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Biomedical subjects

P Bray

Publications and source records attributed to P Bray.

At least 19 recordsLinked to original sources
PubMed1998

Transforming growth factor-beta and receptor tyrosine kinase-activating growth factors negatively regulate collagen genes in smooth muscle of hypertensive rats.

Previous studies have suggested that differences in vascular smooth muscle cell (VSMC) proliferative responses between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats can be attributed to transforming growth factor-beta (TGF-beta) actions. Because vascular collagen content is reported to be lower in SHR than in WKY rats, in this study we investigated in cell culture whether the differences in collagen content might also be attributed to differential actions of TGF-beta on VSMCs from the two strains. Exposure of VSMCs from WKY to the TGF-beta isoforms -beta1, -beta2, or -beta3 induced rapid, transient elevations in mRNAs encoding collagens alpha1(I), alpha2(I), and alpha1(III); maximum increases were apparent by 2 hours and ranged from twofold [collagen alpha1(III)] to ninefold [collagen alpha1(I)]. Thereafter they returned to near basal levels. When VSMCs from SHR were exposed to these TGF-beta isoforms, only reductions in collagen mRNA levels were observed, persisting for 24 hours. Basic fibroblast growth factor and epidermal growth factor, factors known to stimulate production of the TGF-beta1 isoform in VSMCs, also induced a pattern of gene responses similar to those induced by the TGF-beta isoforms in VSMCs from SHR and WKY rats. The simultaneous presence of TGF-beta did not affect the time course or magnitude of the changes in collagens alpha1(I), alpha2(I), or alpha1(III) mRNA levels in SHR or WKY VSMCs. Examination of the induction of c-myc mRNA and immunoreactive oncoprotein content indicated that c-myc is a likely contributor to the downregulation of the collagen gene activity in both SHR and WKY VSMCs despite the differential regulation of its mRNA by TGF-beta1 in the two VSMC lines. Together these data suggest that in VSMCs from SHR, a number of gene responses to TGF-beta, in addition to cell proliferation, appear to be abnormal compared with WKY rats, and the lower than normal collagen levels observed in the vasculature of SHR may be in part due to abnormalities in TGF-beta responsiveness.

Animals↗
PubMed1995

Transforming growth factor-beta 1 and the development of vascular hypertrophy in hypertension.

Transforming growth factor-beta 1 (TGF-beta 1) is a multifunctional cytokine capable of regulating the growth and differentiation of many cell types, as well as regulating their environment in the blood vessel wall. Its production by endothelium and/or vascular smooth muscle is stimulated by biophysical forces, growth factors and also vasoconstrictors. In hypertension TGF-beta 1 gene transcription is most likely elevated by a combination of physical and chemical stimuli with the cytokine acting to increase the production of extracellular matrix proteins or to modulate smooth muscle cellular growth, producing hypertrophy, polyploidy or proliferation. With respect to the latter, TGF-beta 1 potentiates the proliferative effects of many receptor tyrosine kinase-activating growth factors in vascular smooth muscle from SHR, but inhibits such proliferation in WKY smooth muscle. It also differentially affects collagen production by the two cell types. It is suggested that the augmented proliferative response in renal hypertensive SHR, compared to renal hypertensive WKY, is the consequence of these differential effects of TGF-beta 1 on smooth muscle cell proliferation. TGF-beta 1 is also likely to be a significant contributor to the development of vascular hypertrophy in genetic hypertension.

Animals↗
PubMed1994

DNA polymorphisms at the lipoprotein lipase gene and their association with quantitative variation in plasma high-density lipoproteins and triacylglycerides.

Lipoprotein lipase (LPL) plays a critical role in the metabolism of lipoproteins because this enzyme hydrolyzes the triacylglycerides in chylomicrons and very low density lipoproteins. This process influences the production of high-density lipoprotein (HDL), which takes up tissue cholesterol for transport to the liver for excretion. Accordingly, LPL qualifies as a candidate gene for understanding lipid metabolic disorders and atherosclerosis. Studies on the relationship between genetic variation at the LPL locus and lipid phenotypes have produced equivocal results to date. To help clarify this issue, we investigated 144 outwardly healthy male Mediterranean migrants (from Italy and Greece), age between 40 and 70 years and resident in Australia, for associations between two common LPL restriction site polymorphisms and the following lipid and lipoprotein phenotypes: total plasma cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triacylglycerides. A series of analysis of variance tests, controlling for age, body mass index, and ethnicity, showed that the HindIII polymorphism at the LPL locus is significantly associated with both triacylglyceride and HDL cholesterol concentrations in this sample. The PvUII polymorphism, however, showed no association with any lipid. Kruskal-Wallis tests confirmed the significance of the associations between the HindIII RFLP and both HDL (p = 0.008) and triacylglycerides (p = 0.03). When the sample was subdivided into subjects who exhibited primary hypertriacylglyceridemia and normolipidemics, a significant difference was observed in the frequency of HindIII (p < 0.05) but not PvuII genotypes. HindIII heterozygotes (H1,H2) were least and H2,H2 individuals were most at risk for triacylglyceridemia. Examination of the normolipidemic sample revealed some evidence for an independent effect of the PvuII polymorphism on both LDL cholesterol and total cholesterol levels.

Adult↗
PubMed1992

1H NMR assignments and secondary structure of human beta 2-microglobulin in solution.

Sequence-specific resonance assignments of human beta 2-microglobulin (M(r) 12,000) and its secondary structure are determined by 2D NMR techniques. The protein is found to contain two antiparallel beta-sheets each of four beta-strands with the beta-sheets being connected by a single disulfide linkage. No evidence for any regular helical structure is found. Amide proton-solvent-exchange rate constants and 3JHN alpha coupling constants are evaluated.

Amino Acid Sequence↗
PubMed1992

Clustering of C2-H2 zinc finger motif sequences within telomeric and fragile site regions of human chromosomes.

Ninety-three phage clones identified by hybridization with a C2-H2 zinc finger sequence probe have been grouped into 23 genetic loci. Partial sequencing verified that each locus belonged to the zinc finger family. Oligonucleotide primer pairs were developed from these sequences to serve as STS markers for these loci. One or more clones from each locus was mapped onto human metaphase chromosomes by fluorescence in situ hybridization. Several loci map to identical chromosomal regions, indicating the possible presence of multigene clusters. Zinc finger loci were found to reside predominantly either in telomeric regions or in chromosomal bands known to exhibit chromosome fragility. Chromosome 19 carries a disproportionate fraction (10 of 23) of the mapped zinc finger loci.

Amino Acid Sequence↗
PubMed1991

Characterization and mapping of human genes encoding zinc finger proteins.

The zinc finger motif, exemplified by a segment of the Drosophila gap gene Krüppel, is a nucleic acid-binding domain present in many transcription factors. To investigate the gene family encoding this motif in the human genome, a placental genomic library was screened at moderate stringency with a degenerate oligodeoxynucleotide probe designed to hybridize to the His/Cys (H/C) link region between adjoining zinc fingers. Over 200 phage clones were obtained and are being sorted into groups by partial sequencing, cross-hybridization with oligodeoxynucleotide probes, and PCR amplification. Further, the genomic clones were cross-hybridized with a set of 30 zinc finger-encoding cDNAs (Kox1-Kox30) isolated from a human T-cell cDNA library. Four cDNAs (Kox4, Kox7, Kox12, and Kox15) were identified that match one or more genomic clones; these matches were confirmed by nucleotide sequence analysis. One or more clones from each locus were mapped onto human metaphase chromosomes by chromosomal in situ suppression hybridization with fluorescent probe detection. We mapped ZNF7/Kox4 to chromosome 8qter, ZNF19/Kox12 to 16q22, ZNF22/Kox15 to 10q11, and ZNF44/Kox7 to 16p11. The results of these analyses support the conclusion that the human genome contains many, probably several hundred, zinc finger genes with consensus H/C link regions.

Amino Acid Sequence↗
PubMed1991

Survey of small molecule and ion binding to beta 2-microglobulin--possible relation to BEN.

Using a new method which permits rapid detection of ligand binding to cross linked protein films and crystals, we evaluated a spectrum of ligand binding to cross linked amorphous films of beta 2-microglobulin purified from urine of Balkan endemic nephropathy patients. Among more than 50 substances studied, including amino acids, fatty acids, sugars, nucleotides, nucleosides, and different inorganic ions, only polyvalent cations, such as Cu2+, Ca2+, Zn2+, Be2+ and La3+, were found to strongly bind to human beta 2-microglobulin with dissociation constants in the range 10(-6) to 10(-4) M. These cations can release beta 2-microglobulin from HLA complexes leading to an increased beta 2-microglobulin level in serum. These observations suggest a possible mechanism for the release of beta 2-microglobulin to make it available to exert toxic effects on the kidney as a potential pathogenesis of Balkan endemic nephropathy.

Balkan Nephropathy↗
PubMed1990

A guide to the effective use of otoacoustic emissions.

Otoacoustic emission test instruments are now entering routine audiological practice. Two general classes of technique are in use in laboratory work--those employing spectrum analysers to observe the continuous generation of OAEs, both stimulated or unstimulated, and those using transient stimulation and waveform averaging to extract a delayed OAE or "cochlear echo" waveform from ear canal sound. Both methods have particular advantages in clinical applications. The transient OAE type of method has proved very effective in screening applications, particularly in neonates. It is possible to perform noninvasive screening acoustic cochleography in about a minute. The technique is also useful for characterizing cochlear mechanical status prior to long term monitoring. Achieving routinely reliable OAE test performance in clinical and screening applications under nonideal conditions makes special demands on the instrumental design and the response evaluation procedures. The essential requirements are reviewed and discussed in a general and specific context. We have tried to meet these requirements in a transient evoked otoacoustic emission system (the ILO88) which we designed to operate with a personal computer. We report on our design of probe, and our use of evaluation procedures for probe fit, and response quality. Signal processing methods have been developed to reject noncochlear acoustic responses, and to optimise the rejection of patient noise. Examples of its clinical use, and the practical problems typically encountered are given here.

Adult↗
PubMed1990

Platelet aggregation is not necessary for occurrence of Raynaud's phenomenon: a clinical history and laboratory results.

"Raynaud's phenomenon (R.P.) is characterized by a spastic vasoconstriction of hand and/or feet extremities leading to painful ischemic attacks. In the pathogeny of this syndrome the role of a platelet hyperactivation was evidenced. Nevertheless, the responsibility of platelet aggregation remains controversial. We report here the case of a patient presenting with a Glanzmann thrombasthenia defined by the complete lack of platelet aggregation, and showing a typical RP which was confirmed by the measurement of hand temperature and the decrease of digital and hand blood flow. Thus, the description of this case shows that platelet aggregation by itself is not necessary for the occurrence of RP, and encourages for therapeutic purposes the development of vasodilatators rather than platelet antiaggregants agents."

Female↗
PubMed1988

Immunochemical studies of the 36-kDa common beta subunit of guanine nucleotide-binding proteins: identification of a major epitope.

Twenty-four of 24 rabbits immunized with the beta subunit common to guanine nucleotide binding proteins developed antibodies reactive on immunoblots with the 15-kDa (amino-terminal) tryptic fragment of beta. Only 2 of 24 developed antibodies reactive with the 26-kDa (carboxy-terminal) tryptic fragment. The 15-kDa fragment-reactive antibodies were also detected in several nonimmune sera. Antibodies reactive with the 15-kDa fragment could be affinity-purified from all beta-immune sera by adsorption to a fusion protein encoded by a cDNA clone identified by expression vector screening. The 15-kDa fragment antibodies in nonimmune sera did not bind to the fusion protein. Limited amino acid sequence homology between the 36-kDa beta subunit and the protein encoded by the cDNA clone suggested that the amino-terminal decapeptide of beta contains a major epitope. A synthetic decapeptide, corresponding to the amino terminus of the 36-kDa beta subunit, effectively and specifically blocked binding of antibodies in beta-immune sera (but not in beta-reactive nonimmune sera) to nitrocellulose-bound 15-kDa fragment. The 15-kDa fragment-reactive antibodies could be affinity-purified from beta-immune sera on a matrix containing bound decapeptide; affinity-purified antibodies reacted equally well with the 36- and 35-kDa forms of the beta subunit. Native transducin beta/gamma complexes readily blocked binding of 15-kDa fragment-reactive antibodies in immune but not nonimmune sera from binding to the nitrocellulose-bound fragment. The results show that nonimmune sera may contain antibodies directed against an epitope of the 15-kDa fragment that is buried in the native beta/gamma complex. In contrast, the amino terminal decapeptide of the beta subunit is exposed on the surface of the native protein and contains a major antigenic site in both the 35- and 36-kDa forms.

Amino Acid Sequence↗
PubMed1987

Human cDNA clones for an alpha subunit of Gi signal-transduction protein.

Two cDNA clones were obtained from a lambda gt11 cDNA human brain library that correspond to alpha i subunits of G signal-transduction proteins (where alpha i subunits refer to the alpha subunits of G proteins that inhibit adenylate cyclase). The nucleotide sequence of human brain alpha i is highly homologous to that of bovine brain alpha i [Nukada, T., Tanabe, T., Takahashi, H., Noda, M., Haga, K., Haga, T., Ichiyama, A., Kangawa, K., Hiranaga, M., Matsuo, H. & Numa, S. (1986) FEBS Lett. 197, 305-310] and the predicted amino acid sequences are identical. However, human and bovine brain alpha i cDNAs differ significantly from alpha i cDNAs from human monocytes, rat glioma, and mouse macrophages in amino acid (88% homology) and nucleotide (71-75% homology) sequences. In addition, the nucleotide sequences of the 3' untranslated regions of human and bovine brain alpha i cDNAs differ markedly from the sequences of human monocyte, rat glioma, and mouse macrophage alpha i cDNAs. These results suggest there are at least two classes of alpha i mRNA.

Amino Acid Sequence↗
PubMed1987

Reduced expression of multiple forms of the alpha subunit of the stimulatory GTP-binding protein in pseudohypoparathyroidism type Ia.

We examined the expression of the alpha subunit of the stimulatory GTP-binding protein (Gs) in fibroblasts of subjects with pseudohypoparathyroidism (PHP) type Ia by transfer blot hybridization and S1 nuclease analyses. Six subjects with PHP type Ia showed decreased steady-state content of Gs alpha mRNA. S1 nuclease analysis indicates that both long and short forms of Gs alpha mRNA are decreased, with no apparent change in the ratio of long to short forms in PHP compared with normal individuals. It appears likely that in some cases of PHP type Ia the genetic lesion affects the maintenance of mRNA levels for all forms of the Gs alpha subunit.

DNA↗
PubMed1987

An advanced cochlear echo technique suitable for infant screening.

An advanced cochlear echo test technique has been specially developed to tackle some specific problems associated with measurements from infants. The test procedure and data processing combination has greatly improved noise immunity and has given very reliable results on poorly co-operating children. Technical details are given and the results of a study of 105 ears from 55 children are presented. The potential of the advanced technique as a screening test is discussed.

Adolescent↗
PubMed1986

Human cDNA clones for four species of G alpha s signal transduction protein.

lambda gt11 cDNA libraries derived from human brain were screened with oligonucleotide probes for recombinants that code for alpha subunits of G signal transduction proteins. Eleven alpha s clones were detected with both probes and characterized. Four types of alpha s cDNA were cloned that differ in nucleotide sequence in the region that corresponds to amino acid residues 71-88. The clones differ in the codon for alpha s amino acid residue 71 (glutamic acid or aspartic acid), the presence or absence of codons for the next 15 amino acid residues, and the presence or absence of an adjacent serine residue. S1 nuclease protection experiments revealed at least two forms of alpha s mRNA. A mechanism for generating four species of alpha s mRNA by alternative splicing of precursor RNA is proposed.

Amino Acid Sequence↗
PubMed1986

Acoustic emission cochleography--practical aspects.

Otoacoustic emissions are discussed as a means of objectively examining cochlear status. Practical uses of otoacoustic emission recording are reviewed, and the technical requirements of a clinical test are discussed. Details are given of an advanced cochlear echo test procedure, and results from normal and hearing impaired ears are discussed. Finally the alternative technique of distortion product analysis is discussed and results are given.

Biomechanical Phenomena↗
PubMed1985

Delayed treatment of serious decompression sickness.

We report the cases of three patients with residual symptoms from diving decompression sickness, each of whom presented to a recompression chamber three to seven days following original exposure. All three had complete resolution of symptomatology despite the delayed treatment. The late resolution of symptoms is evidence both of residual bubble effect and of distal tissue hypoxia responding to oxygen therapy with the recompression. We recommend that decompression sickness symptoms be treated whenever they are seen, even ten to 14 days postinjury.

Adult↗
PubMed1983

Orogenital sex as a cause of nonfatal air embolism in pregnancy.

A case of nonfatal air embolism from orogenital sex in the 30th week of pregnancy is described. Because of a delay in the diagnosis, the patient did not receive hyperbaric oxygen therapy until 39 hours after the incident. Severe neurologic dysfunction persisted despite hyperbaric therapy. The world literature on orogenital sex in pregnancy with resultant air embolism is reviewed. The pathophysiology of air embolism and the rationale for hyperbaric oxygen treatment are presented. It is strongly recommended that survivors of this form of air embolism be transferred to hyperbaric facilities as soon as possible to reduce the long-term neurologic sequelae.

Adolescent↗