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Biomedical subjects

Z Chen

Publications and source records attributed to Z Chen.

At least 1,351 records · Page 75Linked to original sources

Prolonged infection with hepatitis B virus and association between low blood cholesterol concentration and liver cancer.

OBJECTIVE: To determine whether prolonged infection with hepatitis B virus is associated with a lower blood cholesterol concentration. DESIGN: Cross sectional study. SETTING: 81 villages in rural China with a high prevalence of chronic infection with hepatitis B virus. SUBJECTS: 1556 apparently healthy men aged 35-64 years, randomly selected. MAIN OUTCOME MEASURES: Hepatitis B virus carrier state; plasma concentrations of cholesterol, apolipoprotein B, and apolipoprotein A I. RESULTS: 238 (15%) of the men were positive for hepatitis B surface antigen, indicating that they were chronic carriers. Plasma concentration of cholesterol was 4.2% (0.11 mmol/l) lower among carriers (that is, positive for hepatitis B surface antigen) than among non-carriers (95% confidence interval 0.6% to 8.0% (0.01 to 0.21 mmol/l), p < 0.05), and apolipoprotein B concentration was 7.0% (0.036 g/l) lower (2.8% to 11.2% (0.014 to 0.058 g/l), p < 0.001). In contrast, no association was observed between plasma concentrations of cholesterol or apolipoprotein and hepatitis B that had been eradicated (that is, patient positive for hepatitis B core antibody but negative for hepatitis B surface antigen). CONCLUSIONS: Chronic hepatitis B virus infection, which usually starts in early childhood in China, seems to lead not only to a greatly increased risk of death from liver disease but also to a somewhat lower cholesterol concentration in adulthood. This common cause produces an inverse association between cholesterol concentration and risk of death from liver cancer or from other chronic liver diseases.

Adult↗

Gender differences in the treatment of patients with acute myocardial infarction. A multihospital, community-based perspective.

OBJECTIVE: As part of a community-wide study examining temporal trends in the incidence and survival rates of acute myocardial infarction, we examined differences between the sexes in overall utilization rates and changes over time, therein, of various therapies used in the management of acute myocardial infarction. DESIGN: Nonconcurrent prospective study. PATIENTS: Three thousand three hundred sixty-one men and 2119 women hospitalized with validated acute myocardial infarction in 16 hospitals in the Worcester, Mass, metropolitan area during 1975, 1978, 1981, 1984, 1986, 1988, and 1990. RESULTS: After controlling, by means of a logistic regression analysis, for a variety of patient-related factors that could affect physician prescribing patterns, women were significantly more likely to receive diuretics during hospitalization for acute myocardial infarction, whereas men were significantly more likely to receive antiplatelet agents, lidocaine, and other antiarrhythmic agents. No statistically significant differences were seen between men and women with regard to the use of anticoagulants, beta-blockers, calcium channel blockers, digoxin, nitrates, and thrombolytic agents. Marked increases over time (1975 through 1990) were seen in the use of anticoagulants, antiplatelet agents, beta-blockers, lidocaine, and nitrates in each of the sexes, while declines were seen in the use of digoxin and diuretics. Use of thrombolytic therapy increased between 1986 and 1990, whereas use of calcium channel blockers decreased over this period for both men and women. CONCLUSIONS: The results of this multihospital, population-based, observational study suggest that physician practice patterns in the pharmacologic treatment of men and women hospitalized with acute myocardial infarction are very similar.

Aged↗

Production and characterization of a tumor-specific monoclonal antibody ACT19 recognizing an epitope distinctive from sialosyl-Tn on the TAG72 antigen.

AIMS: A murine monoclonal antibody ACT19 directed at the TAG72 tumor-associated antigen, which was originally defined by the B72.3 antibody, was established. METHODS: This was done by immunizing mice with the bovine mucin followed by the selection of hybridomas secreting antibodies with the desired specificity. In order to better characterize this antibody, its immunoreactivity was compared to that of the B72.3 antibody. RESULTS: The data showed that the ACT19 antibody bound specifically to the TAG72 antigen as the B72.3 antibody did. However, there were some differences between ACT19 and B72.3. Firstly, the immunoreactivity of ACT19 for the bovine mucin was lower than that of B72.3. Secondly, the immunoreactivity of ACT19 for the TAG72 antigen was not inhibited by N-acetylgalactosamine, nor was that of B72.3. Thirdly, ACT19 did not compete the binding reactivity of B72.3 for the TAG72 antigen. This suggests that the epitope defined by ACT19 is different from the siaosyl-Tn epitope recognized by B72.3. Immunoperoxidase staining of various tumors, normal and embryonic tissues for ACT19 was carried out. For the various tumors, only adenocarcinomas from the colon and stomach showed remarkable positivity. All the normal tissues were negative, except for weak positivity involving the zona reticularis of the adrenal cortex, and intestinal goblet cells. Embryonic tissues showed a wide spectrum of positivity with staining of the small and large intestine, stomach and renal tubules. CONCLUSIONS: The ACT19 antibody appears to be a useful marker for colon and stomach cancers, and this additional anti-TAG72 antibody may be useful in conjunction with the B72.3 antibody in pathology and clinical application.

Acetylglucosamine↗

A community-wide perspective of gender differences and temporal trends in the use of diagnostic and revascularization procedures for acute myocardial infarction.

This study compares the overall use, as well as temporal trends, of various diagnostic and revascularization procedures for acute myocardial infarction (AMI) in men and women. The study sample comprised a total of 2,924 men and 1,838 women with validated AMI admitted to any of the 16 teaching and community hospitals in the Worcester, Massachusetts, metropolitan area during 1975, 1978, 1981, 1984, 1986 and 1988. During the period under study there was a significant increase in use of each of the examined procedures during hospitalization for AMI in both men and women. Increasing use of multiple procedures was also seen for each of the sexes. After controlling for a variety of demographic and clinical factors that might affect utilization rates, men were marginally more likely to undergo radionuclide ventriculography, and significantly more likely to undergo Holter monitoring, exercise treadmill testing, cardiac catheterization, and percutaneous transluminal coronary angioplasty than women. However, there were no gender differences in the use of coronary artery bypass grafting. On the other hand, men were significantly less likely to undergo echocardiography. The results of this multihospital, population-based study suggest sex differences in the use of several diagnostic and revascularization procedures during hospitalization for AMI. These differences may be attributed to physicians' practice patterns, although gender bias in the delivery of medical care cannot be excluded. Temporal trends in increased overall use of these procedures raise questions about cost-effectiveness that need to be further addressed.

Age Factors↗

Fusion between a novel Krüppel-like zinc finger gene and the retinoic acid receptor-alpha locus due to a variant t(11;17) translocation associated with acute promyelocytic leukaemia.

We have identified a unique case of acute promyelocytic leukaemia (APL) with a t(11;17) reciprocal chromosomal translocation involving the retinoic acid receptor alpha (RAR alpha) and a previously uncharacterized zinc finger gene. As a result of this translocation, mRNAs containing the coding sequences of the new gene, fused in-frame either upstream of the RAR alpha B region or downstream from the unique A1 and A2 regions of the two major RAR alpha isoforms, are expressed from the rearranged alleles. The above gene, which we have termed PLZF (for promyelocytic leukaemia zinc finger), encodes a potential transcription factor containing nine zinc finger motifs related to the Drosophila gap gene Krüppel and is expressed as at least two isoforms which differ in the sequences encoding the N-terminal region of the protein. Within the haematopoietic system the PLZF mRNAs were detected in the bone marrow, early myeloid cell lines and peripheral blood mononuclear cells, but not in lymphoid cell lines or tissues. In addition, the PLZF mRNA levels were down-regulated in NB-4 and HL-60 promyelocytic cell lines in response to retinoic acid-induced granulocytic differentiation and were very low in mature granulocytes. Our results demonstrate for the first time the association of a variant chromosomal translocation involving the RAR alpha gene with APL, further implicating the RAR alpha in leukaemogenesis and also suggesting an important role for PLZF as well as retinoic acid and its receptors in myeloid maturation.

Amino Acid Sequence↗

Accessory and alloantigen-presenting cell functions of A431 keratinocytes that stably express the B7 antigen.

Because keratinocytes are tolerogenic antigen-presenting cells (APC), we investigated the role of B7/BB-1 in reconstituting defective accessory cell (AC) and APC functions by such nonlymphoid cells. KC were induced to stably express B7/BB-1 by DNA-mediated gene transfection. This single-transformed B7/BB-1+ A431 cell line (but not control A431) functioned as AC for lectin-induced T-cell proliferation, as well as oxidative mitogenesis. This costimulation was dependent on B7/BB-1 expression since the monoclonal antibody BB-1 blocked costimulation of PHA mitogenesis by 75%. After the induction of class II MHC antigen expression by interferon-gamma, B7/BB-1+ KC but not control KC presented alloantigens to resting T-cells in the primary mixed lymphocyte reaction. These data indicate that the stable expression of B7/BB-1 antigen by KC reconstitutes defective AC and alloantigen-presenting activity. The lack of expression of such second signal by normal KC may be responsible for their ability to induce clonal anergy in vitro and in vivo.

Antigen-Presenting Cells↗

A chloroplast DNA deletion located in RNA polymerase gene rpoC2 in CMS lines of sorghum.

Fertile lines of sorghum (Sorghum bicolor) were shown to differ from cytoplasmic male sterile (CMS) lines by the presence of a 3.8 kb HindIII chloroplast DNA fragment in the former and a smaller (3.7 kb) fragment in the latter. DNA/DNA hybridization studies showed that these two fragments are homologous. Fertile plants from S. versicolor, S. almum, S. halepense, and Sorghastrum nutans (Yellow Indiangrass) also have the 3.8 kb fragment, and CMS lines studied containing A1, A2 and A3 cytoplasms have the 3.7 kb fragment. The size difference between the two fragments was localized to a 1.0 kb SacI-HindIII fragment by restriction mapping. A 165 bp deletion, which is flanked by a 51 bp tandem repeat, was identified in the CMS lines by sequencing the clones. Comparison of the two sequences with those from maize, rice, tobacco, spinach, pea, and liverwort revealed that the deleted sequence is located in the middle of the RNA polymerase beta" subunit encoded by the gene rpoC2. The amino acid sequence deleted in the CMS lines is in a monocot-specific region which contains two protein motifs that are characteristic of several transcriptional activation factors, namely, a leucine zipper motif and an acidic domain capable of forming an amphipathic alpha-helix. Further studies designed to determine whether or not the deletion is involved in CMS of sorghum are underway.

Amino Acid Sequence↗

Excretion of methylhippuric acids in urine of workers exposed to a xylene mixture: comparison among three xylene isomers and toluene.

The correlation between exposure to three xylene isomers and resulting urinary excretion of corresponding methylhippuric acid (MHA) isomers was studied among 175 Chinese workers of both sexes who had been predominantly exposed to xylenes (exposure to xylenes accounting for 70% or more of the total exposure on a ppm basis). Nonexposed controls (281 men and women) were also studied to define the background level of MHAs in urine. The solvent exposure of xylene-exposed workers during their workshift was monitored by diffusive sampling of breathing zone air, and MHAs in shift-end urine were determined by high-performance liquid chromatography. Regression analysis showed that the concentration of each MHA isomer correlated significantly with the time-weighted average intensity of exposure to the corresponding xylene isomer, and therefore the correlation between the sum of three xylene isomers in air and that of three MHA isomers in urine was also significant; the slope of the regression line was essentially the same among the three isomers. The calculated regression line suggested that the urinary MHA level after hypothetical exposure to xylenes at 100 ppm will be somewhat less than the proposed biological exposure index and biological tolerance value. Two social habits of smoking and drinking in combination suppressed the conversion of xylenes to MHAs in male workers.

Adult↗

A serum-free medium for hybridoma cell culture.

The effects of several different substances, including insulin, transferrin, ethanolamine, selenite and butyrate on the growth of murine hybridoma 2F7 cells, which secrete monoclonal antibody against small cell lung cancer, were investigated, and a serum-free medium SFM I was formulated. The effects of taurine, spermidine, progesterone and adenine on the cell growth were tested further on the basis of the medium SFM I, and a modified serum-free medium SFM II was established. On the basis of medium SFM II, the substitution tests of ferric citrate for transferrin were carried out, and it was found that transferrin could be replaced. The experiments suggested that the formulated serum-free medium was suitable for 2F7 cell growth and monoclonal antibody secretion, and thus facilitated subsequent purification of monoclonal antibody.

Animals↗

Cloning and improving the expression of Pichia stipitis xylose reductase gene in Saccharomyces cerevisiae.

The intact Pichia stipitis xylose reductase gene (XR) has been cloned and expressed in Saccharomyces cerevisiae. The possible further improvement of the expression of the Pichia gene in the new host was studied. To improve the expression of the XR gene in yeast (Saccharomyces cerevisiae), its 5'noncoding sequence containing the genetic elements for transcription and translation was systematically replaced by that from the yeast genes. It was found that the Pichia genetic signal for transcription of XR is more effective than the yeast TRP5 promoter, but is about half as effective as the yeast strong promoter of the alcohol dehydrogenase gene (ADC1). However, the nucleotide sequence immediately adjacent to the initiation codon of XR, which controls the translation of the gene product, seemed to be five times less effective than the corresponding sequence of the ADC1 gene. By totally replacing its 5'-noncoding sequence with that of the yeast ADC1 gene, the expression of XR in yeast was found to be nearly ten times higher. Furthermore, the cloned Pichia XR described in this article contains very little of its 3'-noncoding sequence. In order to study whether the 3'-noncoding sequence is important to its expression in S. cerevisiae, the intact 3'-noncoding sequences of the yeast xylulokinase gene was spliced to the 3' end of the PADC1-XR structural gene. This latter modification has resulted in a twofold further increase in the expression of the Pichia XR in yeast.

Alcohol Dehydrogenase↗

The rubber elongation factor of rubber trees (Hevea brasiliensis) is the major allergen in latex.

BACKGROUND: Allergy to latex-containing articles is becoming more and more important because it can result in unexpected life-threatening anaphylactic reactions in sensitized individuals. METHODS: A protein of 58 kd with an isoelectric point of 8.45 was purified from raw latex and from latex gloves and identified as the major allergen, completely blocking specific IgE antibodies in the serum of latex-sensitized subjects. The allergen is a noncovalent homotetramer molecule, in which the 14.6 kd monomer was identified, by amino acid composition and sequence homologies of tryptic peptides, to be the rubber elongation factor found in natural latex of the Malaysian rubber tree. RESULTS: Competitive immunoinhibition tests showed that the starch powder covering the finished gloves is the airborne carrier of the allergen, resulting in bronchial asthma on inhalation. The purified allergen can induce allergic reactions in the nanogram range. CONCLUSION: The identification of the allergen (Hev b I) may help to eliminate it during the production of latex-based articles in the future.

Allergens↗

FISH: a useful technique in the verification of clonality of random chromosome abnormalities.

Random chromosome abnormality is an important issue in clinical cytogenetics, especially in cancer cytogenetics. The significance of random abnormalities needs to be well defined. In the present study, ten patients with malignant hematologic disorders were analyzed by classical cytogenetic techniques and fluorescence in situ hybridization (FISH) procedures. Cytogenetic studies showed all ten patients to have a single cell with trisomy, i.e., +8, +8 (5 cases), +12, +15, +18, +20, and +21, respectively. FISH necessitated revision of the cytogenetic diagnosis and confirmed the clonality of these "random" abnormalities.

Adult↗

Protein-based artificial retinas.

Artificial retinas based on the light transducing photoelectric protein bacteriorhodopsin exhibit differential responsivity, edge enhancement and motion detection. Under appropriate conditions, these artificial receptors mimic the differential responsivity characteristic of mammalian photoreceptor cells. The use of orientated bacteriorhodopsin to generate the photoelectrical signal provides rapid responsivity, high quantum efficiency and offers the potential of directly coupling the protein response to charge-sensitive semiconductor arrays. The ability to manipulate the properties of the protein via chemical and genetic methods enhances design flexibility.

Animals↗

The influence of sex and diabetes mellitus on survival following acute myocardial infarction: a community-wide perspective.

The objective of this report was to examine the effects of sex and diabetic status on in-hospital mortality and 12 year survival following hospital discharge among 4109 patients hospitalized between 1974 and 1986 with acute myocardial infarction. Sixteen general hospitals in the Worcester, MA, standard metropolitan statistical area were included. The age-adjusted in-hospital case-fatality rate was significantly higher in diabetic women (23.3%) than in non-diabetic women (18.9%) (p < 0.05) while no significant difference was noted among men. Over a 12 year follow-up period, the relative risk of dying among diabetic men was 1.56 times that for non-diabetic men (95% CI, 1.43, 1.68). Diabetic women were 1.57 times as likely to die as non-diabetic women (95% CI, 1.45, 1.73). Among non-diabetic subjects, men had a 17% excess risk of death compared to women (95% CI, 1.09, 1.25). No significant difference in long-term mortality was noted among diabetic persons. Thus, the "female advantage" observed in the non-diabetic population was eliminated among the diabetic patients. Randomized clinical trials are needed in the diabetic population to identify specific therapies to reduce their increased risk of death.

Aged↗

Plasma microdialysis. A technique for continuous plasma sampling in freely moving rats.

Microdialysis provides a means of continuous plasma sampling without repeated blood drawing. We report here the use of a specially designed and constructed microdialysis probe to sample plasma glucose, protein, and luteinizing hormone from the right atrium of a freely moving rat. Our probe has a unique side-arm tubing, which can be used to draw blood for in vivo probe calibration and infuse heparin continuously to prevent blood clotting. Glucose recovery rate (18%) of the probe remained relatively stable in continuously heparinized rats over 24 hr, but it dropped rapidly to 1% in nonheparinized rats. The concentration of plasma glucose was significantly underestimated, when it was converted from the perfusate concentration based on the in vitro, but not in the in vivo, recovery rate of the probe. The recovery of plasma protein was only 0.07% initially and rapidly declined to about 0.03%. Luteinizing hormone was not detected in the perfusates from either normal or luteinizing hormone-releasing hormone-stimulated rats. These results indicate that continuous heparinization and in vivo probe calibration are essential for successful plasma microdialysis, and our current dialysis membrane can be used to sample non-protein-bound molecules in the plasma.

Animals↗

Differences in antigen-binding affinity caused by a single amino acid substitution in the variable region of the heavy chain.

Site-directed mutagenesis has been used to examine the importance of histidine-99 in the VH CDR3 region of a mouse/human chimeric anti-TAG72 antibody, cB72.3-1-3. The expression vectors mpSV2neo-EP1-V-m4-10C gamma 1, containing seven different mutant VH region fragments (Vm4-10) in association with the immunoglobulin enhancer (E), promoter (P1) and human genomic C gamma 1 region fragments, were transfected into a heavy chain loss mutant cell line B72.3 Mut(K), respectively. Mutant chimeric antibodies cB72.3m4-10 were purified from the transfectant supernates, and their binding affinities for the TAG72 antigen relative to that of the original cB72.3-1-3 antibody were compared. Substitution of histidine-99 by glutamine resulted in a higher affinity antibody (cB72.3m4) whereas substitution by isoleucine resulted in a lower affinity antibody (cB72.3m9). The binding affinity of these mutant antibodies varied nearly eight-fold. It was concluded that the residue at position 99 in the VH CDR3 region is in a 'contact' position in the B72.3/TAG72 antibody-combining site. The polar side-chains of glutamine and asparagine or the ionized side-chains of histidine, arginine or glutamic acid contribute to higher binding affinity, whereas the hydrophobic side-chains of isoleucine, leucine or phenylalanine resulted in a lower binding affinity for the TAG72 antigen.

Amino Acid Sequence↗