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Biomedical subjects

Z Xu

Publications and source records attributed to Z Xu.

At least 19 recordsLinked to original sources
PubMed1996

IL-15 administration following syngeneic bone marrow transplantation prolongs survival of lymphoma bearing mice.

The toxicity and antitumor efficacy of simian IL-15 was compared with human IL-2 in the context of syngeneic BMT. Groups of mice receiving or not receiving anti-CD3 activated splenocytes, termed "T-activated killer" (T-AK) cells, were treated between days 7 and 12 with escalating doses of IL-2 or IL-15 given twice daily. Recipients of IL-2+T-AK or IL-15+T-AK had significantly higher survival rates than saline+T-AK. Tissues from IL-2+T-AK, but not IL-15+Y-AK, treated mice revealed the presence of perivascular infiltrates in the lung and liver consisting of CD8+ T cells and Mac-1+ cells. Our findings demonstrate that IL-15 can be used effectively to stimulate antitumor responses post-BMT and may be associated with less toxicity than IL-2.

Bone Marrow Transplantation↗
PubMed1996

Sodium 2,3-dimercapto-1-propanesulfonate (DMPS) treatment does not redistribute lead or mercury to the brain of rat.

Since there has been concern about whether any of the chelating agents used therapeutically might cause an initial redistribution of heavy metals to the brain and since the sodium salt of 2,3-dimercapto-1-propanesulfonic acid (Dimaval, DMPS) has been used to treat heavy metal intoxication in humans, the hypothesis that DMPS does not redistribute and increase lead or mercuric ions in the brains of rats was tested. Lead acetate at a concentration of 50 mg/l was made available in the drinking water of rats for 86 days. Other rats received intraperitoneal injections of 0.50 mg Hg/kg (as mercuric chloride) each day for 5 days a week for a total of 32 or 41 days. Animals were divided into groups and given, i.p., either 0.27 mmol DMPS/kg body weight or saline, each day for 1, 2, 3 or 4 days. Lead or mercury concentrations of the brain were determined after each group received DMPS for the different number of days. DMPS treatment did not result in any initial increase of lead or mercuric ions in the brain. The mercury content of the kidney decreased. The results of these experiments demonstrated that lead or mercuric ions were not redistributed to or increased in the brains of rats during the initial days of DMPS treatment.

Administration, Oral↗
PubMed1996

Regulation of nuclear envelope assembly/disassembly by MAP kinase.

Mouse eggs arrested in metaphase II display high levels of cdc2/cyclin B1 and MAP protein kinase activities. Following fertilization there is a time-dependent decrease in the activity of each of these protein kinases. The decline in cdc2/cyclin B1 protein kinase correlates with the resumption of meiosis and the emission of the second polar body and precedes the decline in MAP kinase activity, which correlates temporally with the formation of the male and female pronuclear envelopes. These results suggest that high levels of MAP kinase activity are incompatible with the presence of a pronuclear envelope. To test this possibility, we expressed in mouse eggs a constitutively active form of MAP kinase kinase (MEK) whose only known target is p42/p44 MAP kinase. We show that following fertilization cdc2/cyclin B1 kinase activity declines and a second polar body is emitted. The endogenous MAP kinase remains active, however, and no pronuclear envelopes form. Thus, high levels of MAP kinase activity by itself in mouse eggs appear incompatible with the presence of a pronuclear envelope.

Animals↗
PubMed1996

Structure-function analysis of human alpha1,3-fucosyltransferase. Amino acids involved in acceptor substrate specificity.

A series of molecular biology experiments were carried out to identify the catalytic domain of two human alpha1,3/4-fucosyltransferases (fucosyltransferases (FucTs) III and V), and to identify amino acids that function in acceptor substrate binding. Sixty-one and 75 amino acids could be eliminated from the N terminus of FucTs III and V, respectively, without a significant loss of enzyme activity. In contrast, the truncation of one or more amino acids from the C terminus of FucT V resulted in a dramatic or total loss of enzyme activity. Results from the truncation experiments demonstrate that FucT III62-361 (containing amino acids 62-361) and FucT V76-374 (containing amino acids 76-374) are active, whereas shorter forms of the enzymes were inactive. The shortest, active forms of the enzymes are more than 93% identical at the predicted amino acid level, but have distinct acceptor substrate specificities. Thus, FucT III is an alpha1,4-fucosyltransferase, whereas FucT V is an alpha1,3-fucosyltransferase with disaccharide substrates. All but one of the amino acid sequence differences between the two proteins occur near their N terminus. Results obtained from domain swapping experiments demonstrated that the single amino acid sequence difference near the C terminus of these enzymes did not alter the enzyme's substrate specificity. However, swapping a region near the N terminus of the truncated form of FucT III into an homologous region in FucT V produced a protein with both alpha1,3- and alpha1,4-fucosyltransferase activity. This region contains 8 of the amino acid sequence differences that occur between the two proteins.

Amino Acid Sequence↗
PubMed1996

Effects of unilateral or bilateral lesions within the anteroventral third ventricular region on c-fos expression induced by dehydration or angiotensin II in the supraoptic and paraventricular nuclei of the hypothalamus.

This paper reports the effects of AV3V lesions on the pattern of c-fos induced by 24 h dehydration. As expected, bilateral electrolytic lesions within the AV3V region (the ventral median preoptic nucleus) suppressed water intake following 24 h water deprivation. C-fos expression was also suppressed in the supraoptic (SON) and (less completely) in the paraventricular (PVN) nuclei, but not in the subfornical organ (SFO). Unilateral lesions of the AV3V region suppressed c-fos expression in the ipsilateral SON, but this selective ipsilateral effect was less in the PVN. The SFO was again unaffected. Unilateral lesions also suppressed c-fos expression in the ipsilateral SON and PVN (to a lesser degree) following intraventricular infusions of angiotensin II (250 pmol). These results suggest that the cellular response of supraoptic neurons to osmotic stimuli require inputs from the AV3V region, but that this is less absolute for the PVN; that the projection from the ventral AV3V area to the SON is ipsilateral, but that to the PVN may be less lateralised. Activation of the SFO by dehydration is not dependent upon the integrity of the ventral AV3V region. These results are closely comparable to the effects of similar lesions on c-fos expression following intraventricular infusions of angiotensin II, and suggest that the effect of dehydration on forebrain c-fos expression may be related to the central actions of angiotensin II.

Angiotensin II↗
PubMed1996

An unusual group-A rotavirus associated with an epidemic of diarrhea among three-month-old calves.

During the 1992 and 1993 breeding seasons, epidemics of diarrhea among calves approximately 3 months old in a cow/calf operation were reported. Rotavirus was determined to be the probable cause, but because rotavirus typically affects younger calves, further investigations were conducted to determine the characteristics of the virus. Virus isolated from the feces of 1 affected calf was found to be antigenically distinct from the vaccine strain used. The primary water source was a slough, and rapid spread of infection may have been a result of fecal contamination of the slough. In both years, the epidemic began shortly after migrating cattle egrets arrived in the district.

Age Factors↗
PubMed1996

Human CFTR gene sequences in regions flanking exon 10: a simple repeat sequence polymorphism in intron 9.

A 2,908-bp segment of genomic DNA containing exon 10 and flanking intron regions of the human cystic fibrosis transmembrane conductance regulator gene was sequenced. A 30-bp sequence discrepancy and three missing nucleotides were detected when compared to a previously published 831-bp sequence. In the 30-bp region of sequence discrepancy, only a primer based on the new sequence information presented in this study gave products from polymerase chain reaction amplification of cellular DNA and a plasmid DNA encompassing the exon 10 region of CFTR. A 4-bp (TAAA) simple repeat sequence was also identified in intron 9 region. This repeat is dimorphic with nine (TAAA)9 or eleven (TAAA)11 copies on different chromosomes. Eleven repeats were exclusively associated with chromosomes carrying the delta508 mutation. Both 9 and 11 repeats were detected in non-delta508 chromosomes.

Base Sequence↗
PubMed1996

Abundant expression of transcription factor GATA-2 in proliferating but not in differentiated mast cells in tissues of mice: demonstration by in situ hybridization.

Although GATA-binding transcription factors (GATA-1 and GATA-2) are strongly expressed in cultured mast cells (CMCs), their expression in mast cells within tissues has not been reported. We examined the expression of GATA-1 and GATA-2 in skin tissues of mice using Northern blot analysis and in situ hybridization. mRNA for GATA-2 but not for GATA-1 was expressed in skin mast cells of WB-+/+ embryos between days 15 and 17 postcoitum (pc). The expression was downregulated on and after day 18 pc. Skin mast cells did not express GATA-2 after birth either. When the number of skin mast cells was compared with the number of GATA-2 mRNA-expressing cells, GATA-2 mRNA appeared to be expressed by mast cells only when the number was increasing. When the mRNA expression of high-affinity IgE receptor beta-subunit and mast cell carboxypeptidase A was used as differentiation markers, the expression of these mRNAs continued even after the downregulation of GATA-2 expression. To clarify the relationship of the proliferation and GATA-2 expression, proliferating CMCs derived from WBB6F1-+/+ mice were transplanted into the peritoneal cavity of mast cell-deficient WBB6F1-W/Wv mice. The CMCs stopped both the proliferation and GATA-2 expression after the transplantation, suggesting the association of these two parameters in mast cells within tissues of mice.

Animals↗
PubMed1996

The pleiotropic effect of the GTS1 gene product on heat tolerance, sporulation and the life span of Saccharomyces cerevisiae.

We investigated whether or not the potential clock gene, GTS1, of the yeast Saccharomyces cerevisiae, shows pleiotropic effects on the yeast cellular processes. We tested the efect of the Gts1 protein on heat tolerance, sporulation and life-span, by characterizing the phenotypes of transformants with different copy numbers of the gene. We found that the Gts1 protein affects the capacity of heat tolerance in the stationary phase and the speed leading to sporulation in a gene-dose dependent manner, and that both inactivation and overexpression of the gene shortened the life-span of yeast. These results supported the notion that GTS1 affects the biological clock of the yeast S. cerevisiae, although this cannot be definitively concluded because the strain cannot be synchronized with circadian or ultradian rhythms.

Fungal Proteins↗
PubMed1996

Cancer risks among iron and steel workers in Anshan, China, Part I: Proportional mortality ratio analysis.

A standardized proportional mortality ratio (SPMR) study of 8,887 deaths during 1980-1989 among male workers in a large integrated iron-steel complex in Anshan, China, was conducted to provide clues to occupational risk factors. Accidents and cancer accounted for a higher proportion of deaths among the iron-steel workers than among the general male population (SPMR = 1.21; 95% CI = 1.12-1.31 and 1.14; 95% CI = 1.10-1.18, respectively). Among all workers, SPMRs were significantly elevated for stomach, lung, and colorectal cancers (SPMR = 1.37, 1.37, 1.38, respectively), but not other cancers. Risks of stomach cancer appeared to be highest among workers employed in jobs with exposure to iron and coal dust, whereas significant increases in colorectal cancer were seen for loading and other dusty jobs and for administrative and sedentary jobs without dust exposure. Risks of lung cancer appeared increased for a variety of jobs throughout the complex, especially those with probable high levels of exposure to polycyclic hydrocarbons and asbestos. Risk of esophageal cancer was significantly elevated for fire-resistant brick makers, and risk of nonmalignant respiratory disease was significantly elevated for those employed as furnace workers, foundry workers, and fire-resistant brick makers.

Accidents, Occupational↗
PubMed1996

Cancer risks among iron and steel workers in Anshan, China, Part II: Case-control studies of lung and stomach cancer.

Nested case-control interview studies of lung cancer (610 incident cases), stomach cancer (292 incident cases), and 959 controls were conducted to follow up leads from a proportional mortality analysis of deaths among male workers in a large integrated iron-steel complex in Anshan, China. For lung cancer, after adjusting for the significant non-occupational risk factors (smoking, other pulmonary disease, family history of lung cancer, and low consumption of fruit or tea), risks were significantly elevated for those employed for 15 or more years in smelting and rolling (OR = 1.5, CI = 1.1-2.2), in the fire-resistant brick factory (OR = 2.9, CI = 1.4-5.9), in general loading (OR = 2.5, CI = 1.0-6.1), and as coke oven workers (OR = 3.4; CI = 1.4-8.5). For stomach cancer, after adjusting for consumption of pickled vegetables, prior gastric diseases, family history of stomach cancer, low intake of fruits and vegetables, and education, risks were significantly elevated for those employed for 15 or more years in ore sintering and transportation (OR = 2.1, CI = 1.0-4.4), in the fire-resistant brick factory (OR = 2.5, CI = 1.1-5.8), in general loading (OR = 3.2, CI = 1.2-8.9), as boilerworkers and cooks (OR = 2.6, CI = 1.2-5.6), and as coke oven workers (OR = 5.4, CI = 1.8-16.0). For both lung and stomach cancers, significant dose-response gradients were observed for exposure to total dust and benzo(a)pyrene, but not for specific chemical components of dust. Overall, long-term steel workers with exposure to workplace pollutants had a 40% increased risk of both lung and stomach cancers. These case-control studies confirm many of the occupational findings reported in the proportionate mortality analysis, and suggest avenues for further work to evaluate the carcinogenicity of individual components of dust.

Adult↗
PubMed1996

A computer heart model incorporating anisotropic propagation. III. Simulation of ectopic beats.

With the advent of catheter ablation procedures, it has become an important goal to predict noninvasively the site of origin of ventricular tachycardia. Site classifications based on the observed body surface potential maps (BSPMs) during ventricular endocardial pacing, as well as on the patterns of the QRS integrals of these maps, have been suggested. The goals of this study were to verify these maps and their QRS integral patterns via simulation using a computer heart model with realistic geometry and to determine whether the model could improve clinical understanding of these ectopic patterns. Simulation was achieved by initiating excitation of the heart model at different endocardial sites and their overlying epicardial counterparts. This excitation propagated in anisotropic fashion in the myocardium. Retrograde excitation of the model's His-Purkinje conduction system was necessary to obtain realistic activation durations. Simulated BSPMs, computed by placing the heart model inside a numerical torso model, and their QRS integrals were close to those observed clinically. Small differences in QRS integral map patterns and in the positions of the QRS integral map extrema were noted for endocardial sites in the left septal and anteroseptal regions. The simulated BSPMs during early QRS for an endocardial site and its epicardial counterpart tended to be mirror images about the zero isopotential contour, exchanging positive and negative map regions. The simulation results attest to the model's ability to reproduce accurately clinically recorded body surface potential distributions obtained following endocardial stimulation. The QRS integral maps from endocardial sites in the left septal and anteroseptal regions were the most labile, owing to considerable cancellation effects. Conventional BSPMs can be useful to help distinguish between endocardial and epicardial ectopic sites.

Anisotropy↗
PubMed1996

Thioredoxin is required for vacuole inheritance in Saccharomyces cerevisiae.

The vacuole of Saccharomyces cerevisiae projects a stream of tubules a and vesicles (a "segregation structure") into the bud in early S phase. We have described an in vitro reaction, requiring physiological temperature, ATP, and cytosol, in which isolated vacuoles form segregation structures and fuse. This in vitro reaction is defective when reaction components are prepared from vac mutants that are defective in this process in vivo, Fractionation of the cytosol reveals at least three components, each of which can support the vacuole fusion reaction, and two stimulatory fractions. Purification of one "low molecular weight activity" (LMA1) yields a heterodimeric protein with a thioredoxin subunit. Most of the thioredoxin of yeast is in this complex rather than the well-studied monomer. A deletion of both S. cerevisiae thioredoxin genes causes a striking vacuole inheritance defect in vivo, establishing a role for thioredoxin as a novel factor in this trafficking reaction.

Cell-Free System↗
PubMed1996

Subunit composition of neurofilaments specifies axonal diameter.

Neurofilaments (NFs), which are composed of NF-L, NF-M, and NF-H, are required for the development of normal axonal caliber, a property that in turn is a critical determinant of axonal conduction velocity. To investigate how each subunit contributes to the radial growth of axons, we used transgenic mice to alter the subunit composition of NFs. Increasing each NF subunit individually inhibits radial axonal growth, while increasing both NF-M and NF-H reduces growth even more severely. An increase in NF-L results in an increased filament number but reduced interfilament distance. Conversely, increasing NF-M, NF-H, or both reduces filament number, but does not alter nearest neighbor interfilament distance. Only a combined increase of NF-L with either NF-M or NF-H promotes radial axonal growth. These results demonstrate that both NF-M and NF-H play complementary roles with NF-L in determining normal axonal calibers.

Animals↗
PubMed1996

Location and characteristics of nitric oxide synthase in sheep spinal cord and its interaction with alpha(2)-adrenergic and cholinergic antinociception.

BACKGROUND: Nitric oxide synthase is located in the spinal cord dorsal horn and intermediolateral cell column, where it may modulate sensory and sympathetic neuronal activity. However, the biochemical characteristics of this enzyme have not been examined in these different areas in the spinal cord. Although alpha(2)-adrenergic agonists, muscarinic agonists, and nitric oxide may interact in the spinal cord to produce antinociception, these interactions have not been characterized. METHODS: Sheep spinal cord tissue was homogenized ad centrifuged at high sped to separate soluble and membrane-bound fractions. Nitric oxide synthase activity was determined by conversion of [(14)C]-L-arginine to [(14)C]-L-citrulline and its kinetic characteristics, dependency on cofactors, and sensitivity to inhibitors determined. Sheep spinal cord was stained for nicotinamide adenine dinucleotide phosphate diaphorase as a marker for nitric oxide synthase. Antinociception to a mechanical stimulus from intrathecal clonidine alone and with neostigmine was determined and the effects of L-arginine and n-methyl-L-arginine were determined. RESULTS: More than 85% of nitric oxide synthase activity was present in the soluble form and its kinetic, cofactor, and antagonist properties were similar to those of the neuronal isoform of nitric oxide synthase. Biochemical and histochemical studies localized nitric oxide synthase to the superficial dorsal horn and the intermediolateral cell column. Clonidine antinociception was enhanced by L-arginine and neostigmine, but not by D-arginine. Neostigmine's enhancement of clonidine antinociception was blocked by n-methyl-L-arginine. CONCLUSIONS: These results confirm those of previous studies demonstrating localization of nitric oxide synthase to superficial dorsal horn and intermediolateral cell column of mammalian spinal cord, and suggesting its identity as the neuronal isoform. Spinal alpha(2)-adrenergic agonist antinociception may be partly dependent on cholinergic and nitric oxide mechanisms.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1996

Acetylcholine stimulates the release of nitric oxide from rat spinal cord.

BACKGROUND: Acetylcholine causes synthesis of nitric oxide in vascular endothelium, and presumptive evidence in vivo suggests spinally released acetylcholine causes antinociception and increased sympathetic nervous system activity via a nitric oxide mechanism. The purpose of this study was to determine, using a recently described bioassay system, whether acetylcholine stimulates nitric oxide release from spinal cord tissue in vitro. METHODS: Rat thoracolumbar spinal cord slices were incubated in a tissue chamber and perfused with Krebs-Henseleit solution. The perfusate was then passed through endotheliumdenuded rat aortic rings and their tension was measured. Vascular rings were preconstricted with phenylephrine, then were exposed to spinal cord perfusate with increasing concentrations (10(-12)-10(-4)M) of acetylcholine alone or with various antagonists. RESULTS: Acetylcholine perfusion of spinal tissue caused concentration-dependent relaxations of the aortic rings, an effect blocked by each of the muscarinic antagonists, atropine, pirenzepine, and AFDX-116. Acetylcholine-induced relaxation also was antagonized by an inhibitor of nitric oxide synthase (N-methyl-L-arginine), a nitric oxide scavenger (hemoglobin) and an inhibitor of guanylate cyclase (methylene blue). CONCLUSIONS: These results demonstrate release of a vasorelaxant from spinal cord tissue by acetylcholine, which results from an action on muscarinic receptors and exhibits a pharmacology consistent with nitric oxide. Although precise anatomic localization of acetylcholine's action is not possible with this system, these results add to evidence that acetylcholine causes nitric oxide synthesis in the spinal cord.

Acetylcholine↗
PubMed1996

Verification of absorbed dose determined with plane-parallel chambers in clinical electron beams following AAPM Task Group 39 protocol using ferrous sulphate dosimetry.

The absorbed dose values determined with the Exradin and PTW-Markus plane-parallel chambers were compared to the values obtained with the ferrous sulphate dosimetry for a number of the Philips SL25 and the Therac 20 electron beams. For the plane-parallel chambers, the cavity-gas calibration factor Ngaspp, was derived by a direct comparison with a calibrated cylindrical chamber using the three different calibration methods as proposed by the newly published AAPM TG 39 protocol. For the ferrous sulphate dosimetry, an epsilon mG value of 352 x 10(-6) m-2 kg-1 Gy-1 was adopted from ICRU Report No. 35. The average ratio of the dose values determined with the plane-parallel chambers and the dose values determined with the Fricke dosimetry system was 1.001 +/- 1.4%. These measurements are consistent with the AAPM TG 39 protocol.

Biophysical Phenomena↗