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Biomedical subjects

C Yang

Publications and source records attributed to C Yang.

At least 451 records · Page 25Linked to original sources
PubMed1993

A proteolipid protein gene family: expression in sharks and rays and possible evolution from an ancestral gene encoding a pore-forming polypeptide.

The myelin proteolipid proteins (PLP and DM20) are believed to act as "adhesive struts" in the extracellular apposition of the CNS myelin sheath. These proteins have been considered late evolutionary developments, which arose de novo in the antecedents of early tetrapods. However, PCR primed with degenerate oligonucleotides corresponding to common segments of rat PLP/DM20 revealed three novel mRNAs in the brains of two elasmobranchs. These mRNAs are closely related to each other and to mammalian DM20, but lack the sequence that distinguishes PLP from DM20. We term the novel proteolipid proteins DM alpha, DM beta, and DM gamma. At least DM alpha and DM gamma are highly expressed in white matter in myelinating shark brain. The DMs not only are highly homologous to each other, but also contain regions bearing similarities with segments of channel-forming regions of the nicotinic acetylcholine receptor and the glutamate receptor macromolecular complexes. Significantly, we find that across these segments, DM alpha and DM gamma are more similar to the channel proteins than the two channel proteins are to each other.

Amino Acid Sequence↗
PubMed1993

Sulfotransferase-mediated mutagenicity of 1-hydroxymethylpyrene and 4H-cyclopenta[def]chrysen-4-ol and its enhancement by chloride anions.

1-Hydroxymethylpyrene (HMP), a primary benzylic alcohol, and 4H-cyclopenta[def]chrysen-4-ol (OH-CPC), a secondary benzylic alcohol, were investigated for mutagenicity in Salmonella typhimurium (reversion of the his- strain TA98) in the presence of various xenobiotic-metabolizing systems. In the direct test, HMP was inactive and OH-CPC was very weakly active. In the presence of NADPH-fortified postmitochondrial fraction from rat liver (S9/NADPH), no activation of OH-CPC was observed, whereas strong mutagenic effects were elicited by HMP. In the presence of cytosol and 3'-phosphoadenosine-5'-phosphosulfate (PAPS), both alcohols were activated to potent mutagens. For equal mutagenic effects, approximately 650-fold lower concentrations of HMP were required in the cytosol/PAPS-mediated assay than in the S9/NADPH-mediated assay. The cytosol/PAPS-mediated mutagenicity of both alcohols was 3- to 4-fold enhanced, when KCl (125 mM) was present during the exposure. The authentic chloromethylarenes, 1-chloromethylpyrene and 4-chloro-4H-cyclopenta[def]chrysene, showed very strong direct mutagenicity. These results, taken together with previous findings, indicate that both primary and secondary benzylic alcohols derived from polycyclic aromatic hydrocarbons may be activated by sulfotransferases to electrophilic sulfuric acid esters, and by subsequent substitution reaction to further active species such as benzylic chlorides.

Chrysenes↗
PubMed1993

Functional dissection of the human spumaretrovirus transactivator identifies distinct classes of dominant-negative mutants.

The bel1 gene of human spumaretrovirus (HSRV) codes for a 300-amino-acid nuclear protein, termed Bel1, that can strongly activate transcription from the cognate long terminal repeat (LTR) by at least 200-fold. Bel1 can also activate human immunodeficiency virus type 1 (HIV-1) LTR expression. By using site-directed mutagenesis, we have identified distinct regions of Bel1 essential for HSRV LTR activation. The amino-terminal 55 residues, which comprise a highly acidic region followed by a short basic stretch, were dispensable for activation. The distribution of functionally defective mutants indicates that two distinct regions between residues 56 and 300 cooperate to confer full activator function. The larger, more amino-terminal region between residues 56 and 227 is sufficient to minimally activate the HSRV LTR. It contains a region between residues 88 and 110 that is strongly conserved between the simian and human spumavirus transactivators but otherwise lacks obvious homology to known transcriptional activators except for an Arg-rich nuclear localization sequence (NLS) between residues 211 and 225 that can be functionally substituted for by the NLS of the simian virus 40 large T antigen. The carboxy-terminal 73 residues contain two functionally redundant regions that can independently augment the activity of the more N-terminal minimal activator domain by 30- to 90-fold. Comparative analysis of the effect of Bel1 mutations on HSRV and HIV-1 LTR expression revealed a similar requirement of Bel1 domains for activation of the two LTRs. Bel1 is phosphorylated in vivo, and a nuclear localization-defective mutant lacking residues 211 to 222 was severely defective for phosphorylation, whereas various deletion mutations in residues 228 to 300 resulted in a four- to eightfold reduction in phosphate incorporation. When functionally defective bel1 mutants were examined for a dominant-negative phenotype, only mutants lacking a proline-rich basic region between residues 194 and 200 or the NLS between residues 211 and 222 that were found to occupy predominantly nuclear and cytoplasmic locations, respectively, could suppress wild-type Bel1 function efficiently. In identifying two classes of dominant-negative mutants with distinct subcellular localization phenotypes, the mutational analysis of Bel1 has revealed a feature unusual for known transcriptional activators.

Amino Acid Sequence↗
PubMed1993

Experimental study of the effect of IH764-3 on pulmonary fibrosis.

IH764-3 is a potent component isolated from Salvia miltiorrhiza. We have studied the effect of IH764-3 on experimental pulmonary fibrosis in rats and mice treated with a single intratracheal instillation of bleomycin-A6. Three groups of animals were assigned as BLM+saline, BLM+IH764-3 and normal control. The results indicated that in the treated group, lung coefficient, surfactant, hydroxyproline content and FGF activity were significantly lower than those in the control group (P < 0.05, 0.05, 0.001 and 0.05, respectively). Electron microscopic examination showed that pulmonary ultrastructure was markedly better in the treated group: type II alveolar epithelial cells, infiltrating inflammatory cells, proliferating collagen-forming cells, collagen and elastic fibers were obviously fewer in the treated group. These results demonstrate that IH764-3 has prophylactic and therapeutic effects on pulmonary fibrosis.

Animals↗
PubMed1993

[Studies of two conjugates of monoclonal antibody (HIM6) and cytosine arabinoside].

Two conjugates (HIM6-PAD-ara C and HIM6-PLGA-ara C) of the anticancer agent cytosine arabinoside (ara C) and monoclonal antibody (HIM6) against human leukocytes were prepared with dextran T-40 and poly-L-glutamic acid as intermediate carriers, respectively. The drug-antibody conjugates maintained most of the original antigen-binding activity of the free antibody. The ratio of positive bound cells was found to be > 90% by an indirect immunofluorescence assay. The cytotoxicities of HIM6-PAD-ara C and HIM6-PLGA-ara C against antibody-reactive human leukemia HL60 cells were lower than those of free ara C and a mixture of ara C and HIM6 (IC50s of HIM6-PAD-ara C, HIM6-PLGA-ara C, ara C and the mixture of ara C and HIM6 were 0.212, 0.102, 0.028 and 0.024 microgram/ml, respectively), but were similar to those of the intermediates PAD-ara C and PLGA-ara C. On the other hand, these two conjugates showed no cytotoxic its against non-target hepatoma cells. These results indicate that the specific cytotoxicity of the conjugate depends on specific binding to the target surface antigen by the monoclonal antibody in the conjugate molecule.

Antibodies, Monoclonal↗
PubMed1993

Human interferon-gamma has three domains associated with its antiviral function: a neutralizing epitope typing scheme for human interferon-gamma.

An antiviral activity-neutralizing monoclonal antibody (mAb), MIF3037, was developed by the immunization of BALB/c mice with recombinant human interferon-gamma (rhuIFN-gamma). Its neutralizing activity suggests that its epitope may be at or adjacent to a functional domain on the huIFN-gamma. MIF3037 was compared with representative mAb of previously identified epitope-specific groups in a competitive binding assay. In an attempt to determine if there are other functional epitopes recognized by mAb developed with different preparations of huIFN-gamma or different hybridoma screening methods, 14 additional mAb contributed by five other laboratories were similarly analysed. Based on their ability to bind to huIFN-gamma, all the neutralizing mAb except MIF3037 may be classified into three previously defined groups: E1, E2 and E1/E2. Monoclonal antibodies of the E1 group do not compete with those of the E2 group for huIFN-gamma binding, indicating that the E1 and E2 epitopes are distinct domains on the huIFN-gamma important for the antiviral function. Monoclonal antibodies of the E1/E2 group compete with some of the mAb of E1 and/or E2 groups and may bind to regions of the huIFN-gamma that partially overlap the E1 and E2 epitopes. MIF3037 demonstrated no competitive binding inhibition with mAb of the previously identified epitope specificity groups and, therefore, must represent a distinct functional epitope, E3. The huIFN-gamma, therefore, must have at least three distinct functional domains; none of these appeared to be responsible for cell surface receptor binding. Based on this finding, the epitope typing scheme must be extended to include the E3 epitope. The epitope specificity relationships of 13 neutralizing mAb developed by five other laboratories were established which allows correlation of results obtained with these mAb by different laboratories. The location of the epitopes of four widely studied mAb, 69B, 73A, 113B and 220A12, have been deduced based on their competition with the E1 mAb which have recently been mapped.

Animals↗
PubMed1993

Prevention of pathophysiologic and immunomodulatory effects of gastrointestinal nematodiasis in calves by use of strategic anthelmintic treatments.

Effects of strategic anthelmintic treatment on pathophysiologic and immunomologic changes induced by infection with Ostertagia ostertagi and Cooperia oncophora were studied in 2 groups, of 12 calves each: an infected group, inoculated with 200,000 mixed O ostertagi and C oncophora third-stage larvae (L3) on day 1; and an infected-treated group, similarly inoculated, but treated with ivermectin at 9 and 33 days. All calves were also inoculated at 12 weeks with Brucella abortus vaccine, at 13 weeks with bovine rhinotracheitis vaccine (bovine herpesvirus 1), and at 14 weeks with a soluble O ostertagi L3 extract, then were allowed to graze on a contaminated pasture. Four calves from each group were slaughtered at 7, 11, and 19 weeks of the study. Calves of the infected group had significantly (P < 0.05) lower weight gain than did those in the infected-treated group (60.90 kg vs 75.86 kg). They also had high plasma pepsinogen and serum gastrin values, and low serum albumin concentration from 2 or 4 weeks. Calves in the infected-treated group had steady weight gain and no significant changes in albumin and gastrin values. They also had less severe abomasal lesions and higher carcass yield. Compared with calves of the infected-treated group, those of the infected group had significantly (P < 0.05) lower blood lymphocyte reactivity to phytohemagglutinin at 14 and 16 weeks, to concanavalin A at 10 weeks, to pokeweed mitogen at 14 weeks, and to soluble O ostertagi L3 extract at 2, 4, and 14 weeks. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

[Effect of IH764-3 on prolyl hydroxylation in collagen biosynthesis].

Previous study showed that IH764-3 selectively inhibited the synthesis and secretion of collagen, suggesting that the effect of the drug might be due to inhibition of prolyl hydroxylation. In this paper, we report the effect of IH764-3 on prolyl hydroxylation in collagen biosynthesis. Our results showed that the protocollagen substrate (Pro-Pro-Gly)10 9H2O of prolyl hydroxylation by proline hydroxylase isolated from 13-day-old chick embryos in the presence of a-ketoglutarate, ascorbic acid and Fe2+ was inhibited by IH764-3. The inhibition rate was about 50% at a concentration of 0.24 mmol/L. Further investigation demonstrated that IH764-3 did not bind to prolyl hydroxylase, and the inhibition of enzymatic prolyl hydroxylation was found to be due to chelation of the Fe2+ required for the enzymatic reaction. The molar ratio of Fe2+ to IH764-3 (1:3) was determined by the equilibrium movement method, and the chelate was postulated to be a octahedral complex.

Animals↗
PubMed1993

[Clinical study of traditional Chinese medicine susceptible factors for senile lipid metabolic disturbance].

The syndromes among 674 cadres over 45 years in age with case-control study were investigated, and the TCM susceptible factors (TCM-SF) of senile lipid metabolic disturbance (SLMD) were analysed statistically, which indicated that Kidney-Deficiency, Phlegm-Turbid and Blood-Stasis were the main TCM-SF for SLMD. Compared with the results of presenility, it indicated that the Deficiency in origin was the intrinsic factors in development of LMD in presenile and senile period. Among which, Kidney-Deficiency possibly was the main factor. It is inferred the Deficiency in origin might cause the LMD in presenile and senile stage, and develop gradually as Syndrome of Deficiency in origin and Excess in superficiality, the latter aggravate the former as well. Both of these two Syndromes in origin affected the process of lipid metabolism. The results provided the prevention and treatment of SLMD, for further exploring the pathogenic factor and pathogenesis of the disease.

Aged↗
PubMed1993

Immunologic changes in Ostertagia ostertagi-infected calves treated strategically with an anthelmintic.

Immunomodulation by Ostertagia ostertagi and the effects of strategic anthelmintic treatments were studied in 3 groups of 6 calves each: an infected group, inoculated with 100,000 third-stage larvae (L3)/calf at 1 and 28 days; an infected-treated group, similarly inoculated, but treated with ivermectin 9 days after each inoculation; and a noninfected control group. Calves were grazed on 2 previously clean pastures, with the infected and infected-treated calves sharing 1 pasture. All calves were inoculated at 12 weeks with Brucella abortus and infectious bovine rhinotracheitis vaccines, and at 13 weeks with a soluble O ostertagi L3 extract (SLE). Infected and infected-treated calves had lower blood lymphocyte responses to phytohemagglutinin than did control calves at 2, 4, and 14 weeks, whereas the infected calves had higher responses at 6 and 8 weeks (P < 0.05). Responses to pokeweed mitogen followed a similar pattern, whereas those to SLE were low in all calves. Infected and infected-treated calves had increased values of IgG1 to excretory-secretory antigens of L4 larvae, but no changes in the values of IgG1 to SLE. They also had lower values of IgG and IgM to B abortus and antibodies to infectious bovine rhinotracheitis at 13 weeks. The infected-treated calves, however, had higher blood lymphocyte and monocyte counts and lower eosinophil count than did infected calves. They also had reduced abomasal mucosa thickness, abomasal wall weight, and abomasal lymph node weight than infected calves. It was concluded that O ostertagi causes nonspecific suppression of cellular and humoral immunity, hypersensitivity reactions coexisted with immunosuppression, and strategic anthelmintic treatments attenuated hypersensitivity reactions and initiated better immune responses.

Abomasum↗
PubMed1992

Cloning and nucleotide sequence of the Escherichia coli cytidine deaminase (ccd) gene.

The structural gene that encodes cytidine deaminase (cdd) in Escherichia coli was cloned from Kohara phage lambda 365 (7F1), and its nucleotide sequence was determined. Plasmids harboring the gene complemented chromosomal cdd mutations, enhanced cytidine deaminase activity in cell extracts, and directed the synthesis of a protein identical in mass and N-terminal amino acid sequence with cytidine deaminase purified from wild-type bacteria. Metal analysis of the purified, plasmid-encoded deaminase indicated a single atom of tightly bound zinc per subunit. Earlier work has shown that bacterial cytidine deaminase and mammalian adenosine deaminase are remarkably alike in their mechanisms of action, in their free energies of interaction with analogue inhibitors resembling tetrahedral intermediates in nucleophilic substitution, and in their ability to discriminate between analogue inhibitors differing by a single hydroxyl group. In contrast to these shared catalytic similarities, the deduced amino acid sequence of E. coli cytidine deaminase (monomer MW 31,540) differs markedly from the mammalian adenosine deaminase sequence suggesting major differences in their tertiary structures. Nevertheless, cytidine deaminase and mammalian plus bacterial adenosine deaminases share a single region (TVHA) of sequence identity that is tentatively identified as part of the cytidine deaminase active site.

Amino Acid Sequence↗
PubMed1992

Characterization of the unprocessed and processed forms of rab6 expressed in baculovirus/insect cell systems.

Rab6 protein (rab6p) belongs to a family of ras-like GTP-binding proteins thought to be involved in the regulation of intracellular transport in mammalian cells. We have constructed a recombinant baculovirus in order to express rab6p in insect cells. We report here the characterization of four forms of this protein which are found in cytosolic and membrane fractions of infected Sf9 cells. The two major forms are a cytosolic 24 kD protein which represents the unprocessed precursor form of rab6p and a membrane-bound isoprenylated 23 kD protein which represents the processed form. Two other minor forms were also detected: a cytosolic isoprenylated 23 kD protein which may represent a pool in equilibrium with the 23 kD membrane-bound form and a 24 kD non-isoprenylated membrane-bound form which may represent an intermediate in the processing of rab6p.

Animals↗
PubMed1992

Comparative study on the thermostability of collagen I of skin and bone: influence of posttranslational hydroxylation of prolyl and lysyl residues.

Pepsin-solubilized collagen I from skin and bone was analyzed with regard to its thermal stability as a triple helical molecule in solution and after in vitro fibril formation. Collagen I from human control bone was compared with samples showing deficiencies or surplus in the degree of hydroxylation of lysine. The helix to coil transitions were studied by circular-dichroism measurements and limited trypsin digestion. Melting of fibrils from standardized in vitro self-assembly was investigated turbidimetrically. Human control bone collagen I has a maximum transition rate (Tm) at 43.3 degrees C in 0.05% acetic acid. This is 1.9 degrees C above control skin (Tm = 41.4 degrees C), most likely, due to a higher degree of prolyl hydroxylation--0.48 in bone vs. 0.41 in skin collagen I. Lysyl overhydroxylation of human and mouse bone collagen I appears to reduce the Tm slightly (approximately 1 degree C). Underhydroxylated bone collagen has a Tm which is 2 degrees C below control. Melting temperatures of in vitro formed fibrils are an indication for higher thermostability in parallel with an increase of lysyl hydroxylation. Accordingly, the melting temperature of such fibrils from human control skin, 49.3 degrees C, exceeds control bone by 1.4 degrees C. The degree of lysyl hydroxylation in these samples is 0.14 and 0.10, respectively. Further underhydroxylation (0.06) reduced it down to 45.4 degrees C, while extensive overhydroxylation did not continue to increase the thermal stability of fibrils.

Adult↗
PubMed1992

Study on the pathogenic factors of Kashin-Beck disease.

Kashin-Beck disease (KBD) is a chronic osteoarthritic disease, endemic in parts of China. Its etiology is unknown. Selenium deficiency, high concentration of organic matter (mainly fulvic acid) in drinking water, and severe contamination of grain by fungi have been proposed environmental causes. Free radicals, possible mediators between the environmental factors and origin of KBD, have been studied in this work. Drinking water from KBD-affected areas contains a higher level of semiquinone radicals than that from disease-free areas. In animal experiments, fulvic acid (FA) accumulated in the skeletal system as semiquinone radicals. Contamination of grain by Fusarium oxysporum or Alternaria alternata significantly increased the content of semiquinone radicals. Furthermore, corn grown in endemic areas had a higher content of radicals than that from disease-free areas. The g factor values for these radicals from contaminated corn were about 2.0040, in the range of semiquinone radical. In monolayer culture of human embryonic chondrocytes, FA and aqueous extracts of grain contaminated by Fusarium injured the chondrocytes and enhanced lipid peroxidation. Selenite and superoxide dismutase (SOD) protected the cells from injury by these toxins and reduced lipid peroxide. Lower glutathione peroxidase activities and higher levels of lipid peroxidation were also found in the children living in KBD-affected regions. Thus, FA and the mycotoxin, which are seen as exogenous free-radical carriers, are important environmental factors in the pathogenesis of Kashin-Beck disease; and selenium, vitamin C, and vitamin E, which inhibit free-radical formation, are considered to be protective.

Adolescent↗
PubMed1992

Clearance of rat C-reactive protein in vivo and by perfused liver.

The clearance in vivo of rat C-reactive protein (CRP) was studied: (i) in the whole animal and (ii) by using a rat liver perfusion system. Rat CRP is a glycosylated serum protein containing a complex-type biantennary carbohydrate structure on each of its five subunits. The half-life of rat asialo CRP was approximately 5 min. More than 75% of the radioactivity associated with rat asialo CRP and asialo alpha 1-acid glycoprotein (AGP) was recovered in the liver. A small amount of radioactivity (0.8%) associated with rat CRP and rat asialo CRP was found in the lungs. Competitive inhibition of the clearance of 125I-labelled rat asialo CRP from the circulation by asialo AGP was dose dependent, and resulted in a corresponding decrease in the recovery of radioactivity associated with rat asialo CRP in the liver. This indicated that asialo AGP and rat asialo CRP were cleared by the hepatic asialoglycoprotein receptor. This observation was confirmed when the clearance of rat asialo CRP was studied using a rat liver perfusion system. Using this system, the clearance of rat asialo CRP and asialo AGP from the perfusate was inhibited by N-acetylgalactosamine, but not by phosphorylcholine, a ligand through which most of the CRP reactions are mediated. This study provides an example of a circulating serum glycoprotein containing a biantennary carbohydrate structure that is cleared by the asialoglycoprotein receptor.

Animals↗
PubMed1992

Indications and techniques of penetrating keratoplasties, 1985-1988.

Indications and surgical techniques for penetrating keratoplasties (PKs) were evaluated to determine present trends and suggest future directions for PK. Analyses were based on 3,941 PK cases, with questionnaires completed at the time of surgery by 638 surgeons receiving tissue through Tissue Banks International, Inc. between July 1, 1985, and December 31, 1988. The leading indications for PK were pseudophakic corneal edema (PCE) (23%), graft failure (17%), Fuchs' corneal dystrophy (13%), kerataconus (13%), keratitis/scar (12%), and aphakic corneal edema (10%). Indications for PK varied by age and sex. Anterior chamber (AC) lenses accounted for the majority (56%) of PCE cases. Penetrating keratoplasty for PCE occurred within 5 years of cataract surgery for 81% of patients with PC lenses and only 52% of patients with AC lenses. Intraocular lens exchange was performed in most AC and iris-fixed lens PCE cases (65% and 77%, respectively), but less frequently in PC lens cases (17%). A PC lens was placed in 29% of all PCE lens exchange cases. These data have confirmed and expanded observations from smaller studies about leading indications and surgical techniques for PK. Therefore, eye bank data may be useful in describing and monitoring future indications and trends for PK because they provide a broader base of information than that obtained through a single institution.

Adult↗
PubMed1992

Basis of neurovirulence of avirulent rabies virus variant Av01 with stereotaxic brain inoculation in mice.

Av01 is a variant of the challenge virus standard strain of fixed rabies virus that was selected with a neutralizing anti-glycoprotein monoclonal antibody, and has a single amino acid change in the glycoprotein. It is avirulent after both intracerebral and peripheral routes of inoculation in adult mice. In this study, Av01 was found to be neurovirulent with stereotaxic brain inoculation in either the striatum or cerebellum of adult mice. Mice that had been inoculated simultaneously with Av01 by the intracerebral and intrastriatal routes recovered. More infectious virus was present in the brains of mice inoculated intrastriatally than intracerebrally, and more neurons contained rabies virus antigen. However, the topographical distribution of infected neurons was similar with both routes. Serum neutralizing antibodies against rabies virus were produced later and in smaller quantities after intrastriatal inoculation. Av01 is probably neurovirulent after stereotaxic brain inoculation because this route produces both a direct site of viral entry into the central nervous system and a low level of immune stimulation.

Animals↗