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Biomedical subjects

A Zhou

Publications and source records attributed to A Zhou.

At least 91 records · Page 5Linked to original sources
PubMed1997

Interferon action and apoptosis are defective in mice devoid of 2',5'-oligoadenylate-dependent RNase L.

2',5'-Oligoadenylate-dependent RNase L functions in the interferon-inducible, RNA decay pathway known as the 2-5A system. To determine the physiological roles of the 2-5A system, mice were generated with a targeted disruption of the RNase L gene. The antiviral effect of interferon alpha was impaired in RNase L-/- mice providing the first evidence that the 2-5A system functions as an antiviral pathway in animals. In addition, remarkably enlarged thymuses in the RNase L-/- mice resulted from a suppression of apoptosis. There was a 2-fold decrease in apoptosis in vivo in the thymuses and spleens of RNase L-/- mice. Furthermore, apoptosis was substantially suppressed in RNase L-/- thymocytes and fibroblasts treated with different apoptotic agents. These results suggest that both interferon action and apoptosis can be controlled at the level of RNA stability by RNase L. Another implication is that the 2-5A system is likely to contribute to the antiviral activity of interferon by inducing apoptosis of infected cells.

Adenine Nucleotides↗
PubMed1997

Effect of urine-derived compounds on cAMP accumulation in mouse vomeronasal cells.

Urine-derived compounds from the male mouse altered the levels of the second messenger molecule cAMP differentially in female mouse vomeronasal (VN) cells when compared with olfactory cilia. cAMP levels in VN cells increased after exposure to forskolin and GTP-gamma-S, while the levels decreased after exposure to the urine-derived compounds, dehydro-exo-brevicomin (DHB) and 2-(sec-butyl)-4, 5-dihydrothiazole (SBT), in a dose-dependent manner. The general odorant citronellal did not alter cAMP levels. In contrast DHB, SBT and citronellal increased cAMP levels in olfactory cilia. We concluded that urine-derived compounds exert a differential effect on cAMP accumulation in mammalian VN and olfactory receptor neurons.

Acyclic Monoterpenes↗
PubMed1997

Defective prohormone processing and altered pancreatic islet morphology in mice lacking active SPC2.

The prohormone convertase SPC2 (PC2) participates in the processing of proinsulin, proglucagon, and a variety of other neuroendocrine precursors, acting either alone or in conjunction with the structurally related dense-core granule convertase SPC3 (PC3/PC1). We have generated a strain of mice lacking active SPC2 by introducing the neomycin resistance gene (Neor) into the third exon of the mSPC2 gene. This gene insertion results in the synthesis of an exon 3-deleted form of SPC2 that does not undergo autoactivation and is not secreted. The homozygous mutant mice appear to be normal at birth. However, they exhibit a small decrease in rate of growth. They also have chronic fasting hypoglycemia and a reduced rise in blood glucose levels during an intraperitoneal glucose tolerance test, which is consistent with a deficiency of circulating glucagon. The processing of proglucagon, prosomatostatin, and proinsulin in the alpha, delta, and beta cells, respectively, of the pancreatic islets is severely impaired. The islets in mutant mice at 3 months of age show marked hyperplasia of alpha and delta cells and a relative diminution of beta cells. SPC2-defective mice offer many possibilities for further delineating neuroendocrine precursor processing mechanisms and for exploring more fully the physiological roles of many neuropeptides and peptide hormones.

Animals↗
PubMed1997

Urine and urine-derived compounds induce c-fos mRNA expression in accessory olfactory bulb.

Soiled bedding from male mice induced c-fos mRNA expression in the accessory olfactory bulb (AOB) and main olfactory bulb (MOB) of female mice. The increase observed in the AOB, but not the MOB, was dependent on the presence of the vomeronasal organ (VNO). Male urine alone also increased c-fos mRNA expression in the AOB. The urine-derived compounds dehydro-exo-brevicomin (DHB) and sec-butyl-dihydrothiazole (SBT) in combination with major urinary protein (MUP) induced significantly greater c-fos mRNA expression in the AOB than in the MOB. The results indicate that compounds derived from male urine are detected at the AOB and suggest that specific urinary compounds play an important role in AOB-mediated reproductive events.

Alpha-Globulins↗
PubMed1997

PACE4: a subtilisin-like endoprotease with unique properties.

PACE4 is one of the neuroendocrine-specific mammalian subtilisin-related endoproteases believed to function in the secretory pathway. The biosynthesis and secretion of PACE4 have been studied using transfected neuroendocrine and fibroblast cell lines. as well as primary pituitary cultures. ProPACE4 (approx. 106 kDa) is cleaved intracellularly before secretion of PACE4 (approx. 97 kDa); the N-terminal propeptide cleavage is accelerated in a truncated form of PACE4 lacking the Cys-rich C-terminal region (PACE4s). Neither PACE4 nor PACE4s is stored in regulated neuroendocrine secretory granules, whereas pro-opiomelanocortin-derived peptides and prohormone convertase I enter the regulated secretory pathway efficiently. The relatively slow cleavage of the proregion of proPACE4 in primary anterior pituitary cells, followed by rapid secretion of PACE4, is similar to the results for proPACE4 in transfected cell lines. The enzyme activity of PACE4 is distinct from furin and prohormone convertases, both in the marked sensitivity of PACE4 to inhibition by leupeptin and the relative insensitivity of PACE4 to inhibition by Ca2+ chelators and dithiothreitol; PACE4 is not inhibited by the alpha1-antitrypsin Portland variant that is very potent at inhibiting furin. The unique biosynthetic and enzymic patterns seen for PACE4 suggest a role for this neuroendocrine-specific subtilisin-like endoprotease outside the pathway for peptide biosynthesis.

Blotting, Western↗
PubMed1997

Expression of soluble, active human macrophage colony stimulating factor in Escherichia coli.

Human macrophage colony stimulating factor (M-CSF) has been successfully overexpressed in Escherichia coli AD494 (DE3) with an expression level of approximate 26% of the total cellular proteins. The truncated human M-CSF gene encoding the amino-terminal 149 amino acids was subcloned into the prokaryotic expression vector pET11d under the control of the inducible T7 promoter. Nearly 40% of the recombinant protein was in the soluble fraction which showed obvious stimulating effects on mouse macrophage colony formation and had an M-CSF specific activity of approximately 1 x 10(6) units/mg soluble protein.

Animals↗
PubMed1997

Renaturation, purification, and characterization of human plasminogen activator inhibitor type 2 (PAI-2) accumulated at high level in Escherichia coli.

Plasminogen activator inhibitor 2 (PAI-2) is an important regulator of plasminogen activation, which inhibits both tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). In this study we have developed a high-level expression system by inserting a modified PAI-2 gene downstream of the T7 promoter. The expression level of recombinant PAI-2 amounted to 55-60% of total microbial protein. By efficient renaturation and one-step purification, the recombinant protein was purified to homogeneity. The specific activity and yield of recombinant PAI-2 reached 33,000 IU/mg and 10 mg per gram wet weight of Escherichia coli cells, respectively. The second-order rate constant for uPA was 2.6-2.8 x 10(6) M(-1) x s(-1).

Cloning, Molecular↗
PubMed1997

Direct interactions of human natural killer cells with Cryptococcus neoformans inhibit granulocyte-macrophage colony-stimulating factor and tumor necrosis factor alpha production.

Human natural killer (NK) cells and T lymphocytes can bind to and inhibit the growth of the yeast-like organism Cryptococcus neoformans. Binding of target cells to NK or T cells also has the potential to modulate cytokine production by the effector cells. In this study, we assessed the ability of C. neoformans to modulate NK cell production, or in some cases T-cell production, of granulocyte-macrophage colony-stimulating factor (GM-CSF) or tumor necrosis factor alpha (TNF-alpha). We found that freshly isolated human NK cells from most individuals make GM-CSF and TNF-alpha constitutively when cultured in vitro. The addition of C. neoformans to T-cell fractions which do not make GM-CSF constitutively did not affect GM-CSF production, but the addition of C. neoformans to NK cell fractions significantly reduced the amounts of GM-CSF produced in most NK cell samples. The reduction in the amount of GM-CSF in C. neoformans-NK cell cocultures could not be attributed to loss of lymphocyte viability or to C. neoformans adsorbing or degrading the cytokine and was dependent on direct contact between the NK cells and cryptococcal cells. GM-CSF was not the only cytokine to be down-regulated. TNF-alpha production was also diminished when NK cells were incubated with C. neoformans. The regulation of both cytokines was at the transcriptional level because GM-CSF and TNF-alpha mRNA levels were lower in NK cell samples incubated with C. neoformans than in NK cell samples incubated without C. neoformans. Diminished production of constitutively produced cytokines resulting from the interaction of NK cells with cryptococcal cells has the potential to affect phagocytic cells in the immediate regional environment and to damp the immune response.

Cryptococcus neoformans↗
PubMed1997

Preservation of functioning human thyroid "organoids" in the scid mouse. IV. In vivo selection of an intrathyroidal T cell receptor repertoire.

To study the in vivo influence of thyroid cells on the T cell receptor repertoire in human autoimmune thyroid disease, we mixed lymphocyte-free thyrocytes (approximately 1.2 x 10[6]) from patients with Graves' disease with autologous peripheral blood mononuclear cells (PBMC; approximately 1.5 x 10[6]) and transplanted this mixture sc into scid mice while suspended in a basement membrane gel (approximately 0.4 ml). Controls included mice that received either thyrocytes only or PBMC only. The resulting artificial mixed cell thyroid organoids were explanted after 5 weeks, and their T cell receptor repertoire was examined. Of a total of 63 organoids constructed, 60 were recovered (95.2%). Total RNA was extracted and then analyzed by reverse transcription-PCR primarily for human T cell receptor (hTcR) Vbeta gene expression using 21 hTcR Vbeta amplimers. A restricted pattern of hTcR Vbeta gene expression was found, with 6 Vbeta genes (Vbeta5, 6, 7, 8, 13.1, and 18) predominantly expressed [P < 0.05, by ANOVA on ranks and Student-Newman-Keul's (SNK) test]. PBMC and control organoids showed no preferential selection of particular hTcR V gene-expressing T cells. This reductionist, mixed cell, thyroid model reflected earlier observations in human and murine autoimmune thyroid diseases in which a bias in hTcR V gene family expression had been observed. The model permitted in vivo T cell selection and/or enrichment of potentially disease relevant human T cells.

Animals↗
PubMed1997

Detection of major T cell epitopes on human thyroid stimulating hormone receptor by overriding immune heterogeneity in patients with Graves' disease.

To examine the major immunogenic regions of the human TSH receptor (hTSHR), we examined 14 patients with Graves' disease and 14 healthy control subjects for their peripheral blood T cell proliferative responses to 29 synthetic peptides representing the entire ectodomain of the hTSHR (TSHR-ecd). By combining an analytical approach encompassing the grading of peptide-induced responses and nonparametric testing, we obtained evidence for highly significant differences (P = < 0.000001) in the patient group compared with minor differences in the control group (P = 0.045). To account for this difference, we identified four major T cell epitopes (amino acid 247-266, 202-221, 142-161, and 52-71), by multiple comparison analysis, in the patient group. Furthermore, we demonstrated by radiolabeled PCR that the responding T cells were clonally expanding. These findings demonstrate that despite likely differences in human leukocyte antigen type among patients with Graves' disease, several distinct hTSHR epitopes elicited significant responses in the immune system of patients with Graves' disease, and that such patients are most often poorly tolerant to particular epitopes of the TSH receptor ectodomain, The data support the notion of TSHR peptide antigens overriding human immune heterogeneity in patients with Graves' disease, and raise the possibility of applying analog peptide blockade to suppress T cell responsivity.

Adult↗
PubMed1997

[Evaluation of the function of palatine tonsil with regard to phagocytosis].

Trypan blue and Indian ink made in Fuzhou as vital staining dyes were injected into the abdominal cavities of rabbits. Nine days later, the tonsil, thymus, spleen and lymph nodes were examined. Numerous pigment granules were observed in the macrophages of the spleen and lymph node. However, no phagocytosis of pigment granules was found in the palatine tonsil and thymus. It indicated that the function of palatine tonsil as a lymph organ is to contact exogenous antigens and to take part in immune response. It is important for children, especially infants, to establish a complete immune mechanism. The Tonsils reach their maximum development in childhood and thereafter decline. Once the palatine tonsils become chronic foci, surgical removal of the diseased tonsils is necessary.

Animals↗
PubMed1997

[Phase III clinical studies with ondansetron (Qilu) in the prophylaxis of nausea and vomiting induced by non-cisplatin chemotherapy].

OBJECTIVE: This study was undertaken to further determine the clinical value of ondansetron (OND, supplied by Qilu Pharmaceutical Company) in the prophylaxis of nausea and vomiting induced by non-cisplatin chemotherapy. METHODS: A total of 193 patients were enrolled in the multicenter prospective study and were given treatment of non-cisplatin based chemotherapy. All patients were treated with OND 8 mg i.v. once a day during chemotherapy, followed by OND 4 mg orally twice a day for one day after chemotherapy. RESULTS: The effective control rate (0-2 emetic episodes) on the first day was 93.3%. Total control of delayed vomiting (day 2-5) was as high as 94.8 to 99.5%. The mean frequency of vomiting was 0.4, 0.4, 0.2, 0.1 and 0.1, respectively from day 1 to day 5. Adverse effects were minor and tolerable. CONCLUSION: This modified regimen of treatment with OND is effective in the control of vomiting induced by non-DDP chemotherapy.

Adolescent↗
PubMed1997

[Phase III clinical studies with ondansetron (Qilu) in the prophylaxis of nausea and vomiting induced by cisplatin].

OBJECTIVE: To further evaluate the clinical usefulness of ondensetron(OND, supplied by Qilu Pharmaceutical Company) with modified regime in the prevention of cisplatin (DDP)-induced nausea and vomiting. METHODS: A total of 773 patients were enrolled in a multicenter cooperative study. Of them, 330 patients were given i.v. OND 8 mg once or twice a day and 443 patients were given i.v. OND 8 mg plus dexamethasone(DXM) 10 mg once a day during the therapeutic period of DDP, followed by OND 4 mg orally twice a day for two days after DDP treatment. RESULTS: Effective control of acute nausea was achieved in 86.7% and 94.8% of the patients receiving OND alone and OND plus DXM, respectively(P < 0.001). The mean frequency of vomiting was 0.9 times in OND and 0.4 times in OND plus DXM(P < 0.01). Total control of delayed vomiting (day 2-5) was comparable in both groups. Complete inhibition of vomiting (CR rate) was more frequently observed in males than in females. Adverse effects were identical and well tolerated. CONCLUSION: OND with modified regimen is effective in the control of DDP-induced vomiting. It is more effective when OND and DXM are given than OND given alone.

Adolescent↗
PubMed1997

[The clinical course and treatment results of lung metastases from breast cancer].

OBJECTIVE: To analyse the clinical course and treatment result of lung metastases from breast cancer. METHODS: 122 cases with lung metastases from breast cancer were treated by chemotherapy or chemotherapy plus endocrine therapy. Treatment results were assessed according to WHO criteria and survival rate estimated using the life table. RESULTS: The median time from initial treatment of primary tumour to lung metastases was 22 months. Sites of common consecutive metastases were lung, liver and bone. The overall response rate was 48% with a CR rate of 15%. Compared to non-DDP-encompassing regimen, the CR rate was higher in DDP-based chemotherapy (7% versus 21%, P < 0.05) with a longer median survival time (MST). The PR rate was higher in regimen containing anthracycline (48%) than in that without anthracycline (20%, P < 0.01). The response rate was similar between chemotherapy and chemotherapy plus endocrine therapy (P > 0.05). No difference in MST was observed between patients receiving anthracycline- and non-anthracycline-encompassing regimens. The 1-,3-,5- and 10-year survival rate was 77%, 22%, 11% and 10%, respectively. The size of primary tumour, the length of disease-free interval, the number of lung metastases may provide additional information for predicting patients' survival after treatment of lung metastases. CONCLUSION: Combination chemotherapy, especially DDP-based chemotherapy may prolong survival time of patients with lung metastases from breast cancer.

Adult↗
PubMed1997

Research on the mechanism of endothelin inflammatory effects on human mesangial cells.

OBJECTIVE: To investigate the mechanism of endothelin (ET) inflammatory effects on human mesangial cells (HMC). METHODS: The following experiments were performed on cultured HMC after ET-1 stimulation: (1) the expression of tumor necrosis factor-alpha (TNF alpha), interleukin-1 beta (IL-1 beta), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelin-1 (ET-1) itself messenger ribonucleic acid (mRNA) was determined by Northern Blot analysis; (2) the TNF alpha concentration was tested with radioimmunoassay; the IL-1 activity was assayed by the enhancement of thymocyte proliferation in response to mitogen; the surface expression of ICAM-1 and VCAM-1 was measured with cell enzyme linked immunoadsorbent assay (ELISA) analysis. RESULTS: ET-1 (10(-7) mol/L) induced the following changes on HMC: (1) up-regulation of the expression of TNF alpha mRNA and protein; (2) up-regulation of the expression of ICAM-1 and VCAM-1 mRNA and protein; (3) up-regulation of the expression of ET-1 itself mRNA. However, the expression of IL-1 mRNA and protein was not changed. CONCLUSIONS: ET-1 can stimulate HMC to produce TNF alpha, ICAM-1 and VCAM-1, and thereby induce inflammatory effects. ET-1 can also stimulate HMC to up-regulate the expression of ET-1 itself, so as to amplify inflammatory effects. So, ET-1 is actually an inflammatory mediator and may play an important role in the pathogenesis of glomerulonephritis.

Cells, Cultured↗
PubMed1997

[Influence of antisense N-ras 1 gene on smooth muscle cell proliferation after arterial injury].

OBJECTIVES: To develop a new way to prevent the process of restenosis after arterial injury, we transfered the recombinant antisense N-ras 1 gene to the iliac arteries of rabbits after injury and studied the influence of gene therapy with antisense N-ras 1 on the vascular segment. METHODS: The constructed recombinant antisense N-ras 1 gene to deliver into the iliac arteries of rabbits after injury. The rabbits were randomly divided into gene therapy group, vector group, and sense N-ras 1 control. The segments of treatment rabbits were analysed by angiography of vessels, pathological study, Northern blotting, and Western blotting technique. RESULTS: The minimum angiographic lumen diameter measured during gene therapy and at follow-up, for the gene therapy group (at 4 weeks) was 0.80 +/- 0.10mm and the vector control 0.35 +/- 0.13mm (P < 0.01). Histologically, the area of neointima measured, for gene the therapy group (at 4 weeks) was 0.43 +/- 0.05mm2, and the vector control group 0.82 +/- 0.03mm2 (P < 0.01). By using Northern blotting and Western blotting technique, we found that cell's ras mRNA of the vessel segments of gene local delivery was significantly lower than that of the control. Cell's p21 was significantly lower than that of the control. CONCLUSIONS: The antisense N-ras 1 inhibites VSMC proliferation. The result implicates the potential value in future gene therapy of restenosis.

Angioplasty, Balloon↗