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Biomedical subjects

Y Gao

Publications and source records attributed to Y Gao.

At least 433 records · Page 24Linked to original sources
PubMed1994

Substrate activation of brewers' yeast pyruvate decarboxylase is abolished by mutation of cysteine 221 to serine.

Brewers' yeast pyruvate decarboxylase (EC 4.1.1.1), a thiamin diphosphate and Mg(II)-dependent enzyme, isolated from Saccharomyces cerevisiae possesses four cysteines/subunit at positions 69, 152, 221, and 222. Earlier studies conducted on a variant of the enzyme with a single Cys at position 221 (derived from a gene that was the product of spontaneous fusion) showed that this enzyme is still subject to substrate activation [Zeng, X., Farrenkopf, B., Hohmann, S., Jordan, F., Dyda, F., & Furey, W. (1993) Biochemistry 32, 2704-2709], indicating that if Cys was responsible for this activation, it had to be C221. To further test the hypothesis, the C221S and C222S single and the C221S-C222S double mutants were constructed. It is clearly shown that the mutation at C221, but not at C222, leads to abolished substrate activation according to a number of kinetic criteria, both steady state and pre steady state. On the basis of the three-dimensional structure of the enzyme [Dyda, F., Furey, W., Swaminathan, S., Sax, M., Farrenkopf, B., Jordan, F. (1993) Biochemistry 32, 6165-6170], it is obvious that while C221 is located on the beta domain, whereas thiamin diphosphate is wedged at the interface of the alpha and gamma domains, addition of pyruvate or pyruvamide as a hemiketal adduct to the sulfur of C221 can easily bridge the gap between the beta and alpha domains. In fact, residues in one or both domains must be dislocated by this adduct formation. It is very likely that regulation as expressed in substrate activation is transmitted via this direct contact made between the two domains in the presence of the activator.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1994

CGS 15943, an adenosine A2 receptor antagonist, reduces cerebral ischemic injury in the Mongolian gerbil.

The adenosine A2 receptor antagonist CGS 15943 (0.1 mg/kg, i.p.) was tested for cerebroprotective activity in a gerbil stroke model. CGS 15943 markedly reduced stroke injury assessed by locomotor activity monitoring and by histopathological measurement of hippocampal CA1 pyramidal cell injury. It is proposed that a previously demonstrated reduction in the ischemia/reperfusion-evoked release of excitotoxic amino acids following CGS 15943 administration could account for its cerebroprotective actions.

Animals↗
PubMed1994

Prodepin: a new product of the adrenomedullin (ADM) gene has systemic vasodilator activity.

The purpose of the present study was to investigate the effects of products of the ADM gene other than ADM on systemic hemodynamics in the anesthetized rat, rabbit, piglet, cat and dog. Bolus intravenous (i.v.) injections of rat proADM22-41 (3-30 micrograms) significantly decreased systemic arterial pressure (SAP) and systemic vascular resistance in the anesthetized rat. Unlike ADM, rat proADM22-41 markedly increased cardiac output in the rat. Bolus i.v. injections of human proADM22-41 up to 500 micrograms had not effect in all species studied and rat proADM22-41 had no effect in species other than the rat. The present data suggest that rat proADM22-41 is a novel product of the ADM gene other than ADM and possesses marked systemic vasodilator activity. The present data also suggest that the hemodynamic activity of this peptide is species specific.

Adrenomedullin↗
PubMed1994

Persistence of the SV40 early region without expression in permissive simian cells.

SV40 containing recombinant vectors were introduced into permissive simian, non-permissive rodent and semi-permissive human cell lines, and assayed for transformation. All mouse and human cell clones expressed T-antigen (T-Ag) and were morphologically transformed when they contained only the wt T-Ag gene (E-SV40) or the entire wt viral genome with an interrupted late region. However, of 63 simian clones with these recombinant vectors, none became morphologically transformed and T-Ag containing cells were rare or absent. Nearly all simian cell lines made either no detectable early SV40 RNA or only small amounts of viral RNA but contained viral DNA restriction fragments similar to those in the original recombinant vectors. Functional T-Ag genes were recoverable from several cell clones and used to regenerate infectious virus. Hence, T-Ag gene expression had been suppressed. We found two conditions where T-Ag expression was activated. In a BSC-1 cell line containing E-SV40 DNA, subsequent introduction of a vector with a functional viral late coding region (L-SV40) resulted in the appearance of T-Ag and transformation. These findings suggest that L-SV40 sequences activate or enhance T-Ag expression and that this activation requires a functional Vpl gene. We found also, that vectors with E-SV40 DNA from the bipartite variant EL-SV40 consistently transformed simian CV-1 cells. Transformation was shown to be effected by the multiple alterations present in the regulatory region of this variant.

Animals↗
PubMed1994

Truncated bovine herpesvirus-1 glycoprotein I (gpI) initiates a protective local immune response in its natural host.

Current modified live and killed BHV-1 vaccines have not reduced the incidence of bovine herpesvirus-1 (BHV-1), the principal viral agent in bovine respiratory disease complex. The requirement for production of viral proteins for immune study has resulted in the establishment of a cell line which constitutively expresses BHV-1 gpI. A truncated BHV-1 envelope gpI protein was secreted into the culture supernatant of D17 cells transfected with the gpI gene lacking the coding sequence for the transmembrane region (TMR). The transmembrane domain is essential for gpI stability in the envelope, virus infectivity and, most probably, natural killer cell recognition; however, we have tested the possibility that this domain is not required for inducing an adaptive, protective immune response. Immunization of calves with this truncated gpI protein induced gpI-specific nasal IgA, IgG1, serum neutralizing antibodies and gpI-specific peripheral lymphocyte proliferation. All immunized calves were protected from clinical disease after BHV-1 challenge. Further, nine of ten immunized calves had no intranasal viral shedding. One animal shed a minimal amount of virus following challenge, but produced no antibodies to other viral proteins as evidenced by immunoprecipitation of 35S-labelled viral proteins by sera from virus-challenged animals. This study represents the first evidence that a recombinant truncated gpI subunit vaccine can confer local mucosal immunity and establish a strong protective barrier against disease caused by BHV-1 in the natural host. Also, these data demonstrate the feasibility of preventing initial viral replication in the host and distinguishing vaccinated from wild-type virus-infected animals.

Animals↗
PubMed1994

Atropine and cerebral ischemic injury in the Mongolian gerbil.

1. Cerebral ischemia of 5 min duration was induced in unanesthetized gerbils by bilateral occlusion of the carotid arteries. 2. The extent of cerebral damage was assessed by the elevation of motor activity in comparison with control animals and by a histological assessment of the extent of neuronal degeneration in the CA1 area of the hippocampus. 3. Atropine, an antagonist of ACh, at either a low (1 mg/kg) or a high (10 mg/kg) dose administered 15 min prior to the ischemic episode, did not confer protection against cerebral ischemic damage. 4. This finding suggests that ACh does not play a critical role in the generation of ischemia reperfusion injury.

Acetylcholine↗
PubMed1994

A novel cochaperonin that modulates the ATPase activity of cytoplasmic chaperonin.

The folding of alpha- and beta-tubulin requires three proteins: the heteromeric TCP-1-containing cytoplasmic chaperonin and two additional protein cofactors (A and B). We show that these cofactors participate in the folding process and do not merely trigger release, since in the presence of Mg-ATP alone, alpha- and beta-tubulin target proteins are discharged from cytoplasmic chaperonin in a nonnative form. Like the prokaryotic cochaperonin GroES, which interacts with the prototypical Escherichia coli chaperonin GroEL and regulates its ATPase activity, cofactor A modulates the ATPase activity of its cognate chaperonin. However, the sequence of cofactor A derived from a cloned cDNA defines a 13-kD polypeptide with no significant homology to other known proteins. Moreover, while GroES functions as a heptameric ring, cofactor A behaves as a dimer. Thus, cofactor A is a novel cochaperonin that is structurally unrelated to GroES.

Adenosine Triphosphatases↗
PubMed1994

Antidiuretic hormone and exocytosis: lessons from neurosecretion.

Many cells, both single and epithelial, are programmed for exocytosis. In most cases, the contents of cytoplasmic vesicles are delivered rapidly and directly to the extracellular fluid. The process has been intensively studied in the chromaffin cell and the nerve terminal, where, as in other cells, exocytosis is under a complex type of cytoskeletal control. An array of vesicle-associated proteins mediates attachment of the vesicles to the cytoskeleton, their release, and their fusion with the plasma membrane. Two functional pools of vesicles, the releasable and reserve pool, carry out immediate and long-term secretory activity. Some of the mediators of neurotransmitter vesicle fusion, originally thought to be restricted to neurosecretory cells, have now been found in nonneuronal cells. The mammalian collecting duct and the amphibian bladder are also engaged in exocytosis. In both epithelia, antidiuretic hormone (ADH) induces the transfer of water channels from cytoplasmic vesicles to the apical cell membrane. The process is slower than in the nerve terminal and ends with channel placement rather than the extrusion of vesicular contents. Nevertheless, there are several respects in which cytoskeletal control, vesicle positioning in the cell, docking, and fusion may prove to resemble the events in neurosecretion. This review begins with a survey of cytoskeletal structure and function in the erythrocyte, the chromaffin cell, and the nerve terminal and then presents current studies of ADH-induced exocytosis, emphasizing common themes in cytoskeletal control.

Actins↗
PubMed1994

Epithelium acts as a modulator and a diffusion barrier in the responses of canine airway smooth muscle.

The present study was designed to determine the role of the respiratory epithelium as a diffusion barrier and a modulator of the responsiveness of airway smooth muscle to bronchoactive agents. Segments of canine bronchi, with or without epithelium, were suspended in organ chambers and perfused intraluminally. The isometric tension was recorded. Acetylcholine, given intraluminally, induced significantly smaller contractions in bronchi with than in bronchi without epithelium. When this agonist was given extraluminally, no difference in contractions was noted between the tissues. In the presence of acetylcholine and phentolamine, norepinephrine, given either intra- or extraluminally, induced significantly larger relaxations in bronchi with than in bronchi without epithelium. High potassium given intraluminally induced contractions only in bronchi without epithelium; however, in the presence of ouabain, both tissues contracted similarly. When high potassium was given extraluminally, no difference in contraction between tissues with and without epithelium was noted. When [3H]acetylcholine and [3H]norepinephrine were perfused intraluminally, the accumulation of 3H radioactivity in the extraluminal solutions was significantly less in bronchi with than in bronchi without epithelium. These observations suggest that the epithelium acts as both a diffusion barrier and a modulator of the responses of canine airways to bronchoactive agents.

Acetylcholine↗
PubMed1994

Pressure range for release of renomedullary depressor substance in rabbits.

We investigated the relation between renal perfusion pressure and the release of a renal vasodepressor substance in vivo to determine whether this substance was released at physiological pressures. We perfused the left kidneys of anesthetized rabbits using an extracorporeal circuit that allowed renal perfusion pressures to be set at 65 mm Hg (control) and increased to 95, 125, 155, or 185 mm Hg for 30-minute experimental periods. Systemic blood pressure did not change significantly when renal perfusion pressure was maintained at 65 mm Hg throughout. When renal perfusion pressure was increased to 95, 125, 155, or 185 mm Hg, systemic blood pressure fell significantly at rates of 0.17 +/- 0.04, 0.79 +/- 0.31, 0.60 +/- 0.11, and 2.18 +/- 0.79 mm Hg/min, respectively (P < .05). Restoration of renal perfusion pressure to 65 mm Hg abruptly reversed the falls in systemic blood pressure in each group. There was a natriuresis and diuresis that were both pressure related and progressive in the face of each constant level of increased renal perfusion pressure. In summary, there was a continuum of arterial vasodepressor responses across a renal perfusion pressure range from resting pressure to 185 mm Hg. We suggest that the threshold level for the release of significant amounts of a renal medullary depressor substance, probably medullipin, is just above normal arterial blood pressure and that the rate of release increases with increasing arterial pressure.

Animals↗
PubMed1994

Fertility control in laboratory rats and mice after feeding with the antigestagen RU486.

The intermittent use of an antigestagen could prove to be a very effective way of controlling the fertility of rats and mice in the wild. This concept was tested by giving paraffin wax blocks containing cereal grains and the antigestagen Mifepristone, RU486 (150 mg kg-1 block) to male and female laboratory rats and mice in a series of free-choice feeding experiments. There was no significant difference in the consumption of blocks with or without RU486, showing that it was completely palatable to rats and mice, and no aversion developed following refeeding. The average consumption of RU486 by rats was 11 mg kg-1 day-1; mice consumed 37 mg kg-1 day-1. All the females showed persistent oestrous vaginal smears throughout the treatment. When male and female rats and mice were given continuous access to treated paraffin blocks for 30 days, no conceptions occurred. At the end of this time, there was a significant increase in ovarian weight in the treated rats and mice, but no difference in testicular weight. Treated blocks were given to rats for 3 days every 21 days for a total of 115 days. Four dead litters were produced following the first antigestagen treatment on day 21, but no more litters were produced and no treated rats were pregnant when autopsied on day 115. Mice were initially treated for 3 days every 21 days, but some animals continued to produce live young on this schedule. The treatment period was therefore reduced to 3 days every 18 days and no more litters were produced and none of the treated females was pregnant at autopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Fertility control in wild mice after feeding with RU486 or methyl testosterone.

Paraffin blocks containing either no steroid, 150 mg RU486 kg-1, 500 mg methyl testosterone kg-1 or 1500 mg methyl testosterone kg-1 were fed to wild mice (Mus musculus) in addition to the standard laboratory diet in four large (3 m x 3 m) outdoor pens for six months over the summer. The RU486 bait was provided for only 3 days every 18 or 21 days, whereas the methyl testosterone bait was available continuously. From a foundation stock of 20 mice (nine male, eleven female) in each pen, the population had increased to 253 (control), 72 (RU486), 249 (low methyl testosterone concentration) and 103 (high methyl testosterone concentration) at the end of six months, when 17%, 4%, 32% and 13% of the mature females were pregnant in the respective treatment groups. There was little evidence of an increase in the incidence of injuries in the androgen-treated animals. Daily estimation of water consumption in the pens proved to be a good non-invasive way of monitoring population growth during the course of the experiment. Intermittent feeding with a low concentration of RU486 appeared to be much more successful in inhibiting reproduction than continuous feeding with a high concentration of methyl testosterone, and it therefore offers a new method for controlling feral mouse populations.

Animals↗
PubMed1994

Relaxant effects of calcitonin gene-related peptide on isolated small renal arteries in stroke-prone spontaneously hypertensive rats.

The relaxant effects of calcitonin gene-related peptide (CGRP) on the 3rd branches of renal arteries obtained from stroke-prone spontaneously hypertensive rats (SHRSP), and Wistar-Kyoto rats (WKY) were investigated in vitro. CGRP elicited concentration-dependent relaxation, and the relaxant response was not affected by the mechanical removal of endothelium in either SHRSP or WKY. The CGRP-induced relaxant response was markedly greater in SHRSP than in WKY, whereas there was no significant difference in acetylcholine-induced relaxation, which was endothelium-dependent, between the two groups. Additionally, significantly enhanced reactivity to CGRP was also shown in spontaneously hypertensive rats compared to WKY; however, this reactivity was less than that observed in SHRSP. There were also no significant differences between WKY and SHRSP in the relaxation induced by forskolin, dibutyryl cyclic AMP, and 3-isobutyl-1-methylxanthine (IBMX). CGRP-induced relaxation was significantly potentiated in similar manner by the pretreatment with IBMX in both WKY and SHRSP. Incubation with glibenclamide (10(-6) M) had no effect on CGRP-induced relaxation in either group, the WKY or the SHRSP. These results suggest that CGRP produces endothelium-independent relaxation in the small renal arteries in the rat, and that the increased CGRP-induced relaxant response found in SHRSP may not be associated with the altered vasodilation mediated by cyclic AMP, or with functional changes in ATP-sensitive potassium channels.

Acetylcholine↗
PubMed1994

[A murine model of mammary adenocarcinoma (VI TA2MA-891) with high rate of spontaneous metastases in the lungs].

The primary donor tumor was a spontaneous mammary tumor which arose in a 348-day-old female TA2 mouse. The pedigree number of that mouse was 0901-1423. The mouse was sacrificed for serial s.c. transplantation with 3 isogeneic hosts on January 19, 1989 and a total of 27 generations succeeded by the end of April, 1992. The primary donor tumor was diagnosed pathologically as a type B mouse mammary adenocarcinoma (Dunn 1959). The incidence of this serial s.c. transplantation tumor is 100% after inoculation. The latency period is 4-7 days and the lifetime of tumorbearing mice is about 47 days. The spontaneous metastatic rates in the lungs was 100% after the 11th generations. The earliest metastasis seen in the lung under light microscopy was on the 10th day after inoculation, and the earliest seen by gross examination was on about the 35th day. The transplanted tumor grew slowly from the 4th day to the 21st day after inoculation and then grew rather fast from the 22nd to the 47th day. The average size of the transplanted tumor obtained from 10 recipient mice on the 47th day after inoculation was 4.93cm3. Seven anticancer drugs were administered respectively for a sensitivity test. The taking rates of the transplanted tumor using 4 of the 7 drugs were as follows: 5-fluorouracil 29.27% (P < 0.05); thio-tepa 44.80% (P < 0.01); cyclophosphamide 95.31% (P < 0.01); and bleomycin 96.27% (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1994

[The changes of urine protein and serum beta 2-microglobulin in autoimmune thyroid disease].

Because of the different observed results about the microproteinuria in autoimmune thyroid disease, serum B2-MG, urine B2-MG, albumin and immunoglobin by RIA in 39 untreated autoimmune thyroid disease (AITD) (28 with Graves disease and 11 with Hashimoto disease) had been observed. Micro-proteinuria was found in 28.6% of patients with Graves disease and in 45.5% with Hashimoto disease; Serum B2-GM concentrations were significantly increased in Graves disease compared with that of controls. Our results suggest that the lesions present in both glomerulus and tubulus in AITD. The mechanism of them had been discussed in this paper.

Adult↗
PubMed1994

[A genetic study of adult polycystic kidney disease].

The 3'HVR has been considered as the most useful probe in making the linkage analysis of adult polycystic kidney disease (APKD). We examined three APKD families using this probe. Their polymorphism information was then computed for linkage study using LINKAGE package and computer programme HOMOG for homogeneity test. One family was defined as non PKD 1, because the disease locus was failed to show linkage to the 3'HVR marker. Of the other two families, one can still not be identified as non PKD1, but had distinguishable meiotic recombinations, another was in favour of linkage to 3'HVR and therefore judged to be PKD1. The presence of genetic heterogeneity could significantly reduce the value of linked probe analysis as a tool for gene diagnosis of APKD.

Adolescent↗
PubMed1994

[Application of SRK II formula and measurement of A constant of KM intraocular lens].

The characteristics and distribution of the axial lengths and the results of keratometric measurements of 757 eyes with senile cataracts were reported and their relationship was discussed. The range of the axial lengths was 19.53-33.74 mm, the mean value being 23.81 +/- 2.26 mm (mean +/- SD), the eyes with longer axial lengths accounting for 21.8% and the eyes with axial lengths over 27 mm, 8.59%. The range of the degrees of the corneal curvatures was 39.75-50.50 D, the mean value being 44.47 +/- 0.78 D. The corneal curvatures of the eyes with shorter axial lengths are increased markedly with the shortening of the axial lengths. However, the corneal curvatures of the eyes with longer axial lengths are not decreased significantly with the lengthening of the axes. The A constant of KM intraocular lens we measured is 116.86 and the post-operative mean anterior chamber depth is 3.63 +/- 0.28 mm. If the C value is + 1.5 in eyes with 21-22 mm axial lengths, 0 in eyes with 22-24.5 mm and -0.5 in eyes with > 24.5, > 27, > 28.5 mm, the predictive error seen post-operatively is the smallest.

Aged↗