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Biomedical subjects

Z Zhou

Publications and source records attributed to Z Zhou.

At least 163 records · Page 9Linked to original sources
PubMed2000

Bleomycin-induced pulmonary injury in mice deficient in SPARC.

SPARC (secreted protein, acidic and rich in cysteine) is a component of the matrix that appears to regulate tissue remodeling. There is evidence that it accumulates in the lung in the setting of pulmonary injury and fibrosis, but direct evidence of its involvement is only now emerging. We therefore investigated the development of pulmonary fibrosis induced by bleomycin administered either intratracheally or intraperitoneally in mice deficient in SPARC. Bleomycin (0.15 U/mouse) given intratracheally induced significantly more pulmonary fibrosis in mice deficient in SPARC compared with that in wild-type control mice, with the mutant mice demonstrating greater neutrophil accumulation in the lung. However, in wild-type and SPARC-deficient mice given intraperitoneal bleomycin (0.8 U/injection x 5 injections over 14 days), the pattern and severity of pulmonary fibrosis, as well as the levels of leukocyte recruitment, were similar in both strains of mice. These findings suggest that the involvement of SPARC in pulmonary injury is likely to be complex, dependent on several factors including the type, duration, and intensity of the insult. Furthermore, increased neutrophil accumulation in the peritoneal cavity was also observed in SPARC-null mice after acute chemical peritonitis. Together, these data suggest a possible role for SPARC in the recruitment of neutrophils to sites of acute inflammation.

Animals↗
PubMed2000

Evidence for paracrine signaling between macrophages and bovine adrenal chromaffin cell Ca(2+) channels.

The adrenal gland contains resident macrophages, some of which lie adjacent to the catecholamine producing chromaffin cells. Because macrophages release a variety of secretory products, it is possible that paracrine signaling between these two cell types exists. Of particular interest is the potential paracrine modulation of voltage-gated calcium channels (I(Ca)), which are the main calcium influx pathway triggering catecholamine release from chromaffin cells. We report that prostaglandin E(2) (PGE(2)), one of the main signals produced by macrophages, inhibited I(Ca) in cultured bovine adrenal chromaffin cells. The inhibition is rapid, robust, and voltage dependent; the activation kinetics are slowed and inhibition is largely reversed by a large depolarizing prepulse, suggesting that the inhibition is mediated by a direct G-protein betagamma subunit interaction with the calcium channels. About half of the response to PGE(2) was sensitive to pertussis toxin (PTX) incubation, suggesting both PTX-sensitive and -insensitive G proteins were involved. We show that activation of macrophages by endotoxin rapidly (within minutes) releases a signal that inhibits I(Ca) in chromaffin cells. The inhibition is voltage dependent and partially PTX sensitive. PGE(2) is not responsible for this inhibition as blocking cyclooxygenase with ibuprofen did not prevent the production of the inhibitory signal by the macrophages. Nor did blocking the lipoxygenase pathway with nordihydroguaiaretic acid alter production of the inhibitory signal. Our results suggest that macrophages may modulate I(Ca) and catecholamine secretion by releasing PGE(2) and other chemical signal(s).

Adrenal Medulla↗
PubMed2000

Lung disease associated with the IVS8 5T allele of the CFTR gene.

Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene. The 5T allele in intron 8 (IVS8) causes abnormal splicing in the CFTR gene, and is associated with lung disease when it occurs in cis with a missense mutation in the CFTR gene, R117H. However, the 5T variant alone has not been reported to cause lung disease. We describe two adult female patients with CF-like lung disease associated with the 5T allele. One patient's genotype is 5T-TG12-M470V/5T-TG12-M470V, and the other is DeltaF508/5T-TG12-M470V; full sequencing of the CFTR gene revealed no other mutation on the same allele as the 5T variant. The levels of full-length CFTR mRNA in respiratory epithelia were very low in these patients (11 and 6%, respectively, of total CFTR mRNA expression). Both patients had defective CFTR-mediated chloride conductance in the sweat ductal and/or acinar epithelia (sweat chloride, mmol/L, mean +/- SEM: 40.0 +/- 5.0 [n = 8 samples] and 80. 0 +/- 3.5 [n = 6 samples]) and airway epithelia (mV, mean +/- SEM CFTR-mediated Cl(-) conductance of 1.2 +/- 2.2 [n = 5 studies] and -6.75 +/- 8.1 [n = 4 studies]). These data suggest that the 5T polythymidine tract sequence on specific haplotype backgrounds (TG12 and M470V) may cause a low level of full-length functional CFTR protein and CF-like lung disease.

Age of Onset↗
PubMed2000

Cellular and subcellular localization of catalase in the heart of transgenic mice.

Previous studies have described a cardiac-specific, catalase-overexpressing transgenic mouse model that was used to study myocardial oxidative injury. This study was undertaken to demonstrate cellular and subcellular localization of catalase in the hearts of transgenic mice. By the light microscopic immunoperoxidase method, we found that the overexpressed catalase was exclusively localized in cardiomyocytes. The ratios of immunoreactive cardiomyocytes in the heart were quite different among three transgenic lines examined but agreed with the elevated levels of catalase activity. In the cardiac blood vessels, positive cells were found in the walls of pulmonary veins and the vena cava, which consist of cardiomyocytes, but not in the pulmonary arteries, aorta, or cardiac valves. The electron microscopic immunogold method revealed that the elevated catalase was in sarcoplasm, nucleus, and peroxisomes, but not in mitochondria. In contrast to these distributions, catalase in the non-transgenic cardiomyocytes was in peroxisomes only. In addition, the number and size of peroxisomes in the transgenic cardiomyocytes were markedly increased, but no other ultrastructural changes were observed in comparison with those of non-transgenic mice. These results demonstrated that the elevated catalase in transgenic mouse heart is localized in cardiomyocytes and is distributed to peroxisomal and extraperoxisomal, but not mitochondrial, compartments.

Animals↗
PubMed2000

Enhancement of delayed afterdepolarizations and triggered activity by class III antiarrhythmic drugs: multiple effects of E-4031 and dofetilide.

The effects of class III antiarrhythmic agents E-4031 and dofetilide were studied on action potentials and subthreshold delayed afterdepolarizations (DADs) induced by the cardiac glycoside acetylstrophanthidin (AS) in isolated cardiac Purkinje fibers. Action potentials were recorded from cardiac Purkinje fibers using microelectrode techniques. E-4031 and dofetilide consistently increased DAD amplitude, occasionally caused triggered action potentials and shortened action potential duration. The application of E-4031 without prior AS exposure, resulted in the typical class III antiarrhythmic effects of action potential lengthening and the induction of early afterdepolarizations. These findings suggest that under our conditions of AS-induced cell Ca2+ overload, the effects of the "pure" class III antiarrhythmic drugs, E-4031 and dofetilide, are markedly different from those found in non-Ca2+ loaded cells. This may represent an additional electrophysiological mechanism for class III antiarrhythmic drug toxicity.

Action Potentials↗
PubMed2000

Functional gap junctions between osteocytic and osteoblastic cells.

Morphological evidence shows that osteocytes, bone cells that exist enclosed within bone matrix, are connected to one another and to surface osteoblasts via gap junctions; however, it is unknown whether these gap junctions are functional. Using a newly established murine osteocytic cell line MLO-Y4, we have examined functional gap junctional intercellular communication (GJIC) between osteocytic cells and between osteocytic and osteoblastic cells. In our hands, MLO-Y4 cells express phenotypic characteristics of osteocytic cells including a stellate morphology, low alkaline phosphatase activity, and increased osteocalcin messenger RNA (mRNA) compared with osteoblastic cells. Northern and Western blot analysis revealed that MLO-Y4 cells express abundant connexin 43 (Cx43) mRNA and protein, respectively. Lucifer yellow dye transferred from injected to adjacent cells suggesting that osteocytic cells were functionally coupled via gap junctions. Functional GJIC between osteocytic and osteoblastic (MC3T3-E1) cells was determined by monitoring the passage of calcein dye between the two cell types using a double labeling technique. The ability of bone cells to communicate a mechanical signal was assessed by mechanically deforming the cell membrane of single MLO-Y4 cells, cocultured with MC3T3-E1 cells. Deformation induced calcium signals in MLO-Y4 cells and those elicited in neighboring MC3T3-E1 cells were monitored with the calcium sensitive dye Fura-2. Our results suggest that osteocytic MLO-Y4 cells express functional gap junctions most likely composed of Cx43. Furthermore, osteocytic and osteoblastic cells are functionally coupled to one another via gap junctions as shown by the ability of calcein to pass between cells and the ability of cells to communicate a mechanically induced calcium response.

Animals↗
PubMed2000

TGFbeta1 selectively up-regulates CCR1 expression in primary murine astrocytes.

Chemokine receptors dictate the cellular responses to chemokines on target cells. Therefore, the regulation of expression of chemokine receptors is likely a crucial point for the regulation of chemokine action. Here we show that CC chemokine receptor 1 (CCR1) expression by primary mouse astrocytes is increased after transforming growth factor beta1 (TGFbeta1) stimulation. TGFbeta1 caused a pronounced up-regulation of CCR1 mRNA in a concentration- and time-dependent manner. TGFbeta1-mediated increase of CCR1 mRNA accumulation resulted in increased CCR1 protein expression and augmented cell migration to a physiological ligand, macrophage inflammatory protein-1alpha (MIP-1alpha). The half life of CCR1 mRNA in the presence and absence of TGFbeta1 stimulation was comparable, suggesting that TGFbeta1-induced CCR1 mRNA accumulation occurred at the transcriptional level. TGFbeta1 did not affect CCR1 mRNA expression in hematopoietic cells, indicating that TGFbeta1 effect on CCR1 expression in primary astrocytes is cell-type specific. This is the first evidence that TGFbeta1 may modulate central nervous system (CNS) inflammation in part by affecting chemokine receptor expression on astrocytes.

Animals↗
PubMed2000

Immunohistochemical staining of the mismatch repair gene, hMSH2, and survival in patients with ovarian carcinoma.

OBJECTIVE: hMSH2 is a mismatch repair gene. The protein of this gene can be demonstrated by immunohistochemical methods. The authors wanted to analyze whether the percent of positive nuclear area staining of the hMSH2 protein correlated with survival in patients with ovarian carcinoma. METHODS: One hundred and two patients with epithelial ovarian carcinoma were studied. Slides were prepared from snap frozen tissue. Quantification of staining and DNA index were performed using image analysis. In addition to hMSH2, FIGO stage, grade, histology, and level of cytoreduction were analyzed as prognostic factors. RESULTS: Mean follow-up was 64 months and median was 59 months. Nineteen patients had stage I cancers, 4 stage II, 59 stage III, and 20 stage IV. Optimal cytoreduction was accomplished in 71% of patients. hMSH2 staining was significantly higher in better differentiated tumors (p=0.006), but there was no difference in staining among the FIGO stages (p=0.43). Cox regression analysis revealed FIGO stage (p=0.0005), level of cytoreduction (p=0.006) and hMSH2 staining (p=0.016) to be independent predictors of survival in patients with ovarian carcinoma. CONCLUSION: The hMSH2 protein can be demonstrated by immunohistochemical methods and quantified by image analysis. hMSH2 staining was shown to be an independent prognostic indicator of survival in patients with ovarian carcinoma.

Adult↗
PubMed2000

Intranasal therapy with an adenoviral vector containing the murine interleukin-12 gene eradicates osteosarcoma lung metastases.

The purpose of these studies was to determine the effect of adenovirus-mediated interleukin-12 (IL-12) gene transfer on the growth and development of osteosarcoma (OS) lung metastases in nude mice. A nude mouse model was produced by repetitive cycling of human SAOS OS cells through the lung. The resultant SAOS-LM6 cell line produced microscopic lung metastases by 5-6 weeks after i.v. injection of the tumor cells, with visible lung metastases present 8 weeks after injection. Transfection of SAOS-LM6 cells with a plasmid containing the murine IL-12 gene resulted in a decrease in metastatic potential. Animals injected with IL-12-transfected clones had fewer metastases compared with mice injected with SAOS-LM6 cells transfected with a control plasmid. Furthermore, nasal delivery of an adenoviral vector containing the murine IL-12 gene resulted in the inhibition of pulmonary metastases. Together, these data indicate that IL-12 may be an effective agent against OS and that nasal delivery may offer a unique way to deliver the gene to the local tumor environment, potentially decreasing systemic toxic effects.

Adenoviridae↗
PubMed2000

De novo synthesis of proteinase 3 by cytokine primed circulating human polymorphonuclear neutrophils and mononuclear cells.

OBJECTIVE: When polymorphonuclear neutrophils (PMN) and peripheral blood monocytes (PBMC) are stimulated with tumor necrosis factor alpha (TNF-alpha), preexisting granule stored proteinase 3 (PR3) is translocated to the surface of their plasma membrane. We investigated whether PR3 gene reactivation and new PR3 protein production were also features of priming by cytokine. METHODS: Normal human PMN and PBMC were isolated and stimulated in vitro with TNF-alpha. They were harvested at different intervals and subjected to total RNA and protein analysis. PR3 mRNA was identified by reverse transcription polymerase chain reaction, Northern blot, and sequencing. De novo PR3 synthesis was evaluated by metabolic labeling with [35S] methionine followed by immunoprecipitation using anti-neutrophil cytoplasmic antibodies from serum of patients with active Wegener's granulomatosis and mouse monoclonal anti-native PR3 antibodies. RESULTS: Resting PMN and PBMC do not express PR3 mRNA. During priming, PR3 mRNA appears in PMN at 2 h, peaks at 6 h, and has disappeared at 12 h. By comparison, in primed PBMC, PR3 mRNA appears at 6 h, peaks at 12 h, and disappears at 24 h. Immunoprecipitation of metabolically labeled PR3 revealed new synthesis of PR3 by both cell types, a process that was inhibited by cycloheximide. CONCLUSION: Primed PMN and PBMC can express PR3 mRNA and synthesize new PR3 protein, providing an alternative source to membrane PR3. Whether that small amount of inducible PR3 has a primary structure, a localization, or a role different from those of preformed PR3 stored in granules remains to be clarified.

Autoantigens↗
PubMed2000

Intermediate and late rheumatoid arthritis treated by tonifying the kidney, resolving phlegm and removing blood stasis.

Eighty-seven cases of intermediate and late rheumatoid arthritis were treated with Instant Shu Guan Wen Jing Granules ([symbol: see text] Relaxing Joints by Warming Channels) and Instant Shu Guan Qing Luo Granules ([symbol: see text] Relaxing Joints by Removing Heat from the Lung Channel) to tonify the kidney, resolve phlegm and remove blood stasis, and compared with 41 cases treated with Instant Wang Bi Granules ([symbol: see text] Prescription for Arthralgia-syndrome). The treatment produced a clinical cure rate of 54.0% and a total effective rate of 90.8% as in against 29.3% and 73.2% respectively in the control group. The difference was significant (P < 0.01). Improvement in main symptoms and laboratory findings in the treatment group was all more marked than that in the control group (P < 0.05 or P < 0.01), with no side effects observed.

Adult↗
PubMed2000

Construction of the recombinant retrovirus vector of HBV-S gene and it's expression in eukaryotic cells.

OBJECTIVE: To investigate the effectiveness of recombinant retrovirus vector in gene therapy. METHODS: The retroviral vector PLXSN-S was constructed and transferred into PA317 by means of electroporation, then HepG(2), P815, and EL4 cells were infected with the pseudovirus produced from PA317, which highly expressed HBsAg. HBsAg expression was tested by RT-PCR and ELISA. RESULTS: HBsAg was expressed variously in the eukaryotic cells mentioned above. HBsAg (A value) of the cell supernatants (48 h) were 0.92, 0.09, 0.47, respectively. CONCLUSION: The vector used in this study is an effective one to carry genes of interest to target cells and it may be useful in the test for gene therapy.

Cell Line↗
PubMed2000

[Stress-corrosion test of TIG welded CP-Ti].

In this study TIG (Tungsten Inert Gas) welded CP-Ti were subjected to stress-corrosion test under 261 MPa in artificial saliva of 37 degrees C for 3 months. No significant difference was noted on mechanical test (P > 0.05). No color-changed and no micro-crack on the sample's surface yet. These results indicate that TIG welded CP-Ti offers excellent resistance to stress corrosion.

Biocompatible Materials↗
PubMed2000

Leukoplakia and angiopoiesis resistance of Herba Erigerontis.

OBJECTIVE: To evaluate the effects of Herba Erigerontis on angiopoiesis and carcinogenesis; to seek an effective drug for prevention of leukoplakia progression to carcinoma and to stop the mechanism of angiopoiesis. METHODS: Carcinomatous conversions of golden hamster cheek pouches induced by Salley way and inhibited by Herba Erigerontis. Ink perfusion, analysis of images, resin cast form of micro-vessel, a-SMA detection and histopathological examination were applied to observe their changing patterns. RESULTS: The rate of leukoplakia conversion to tumor of the Herba Erigerontis group was half that of model group. The proportion of normal cells was approximately 4 times greater than that of model. The a-SMA levels of the Herba Erigerontis treated group was higher than that of model (P < 0.001). There was no significant difference between angeion vessel area and density (P > 0.05) in these 2 groups, which were elevated compared to the control. Nevertheless, the resin casts of the microvasculature in the Herba Erigerontis group showed that its configuration and spatial arrangement was similar to the control group. CONCLUSIONS: Herba Erigerontis has the function of inhibiting leukoplakia progression to tumor. This may be due to its ability to upregulate the expression of a-SMA. It has no obvious effect on angio-hyperplasia and expansion in the course of leukoplakia progression to tumor. However, it may preserve the angio-configuration and spatial arrangement and keep intact the angeion vessel wall. Its mechanism of promoting blood circulation may be through removing blood stasis and benign angiopoiesis so as to resist carcinogenesis.

Actins↗
PubMed2000

Enhanced oxidant stress in synovial vessels of patients on hemodialysis.

OBJECTIVE: To test the hypothesis that the susceptibility of synovial vessels to redox uncoupling which could result in oxidative damage capable of promoting beta 2-microglobulin (beta 2 m) deposition. METHODS: The expression of oxidative markers by microvascular endothelial cells in hemodialysis (HD) patients, non-uremic patients and normal subjects was determined using immunostaining and Northern blotting. RESULTS: Synovial vascular endothelial cells of HD patients exhibited evidence of oxidant stress: induction of malondialdehyde (MDA) epitopes and heme oxygenase. These oxidative markers were not detectable in microvascular endothelial cells of other tissues from HD patients, as well as in the synovial vessels of non-uremic or normal controls. Higher levels of heme oxygenase mRNA in synovia were seen in patients with beta 2 m deposition compared with patients without beta 2 m deposition. CONCLUSIONS: Oxidative damage of the synovial microvasculature in uremic patients may be one of the factors which can promote deposition of beta 2 m in osteoarticular tissue.

Adult↗
PubMed2000

Activated protein C resistance in antiphospholipid thrombosis syndrome.

OBJECTIVE: To explore the correlation between antiphospholipid antibodies (APA), activated protein C resistance (APCR) and antiphospholipid thrombosis (APL-T) syndrome and further investigate the mechanism of thrombosis in APL-T syndrome. METHODS: ELISA, PTT-LA and APTT +/- APC methods were used to detect anticardiolipin antibodies (ACA), lupus anticoagulants (LA) and APC R in 20 APL-T syndrome patients. RESULTS: Twenty patients were diagnosed as APL-T. ACA-IgG, M and LA are strongly associated with APL-T. The incidence of APCR in APL-T (75%) was significantly higher than that of the normal group (5%). CONCLUSION: There was high prevalence of APCR in APL-T, which was strongly associated with LA. It is proposed that acquired APCR induced by APA is a key to understanding thrombosis in Chinese APL-T patients.

Activated Protein C Resistance↗
PubMed2000

[Experimental study on the influence of Gynostemma pentaphyllam Mak upon point mutation of Ha-ras oncogene in blocking leukoplakia from canceration].

OBJECTIVE: To study the influence of Gynostemma pentaphyllam Mak (GP) upon point mutation of Ha-ras oncogene the molecular mechanism of GP in blocking canceration, and the relationship between Ha-ras oncogene and canceration of leukoplakia. METHODS: DMBA induced carcinogeneses of the buccal pouch mucosa of the hamsters were divided into leukoplakia model group(LKG) and GP treated group(GPG). Point mutation (codon 61) of Ha-ras oncogene was detected by PCR-SSCP in both groups. RESULTS: The mutation incidence of LKG was 22.96%, while the mean incidence of GPG was 7.59% (The incidences of C20-OH group, glucoside group and aglucon group were 5.32%, 6.25% and 11.00% respectively). When treated with DMBA for 4 to 8 weeks, the mutation incidence of LKG ranged from 11.10% to 40.00%, while GPG ranged from 0 to 10.70%. CONCLUSIONS: GP has outstanding cancer blocking effect chiefly affected by free C20-OH. Mutation of Ha-ras oncogene plays an important role in leukoplakia canceration.

9,10-Dimethyl-1,2-benzanthracene↗