Search PubMed⌕ Search

Biomedical subjects

W Zhao

Publications and source records attributed to W Zhao.

At least 343 records · Page 19Linked to original sources
PubMed1995

HU-211, a novel noncompetitive N-methyl-D-aspartate antagonist, improves neurological deficit and reduces infarct volume after reversible focal cerebral ischemia in the rat.

BACKGROUND AND PURPOSE: HU-211 is a nonpsychotropic cannabinoid analogue that has been shown to act as a functional N-methyl-D-aspartate receptor blocker. We investigated the neuroprotective efficacy of HU-211 in a model of reversible middle cerebral artery occlusion (MCAo) in rats. METHODS: Male Wistar rats were anesthetized with halothane and subjected to 90 minutes of temporary MCAo by retrograde insertion of an intraluminal nylon suture, coated with poly-L-lysine, through the external carotid artery into the internal carotid artery and MCA. The drug (HU-211 in cosolvent, 4 mg/kg IV) or vehicle was administered in a blinded fashion 70 minutes after onset of MCAo. Behavioral tests were evaluated during occlusion (60 minutes) and for a 3-day period after MCAo. Three days after MCAo, brains were perfusion-fixed, and infarct volumes were determined. RESULTS: HU-211 significantly improved the neurological score compared with vehicle during the 3 days after MCAo. Treatment with HU-211 also significantly reduced both infarct volume (mean +/- SEM, 66.6 +/- 12.5 versus 149.8 +/- 36.3 mm3) and brain swelling (2.61 +/- 1.33% versus 6.66 +/- 1.24%) compared with vehicle-treated rats (n = 17 in each group). CONCLUSIONS: These results demonstrate the neuroprotective ability of HU-211 in focal cerebral ischemia as judged by neurological score, infarct size, and brain swelling. Reversible MCAo with the use of a poly-L-lysine-coated intraluminal suture proved to be a reliable and effective modification of this technique, yielding consistent results.

Animals↗
PubMed1995

Influence of different doses of methyl ethyl ketone on 2,5-hexanedione concentrations in the sciatic nerve, serum, and urine of rats.

Rats were injected subcutaneously with 2,5-hexanedione (2,5-HD 2.6 m mol/kg) alone (HD group) or with 2,5-HD and methyl ethyl ketone (MEK) (2.6 m mol/kg of each agent, HD&MEK group) or with 2,5-HD 2.6 m mol/kg and 5 times that dose (13.0 m mol/kg) of MEK (HD&5MEK group). The concentration of 2,5-HD in serum and in the sciatic nerve was determined 0.5, 1, 2, 4, 8, and 16 h after administration. Urinary 2,5-HD concentration was determined from the beginning of administration up to 16 h afterward. 1) The concentration of 2,5-HD in the serum, the sciatic nerve, and the urine was increased significantly (p < 0.05) in the co-administered groups; the higher the MEK doses were, the greater was the increase. 2) The clearance of 2,5-HD from both the serum and the sciatic nerve was delayed in the co-administered groups. The highest concentration in serum and the sciatic nerve appeared at 1 and 2 h respectively. After administration, the biological halflife (t1/2) of 2,5-HD from 1 to 8 h in serum was 6.5, 5.8 and 12.0 h for the HD, HD&MEK, and HD&5 MEK groups respectively. From 8 to 16 h, the t1/2 in serum was 1.2, 3.2 and 16.6 h for the HD, HD&MEK, and HD&5MEK groups, respectively. In nerve tissue, the prolongation of clearance in the co-administered groups was greater than that in serum, the t1/2 from 2 to 8 h being 5.2, 9.6 and 19.9 h for the HD, HD&MEK, and HD&5MEK groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Experimental autoimmune insulitis. Induction by T lymphocytes specific for a peptide of proinsulin.

Type I diabetes, an autoimmune disease that occurs in humans and animals, is characterized by the destruction of insulin-secreting islet beta-cells of the pancreas. Antibodies directed toward multiple islet protein can be detected before diagnosis of type I diabetes; however, the identity of the inciting autoantigen(s) that targets beta-cells for destruction has not been defined. Autorecognition of many self-proteins by CD4+ T lymphocytes is restricted by the products of class II immune response genes of the major histocompatibility complex (MHC), and in human type I diabetes such a MHC association has been described. The present study uses a rat MHC class II (RT1.Bl) peptide binding motif to predict potentially autoreactive CD4+ T cell epitopes in two key islet beta-cell constituents: the enzyme glutamic acid decarboxylase (GAD) and the insulin precursor hormone proinsulin (PI). Seventeen-amino-acid-long peptide fragments of GAD and PI containing the binding motif were synthesized and used to generate peptide-specific, MHC class II-restricted, CD4+ T cell lines. Once established, the T cell lines specific for rat islet GAD and PI were adoptively transferred to naive, MHC-compatible rats. At 10 days after transfer, insulitis had developed in rats receiving PI-specific T cells, whereas no insulitis was observed in pancreata of rats receiving GAD-specific T cells. Of particular interest is the finding that the pathogenic T cell epitope identified in PI spans the endogenous cleavage site between the B-chain and C-peptide of insulin. Moreover, the PI-specific T cells were able to react specifically with material produced in vitro by a rat insulinoma cell line. These results demonstrate that pathogenic T cell epitopes can be located in portions of molecules that are subsequently degraded during normal enzymatic processing. As PI is found highest concentrations in the beta-cells of pancreatic islets, it is possible that this molecule and not its individual degradation products (ie, insulin and C-peptide) might serve as an autoantigen in the pathogenesis of type I diabetes.

Amino Acid Sequence↗
PubMed1995

Evaluation of serum troponin T measurement in acute myocardial infarction.

The release kinetics of the cardiac specific troponin T (cTnT), measured by an immunosorbent assay, in 32 patients with acute myocardial infarction (AMI) was evaluated. In 8 AMI patients (25%), the release kinetics of serum cTnT showed biphasic serum concentration curves with a large peak at 10 to 18 hours after onset and the serum cTnT concentrations were up to 30 to 120 times of the normal upper limit-detected (0.2 microgram/ml), and another samll cTnT peak at 70 to 100 hours after onset of pain. The serum cTnT measurements in the remaining 24 AMI patients (75%) gave only one large peak which was around 32 to 108 hours after onset of pain. cTnT appeared in serum as early as 3 to 4 hours and remained elevated until 240 hours after the infarctions. The results indicated that (1) cTnT was a sensitive and specific marker of AMI; (2) the biphasic curve of cTnT releae in general, the ratio of cTnT at around 14 to 32 (14/32) > 1 in particular, may be a useful marker suggesting early reperfusion; (3) the continuous elevation of serum cTnT in AMI course might be a prognostic indicator for unfavorable outcomes.

Aged↗
PubMed1995

[Prognosis of Graves disease treated with different modalities of therapy].

A retrospective study on the prognosis of Graves disease was carried out. 224 cases, whose treatment has been stopped for 6 months to more than 10 years, were divided into 3 groups. 82 cases received long-term antithyroid drug therapy, 100 cases were treated with radioactive 131I and 42 cases had subtotal thyroidectomy. The prognosis was evaluated for 4 items according to clinical and laboratory investigations. The cured rate of long-term drug therapy in this study was higher than that reported by most of other authors, 131I therapy was the best among the 3 modalites of therapy. The incidence of permanent hypothyroidism was fairly low in the thyroidectomy group. 97.3% of the patients with exophthalmos showed improvement after treatment in all the 3 groups.

Adolescent↗
PubMed1995

Effect of nitric oxide on in vitro responsiveness of bovine bronchus and pulmonary vessels.

Experiments were conducted in bovine isolated bronchi and pulmonary vessels to test whether nitric oxide (NO) could reduce carbachol and hypoxia or KCl (120 mM) induced contraction. Segments of bronchus or pulmonary vessels were slipped around a water-filled balloon connected to a pressure transducer, and mounted in 3 ml thermostated chamber filled with Krebs-Henseleit solution equilibrated with different gas mixtures. NO-CO2-N2 mixtures containing 10, 50 or 100 ppm NO were prepared. The effect of methylene blue on intrinsic tone and the bias effect of residual red blood cells were assessed. The results demonstrate that NO has no obvious effect on the intrinsic tone, the force generated by carbachol stimulation, or the spontaneous relaxation after removal of carbachol, in bronchi, with the exception of 100 ppm which increased the relaxing rate in small bronchi. By contrast, 50 and 100 ppm NO caused 53 and 61% decrease in the hypoxia-induced pulmonary arterial contraction, respectively. One hundred ppm NO caused 40, 38, 50 and 66% decrease in the KCl-induced contraction in pulmonary artery (PA), small pulmonary artery (SPA), small pulmonary vein (SPV) and pulmonary vein (PV), respectively. Sodium nitroprusside (10(-5) M) and isoproterenol (10(-5) M) reduced the carbachol-induced increase in bronchial pressure by 80% and nearly 100%, respectively. The residual concentration of haemoglobin in the chamber cannot explain the lack of effect of NO on the bronchi.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Endothelin-1 as a putative modulator of erectile dysfunction. II. Calcium mobilization in cultured human corporal smooth muscle cells.

PURPOSE: To gain mechanistic insight into the actions of endothelin-1 (ET-1) in human erectile tissue. MATERIALS AND METHODS: Fura-2 based digital imaging microscopy was used to measure intracellular calcium levels in discrete cellular regions (cytosol and nucleus) in single cultured human corporal smooth muscle cells derived from corporal tissue excised from 3 patients with organic erectile dysfunction, as well as 2 patients with documented erections. RESULTS: Endothelin-1 elicited a transient and concentration-dependent increase in cytosolic and nuclear calcium levels in cells from both patient populations. However, while the peak amplitudes of the ET-1-induced cytosolic calcium increases were similar in cells from the 2 patient populations, the observed increases in nuclear calcium levels were much more pronounced in cells from patients with organic erectile dysfunction than in patients with documented erections. CONCLUSIONS: Endothelin-1, by virtue of its ability to increase both cytosolic and nuclear calcium levels, may serve not only as a critical determinant of corporal tissue tone, but also as a modulator of cellular proliferation and phenotypic expression.

Biological Transport↗
PubMed1995

An interferon-inducible molecule on brain endothelium which controls lymphocyte adhesion mediated by integrins.

We undertook a search for cytokine-inducible molecules present on brain endothelium and which are involved in the control of lymphocyte adhesion. We screened 39 monoclonal antibodies (mAb) against rat brain endothelium in vitro, and identified five recognizing cytokine-inducible molecules. None of the 39 antibodies blocked lymphocyte adhesion, but one antibody (4A2), produced a 400% enhancement of lymphocyte binding. The 4A2 antigen is induced on brain endothelium by interferon-gamma (INF-gamma) but not tumour necrosis factor-alpha (TNF-alpha), at 6-48 hr. It is preferentially expressed near inter-endothelial cell junctions, but it also expressed on all lymphocytes and weakly on aortic endothelium in vitro. In vivo, it is not detectable on cells in the normal central nervous system (CNS), however it appears in the CNS during T-cell mediated immune reactions. Triggering of cells via this molecule enhances integrin-mediated adhesion of lymphocytes to brain endothelium, primarily via LFA-1. Unlike ICAM-1, 4A2 antigen is induced on endothelium of both Lewis and PVG strains. Although, it has some functional properties of human CD31, the 4A2 antigen is not rat CD31. The cellular localization of this molecule, its actions on integrin-mediated adhesion and its induction by IFN-gamma, all indicate that the 4A2 antibody recognizes a molecule involved in the control of lymphocyte migration into the brain.

Animals↗
PubMed1995

[Studies on diagnosis for occupationally chronic toxic hepatopathy].

Data from 10-to-17-year periodical physical examinations for 10,858 employees exposed to hepatotoxic chemicals were sorted out and analyzed, and 1,514 cases of suspected chronic toxic hepatopathy were detected. Causes of under-recognition of those were: (1) liver function tests now available being not sensitive enough; (2) limitations of conventional methods for diagnosis of hepatopathy by excluding other disorders; and (3) lack of diagnostic criteria for it. In the light of existing problems, the following diagnostic procedures were applied in the studies: (1) analyzing data dynamically to understand when and to what extent the liver damaged during their work; (2) exploring several more sensitive liver function tests to be used in the diagnosis, and (3) incorporating industrial hygienic files into clinical data to get preliminary diagnosis for it, and then to differentiate from other disorders and to establish a definite conclusion. With these procedures, diagnosis of occupationally chronic toxic hepatopathy was established in 1,035 cases of 1,514 suspected ones.

Benzamides↗
PubMed1995

[Detection of p53 mutation using PCR-SSCP silver staining method].

A simple and sensitive technique to detect point mutation of the p53 gene using silver staining method for single-strand conformation polymorphism analysis of polymerase chain reaction (PCR-SSCP) is reported. In this study, the aberrations of the p53 gene (exon 6-8) in clinical specimens of primary cervical carcinoma were examined. Of 27 tumor tissues 2 samples showed mutations of p53 exon 7. Absence of abnormal bands in the p53 exon 6-8 in all ten normal cervical tissues. It appears that inactivation of p53 gene by point mutation is infrequent in clinical samples of human cervical carcinomas.

Base Sequence↗
PubMed1995

[The sensitizing role of the anti-idiotypic monoclonal antibody-NP30 of Schistosoma japonicum in egg granuloma formation].

C57BL/6 mice sensitized intraperitoneally with the anti-idiotypic monoclonal antibody-NP30 of Schistosoma japonicum and then injected with vital egg suspension directly into spleen were used as the experimental models of hepatic egg granulomas in this study. The soluble egg antigen(SEA) sensitized group was used as positive control and the SP2/0 ascites injected group as negative control. The results showed that the size and volume of hepatic egg granulomas in the NP30 sensitized group increased obviously 4 days after egg injection and that a large number of eosinophiles appeared in egg granulomas. The size and volume of egg granulomas reached the peak values at d8 and d15 after egg injection, respectively. The peak values of the NP30 sensitized group were similar to those of the SEA sensitized group (P > 0.05). The size and volume of egg granulomas in the SP2/0 ascites injected group did not reach the peak values, which were less than those of the group sensitized with NP30 (size: P < 0.05; volume: P < 0.01), until d32 after egg injection. Our study suggests that NP30 may play a sensitizing role in the formation of hepatic egg granulomas.

Animals↗
PubMed1995

[Human papillomavirus, human cytomegalovirus and p53 gene in cervical carcinoma].

OBJECTIVE: To investigate the role of human papillomavirus (HPV) human cytomegalovirus (HCMV) infections and p53 gene mutations in the oncogenesis of cervical cancer and to clarify the association between p53 inactivation and the presence of HPV DNA. METHODS: We examined 38 primary cervical carcinomas and 21 normal cervical specimens for the presence of HPV and HCMV DNA sequences by multiple primers PCR and nest primers PCR. The structure of p53 gene (exons 6-8) was also analyzed by PCR-SSCP silver staining method. RESULTS: Mutations of p53 gene (exon 7) were detected in 2 of 38 tumors. One of the cases with p53 mutation was positive for HPV 16 and two positive for HCMV. HPV 16 and 18 infections were noted in 63.2% (24/38) of the tumors, the positive rate of HCMV was 84.2% (32/38). However, HPV 16,18 and HCMV infection occurred in 4.8% and 38.1% respectively in 21 normal cervical specimens. 21 of the 24 HPV 16,18 positive tumors were also HCMV positive, but none of the normal cervical tissues was infected with both HPV and HCMV. CONCLUSION: Detection of p53 mutations in cervical carcinoma is infrequent and apparently independent of HPV infection. Cervical carcinoma is strongly associated with HPV 16 and 18 infection. A synergistic interaction may occur between HPV and HCMV infections in the oncogenesis of cervical cancer.

Carcinoma, Squamous Cell↗
PubMed1994

Insertional mutation of int protooncogenes in the mammary tumors of a new strain of mice derived from the wild in China: normal- and tumor-tissue-specific expression of int-3 transcripts.

A new mouse strain, Mus musculus Jyg, has been isolated from the wild in China. After several generations of inbreeding, Jyg mice have been found to develop mammary adenocarcinomas at a high incidence (70-80%). In order to understand the mechanism by which mammary tumors are induced in these mice, we analyzed 23 available mammary tumors and liver tissues with regard to mouse mammary tumor virus (MMTV) proviral integrations and the pattern of int oncogene (Wnt-1, int-2/Fgf-3, and int-3) rearrangements and expression. We found that (1) Jyg mice do not carry endogenous MMTV; (2) all tumors showed multiple MMTV proviral integrations and expressed high levels of MMTV; (3) Jyg MMTV is distinguishable from other MMTV strains; (4) a high percentage of the tumors (70%) had insertional mutations in int loci (Wnt-1, 26%; int-2, 13%; and int3, 43%); and (5) unlike Wnt-1 and int-2, a 5.9-kb int-3-related transcript is expressed in developing mouse embryos of all stages and adult mouse tissues including mammary tumors, whereas a 2.4- to 3.6-kb transcript is expressed only in Jyg mammary tumors with int-3 mutations. Taken together, this newly developed mouse strain and the milk-borne MMTV that it carries constitute a novel system for studies of the host and viral specificity of insertional mutagenesis of multiple int protooncogenes by MMTV and the role of these genes in the pathogenesis of mouse mammary carcinomas and tumor cell heterogeneity.

Animals↗
PubMed1994

Identification of an N-terminally acetylated encephalitogenic epitope in myelin proteolipid apoprotein for the Lewis rat.

Proteolipid apoprotein (PLP) is a major component of the central nervous system myelin. As such, it is capable of inducing experimental allergic encephalomyelitis (EAE) in many subhuman species. On the basis of a putative MHC class II binding motif in Lewis rats (RT-1B1) recently identified in our laboratory, the present study identifies one pathogenic T cell epitope of PLP for the Lewis rat, located in the area between amino acid residues 217 and 240. Four overlapping synthetic peptides derived from this region were tested for their antigenicity and encephalitogenicity. Although the longer peptides could not induce EAE in the Lewis rats in their "theoretically" native form after immunization, they were endowed with encephalitogenic ability when modified by N-terminal acetylation. All animals immunized with N-acetylated peptides PLP 217-233 and PLP 224-240 developed inflammation in the lower spinal cord, but with very low incidence of clinical EAE (1 of 12). In contrast, none of the animals immunized with nonacetylated peptides developed either clinical or histologic EAE. Mild inflammation of the spinal cord was also found in two of four rats immunized with N-acetylated peptide PLP 220-234. The animals immunized with the decapeptide, N-acetylated PLP 224-233, did not develop inflammation of the spinal cord. Despite the low incidence of clinical disease, it was possible to generate vigorous T cell lines against all the peptides synthesized from this region of PLP.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗
PubMed1994

Identification of myocarditogenic peptides derived from cardiac myosin capable of inducing experimental allergic myocarditis in the Lewis rat. The utility of a class II binding motif in selecting self-reactive peptides.

Cardiac myosin (CM) has been implicated as an autoantigen in the induction of experimental allergic myocarditis (EAM). At the present time no myocarditogenic peptides of CM have been identified. To identify CM peptides with myocarditogenic properties we have made use of a putative binding motif for the MHC class II molecule RT1.BI in the rat. The amino acid sequence of CM alpha-chain was scanned and found to contain nine peptides that contain this binding motif, three peptides found only in the cardiac form of myosin were chosen for further study. This manuscript describes the identification of two CM peptides capable of inducing EAM in the Lewis rat. In doing so this study demonstrates the utility of an MHC class II binding motif to (correctly) predict pathogenic, autoimmunity inducing, peptides. Peptides, CM 1, and CM 2 are the first peptides described that are capable of inducing EAM in rats. The utilization of CM 2 peptide has permitted the establishment of a long term, Ag specific cell line capable of adoptively transferring EAM. Moreover, the establishment of CM 2 specific T lymphocyte lines has permitted the description of a detailed proliferative response of a myocarditogenic cell line to a specific cardiac Ag. The identification of CM 1 and 2 formally proves that CM, and not a co-purified contaminant, is an Ag in EAM. Finally, this report documents that experimentally induced giant cell myocarditis is not a separate disease entity arising from a distinct cardiac Ag or CM epitope from regular myocarditis.

Amino Acid Sequence↗