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Biomedical subjects

M Zhang

Publications and source records attributed to M Zhang.

At least 793 records · Page 44Linked to original sources

Cytochrome b5 Is Essential for Cytochrome P450 6D1-Mediated Cypermethrin Resistance in LPR House Flies

Cytochrome P450 monooxygenase-mediated detoxification is a very important mechanism of resistance to insecticides. In the LPR strain of house fly, the major mechanism of resistance to pyrethroids is monooxygenase-mediated metabolism due to the overexpression of cytochrome P450 6D1 (CYP6D1). Although the role of CYP6D1 in pyrethroid resistance has been demonstrated, there is no information as to whether cytochrome b5 is involved in this reaction and what the major CYP6D1-specific metabolite is. Using a cytochrome b5 antiserum we demonstrate that cytochrome b5 is required for the elevated level of CYP6D1-mediated cypermethrin metabolism observed in microsomes from the resistant LPR strain compared to a susceptible strain. Therefore, cytochrome b5 is directly involved in this monooxygenase-mediated resistance. NADH has no significant effect on this metabolism, suggesting that in vitro the second electron source for CYP6D1 is NADPH when cypermethrin is the substrate. Using GC-MS, the primary CYP6D1 specific metabolite formed in vitro was identified as 4'-OH cypermethrin.

Journal Article↗

Epidermal growth factor modulates cell attachment to hyaluronic acid by the cell surface glycoprotein CD44.

Cell adhesion to and migration through extracellular matrices (ECM) are critical events in tumor invasion and metastasis. Previous work by us had demonstrated that signaling of epidermal growth factor receptor (EGFR) confers an oncogenic phenotype on NR6 cells and that these cells when transfected with holo EGFR demonstrate greater motility and invasiveness than cells carrying a carboxy-terminal truncated EGFR. Recently, a cell surface glycoprotein, CD44, has been implicated in cell-ECM adhesion involved in tumor cell migration, signal transduction, and metastasis. We investigated whether EGF regulates cellular interactions with ECM components, and in particular, hyaluronate, by modulating CD44 expression. In vitro cell attachment assays on hyaluronate-coated plates demonstrated similar basal level of binding (approximately 33%) for murine NR6 parental cells devoid of endogenous EGFR (P) or expressing wild-type EGFR (WT), while a time-dependent increase in binding was observed in WT cells stimulated with EGF. Additionally, utilizing monoclonal antibody blocking assays, CD44, but not EGFR, was shown to be directly involved in this attachment. Both WT and P cells possessed equivalent 95 kDa bands on immunoblots, corresponding to CD44. The existence of CD44 mRNA was verified by RT-PCR using synthetic oligonucleotides in which a 1.1 kb cDNA was detected in both cell lines and confirmed by DNA sequencing. After 24-h exposure to exogenous EGF, an increase in CD44 protein and mRNA expression was found in WT cells, but not in P cells, supporting the contention that a functional EGFR signaling pathway is required for CD44 regulation. Thus, EGF stimulates cell binding to hyaluronate in vitro by regulating CD44 expression.

Animals↗

Intraoperative use of mitomycin in trabeculectomy.

Mitomycin (0.2 mg/ml) was applied intraoperatively to 26 glaucomatous patients (33 eyes) during conventional trabeculectomy procedure. Most of them were considered to be at high risk of surgical failure. The conjunctival flap was fornix-based in 9 patients (11 eyes). The success rate was 84.8% without any serious side effect.

Female↗

Some novel N-fatty acyl derivatives of a microbial galactosaminan.

Novel seven N-fatty acyl derivatives (degree of substitution 0.78-0.96) of a microbial galactosaminan were prepared in 59-79% yields by its reaction with fatty acid anhydrides in aqueous acetic acid-methanol. N-Acetyl and N-propionyl derivatives were soluble in water, aqueous 2% sodium hydroxide, and aqueous 2% acetic acid, but N-higher fatty acyl (> C6) derivatives were insoluble. Gel was not formed in these reactions.

Acylation↗

Purification and characterization of cytochrome b5 reductase from the house fly, Musca domestica.

NADH-cytochrome b5 reductase (b5R) from the house fly was purified through solubilization of microsomes with Triton X-100 followed by DEAE, carboxylmethyl and 5'-ADP affinity column chromatography. Yields of 9% with a 320-fold increase in NADH-ferricyanide reductase specific activity and 2% with a 76-fold increase in NADH-cytochrome b5R specific activity were obtained. Two forms of b5R, a major form with the apparent molecular mass of 31 kDa and a minor form of 33 kDa, were obtained. Both forms of purified b5R could reduce cytochrome b5 and both could use NADH or NADPH as an electron donor, although NADH was more efficient. Kinetics of the b5R activities were also studied. The 31-kDa b5R consists of integral of 291 amino acids with the NH2-terminal sequence of Thr-Ala-Arg-Leu-Arg-Thr-Leu-Ile-Asp-Ala. An antiserum developed against the 31-kDa b5R recognized both forms of b5R. Using this polyclonal antiserum as a probe, immunologically reactive proteins were found in microsomes from five species of Diptera, mouse and rat liver but not in spider mites nor insects from other orders.

Amino Acid Sequence↗

Intensity-dependent peak shift in cochlear transfer functions at the cellular level, its elimination by sound exposure, and its possible underlying mechanisms.

Our systematic study of cochlear transfer functions has confirmed earlier results that, in a normal cochlea, the cochlear AC responses at any given cochlear location do not have a fixed best frequency at which the response is maximal. The best frequency depends on sound intensity, shifting to lower frequencies as the intensity is increased. This phenomenon may account for the so called 'half-octave shift' of maximum cochlear damage relative to the frequency of the damaging sound observed in studies of auditory noise exposure. Our experimental results combined with the results of others and with our model studies bring us to the conclusion that, at low to moderate sound intensities, the dependence of the best frequency on sound intensity is due to an effect of the active feedback, which decreases as sound intensity increases. Consequently, the feedback, when present, must shift the best frequency upward.

Acoustic Stimulation↗

Frictional action at lower limb/prosthetic socket interface.

The frictional action at stump/socket interface is discussed by a simplified model and finite element model analyses and clinical pressure measurements. The friction applied to the stump skin produces stresses within tissue and these stresses may damage the tissues and affect their normal functions. The combination of normal and shear stresses is considered to be a critical factor leading to amputee's discomfort and tissue damage. However, friction at the stump/socket interface has a beneficial action. A simplified residual limb model and a finite element model using real geometry have been developed to analyse the support action of friction. Both results show that the friction plays a critical role both in supporting the load of the amputee's body during the support phase of the gait cycle and in preventing the prosthesis from slipping off the limb during swing phase. Pressure at the below-knee socket during walking were measured with conditions of different friction. The results reveal that a larger pressures was produced at the lubricated interface than at the normal interface. A proper choice of coefficient of friction will balance the requirements of relief of load stress and reduction of slip with the general ability to support loads.

Amputation Stumps↗

Electron microscopic observations of the lymphatic vessels of the mammalian testis.

This paper is a report on preliminary investigations into the morphology of elastic fibers surrounding the lymphatic vessels of the testis, and it includes a description of the three-dimensional architecture of the lymph vessels and elastic fibers of the mammalian testis obtained by indirect injection of glutaraldehyde and Mercox. Different types of filaments and blind ends were observed. The filaments repeatedly divide and fuse to form the reticular networks. These networks provide a specific microenvironment for the lymphatic vascular system under different physiological and pathological conditions.

Animals↗

Fibroblast growth factor receptor 2 mutations in Beare-Stevenson cutis gyrata syndrome.

Beare-Stevenson cutis gyrata syndrome (MIM 123790) is an autosomal dominant condition characterized by the furrowed skin disorder of cutis gyrata, acanthosis nigricans, craniosynostosis, craniofacial dysmorphism, digital anomalies, umbilical and anogenital abnormalities and early death. Many of these features are characteristic of some of the autosomal dominant craniosynostotic syndromes. Mutations in Crouzon, Jackson-Weiss, Pfeiffer and Apert syndromes have been reported in the FGFR2 extracellular domain. In Crouzon syndrome patients with acanthosis nigricans, a recurrent mutation occurs in the transmembrane domain of FGFR3. We now describe the detection of FGFR2 mutations in the Beare-Stevenson cutis gyrata syndrome. In three sporatic cases, a novel missense mutation was found causing an amino acid to be replaced by a cysteine; two had the identical Ty375Cys mutation in the transmembrane domain and one had a Ser372Cys mutation in the carboxyl-terminal end of the linker region between the immunoglobulin III-like (Iglll) and transmembrane domains. In two patients, neither of these mutations were found suggesting further genetic heterogeneity.

Abnormalities, Multiple↗

Effects of hepatic stimulator substance, herbal medicine, selenium/vitamin E, and ciprofloxacin on cirrhosis in the rat.

BACKGROUND & AIMS: Cirrhosis is a potentially lethal condition for which there is no proven effective therapy. The aim of this study was to compare the effects of hepatic stimulator substance, traditional Chinese herbal medicine, selenium plus vitamin E, and ciprofloxacin treatment on biochemical and histological features of fibrosis in rats with carbon tetrachloride (CCl4)/ethanol-induced cirrhosis. METHODS: One hundred twenty adult Wistar rats were divided into six study groups (20 rats/group): healthy controls, CCl4/ethanol-injured rats left untreated, and CCl4/ethanol-injured rats treated for 4 weeks with either hepatic stimulator substance, traditional Chinese herbal medicine, a combination of selenium plus vitamin E, or ciprofloxacin. After the 4-week treatment, rats were killed and the following parameters of hepatic fibrosis were determined: hepatic hydroxyproline and proline levels, serum hyaluronic acid concentrations, and histological staining of hepatic tissue. RESULTS: Hepatic fibrosis was significantly improved in all four treated groups compared with the untreated CCl4/ethanol-injured controls. Improvements were most striking in the groups treated with traditional Chinese herbal medicine and ciprofloxacin. CONCLUSIONS: The data indicate that hepatic stimulator substance, traditional Chinese herbal medicine, selenium plus vitamin E, and ciprofloxacin significantly decrease the amount of hepatic fibrosis caused by CCl4/ethanol injury in rats.

Animals↗

A finite element analysis of the load transfer between an above-knee residual limb and its prosthetic socket--roles of interface friction and distal-end boundary conditions.

A nonlinear finite element model was developed to investigate the manner of the load transfer between the above-knee residual limb and its prosthetic socket. The model was two-dimensional (2-D) with consideration of nonlinear boundary conditions and large deformation. Interface elements were used to simulate the friction/slip conditions between skin and the socket. Different distal-end conditions, including air cushion distal-end loading, were simulated to explore their influences on the load transfer.

Amputation Stumps↗

Development of an arabinose-fermenting Zymomonas mobilis strain by metabolic pathway engineering.

The substrate fermentation range of the ethanologenic bacterium Zymomonas mobilis was expanded to include the pentose sugar, L-arabinose, which is commonly found in agricultural residues and other lignocellulosic biomass. Five genes, encoding L-arabinose isomerase (araA), L-ribulokinase (araB), L-ribulose-5-phosphate-4-epimerase (araD), transaldolase (talB), and transketolase (tktA), were isolated from Escherichia coli and introduced into Z. mobilis under the control of constitutive promoters that permitted their expression even in the presence of glucose. The engineered strain grew on and produced ethanol from L-arabinose as a sole C source at 98% of the maximum theoretical ethanol yield, based on the amount of consumed sugar. This indicates that arabinose was metabolized almost exclusively to ethanol as the sole fermentation product, with little by-product formation. Although no diauxic growth pattern was evident, the microorganism preferentially utilized glucose before arabinose, apparently reflecting the specificity of the indigenous facilitated diffusion transport system. This microorganism may be useful, along with the previously developed xylose-fermenting Z. mobilis (M. Zhang, C. Eddy, K. Deanda, M. Finkelstein, and S. Picataggio, Science 267:240-243, 1995), in a mixed culture for efficient fermentation of the predominant hexose and pentose sugars in agricultural residues and other lignocellulosic feedstocks to ethanol.

Arabinose↗

Interleukin-10 downregulates Mycobacterium tuberculosis-induced Th1 responses and CTLA-4 expression.

To characterize the mechanism by which interleukin 10 (IL-10) inhibits Th1 responses to intracellular pathogens, we evaluated the interaction between IL-10 and Mycobacterium tuberculosis-induced gamma interferon (IFN-gamma) production by peripheral blood mononuclear cells from persons across the spectrum of tuberculous infection. M. tuberculosis-induced IFN-gamma production was highest in healthy tuberculin reactors, intermediate in human immunodeficiency virus (HIV)-negative tuberculosis patients, and lowest in HIV-infected tuberculosis patients. Neutralizing antibodies to IL-10 increased IFN-gamma production in HIV-infected and HIV-negative tuberculosis patients by enhancing monocyte IL-12 production. Expression of the T-cell-costimulatory molecule CTLA-4 was depressed in M. tuberculosis-stimulated peripheral blood mononuclear cells from tuberculosis patients, and anti-IL-10 and Il-12 upregulated expression of CTLA-4. These findings provide evidence that intracellular pathogens can inhibit Th1 responses and downregulate expression of specific costimulatory molecules.

Abatacept↗

Absence of a prominent Th2 cytokine response in human tuberculosis.

Depressed Th1 responses are a prominent feature of human tuberculosis, but an enhanced Th2 response has not been detected in peripheral blood T cells stimulated in vitro with Mycobacterium tuberculosis. In disease due to Mycobacterium leprae, Th2 cells predominate in tissue lesions of patients with extensive disease but are absent from peripheral blood. To determine if Th2 cells are present in tissue lesions of tuberculosis patients, we evaluated patterns of cytokine expression in lymph nodes from tuberculosis patients with or without human immunodeficiency virus infection and in controls without tuberculosis. Gamma interferon and interleukin-10 (IL-10) mRNA expression in tuberculosis patients with or without human immunodeficiency virus infection was high, whereas IL-4 expression in the same patients was low. Immunolabeling studies showed that macrophage production of IL-12 was increased in lymph nodes from tuberculosis patients, that gamma interferon was produced by T cells, and that IL-10 was produced by macrophages rather than Th2 cells. These results indicate that Th2 responses are not enhanced either systemically or at the site of disease in human tuberculosis.

HIV Infections↗

Protein kinase C modulation of cardiomyocyte angiotensin II and vasopressin receptor desensitization.

Angiotensin II (Ang II) and arginine vasopressin (AVP) increased intracellular free Ca2+ concentration [Ca2+]i and/or the [Ca2+]i transient rate (CaTR) in cultured neonatal rat cardiomyocytes. These agents increased membrane-bound protein kinase C (PKC) with peak activity at 5 and 10 minutes, respectively. Two-minute exposure to Ang II produced homologous desensitization to a repeated stimulation with Ang II and heterologous desensitization to AVP. Two-minute exposure to AVP also produced homologous desensitization to AVP but not heterologous desensitization to Ang II. When the AVP exposure time was increased from 2 to 10 minutes coincident with maximal AVP-mediated PKC activation, heterologous desensitization to Ang II was also observed. Acute activation (15 minutes) of PKC by phorbol 12-myristate 13-acetate (PMA) blocked responsiveness to both Ang II and AVP. When PKC activation was inhibited by 20 hours of prior exposure to PMA, as confirmed by PKC assay, homologous desensitization of Ang II still occurred, confirming an alternative mechanism(s) for homologous desensitization in the cardiomyocytes. In contrast, 20-hour PMA suppression of PKC markedly diminished the ability of the cardiomyocytes to exhibit AVP-mediated heterologous desensitization for Ang II. These data indicate that PKC activation plays a primary role in mediating vasopressin V1 receptor-induced heterologous desensitization of the Ang II receptor and participates in a hierarchy of two or more kinase systems mediating homologous desensitization of the Ang II receptor in cardiomyocytes.

Analysis of Variance↗

The homeobox gene GLABRA2 is required for position-dependent cell differentiation in the root epidermis of Arabidopsis thaliana.

The role of the Arabidopsis homeobox gene, GLABRA 2 (GL2), in the development of the root epidermis has been investigated. The wild-type epidermis is composed of two cell types, root-hair cells and hairless cells, which are located at distinct positions within the root, implying that positional cues control cell-type differentiation. During the development of the root epidermis, the differentiating root-hair cells (trichoblasts) and the differentiating hairless cells (atrichoblasts) can be distinguished by their cytoplasmic density, vacuole formation, and extent of elongation. We have determined that mutations in the GL2 gene specifically alter the differentiation of the hairless epidermal cells, causing them to produce root hairs, which indicates that GL2 affects epidermal cell identity. Detailed analyses of these differentiating cells showed that, despite forming root hairs, they are similar to atrichoblasts of the wild type in their cytoplasmic characteristics, timing of vacuolation, and extent of cell elongation. The results of in situ nucleic acid hybridization and GUS reporter gene fusion studies show that the GL2 gene is preferentially expressed in the differentiating hairless cells of the wild type, during a period in which epidermal cell identity is believed to be established. These results indicate that the GL2 homeodomain protein normally regulates a subset of the processes that occur during the differentiation of hairless epidermal cells of the Arabidopsis root. Specifically, GL2 appears to act in a cell-position-dependent manner to suppress hair formation in differentiating hairless cells.

Arabidopsis↗

Physicians contracting with managed care, Medicare, and Medicaid.

Managed care has become an ever important form of health care delivery, yet little is known about the characteristics of providers contracting with managed care organizations. Using data from a national survey of 4,729 physicians, we find that market conditions, specialty, and sociodemographics all affect a physician's decision to contract with managed care. Moreover, most of these characteristics also have similar effects on a physician's decisions to participate in Medicare and Medicaid. The latter result implies that physicians view managed care, Medicare, and Medicaid similarly when making contracting decisions, although financial incentives in these insurance programs are different.

Age Factors↗