PubMed Health⌕ Search

Biomedical subjects

W J Zhang

Publications and source records attributed to W J Zhang.

At least 19 recordsLinked to original sources
PubMed1992

Haplospecific polymorphism between HLA B and tumor necrosis factor.

Polymorphisms were sought between HLA B and tumor necrosis factor (TNF) using three genomic probes. Extensive polymorphism was detected within a panel of 50 cell lines including 37 homozygotes representing 21 different ancestral haplotypes (AH). Following Taq I digestion of genomic DNA, we observed three allelic patterns with probe X (R17A) and four with probe V (R9A). Seven different allelic patterns were found with probe Y (M20A) after Taq I + Rsa I digestion. Family studies showed that the Y, X, and V alleles were inherited and segregated with HLA haplotypes. A striking feature of the allelic patterns detected by these probes was that cells with the same AH had identical Y, X, and V alleles (i.e., the alleles were haplotypic). Of 15 different Y-X-V haplotypes observed, 11 were found to be specific for a particular AH (i.e., were haplospecific). Four were shared by more than one AH, but in these instances there were extensive similarities in other regions within the major histocompatibility complex (MHC), for example, the Japanese 46.2 (HLA Bw46-DRw8) and the Chinese 46.1 (Bw46-DR9) share all alleles between HLA C and C4 and differ only in class II, suggesting their relatively recent divergence by recombination between C4 and DR. Surprisingly, two insulin-dependent diabetes mellitus (IDDM)-resistant but race-specific AHs 52.1 (Bw52-DRB1*1502, Japanese) and 7.1 (B7-DRB1*1501, Caucasoid) carry the same Y-X-V haplotype, suggesting the possibility of localizing gene(s) relevant to IDDM. The present study confirms that MHC AHs have been conserved en bloc, including the region between HLA B and TNF.

Alleles↗
PubMed1992

Sequence differences between HLA-B and TNF distinguish different MHC ancestral haplotypes.

The HLA-B locus is extremely polymorphic. We have sequenced a region, CL, telomeric of HLA-B that also shows a high degree of allelic variation which we have shown previously by RFLP analysis. The polymorphism can be accounted for by sequence variation in duplicated, reiterated sequence elements called geometric elements. Comparison of the CL1 and CL2 sequences from the 57.1, 8.1, 18.2 and 7.1 ancestral haplotypes revealed that the lengths of the elements vary, both between the duplicated loci within a haplotype and between haplotypes, apparently because certain sequences are inserted or deleted. It is possible, using the polymerase chain reaction, to amplify these elements in genomic DNA from ancestral haplotypes for which sequence data of the CL region are not available and to obtain gel patterns which are characteristic of different ancestral haplotypes. The most striking feature of the data is the fact that the majority of the CL patterns are haplospecific; i.e. have a particular pattern that is unique for a particular ancestral haplotype and can be used to type these ancestral haplotypes. At least 12 different allelic patterns have been identified within a panel of 29 cell lines representing 16 ancestral haplotypes. For these 16 ancestral haplotypes, all examples of each haplotype have the same CL pattern. The haplotypic nature of the patterns confirms that ancestral haplotypes are conserved chromosomal segments and that coding and non-coding sequences are identical by descent from a remote ancestor.

Base Sequence↗
PubMed1992

[Correlation among electrocardiogram, important risk factors of coronary artery diseases and coronary lesion in patients with chest pain].

Clinical and angiographic data from 103 patients with chest pain were evaluated to determine their correlation with ST-T abnormality in resting electrocardiogram. Univariate analysis suggested that male sex, hypertension, old myocardial infarction, severe coronary lesion, multiple vessel lesion and left ventricular wall motion abnormality significantly increase the likelihood of ST-T abnormality. Multivariate analysis suggested that male sex, hypertension and left ventricular wall motion abnormality were significant independent predictors of abnormal ST-T. It is essential to improve the electrocardiographic accuracy of diagnosing CAD so as to help clinical doctors in preventing and treating this disease.

Adult↗
PubMed1992

Effects of copper and selenium on electric parameters of cultured myocardial cells damaged by xanthine-xanthine oxidase.

Addition of xanthine 0.42 mmol.L-1 and xanthine oxidase 5.3 nmol.L-1 (X-XO) to the culture medium increased the amplitude of ESR spectra of myocardial cells, demonstrating an increase in free radical contents; diminished the action potential parameters significantly and reduced the input impedances from 0.34 +/- 0.11 to 0.24 +/- 0.1 M omega, expressing a typical electrical appearance of membrane damage. Supplying Cu 62.5 ng.ml-1 and/or Se 173 ng.ml-1 to the medium brought all of the electric parameters and the free radical content of myocardial cells back to normal. The results indicate that both the two trace elements are able to scavenge free radicals, thus antagonizing X-XO, which induces damage to myocardial cells.

Action Potentials↗
PubMed1991

Cisplatin as a radiosensitizer in clinical practice: a pilot study.

Fifty-four patients with inoperable cancers were treated with a combination of cisplatin and radiotherapy from May 1984 to February 1989. Cisplatin was administered at a dose of 40 mg/week, for a total dose of 160-320 mg, during radiation therapy. In 4 cases with brain metastases, the cisplatin dose was 40 mg/m2. Cisplatin concentration in blood was measured using the flameless atomic absorption spectrophotometric method. Radiation therapy was delivered by a 6 MV X-ray or a cobalt-60 unit up to a total dose of 50-70 Gy. Among the 54 patients, 89% (48) responded to the treatment regimen; complete responses (CR) and partial responses (PR) were 56% and 33%, respectively. Six patients were stable in their disease. Among the 30 patients who had CR's, the 1-year survival rate was 88% (21/24). Two patients (7%) had local relapse. However, among PRs, the 1-year survival rate was 33% (4/12) and local failure (61%) (11/18). Objective tumor response was observed in 4 cases with brain metastasis, 2 of the 4 patients were alive for more than 6 months. Toxic effects were moderate and consisted of emesis and myelosuppression. Grade III bone marrow suppression amounted to 11%, and the interval of recovery was relatively long compared with that reported in the literature. Further prospective controlled studies are recommended.

Adult↗
PubMed1991

The genomic structure of two ancestral haplotypes carrying C4A duplications.

Two major histocompatibility complex (MHC) ancestral haplotypes (AH) HLA A24, Bw52, C2C, BfS, C4A3+2, C4BQO, DRw15, DQw6 (52.1) and HLA A24, Cw7, B7, C2C, BfS, C4A3+3, C4B1, DR1, DQw5 (7.2), which occur with the haplotype frequencies of approximately 10% and 4% respectively in the Japanese population, carry duplicated C4A alleles by C4 allotyping. Southern blot analysis with Taq I indicated that the 52.1 AH has two C4 genes defined by 7.0 kilobase (kb) and 6.0 kb C4 hybridizing fragments but both encode C4A allotypes, being C4A3 and C4A2 respectively. The 7.2 AH carries two C4A3 and one C4B1 alleles and restriction length polymorphism (RFLP) analysis with Taq I showed that 6.0 kb and 7.0 kb fragments are in the proportion of 2:1. By pulsed field gel electrophoresis (PFGE) analysis, the lengths of the Pvul fragments carrying C4 and Cyp21 genes were approximately 390 kb for 52.1 and 440 kb to 7.2. The results indicate that the RFLP markers do not correlate with C4 isotype (A or B) or allotype and that the C4 gene copy number is a function of the number of genomic blocks containing C4 and Cyp21.

Alleles↗
PubMed1991

The effect of calcitonin gene-related peptide on arrhythmia caused by adenosine diphosphate and desacetyldigilanide-C in rats.

We investigated the effect of calcitonin gene-related peptide on the arrhythmia induced by two drugs in rats. The results of our experiments have proved that calcitonin gene-related peptide could reduce the degree of atrioventricular block, protect against the attacks of sinus standstill and ventricular fibrillation produced by adenosine diphosphate, and improve restoration of sinus rhythm. Calcitonin gene-related peptide was able to eliminate sinus standstill and ventricular fibrillation resulting from administration of desacetyldigilanide-C. These results demonstrate that calcitonin gene-related peptide has strong antiarrhythmic effects in experimental animals.

Adenosine Diphosphate↗
PubMed1991

Major histocompatibility complex ancestral haplotypes in the chimpanzee: identification using C4 allotyping.

In humans, certain major histocompatibility complex (MHC) supratypes mark unique DNA segments which have been conserved from a common but remote ancestor. In order to determine whether these ancestral haplotypes (AHs) exist in nonhuman primates, C4 allotyping was undertaken on 71 chimpanzees. Four large pedigrees were available. There are at least seven codominant C4 alleles at two loci. Null alleles are also present. It was possible to assign class I, class II, and C4 alleles to 37 unrelated haplotypes; several supratypes occurred two or more times. These putative AHs included some with alleles which resemble those carried by certain human AHs. These data provide evidence that similar MHC AHs are present in the chimpanzee and human. The present approach provides a basis for comparative studies examining the evolutionary and functional significance of the MHC.

Animals↗
PubMed1991

Major histocompatibility complex (MHC) complement deficiency, ancestral haplotypes and systemic lupus erythematosus (SLE): C4 deficiency explains some but not all of the influence of the MHC.

In 1982 we reported that among Caucasians with systemic lupus erythematosus (SLE) there is an increased frequency of C4A null. As this allele occurs on the HLA-A1,B8,BfS, C4AQO,B1,DR3 (8.1) supratype, we suggested this accounted for the reported association of B8 and DR3. Since then we have shown that many supratypes including 8.1 identify unique segments of DNA conserved from a common but remote ancestor. Many of these ancestral haplotypes (AH), including 8.1, carry disease genes and some bear C4 null. We have therefore tested the hypothesis that in SLE C4 null alleles are directly involved by examining (1) whether all or only some AH bearing C4 null alleles are increased, (2) whether C4 null is increased in all racial groups examined, and (3) whether C4 null is associated with the presence of antinuclear antibodies (ANA) in the absence of SLE. We performed HLA and complement allotyping on 62 Australian Caucasians and 9 Australian aborigines with SLE and on the 10 out of 133 healthy individuals with 7 or more international units of ANA. Our data confirm an association of C4A null in Australian Caucasians (gene frequency 0.30 versus 0.15 in controls) and show an increased frequency of C4B null in Australian aborigines (gene frequency 0.33 versus 0.22). A review of an extensive literature shows C4A and/or C4B null are increased in all racial groups examined. On the other hand, the HLA-A3,B7,BfS,C4A3,B1,DR2 (7.1) AH rather than C4 null is associated with ANA in health. Our data indicate that while C4 nulls contribute to MHC susceptibility, other genes are likely to be involved.

Alleles↗
PubMed1991

[Investigation of C4 haplotypes in Han nationality of Hubei Province in China].

C4 haplotypes of 93 unrelated families of Han nationality in Hubei Province were determined by means of a method established in our laboratory based on the techniques recommended in the 4th International Workshop for the Genetics of Complement and the method of Carboxypeptidase B developed by Zhang in Australia. 310 C4 haplotypes were analysed. The haplotype frequency of A3B1 (0.4194) was found to be the highest in Han nationality of Hubei in China. The others are as follows: A3B2: 0.1161, A2B1 and A4B2: both 0.0903, AQOB1: 0.0645, A3BQO: 0.0548, AQOBQO: 0.0322, A2B2: 0.0256, A4B1: 0.0161, A2B92: 0.0129. Some kinds of rare haplotypes were also discovered. Significant positive-linkage disequilibrium parameters (delta) were found in haplotypes of A4B2, AQOBQO and A2B92, while the significant negative delta was observed in that of A4B1 and AQOB2. Our data were compared with those of Japanese, Caucasian in USA and Germany, Negroids in South Africa are discussed in the paper. The differences among them.

Asian People↗
PubMed1990

Differences in gene copy number carried by different MHC ancestral haplotypes. Quantitation after physical separation of haplotypes by pulsed field gel electrophoresis.

We have examined the hypothesis that MHC ancestral haplotypes have a specific content of genes regulating the extent of autoimmune reactions. Gene copy number was quantitated by objective densitometry after PFGE was used to separate heterozygous AHs of different lengths. Initially we analyzed examples of known gene copy number at the C4 and 21 hydroxylase loci and showed that the approach provides predictable results. We then studied heterozygotes containing one characterized and one uncharacterized AH with particular attention to the gene copy number at the C4, Cyp21, and DRB loci. Each AH studied has a characteristic gene copy number at each locus studied. The same may be true of TNF, but other possibilities must be considered. AHs are markers for extensive chromosomal segments including particular numbers of several functional genes. Since AHs mark susceptibility to autoimmune disease, differences in gene copy number may be implicated.

Blotting, Southern↗
PubMed1990

Protective action of selenium and manganese on xanthine and xanthine oxidase induced oxidative damage to cultured heart cells.

Ventricular myocytes from neonatal Wistar rats were cultured with 80% Dulbecoo's modified Eagle medium and 20% fetal bovine serum. An appropriate amount of xanthine and xanthine oxidase was added to the culture medium to increase the content of free radicals in cardiac cells. Variation in action potential and input impedance of cardiac myocytes indicated the oxidative damage to the membrane. The ultrastructure of heart cells, characteristically the myofilaments and mitochondria, was damaged. Electron spin resonance measurement demonstrated that xanthine and xanthine oxidase elevated the free radical content, while selenium (Se) and manganese (Mn) reduced the free radicals in cultured heart cells. Supplementation of 0.173 microgram/ml Se and 0.1 microgram/ml Mn into the culture medium separately or simultaneously antagonized the damage induced by xanthine and xanthine oxidase. The possible mechanism might be the production of superoxide anion free radical leading to free radical damage to cardiac cells. Se and Mn might play a role as scavengers through glutathione peroxidase and superoxide dismutase respectively and thus protect cardiac cells from free radical damage.

Action Potentials↗
PubMed1988

Influence of C4 null genes on infection with human immunodeficiency virus.

The hypothesis that complement is important in the host response to human immunodeficiency virus (HIV) was tested. Complement C4 and Bf allotypes were determined in 26 patients who fulfilled the diagnostic criteria for persistent generalised lymphadenopathy due to HIV, 72 homosexuals who were negative for antibody to HIV, and 185 control subjects drawn from the local population. HLA-A, B, and DR were also typed and the phenotypes examined for the presence of supratypes and C4BQ0. Eleven patients (42%) had C4B null alleles compared with only 13 (18%) homosexuals who were negative for antibody and 28 (15%) controls. From estimates of gene frequencies the difference between the patients with lymphadenopathy and the controls was significant after conservative correction. In the patients only a minority (six) of the C4B null alleles were contained within ancestral haplotypes. Together with the fact that C4 null alleles result in partial deficiency of C4, this finding suggests that products of complement genes are important in infection with HIV or its consequences, or both. A role is proposed for complement and Fc receptors.

Acquired Immunodeficiency Syndrome↗
PubMed1988

C4 allotyping on plasma or serum: application to routine laboratories.

Allotypes of the fourth component of complement (C4) can be detected by electrophoresis and immunofixation after treatment of EDTA plasma with neuraminidase (NAse). We have assessed the value of additional treatment with carboxypeptidase B (CPseB). Following treatment with CPseB + NAse, each allele is resolved into a single band, permitting clear definition of overlapping bands seen following treatment with NAse alone. More importantly, C4 allotypes can be determined using stored heparinized plasma or serum. Most C4 null alleles can be assigned without requiring family studies. The approach described is suitable for routine use by tissue typing laboratories.

Alleles↗