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Biomedical subjects

Y Sun

Publications and source records attributed to Y Sun.

At least 793 records · Page 44Linked to original sources
PubMed1995

Connective tissue: a metabolic entity? .

The heart is composed of parenchyma (cardiac myocytes) and stroma (connective tissue). Stroma is presumed inert and therefore little attention has been paid to its regulation. Contrary to this notion, evidence presented here raises the possibility that connective tissue is a metabolically active entity capable of regulating peptide hormone generation and degradation and these hormones, in an autocrine manner, regulate collagen turnover. This concept has evolved from quantitative in vitro autoradiography (using 125I-351A), which localized angiotensin converting enzyme (ACE) binding density within the heart. A heterogenous distribution was found. Low-density ACE is present within atria and ventricles. At sites of high collagen turnover, such as valve leaflets, adventitia and fibrous tissue of diverse etiologic origins. ACE binding density is high and independent of circulating angiotensin II. ACE-producing cells at these sites, identified by monoclonal ACE antibody and 125I-351A binding, include fibroblast-like alpha actin-containing cells that express the transcript for type I collagen (in situ hybridization). Receptor-ligand binding for angiotensin II and bradykinin is found in fibrous tissue, where these peptides may provide for a reciprocal regulation of fibroblast collagen turnover. Connective tissue formation is attenuated by ACE inhibition or antagonism of type I angiotensin II receptor. Thus, emerging evidence raises the possibility that stroma and its cellular constituents is a dynamic, metabolically active entity regulating its own peptide hormone composition and, in turn, its turnover of fibrillar collagen.

Animals↗
PubMed1995

The scalene reflex: relationship between increased median or ulnar nerve pressure and scalene muscle activity.

Neck pain, headaches, upper thoracic pain, and dystonic scalene muscles are common findings in patients who have severe entrapment neuropathies of the upper extremities. This problem was taken to the laboratory in an attempt to discover the correlation between distal entrapment neuropathies, brachial plexus entrapments, and prominent scalenus muscles. When increased pressure (over 40 mmHg) was applied to the median and ulnar nerves in the forelimbs of eight goats, increased electromyographic activity was noted in the ipsilateral scalenus muscle. Pressures ranging from 100 to 150 mmHg caused increased electromyographic activity on the contralateral scalene muscle, and the authors postulate that it is mediated by the gamma afferent and efferent system. This relationship may explain the commonly found neck pain and muscle spasm in patients with peripheral neuropathies, and it represents a link between the somatic efferent nerves and the gamma motor neuron system. At present, the same phenomenon has been documented in 30 humans with the diagnosis of brachial plexus entrapment.

Animals↗
PubMed1995

Functional characterization of the 180-kD ribosome receptor in vivo.

A cDNA encoding the 180-kD canine ribosome receptor (RRp) was cloned and sequenced. The deduced primary structure indicates three distinct domains: an NH2-terminal stretch of 28 uncharged amino acids representing the membrane anchor, a basic region (pI = 10.74) comprising the remainder of the NH2-terminal half and an acidic COOH-terminal half (pI = 4.99). The most striking feature of the amino acid sequence is a 10-amino acid consensus motif, NQGKKAEGAP, repeated 54 times in tandem without interruption in the NH2-terminal positively charged region. We postulate that this repeated sequence represents a ribosome binding domain which mediates the interaction between the ribosome and the ER membrane. To substantiate this hypothesis, recombinant full-length ribosome receptor and two truncated versions of this protein, one lacking the potential ribosome binding domain, and one lacking the COOH terminus, were expressed in Saccharomyces cerevisiae. Morphological and biochemical analyses showed all proteins were targeted to, and oriented correctly in the ER membrane. In vitro ribosome binding assays demonstrated that yeast microsomes containing the full-length canine receptor or one lacking the COOH-terminal domain were able to bind two to four times as many human ribosomes as control membranes lacking a recombinant protein or microsomes containing a receptor lacking the NH2-terminal basic domain. Electron micrographs of these cells revealed that the expression of all receptor constructs led to a proliferation of perinuclear ER membranes known as "karmellae." Strikingly, in those strains which expressed cDNAs encoding a receptor containing the putative ribosome binding domain, the induced ER membranes (examined in situ) were richly studded with ribosomes. In contrast, karmellae resulting from the expression of receptor cDNA lacking the putative ribosome binding domain were uniformly smooth and free of ribosomes. Cell fractionation and biochemical analyses corroborated the morphological characterization. Taken together these data provide further evidence that RRp functions as a ribosome receptor in vitro, provide new evidence indicating its functionality in vivo, and in both cases indicate that the NH2-terminal basic domain is essential for ribosome binding.

Amino Acid Sequence↗
PubMed1995

Myocardial fibrosis in hypertensive heart disease: an overview of potential regulatory mechanisms.

Myocardial fibrosis in hypertensive heart disease (HHD) can present as a reactive process, involving intramyocardial coronary arteries and arterioles with extensions of collagen into the neighbouring interstitial space, and as a replacement for necrotic cardiac myocytes. Fibrosis adversely affects myocardial stiffness and therefore regulatory mechanisms are of considerable interest. Mechanisms responsible for scarring (reparative fibrosis) are based on factors that adversely influence myocyte survival. This topic is not covered in this brief review. Mechanisms responsible for the perivascular/interstitial fibrosis that appear in both the normotensive, non-hypertrophied right and the pressure overloaded, hypertrophied left ventricule in HHD are addressed herein. They include: (a) angiotensin II (Ang II)-mediated coronary vascular hyperpermeability with subsequent fibrosis; (b) direct hormonal regulation of fibroblast collagen turnover, whereby Ang II, aldosterone and/or endothelins may be involved; (c) autocrine and paracrine signalling between fibroblasts and/or endothelial cells that alters collagen synthesis and degradation and which includes an angiotensin converting enzyme found in fibrous tissue. Collagen turnover in the myocardium is a dynamic process and fibrous tissue is anything but inert.

Animals↗
PubMed1995

Structural remodelling of the heart by fibrous tissue: role of circulating hormones and locally produced peptides.

Symptomatic heart failure is accompanied by diastolic ventricular dysfunction due largely to an extensive reactive and reparative fibrosis. Experimental evidence suggests a clear association between myocardial fibrosis and chronic inappropriate elevations in circulating angiotensin II (Ang II) and/or aldosterone. Although not entirely elucidated, injury follows Ang II-associated release of adrenal medullary catecholamines and aldosterone-induced myocardial potassium depletion. Increasing evidence indicates locally produced cardiac Ang II plays an important role in tissue repair that may underlie myocardial remodelling, the fibrous tissue accumulation both at and remote to the site of myocardial infarction (MI). Angiotensin converting enzyme (ACE) binding density markedly increases at these fibrous tissue sites after experimental MI, indicating an involvement in wound healing regardless of the cause and location of fibrosis; cells expressing Ang II receptors are primarily myofibroblasts. Therapy with ACE inhibitors and aldosterone receptor antagonist have each been shown to attenuate development of fibrosis.

Aldosterone↗
PubMed1995

Polymorphisms within the atrial natriuretic peptide gene in essential hypertension.

OBJECTIVE: To investigate polymorphisms in the atrial natriuretic peptide gene of African Americans at intron two (Hpall) and exon three (Scal). RESULTS: The allele frequency of the Hpall mutation was 25% in the hypertensive group (n =60) compared with only 3.4% in normotensive individuals (n = 44, P < 0.0001). The genotype heterozygote for the present mutation was much more common among those with hypertension (50 versus 6.8%, P < 0.0001). The groups were no different for the Scal site alone, although the two mutations were present together more often in the hypertensive group. The Hpall mutation was associated with hypertension in this typically salt-sensitive population.

Adult↗
PubMed1995

Identification and characterization of the protein product of gene 67 in equine herpesvirus type 1 strain Ab4.

Equine herpesvirus type 1 (EHV-1) strain Ab4 gene 67 has no counterpart in any herpesvirus sequenced to date. To identify and characterize the product of EHV-1 gene 67, we have expressed the putative amino acids 11 to 260 encoded by gene 67 as a beta-galactosidase fusion protein in Escherichia coli. The expressed fusion protein has been used to generate an antiserum raised against the gene 67 product. Immunoblotting and immunoprecipitation experiments have revealed that the anti-67 serum specifically recognizes a polypeptide with an M(r) of 36,000 (the 36K polypeptide) in infected cell extracts. The gene 67 protein is regulated as an early polypeptide in EHV-1 strain Ab4 infected cells and post-translational modification experiments have revealed that the protein is phosphorylated, but not glycosylated. The gene 67 protein has been transiently expressed in BHK-21/C13 cells using plasmid pCMV67, which contains the putative gene 67 ORF under the control of the cytomegalovirus immediate early promoter. Immunoblotting experiments with anti-67 have shown that the 36K protein is expressed at high levels in transfected cells. From both immunofluorescence and cellular fractionation experiments it is concluded that the gene 67 protein is associated with intracellular membranes and produces novel ribbon or filament-like structures within the cytoplasm of infected cells. We have demonstrated that the gene 67 product is a component of the virion nucleocapsid/tegument.

Animals↗
PubMed1995

Population diversity of B-locus alleles observed by high-resolution DNA typing.

HLA B-locus typing by group-specific PCR and hybridization with SSOP was performed in 81 10th IHWS B cell lines and 334 selected subjects of our local panel, from four ethnic groups. Most of the B-locus serological specificities were well defined. However, some antigens like B41, B58, B56, the splits of B14, and some subtypes of B5, were not accurately assigned by serology. In the panel studied, we found 17 hybridization patterns that corresponded to probable new alleles. New patterns occurred in the four ethnic groups examined. Multiple subtypes of B35, B5, B15, B41, B44, B57, B58, B70, B14, B40, B22 were found in subjects of the same ethnic group. In view of the poor serological definition of some alleles, and the occurrence of multiple subtypes in the same ethnic population, it appears that high resolution B-locus typing may be an important addition for detection of potentially relevant HLA incompatibilities in transplantation. It should also be valuable for population studies and for the investigation of HLA associations with diseases.

Amino Acid Sequence↗
PubMed1995

Replicative function and neutralization sensitivity of envelope glycoproteins from primary and T-cell line-passaged human immunodeficiency virus type 1 isolates.

The structure, replicative properties, and sensitivity to neutralization by soluble CD4 and monoclonal antibodies were examined for molecularly cloned envelope glycoproteins derived from human immunodeficiency virus type 1 (HIV-1) viruses either isolated directly from patients or passaged in T-cell lines. Complementation of virus entry into peripheral blood mononuclear cell targets by primary patient envelope glycoproteins exhibited efficiencies ranging from that observed for the HXBc2 envelope glycoproteins, which are derived from a T-cell line-passaged virus, to approximately fivefold-lower values. The ability of the envelope glycoproteins to complement virus entry roughly correlated with sensitivity to neutralization by soluble CD4. Laboratory-adapted viruses were sensitive to neutralization by monoclonal antibodies directed against the CD4-binding site and the third variable (V3) loop of the gp120 glycoprotein. By comparison, viruses with envelope glycoproteins from primary patient isolates exhibited decreased sensitivity to neutralization by these monoclonal antibodies; for these viruses, neutralization sensitivity correlated with replicative ability. Subinhibitory concentrations of soluble CD4 and a CD4-binding site-directed antibody significantly enhanced the entry of viruses containing envelope glycoproteins from some primary patient isolates. The sensitivity of viruses containing the different envelope glycoproteins to neutralization by soluble CD4 or monoclonal antibodies could be predicted by assays dependent on the binding of the inhibitory molecule to the oligomeric envelope glycoprotein complex but less well by assays measuring binding to the monomeric gp120 glycoprotein. These results indicate that the intrinsic structure of the oligomeric envelope glycoprotein complex of primary HIV-1 isolates, while often less than optimal with respect to the mediation of early events in virus replication, allows a relative degree of resistance to neutralizing antibodies. The interplay of selective forces for higher virus replication efficiency and resistance to neutralizing antibodies could explain the temporal course described for the in vivo emergence of HIV-1 isolates with differing phenotypes.

Antibodies, Monoclonal↗
PubMed1995

Influence of valine flooding on channeling of valine into tissue pools and on protein synthesis.

Rates of valine incorporation into protein were measured under control and valine-"flooding" conditions and included correction for the degree of recycling of unlabeled valine derived from the steady-state breakdown of tissue protein into the precursor pool (tRNA bound). The correction factor lambda, which is the ratio of the steady-state specific activity of valine in the tissue tRNA-bound pool to that in the arterial plasma, was determined for each of the tissues. In controls, values of lambda ranged from 0.31 in adrenals to 0.54 in heart; in flooded animals, values were higher, but only in liver was the value of lambda close to 1.0. In control and flooded rats, rates of protein synthesis were highest in liver and adrenals and lowest in skeletal muscle, with intermediate values in brain and heart. Flooding resulted in increased rates of protein synthesis in liver and decreased rates in adrenals. Rates of protein synthesis in brain, heart, and skeletal muscle were not statistically significantly affected by flooding.

Animals↗
PubMed1995

Mathematical model that characterizes transmitral and pulmonary venous flow velocity patterns.

The transmitral and pulmonary venous flow velocity (TMFV and PVFV, respectively) patterns are related to the physiological state of the left heart by use of an electrical analog model. Filling of left ventricle (LV) through the mitral valve is characterized by a quadratic Bernoulli's resistance in series with an inertance. Filling of the left atrium (LA) through the pulmonary veins is represented by a lumped network of linear resistance, capacitance, and inertance. LV and LA are each represented by a time-varying elastance. A volume dependency is incorporated into the LV model to produce physiological pressure-volume loops and Starling curves. The state-space representation of the analog model consists of 10 simultaneous differential equations, which are solved by numerical integration. Model validity is supported by the following. First, the expected effects of aging and decreasing LV compliance on TMFV and PVFV are accurately represented by the model. Second, the model-generated TMFV and PVFV waveforms fit well to pulsed-Doppler recordings in normal and postinfarct patients. It is shown that the TMFV deceleration time is prolonged by the increase in LV compliance and, to a lesser extent, by the increase in LA compliance. A shift from diastolic dominance to systolic dominance in PVFV occurs when LA compliance or pulmonary perfusion pressure increases or when LV compliance or mitral valve area decreases. The present model should serve as a useful theoretical basis for echocardiographic evaluation of LV and LA functions.

Animals↗
PubMed1995

Rates of local cerebral protein synthesis in the rat during normal postnatal development.

The degree of recycling of leucine derived from protein breakdown into the precursor pool for protein synthesis was measured in rat brain at different postnatal ages, and age-specific values were used in the calculation of regional (local) rates of cerebral leucine incorporation into protein (lCPSleu) in 44 brain regions and the brain as a whole. Early in development, a greater fraction of the precursor leucine pool is derived from protein breakdown, indicating that protein degradation is higher in young rats compared with adults. In whole brain and in most regions, values for lCPSleu were highest at 10 days and gradually decreased with age. By 60 days of age, values in cortex were approximately 60% of those at 10 days of age. In the paraventricular and supraoptic nuclei of the hypothalamus, however, lCPSleu increased during development, reaching peak values in adults. In white matter of the cerebellum and the cerebrum, peaks of lCPSleu were reached at 14 and 21 days, respectively, approximately at the times of maximum rates of myelination.

Aging↗
PubMed1995

Role of the proneural gene, atonal, in formation of Drosophila chordotonal organs and photoreceptors.

The Drosophila gene atonal encodes a basic helix-loop-helix protein similar to those encoded by the proneural genes of the achaete-scute complex (AS-C). The AS-C are required in the Drosophila PNS for the selection of neural precursors of external sense organs. We have isolated mutants of atonal, which reveal that this gene encodes the proneural gene for chordotonal organs and photoreceptors. In atonal mutants, all observable adult chordotonal organs, and almost all embryonic chordotonal organs fail to form; all adult photoreceptors are missing. For both types of sense organ, this defect is already apparent at the level of precursor formation. Therefore it is a failure in the epidermal-neural decision process i.e. a proneural defect. The failure to form photoreceptors results in atrophy of the atonal mutant imaginal disc, due to apoptosis and lack of stimulation of division. Lack of photoreceptors should also eliminate signalling that arises from differentiating photoreceptors and is required for morphogenetic furrow movement in the wild-type eye disc. Nevertheless, a remnant morphogenetic furrow is still observed in the atonal mutant disc. This presumably reflects the process of furrow initiation, which would not depend on signals from developing photoreceptors.

Animals↗
PubMed1995

A practical procedure for the cryopreservation of marrow cells intended for autotransplantation.

A simple and practical method of unfractionated bone marrow processing and cryopreservation was studied. The date shows that RBCs can be rapidly sedimented by methylcellulose or sodium carboxymethyl starch within 15-45 min. The cells can be cryopreserved in a mixture consisting of 5% DMSO, 6% HES and 4% Albumin prepared in a Lactated Ringer solution which is widely used, and can be simply immersed into a -80 degrees C freezer and stored in liquid nitrogen until infusion. Recovery percentages of nucleated cell, cell viability and CFU-G were similar to those cryopreserved with the conventional method. Clinical toxicity was mild in 12 infused patients. Of them 8 patients had received high dose chemotherapy +/- TBI and their peripheral WBC recovery was rapid. The recovery of WBC or Platelet (PLT) in the study group was similar to that of the control group whose marrow cells were cryopreserved in 10% DMSO. Therefore, cells cryopreserved with this method can also accelerate the hematopoietic recovery in myeloablatively treated patients.

Adolescent↗
PubMed1995

Extracorporeal circulation for great vessels surgery: a review of 131 cases.

A retrospective analysis of 131 cases of major vascular surgery, mainly aneurysms of the ascending and descending aorta, was undertaken to determine whether use of different bypass methods chosen according to location of the individual lesions resulted in improved results. For the 93 cases of ascending aortic aneurysm, the method for cardiac protection was improved by the use of continuous retrograde coronary sinus perfusion with cardioplegic blood. In sixteen cases with dissection involving the aortic arch, deep hypothermic circulatory arrest and continuous retrograde cerebral perfusion through the superior vena cava was employed for brain protection. The safe brain circulation arrest time was thus prolonged to the longest record of 81 minutes. Among the group of 93 cases, there were four operative and four hospital deaths, giving a mortality rate of 8.6% (8/93). For the 34 cases of descending aortic aneurysms, left heart bypass was employed to avoid ischemia of the heart, lungs, brain, and the abdominal organs; the operative mortality rate was 8.8% (3/34). In three cases of interrupted aortic arch, separate upper and lower body perfusion under deep hypothermia with low flow rate perfusion for the upper body provided the necessary conditions for radical surgery. In one patient with Budd-Chiari syndrome, a total corrective surgery was achieved under right heart bypass.

Adult↗