non-(Gly-X-Y)n segments that occur at relatively conserved locations in each polypeptide. Sets of cysteine residues flank the (Gly-X-Y)n domains in all of the polypeptides. The genes can be placed into three families based upon amino acid sequence similarities. Genes within a family do not always exhibit similar developmental expression programs, suggesting that structural and regulatory regions of the genes have evolved separately. The codon usage in the genes is highly asymmetrical, with adenine appearing in the third position of 85% of the glycine codons, and 93% of the proline codons.

Amino Acid Sequence↗

A comparison of plasma cholesterol, triglycerides and high density lipoprotein cholesterol levels in women using contraceptive pills and a control group.

Plasma cholesterol, triglycerides and HDL cholesterol levels were compared in a group of 45 young, normotensive, nonobese and nondiabetic women who used modern combined minidose contraceptive pills, to a matched group of 39 women who did not use any hormonal preparations. Our results show an increase in triglyceride levels as well as significant increase in cholesterol level in the 'pill' users group. We failed to show a significant change in HDL cholesterol levels and HDL cholesterol to total cholesterol ratio between the two groups. Our results concerning triglyceride levels are in consent to previous studies in the medical literature, while the elevation in cholesterol levels has rarely been reported in contemporary papers about minidose pill users. It seems that the contradicting effect of estrogen and progesterone on plasma HDL levels neutralizes each other's effect on this lipoprotein fraction. The elevation in plasma triglycerides and cholesterol may have importance in the vascular abnormalities seen in such pill users.

Adult↗

Target sequences for the C. elegans transposable element Tc1.

The target sequences for two independent insertions of the transposable element Tc1 from Caenorhabditis elegans show homology. Because both insertions are at palindromic TA/AT sequences, the exact boundaries of Tc1 cannot be distinguished; Tc1 could be 1610 bp and flanked by a 2-bp duplication of the target site or it could be 1612 bp and without target site duplication. The latter possibility implies a novel manner for insertion of a transposable element.

Animals↗

Sequence of the C. elegans transposable element Tc1.

The complete nucleotide sequence was determined for Tc1, a transposable element in the nematode Caenorhabditis elegans. The 1610-base-pair element terminates in 54-base-pair perfect inverted repeats and is flanked by a 2-base-pair duplication of the target sequence. The Tc1 sequence contains two long open reading frames on the same DNA strand but in different translational reading frames. The positions of transcriptional control sequences suggest that a single transcript is made, which could produce two polypeptides, 273 and 112 amino acids in length. These features, i.e. terminal repeats, target site duplication and open reading frames, make Tc1 similar to transposable elements from other species.

Animals↗

Analysis of a transposable element in Caenorhabditis elegans.

A transposable element, designated Tc1, has been characterized in Caenorhabditis elegans. Tc1 is 1.7 kilobases long, has an inverted terminal repeat of less than 100 base pairs, and is repeated as a highly conserved element. The copy number and genomic positions of Tc1 are extremely variable among strains, implying that Tc1 is mobile. However, progeny of interstrain crosses did not show hybrid dysgenic traits that might be due to Tc1 transposition.

Animals↗