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Biomedical subjects

Z Zhong

Publications and source records attributed to Z Zhong.

At least 91 records · Page 5Linked to original sources
PubMed1998

Stimulation of oxygen uptake by prostaglandin E2 is oxygen dependent in perfused rat liver.

The aim of this study was to determine if the effect of prostaglandin E2 (PGE2) on hepatic oxygen uptake was affected by oxygen tension. Livers from fed female Sprague-Dawley rats were perfused at normal or high flow rates (4 or 8 ml . g-1 . min-1) to vary local oxygen tension within the liver lobule. During perfusion at normal flow rates, PGE2 (5 microM) infusion increased oxygen uptake by about 50 micromol . g-1 . h-1; however, when livers were perfused at high flow rates, the increase was nearly twice as large. Simultaneously, glucose output was increased rapidly by about 50%, whereas glycolysis was decreased about 60%. When flow rate was held constant, increases in oxygen uptake due to PGE2 were proportional to oxygen delivery. Infusion of PGE2 into livers perfused at normal flow rates increased state 3 rates of oxygen uptake of subsequently isolated mitochondria by about 25%; however, rates were increased 50-75% in mitochondria isolated from livers perfused at high flow rates. Thus it is concluded that PGE2 stimulates oxygen uptake via mechanisms regulated by oxygen tension in perfused rat liver. High flow rates also increased basal rates of oxygen uptake: this increase was prevented by inactivation of Kupffer cells with GdCl3. In addition, conditioned medium from Kupffer cells incubated at high oxygen tension (75% oxygen) stimulated oxygen uptake of isolated parenchymal cells by >30% and elevated PGE2 production about twofold compared with Kupffer cells exposed to normal air-saturated buffer (21% oxygen). These effects were blocked completely by both indomethacin and nisoldipine. These data support the hypothesis that oxygen stimulates Kupffer cells to release mediators such as PGE2 which elevate oxygen consumption in parenchymal cells, possibly by mechanisms involving cyclooxygenase and calcium channels.

Animals↗
PubMed1998

Cyclosporin A increases hypoxia and free radical production in rat kidneys: prevention by dietary glycine.

The major side effect of cyclosporin A is severe nephrotoxicity. It is likely that cyclosporin A causes vasoconstriction leading to hypoxia-reperfusion injury; therefore, these experiments were designed to attempt to obtain physical evidence for hypoxia and free radical production in kidney following cyclosporin A. Rats were treated daily with cyclosporin A (25 mg/kg ig) for 5 days, and pimonidazole, a hypoxia marker, was injected 2 h after the last dose of cyclosporin A. A dose of alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) was injected 3 h after cyclosporin A to trap free radicals. Cyclosporin A doubled serum creatinine and decreased glomerular filtration rates by 65% as expected. Pimonidazole adduct binding in the kidney was increased nearly threefold by cyclosporin A, providing physical evidence for tissue hypoxia. Moreover, cyclosporin A increased 4-POBN/radical adducts nearly sixfold in the urine but did not alter levels in the serum. Glycine, which causes vasodilatation and prevents cyclosporin A toxicity, minimized hypoxia and blocked free radical production; however, it did not alter cyclosporin A blood levels. These results demonstrate for the first time that cyclosporin A causes hypoxia and increases production of a new free radical species exclusively in the kidney. Therefore, it is concluded that cyclosporin A causes renal injury by mechanisms involving hypoxia-reoxygenation, effects which can be prevented effectively by dietary glycine.

Animals↗
PubMed1998

Medical applications of diffraction enhanced imaging.

We have developed a new X-ray imaging technique, diffraction enhanced imaging (DEI), which can be used to independently visualize the refraction and absorption of an object. The images are almost completely scatter-free, allowing enhanced contrast of objects that develop small angle scattering. The combination of these properties has resulted in images of mammography phantoms and tissues that have dramatically improved contrast over standard imaging techniques. This technique potentially is applicable to mammography and other fields of medical X-ray imaging and to radiology in general, as well as possible use in nondestructive testing and X-ray computed tomography. Images of various tissues and materials are presented to demonstrate the wide applicability of this technique to medical and biological imaging.

Journal Article↗
PubMed1998

Kupffer cell-dependent reperfusion injury in liver transplantation: new clinically relevant use of glycine.

Kupffer cell-dependent reperfusion injury occurs to the liver following transplantation, most often in fatty livers which fail most frequently due to primary nonfunction. Failure was largely blocked with Carolina rinse solution, which contains glycine, and prevents the activation of Kupffer cells. Furthermore, gentle in situ organ manipulation, which cannot be prevented using standard harvesting techniques, has a detrimental effect on survival. These effects were also prevented by glycine. Since proteolytic activity is increased in both fatty and manipulated livers, amino acids were measured in rinse effluents collected at harvest. A combination of four amino acids correlated with graft function. It is concluded that glycine could be beneficial in clinical liver transplantation to prevent reperfusion injury, and that amino acids measured at harvest may predict graft function.

Fatty Liver↗
PubMed1997

Prevention of cyclosporine-induced nephrotoxicity with dietary glycine.

BACKGROUND: The nonessential amino acid glycine has been used previously to prevent hypoxic and ischemic injury to kidney tissue in vitro. Furthermore, it was recently shown that glycine prevents activation of macrophages and neutrophils in vitro. Because there is some evidence that the immunosuppressant cyclosporine causes nephrotoxicity through a hypoxia-reoxygenation mechanism that could involve infiltration and activation of macrophages and neutrophils, we hypothesized that dietary glycine could prevent this injury. METHODS: Rats were fed a diet containing glycine (5%) or a control diet for 3 days before cyclosporine treatment. To produce nephrotoxicity, cyclosporine (25 mg/kg daily by gavage) was administered for 28 days while animals were maintained on glycine or control diets. Serum creatinine, urea, glomerular filtration rates, and kidney histology were evaluated in different treatment groups. RESULTS: All rats gained weight; however, overall weight gain in the cyclosporine, glycine, and cyclosporine+glycine groups was significantly less by about 40% compared with the control group. Diet consumption was not statistically different between the groups. As expected, cyclosporine caused kidney damage in the rats fed control diet, reflected in significantly elevated serum urea and creatinine. In addition, cyclosporine treatment decreased glomerular filtration rate by nearly 70%, caused proximal tubular dilation and necrosis as well as increased macrophage and neutrophil infiltration into the kidney. Dietary glycine prevented or minimized kidney damage due to cyclosporine in all parameters studied nearly completely. Furthermore, feeding glycine for up to 1 month had no detrimental effect on kidney function. CONCLUSIONS: Dietary glycine is a safe and effective treatment to reduce the nephrotoxicity of cyclosporine.

Animal Feed↗
PubMed1997

STAT signaling is active during early mammalian development.

Cytokine activation of gene expression can be mediated through signal transducer and activator of transcription (STAT) signaling pathways resulting in expression of target genes. Because many cytokines have important regulatory roles during early development, we wanted to ascertain whether STAT signaling was also active at this time and could therefore have important roles in mediating developmental processes. We have found that Stat1 and Stat3 mRNAs are present in both maternal and extraembryonic tissues during early postimplantation stages of murine development. Furthermore, analyses of STAT activity in E4.5-E9.5 decidual swellings by electrophoretic mobility shift assay demonstrated that Stat3 protein was active during this early developmental period. The identification of activated Stat3 demonstrates that STAT signaling functions during early postimplantation development in the mouse are likely to be important during early embryogenesis.

Animals↗
PubMed1997

Diffraction enhanced x-ray imaging.

Diffraction enhanced imaging is a new x-ray radiographic imaging modality using monochromatic x-rays from a synchrotron which produces images of thick absorbing objects that are almost completely free of scatter. They show dramatically improved contrast over standard imaging applied to the same phantom. The contrast is based not only on attenuation but also the refraction and diffraction properties of the sample. This imaging method may improve image quality for medical applications, industrial radiography for non-destructive testing and x-ray computed tomography.

Biophysical Phenomena↗
PubMed1997

Single-and dual-energy CT with monochromatic synchrotron x-rays.

We explored the potential for clinical research of computed tomography (CT) with monochromatic x-rays using the preclinical multiple energy computed tomography (MECT) system at the National Synchrotron Light Source. MECT has a fixed, horizontal fan beam with a subject apparatus rotating about a vertical axis; it will be used for imaging the human head and neck. Two CdWO4-photodiode array detectors with different spatial resolutions were used. A 10.5 cm diameter acrylic phantom was imaged with MECT at 43 keV and with a conventional CT (CCT) at 80 kVp: spatial resolution approximately equal to 6.5 line pairs (lp)/cm for both; slice height, 2.6 mm for MECT against 3.0 mm for CCT; surface dose, 3.1 cGy for MECT against 2.0 cGy for CCT. The resultant image noise was 1.5 HU for MECT against 3 HU for CCT. Computer simulations of the same images with more precisely matched spatial resolution, slice height and dose indicated an image-noise ratio of 1.4:1.0 for CCT against MECT. A 13.5 cm diameter acrylic phantom imaged with MECT at approximately 0.1 keV above the iodine K edge and with CCT showed, for a 240 micrograms I ml-1 solution, an image contrast of 26 HU for MECT and 13 and 9 HU for the 80 and 100 kVp CCT, respectively. The corresponding numbers from computer simulation of the same images were 26, 12, and 9 HU, respectively. MECT's potential for use in clinical research is discussed.

Acrylates↗
PubMed1997

Monochromatic energy-subtraction radiography using a rotating anode source and a bent Laue monochromator.

A system for area-beam energy-subtraction monochromatic radiography was developed and tested. It utilizes a bent Laue crystal monochromator developed at the National Synchrotron Light Source (NSLS), and a compact rotating anode X-ray source developed at the Science Research Laboratory (SRL). The K(alpha) characteristic lines (both K(alpha 1) and K(alpha 2) of the cerium and barium targets were diffracted by the monochromator and used for the above- and below-K-edge imaging, respectively, of phantoms with iodine contrast agents. Digital subtraction of the images produced an iodine image.

Angiography, Digital Subtraction↗
PubMed1997

Role of free radicals in primary nonfunction of marginal fatty grafts from rats treated acutely with ethanol.

Acute treatment with one large dose of ethanol, which mimics binge drinking, causes marginal fatty liver and decreases survival significantly after liver transplantation in rats, yet mechanisms remain unclear. Therefore, we evaluated the possible role of free radicals in primary nonfunction caused by acute ethanol. Female donor rats were administered ethanol (5 g/kg orally) 20 hr before explantation, and grafts were stored in UW cold storage solution for 24-42 hr before implantation. Free radicals were trapped with alpha-(4-pyridyl 1-oxide)-N-tert-butylnitrone after transplantation, and adducts were detected using electron spin resonance spectrometry. Ethanol increased a carbon-centered radical adduct in bile approximately 2-fold and elevated serum lipid hydroperoxides approximately 4-fold. Ethanol also increased transaminase release 3.7-fold and decreased bile production by 55%. Catechin, a free radical scavenger, minimized the increase in free radicals, blunted transaminase release, and elevated bile production significantly, indicating that free radical production plays an important role in ethanol-induced fatty graft injury. GdCl3 (20 mg/kg intravenously), a selective Kupffer cell toxicant, largely blocked the increases in free radical and lipid hydroperoxide production caused by ethanol. In addition, ethanol nearly doubled white blood cell adhesion after transplantation, leading to increased superoxide production in fatty grafts. GdCl3 largely blocked leukocyte adhesion as well as superoxide production. Allopurinol, an inhibitor of xanthine oxidase, also diminished free radical production, blunted transaminase release, and improved bile production in fatty grafts significantly. Taken together, we conclude that free radical formation increases in ethanol-induced fatty grafts due mainly to activation of Kupffer cells and increased adhesion of white blood cells. Antioxidants can effectively block free radical formation and minimize injury to marginal fatty grafts caused by binge drinking.

Animals↗
PubMed1997

Peptide epitopes recognized by a human anti-cryptococcal glucuronoxylomannan antibody.

Cryptococcus neoformans causes meningitis in 6 to 8% of individuals with AIDS. Recently, immunotherapeutic modalities including antibody therapy have been proposed for the treatment of cryptococcal meningitis in AIDS patients. This is a rational approach because existing antifungal agents fail to eradicate the infection in the setting of profound immunosuppression. Both murine and human antibodies elicited by the investigational cryptococcal capsular polysaccharide vaccine glucuronoxylomannan-tetanus toxoid (GXM-TT) have been shown to be biologically functional in different model systems. The human immunoglobulin M (lambda) GXM monoclonal antibody (MAb) 2E9 expresses idiotypes that are also found in naturally occurring anti-GXM antibodies and opsonic GXM-TT sera. However, the specificity of human anti-GXM antibodies and their possible role in protection against cryptococcosis are not known. In an effort to discover epitopes that are recognized by human anti-GXM antibodies, we screened a random decapeptide phage display library with the human anti-GXM MAb 2E9. An enzyme-linked immunosorbent assay (ELISA)-based screening method led to the selection of phages with peptide inserts that bound 2E9 and inhibited 2E9-GXM binding. Analysis of the amino acid sequences of these phages revealed an increased frequency of combinations of QTGLD residues. Inhibition ELISAs demonstrated that phages with QTG/TL/D motifs inhibited 2E9-GXM binding better than phages with different motifs. A peptide synthesized from one of the inhibitory phages, peptide 13 (GMDGT QLDRW), inhibited GXM binding to solid-phase 2E9 and 2E9 binding to solid-phase GXM. Peptide 13 also inhibited the GXM binding of GXM-TT immune sera and naturally occurring serum antibodies from human immunodeficiency virus (HIV)-negative, but not HIV-positive, individuals. Taken together, our data indicate that the peptide epitopes selected by 2E9 mimic GXM epitopes and that peptide 13 may be a mimotope of a GXM epitope that is recognized by human anti-GXM antibodies.

AIDS-Related Opportunistic Infections↗
PubMed1997

Fc gammaRIIa polymorphism in human immunodeficiency virus-infected children with invasive pneumococcal disease.

Invasive pneumococcal disease (IPD) occurs frequently in HIV-infected children and adults. Defects in complement function, opsonic capsular antibodies, and Fc receptor antibody-mediated phagocytosis could contribute to impaired host defense against Streptococcus pneumoniae. The objective of this study was to define the distribution of the three Fc gammaRIIa genotypes in HIV+ children, including those with IPD. Forty-eight HIV+ Hispanic children, including eight with IPD, followed at Bronx-Lebanon Hospital Center, Bronx, New York, nine HIV+ adults with IPD, and 56 HIV- Hispanic control subjects were studied. The children and adults were identified retrospectively except for one child who developed IPD during the study. Fc gammaRIIa genotypes were determined by PCR amplification of the Fc gammaRIIa locus from genomic DNA samples and hybridization of the PCR products with allele-specific oligonucleotides. Naturally occurring serum antibodies reactive with four pneumococcal polysaccharide serotypes were determined by ELISA in seven of eight children with IPD. There were no statistical differences in Fc gammaRIIa genotypes between HIV+ children with and without IPD, HIV+ adults with IPD, or HIV- Hispanics. The predominant IgG subclass of pneumococcal polysaccharide binding antibodies in the seven HIV+ children with IPD studied was IgG1. The distribution of Fc gammaRIIa genotypes in HIV+ children with and without IPD is similar to that of the normal Hispanic population. The prospect of passive immunotherapy with specific anticapsular antibodies might be a promising alternative for the treatment and/or prevention of IPD in HIV+ children and other immunodeficient groups.

AIDS-Related Opportunistic Infections↗
PubMed1997

Study of a calculation method for healthy life expectancy.

"To develop a calculation method for healthy life expectancy which would be suitable for China we analyzed the healthy life expectancy of urban residents in China, employing data on residents' deaths and data available from the 1993 national survey for health services and family health conditions.... Results of the study show that the ratio of healthy life expectancy to life expectancy decreases with the increase of the residents' age; healthy life expectancy for females is higher than that for males; [and] healthy life expectancy for residents of large cities is lower than that for residents of medium and small cities."

Age Factors↗
PubMed1996

Differential activation of acute phase response factor/Stat3 and Stat1 via the cytoplasmic domain of the interleukin 6 signal transducer gp130. II. Src homology SH2 domains define the specificity of stat factor activation.

Distinct yet overlapping sets of STAT transcription factors are activated by different cytokines. One example is the differential activation of acute phase response factor (APRF, also called Stat3) and Stat1 by interleukin 6 and interferon-gamma. Interleukin 6 activates both factors while, at least in human cells, interferon-gamma recruits only Stat1. Stat1 activation by interferon-gamma is mediated through a cytosolic tyrosine motif, Y440, of the interferon-gamma receptor. In an accompanying paper (Gerhartz, C., Heesel, B., Sasse, J., Hemmann, U., Landgraf, C., Schneider-Mergener, J., Horn, F., Heinrich, P. C., and Graeve, L. (1996) J. Biol. Chem. 271, 12991-12998), we demonstrated that two tyrosine motifs within the cytoplasmic part of the interleukin 6 signal transducer gp130 specifically mediate APRF activation while two others can recruit both APRF and Stat1. By expressing a series of Stat1/APRF domain swap mutants in COS-7 cells, we now determined which domains of Stat1 and APRF are involved in the specific recognition of phosphotyrosine motifs. Our data demonstrate that the SH2 domain is the sole determinant of specific STAT factor recruitment. Furthermore, the SH2 domain of Stat1 is able to recognize two unrelated types of phosphotyrosine motifs, one represented by the interferon-gamma receptor Y440DKPH peptide, and the other by two gp130 YXPQ motifs. By molecular modeling, we propose three-dimensional model structures of the Stat1 and APRF SH2 domains which allow us to explain the different binding preferences of these factors and to predict amino acids crucial for specific peptide recognition.

Acute-Phase Proteins↗
PubMed1996

Destruction of Kupffer cells increases survival and reduces graft injury after transplantation of fatty livers from ethanol-treated rats.

This study investigated the role of Kupffer cells on survival and graft injury in transplanted fatty livers from rats treated acutely with ethanol. Donor rats were given ethanol (5 g/kg, by mouth) 20 hours before explantation, and liver grafts were preserved in University of Wisconsin cold storage solution for 24 to 42 hours prior to implantation. Blood samples were taken from the inferior vena cava for 3 hours after implantation. During this time, serum aspartate transaminase levels increased gradually from 122 U/L to 597 U/L in control rats, while ethanol treatment elevated values to 2,278 U/L. Gadolinium chloride (20 mg/kg, given intravenously to recipients 24 hours before explantation), a selective inactivator of Kupffer cells, minimized the increase in aspartate transaminase levels significantly. After implantation of grafts cold-stored for 42 hours, survival rates were 88% in control rats but only 33% in ethanol-treated rats. Gadolinium chloride improved survival nearly to control values. Ethanol nearly doubled white blood cell adhesion, an effect also largely blocked by gadolinium chloride. Further, alpha-(4-pyridyl 1-oxid)-N-tert-butylnitrone radical adducts detected in the bile were increased twofold by ethanol treatment. This effect was also reversed by gadolinium chloride. Taken together, these data indicate that survival is poorer and graft injury is greater in fatty livers from ethanol-treated rats. Inactivation of Kupffer cells minimized graft damage, most likely by improving hepatic microcirculation and diminishing lipid peroxidation.

Analysis of Variance↗
PubMed1996

Opsonization of Cryptococcus neoformans by human anticryptococcal glucuronoxylomannan antibodies.

Cryptococcal meningitis occurs in 6 to 8% of human immunodeficiency virus-infected individuals. Despite the availability of powerful antifungal agents that are active against Cryptococcus neoformans, these drugs generally fail to cure cryptococcal infections in immunocompromised hosts. Alternative approaches to prevention and therapy of cryptococcosis are urgently needed. Complement promotes phagocytosis of C. neoformans, but human antibodies to cryptococcal capsular polysaccharide have not been shown to function as complement-independent opsonins. The goal of our studies was to characterize the in vitro biological function of human antibodies to glucuronoxylomannan (GXM) from individuals immunized with a GXM-tetanus toxoid (GXM-TT) vaccine. We studied sera from nine vaccinees that manifested good serologic responses to GXM-TT. The results indicate that GXM-TT-elicited antibodies promote phagocytosis of C. neoformans by both murine J774 cells and human peripheral blood mononuclear cells (PBMCs). The two sera with the highest titers of anti-GXM immunoglobulin G2 antibodies were the most opsonic. When PBMC Fc gamma RIIa receptors were blocked, a 75% decrease in phagocytosis occurred following incubation of the PBMCs with C. neoformans opsonized with these sera. Our data indicate that, in the absence of complement, human anti-GXM-TT antibodies are opsonic and that antibodies of the immunoglobulin G2 isotype are effective opsonins.

Adjuvants, Immunologic↗