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Biomedical subjects

J Zhu

Publications and source records attributed to J Zhu.

At least 595 records · Page 33Linked to original sources
PubMed1996

Rad, a novel Ras-related GTPase, interacts with skeletal muscle beta-tropomyosin.

Rad, a prototypic member of a subfamily of Ras-related GTPases, is overexpressed in skeletal muscle of type II diabetic humans. By expression screening of mouse embryo and human skeletal muscle cDNA libraries, we found that Rad interacted with skeletal muscle beta-tropomyosin. In the mouse skeletal muscle cell line C2C12, this interaction was significantly increased by the calcium ionophore A23187. A23187 also caused a time- and concentration-dependent decrease in total cellular Rad with increased interaction between tropomyosin and Rad in the detergent-soluble fraction and the appearance of Rad in the cytoskeleton. In C2C12 cells stably overexpressing a putative dominant negative mutant of Rad (S105N), there was an increase in the amount of tropomyosin in Rad immunoprecipitates. In cells overexpressing wild type Rad, much of Rad was associated with the cytoskeleton and was no longer responsive to A23187. In far-Western blotting and guanine nucleotide saturation studies, GDP-Rad bound to tropomyosin far better than GTP-Rad. We conclude that Rad interacts with skeletal muscle beta-tropomyosin and the cytoskeleton in a guanine nucleotide-dependent manner. These data suggest that Rad may be involved in skeletal muscle motor function and cytoskeletal organization.

Animals↗
PubMed1996

Retinoic acid regulatory pathways, chromosomal translocations, and acute promyelocytic leukemia.

Retinoic acids (RAs) exert a broad range of physiologic actions during embryonic development and adult life. Two families of RA receptors, retinoic acid receptor (RAR) and retinoid X receptor (RXR), have been identified. The therapeutic effect of all-trans-RA (ATRA) in induction of remission for acute promyelocytic leukemia (APL) has largely been proved, and this has, over the past 10 years, greatly stimulated research on oncogenesis and RA-regulated differentiation pathways. In APL, one of the RAR genes, RARA, is fused to PML in the great majority of patients as a result of the chromosomal translocation t(15; 17). However, a small subset of APL patients have a different fusion gene, PLZF-RARA, resulting from the variant translocation t(11;17). A third translocation, t(5;17), in which the NPM gene is fused to RARA, has been described. Current data suggest that PML-RAR alpha and PLZF-RAR alpha fusion receptors may play an important role in the development of APL and that PML-RAR alpha could be the target of ATRA differentiation therapy. Characterization of the genes regulated by retinoic acid may open up new prospects for an understanding of the mechanisms of ATRA differentiation therapy for APL and may help to extend the concept of cancer-targeting treatment to other types of leukemias or solid tumors.

Adult↗
PubMed1996

Linkage mapping of microdissected clones from distal mouse chromosome 16.

A total of 38 unique segments generated by microdissection of mouse chromosome 16 (MMU16), sequence independent amplification (SIA) and cloning were sequentially mapped on the distal portion of the chromosome with two mouse backcross panels. Some reference markers from other sources were retyped in the panels and results integrated with those for our microdissected DNA segments. The clone map is most highly refined in its distal portion, which stretches from reference marker D16Mit71 to D16Mit5, and the highest density of clones is in the region defined by markers D16Mit5 and D16Mit141. This map on distal mouse chromosome 16 should be a useful tool for the mouse genome project and for studies of genes in the region.

Animals↗
PubMed1996

A common-lines based method for determining orientations for N > 3 particle projections simultaneously.

A method is proposed for determining the directions of projections. An arbitrary number of projections of unknown three-dimensional structure are simultaneously used as input. The method is based on common lines and uses a new discrepancy measure accounting for the uneven distribution of common lines in angular space. An application to the 70S Escherichia coli ribosome data obtained from an energy-filtering electron microscope is described.

Algorithms↗
PubMed1996

Injury induces rapid changes in hepatocyte nuclear factor-1: DNA binding.

BACKGROUND: Transcriptional regulation in the liver plays a critical role in mediating the acute phase response to injury. The molecular mechanisms driving these transcriptional events, however, are poorly defined in vivo. The liver-specific transcription factor hepatocyte nuclear factor (HNF)-1 binds to the 5' upstream region of many acute phase genes. To explore the connection between injury and transcriptional regulatory mechanisms, we investigated the effect of injury on HNF-1 binding activity. METHODS: Liver nuclear extracts were prepared from animals after burn or anesthetized sham burn injury. HNF-1 binding activity, affinity, and off rate were assessed by electrophoretic mobility shift analysis. RESULTS: HNF-1 binding activity decreased by 28% 1 1/2 hours after injury. The dissociation constant for HNF-1 increased from 0.6 nm to 11.8 nm at 1 1/2 hours after burn injury partly because of an increase in off rate for the HNF-1: DNA complex. CONCLUSIONS: Burn injury leads to a significant decrease in HNF-1 binding activity as a result of decreased affinity of HNF-1 for DNA. These injury-induced alterations in binding of a liver-specific transcription factor for its DNA binding site represent a mechanism for rapidly modulating acute phase gene transcription in vivo.

Animals↗
PubMed1996

Mixed model approaches for diallel analysis based on a bio-model.

A MINQUE(1) procedure, which is minimum norm quadratic unbiased estimation (MINQUE) method with 1 for all the prior values, is suggested for estimating variance and covariance components in a bio-model for diallel crosses. Unbiasedness and efficiency of estimation were compared for MINQUE(1), restricted maximum likelihood (REML) and MINQUE theta which has parameter values for the prior values. MINQUE(1) is almost as efficient as MINQUE theta for unbiased estimation of genetic variance and covariance components. The bio-model is efficient and robust for estimating variance and covariance components for maternal and paternal effects as well as for nuclear effects. A procedure of adjusted unbiased prediction (AUP) is proposed for predicting random genetic effects in the bio-model. The jack-knife procedure is suggested for estimation of sampling variances of estimated variance and covariance components and of predicted genetic effects. Worked examples are given for estimation of variance and covariance components and for prediction of genetic merits.

Alleles↗
PubMed1996

Ultraviolet B irradiation and cytomegalovirus infection synergize to induce the cell surface expression of 52-kD/Ro antigen.

Cultured human fibroblasts (MRC-5) have been previously demonstrated to express calreticulin, but not Ro autoantigen, on their surface after human cytomegalovirus (CMV) infection. The present study addresses the question of whether other stimuli, alone or in combination with CMV, can induce the surface expression of Ro autoantigens on human fibroblasts. Using a fixed-cell ELISA to detect autoantigen expression, a synergistic effect between ultraviolet B (UVB) exposure and CMV infection on the surface expression of 52-kD/Ro antigen, but not 60-kD/Ro or calreticulin, was observed. The enhanced expression of 52-kD/Ro antigen was significant and specific, compared with untreated cells, cells infected with CMV alone or irradiated with UVB only, and cells subjected to other treatments, such as low pH. Immunofluorescence studies confirmed these findings and indicated that cells expressed 52-kD/Ro protein on their surface at 24 h after a combined UVB and CMV treatment. These studies provide evidence that synergy between UVB irradiation and CMV infection may play a role in the induction of cell surface expression of the human autoantigen, 52-kD/Ro.

Amino Acid Sequence↗
PubMed1996

Functional assessment of peripheral nerve injury and repair.

Based on 191 follow-ups of patients with peripheral nerve injury and repair, the authors suggest that a reasonable assessment should consist of motor, sensory, and autonomic nerve indices. It is also suggested that a method of functional assessment about the autonomic nerve should be included. The method of evaluating motor function should be selected according to the site of the nerve injury. Lovett's method was adopted for nerve injury at the wrist and lower third of the forearm, as well as the British Medical Research Council (BMRC) method for nerve injury at the upper forearm or other nerves. Standards and grades of the BMRC should be raised somewhat, in order to compare more consistently with the results obtained using the method of Lovett; then both can be correlated satisfactorily.

Adult↗
PubMed1996

Genetic variation in the strongly canalized sex pheromone communication system of the European corn borer, Ostrinia nubilalis Hübner (Lepidoptera; Pyralidae).

The major difference in pheromone production between the so-called E and Z strains of the European corn borer Ostrinia nubilalis is controlled by two alleles at a single autosomal locus. E-strain females produce an (E)-11-tetradecenyl acetate pheromone with 1-3% of the Z isomer, whereas Z-strain females produce the opposite blend. In laboratory-reared insects we found that F1 females produced, on average, a 71:29 E/Z ratio, but the distribution was clearly bimodal. The variability in pheromone blend produced by heterozygous females could be explained by the existence of two different alleles in the Z strain which in combination with the E-strain allele for the major production locus cause the production of a component mixture either high or low in the F isomer. In addition, evidence was found for an independently inherited factor, existing in the E strain, with a dominant effect on the amount of E isomer produced by females homozygous for Z-alleles at the major production locus. Thus, the low variability normally found in the pheromone mixture produced by O. nubilalis and other moth females may, by canalization, hide a considerable amount of underlying genetic variation.

Animals↗
PubMed1996

Shanghai trial of nifedipine in the elderly (STONE).

OBJECTIVE: To assess the effectiveness of nifedipine treatment in elderly hypertensives. METHODS: A single-blind trial was conducted under the direction of the Shanghai Institute of Hypertension in 1632 subjects aged 60-79 years alternatively allocated to either nifedipine or placebo after a 4-week placebo run-in period between 1987 and 1990 with mean follow-up of 30 months. Clinical events and risk modification were analysed in collaboration with the University of Montreal. Seventy-four patients with severe hypertension were reallocated to active nifedipine treatment after placebo run-in. RESULTS: Cox's proportional hazards model accounting for covariates demonstrated a highly significant decrease in the probability of events: 'original treatment assignment' analysis indicated that 77 events occurred in the placebo and 32 in the nifedipine group. Similar significances were achieved with 'actual treatment' or 'changes excluded' (excluding reallocated subjects) analyses. A significant reduction in relative risk was observed for strokes and severe arrhythmia with an overall decrease from 1.0 to 0.41 (95% confidence interval 0.27-0.61). CONCLUSION: Nifedipine treatment diminished the number of severe clinical outcomes in elderly hypertensives significantly.

Aged↗
PubMed1996

The efficacy of intrathecal injection of sufentanil using a microspinal catheter for labor analgesia.

Intrathecal sufentanil can provide labor analgesia. We investigated the efficacy of multiple injections and the maternal and neonatal effects of intrathecal sufentanil during labor. Seventeen healthy women in active labor received multiple injections of intrathecal sufentanil of 5 micrograms each through microspinal catheters. Overall maternal satisfaction of analgesia was quantified using 10 cm visual analogue scales and side effects were evaluated. Neonatal outcome was also determined. Onset of analgesia was less than 5 min after the first injection and lasted approximately 148 min. Tolerance developed for the successive injections. The mean onset times were 12.9 and 20.1 min and the durations were 76.6 and 33.9 min for the second and third injections, respectively (P < 0.05). Failure to obtain analgesia developed in all patients after the forth injection. No motor blockade was observed in any of the patients. Mild or moderate pruritus developed in 88% of the patients. Mean systolic blood pressure decreased by a maximum of 11.3% at 30 min and up to 90 min (P < 0.05) after the first injection; three patients required ephedrine treatment. No significant hemodynamic changes were observed after subsequent injections. Five patients experienced transient decrease in sensation. Neonatal status, as evaluated by Apgar scores, Neurological Adaptive Capacity Scores (NACS), fetal heart rate (FHR), and umbilical cord acid-base status, were within normal limits. Results from our study suggest that multiple small doses of sufentanil administered intrathecally provided satisfactory analgesia for parturients with short duration of labor since acute tolerance developed with multiple injections. High incidence of mild or moderate pruritus was observed during the study. Close attention should be given to hemodynamically unstable patients when this technique is applied.

Adult↗
PubMed1996

Pleiotropic phenotypes caused by genetic ablation of the receiver module of the Agrobacterium tumefaciens VirA protein.

The VirA protein of Agrobacterium tumefaciens is a transmembrane sensory kinase that phosphorylates the VirG response regulator in response to chemical signals released from plant wound sites. VirA contains both a two-component kinase module and, at its carboxyl terminus, a receiver module. We previously provided evidence that this receiver module inhibited the activity of the kinase module and that inhibition might be neutralized by phosphorylation. In this report, we provide additional evidence for this model by showing that overexpressing the receiver module in trans can restore low-level basal activity to a VirA mutant protein lacking the receiver module. We also show that ablation of the receiver module restores activity to the inactive VirA (delta324-413) mutant, which has a deletion within a region designated the linker module. This indicates that deletion of the linker module does not denature the kinase module, but rather locks the kinase into a phenotypically inactive conformation, and that this inactivity requires the receiver module. These data provide genetic evidence that the kinase and receiver modules of VirA attain their native conformations autonomously. The receiver module also restricts the variety of phenolic compounds that have stimulatory activity, since removal of this module causes otherwise nonstimulatory phenolic compounds such as 4-hydroxyacetophenone to stimulate vir gene expression.

Agrobacterium tumefaciens↗
PubMed1996

c-ABL tyrosine kinase activity is regulated by association with a novel SH3-domain-binding protein.

The c-ABL tyrosine kinase is activated following either the loss or mutation of its Src homology domain 3 (SH3), resulting in both increased autophosphorylation and phosphorylation of cellular substrates and cellular transformation. This suggests that the SH3 domain negatively regulates c-ABL kinase activity. For several reasons this regulation is thought to involve a cellular protein that binds to the SH3 domain. Hyperexpression of c-ABL results in an activation of its kinase, the kinase activity of purified c-ABL protein in the absence of cellular proteins is independent of either the presence or absence of a SH3 domain, and point mutations and deletions within the SH3 domain are sufficient to activate c-ABL transforming ability. To identify proteins that interact with the c-ABL SH3 domain, we screened a cDNA library by the yeast two-hybrid system, using the c-ABL SH3SH2 domains as bait. We identified a novel protein, AAP1 (ABL-associated protein 1), that associates with these c-ABL domains and fails to bind to the SH3 domain in the activated oncoprotein BCRABL. Kinase experiments demonstrated that in the presence of AAP1, the ability of c-ABL to phosphorylate either glutathione S-transferase-CRK or enolase was inhibited. In contrast, AAP1 had little effect on the phosphorylation of glutathione S-transferase-CRK by the activated ABL oncoproteins v-ABL and BCRABL. We conclude that AAP1 inhibits c-ABL tyrosine kinase activity but has little effect on the tyrosine kinase activities of oncogenic BCRABL or v-ABL protein and propose that AAP1 functions as a trans regulator of c-ABL kinase. Our data also indicate that loss of susceptibility to AAP1 regulation correlates with oncogenicity of the activated forms of c-ABL.

Amino Acid Sequence↗
PubMed1996

Topoisomerase I involvement in illegitimate recombination in Saccharomyces cerevisiae.

Chromosome aberrations may cause cancer and many heritable diseases. Topoisomerase I has been suspected of causing chromosome aberrations by mediating illegitimate recombination. The effects of deletion and of overexpression of the topoisomerase I gene on illegitimate recombination in the yeast Saccharomyces cerevisiae have been studied. Yeast transformations were carried out with DNA fragments that did not have any homology to the genomic DNA. The frequency of illegitimate integration was 6- to 12-fold increased in a strain overexpressing topoisomerase I compared with that in isogenic control strains. Hot spot sequences [(G/C)(A/T)T] for illegitimate integration target sites accounted for the majority of the additional events after overexpression of topoisomerase I. These hot spot sequences correspond to sequences previously identified in vitro as topoisomerase I preferred cleavage sequences in other organisms. Furthermore, such hot spot sequences were found in 44% of the integration events present in the TOP1 wild-type strain and at a significantly lower frequency in the top1delta strain. Our results provide in vivo evidence that a general eukaryotic topoisomerase I enzyme nicks DNA and ligates nonhomologous ends, leading to illegitimate recombination.

Base Sequence↗
PubMed1996

Immunologic alterations in bleomycin-treated mice: role of pulmonary fibrosis in the modulation of immune responses.

Among the side effects of bleomycin (BLM), a drug frequently used in the treatment of lymphomas and squamous-cell carcinomas, is pneumonitis with pulmonary fibrosis. The most prominent biochemical lesion associated with pulmonary fibrosis, a chronic debilitating and sometimes fatal disease, is an increase in the levels of collagen in the lung parenchyma. The mechanisms involved in the induction of this disease are still unclear, although results have suggested that the development of fibrosis may be immunologically mediated. There have, however, been no reports in the literature on the frequency and function of lymphocytes in the regional and systemic lymphoid tissues in BLM-induced pulmonary fibrosis. We therefore conducted a study, in which we inoculated C57Bl/6 mice intratracheally with BLM or saline, and tested the animals' lymphoid cells for various cell-mediated and humoral immune responses. The results indicated an increase in the number of lymphocytes in the lung-associated hilar lymph nodes, whereas the number of splenic lymphocytes was reduced as compared with control mice. Moreover, there was a significant inhibition of the antibody response to sheep erythrocytes in both the spleen and hilar lymph nodes of BLM-treated mice. Inhibition of the immune system appeared to be associated with the development of pulmonary fibrosis, and not to result from BLM toxicity, since the immune response of mice was not inhibited when they were injected with an identical dose of BLM under conditions that did not cause pulmonary fibrosis. Moreover, inhibition of splenic antibody responses was also observed in a hapten-induced model of pulmonary fibrosis, providing additional evidence that the induction of fibrosis and not the chemical toxicity of BLM was responsible for the modulation of immune responses.

Animals↗