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Biomedical subjects

Z Tang

Publications and source records attributed to Z Tang.

At least 109 records · Page 6Linked to original sources

Mitochondrial DNA deletions are associated with ischemia and aging in Balb/c mouse brain.

Deletions in the mitochondrial DNA (mtDNA) of Balb/c mouse cerebrums, resembling deletions found in elderly humans or in patients with certain disorders, were detected by PCR. Analysis was carried out on mice of various ages and on mice in which the bilateral common carotid arteries had been incompletely ligated to reconstruct cerebral ischemia. A 3,867 bp mtDNA deletion was present only in old or ischemic mouse groups. Among the non-ischemic groups, it was found in 0 of 12 weaning, 0 of 12 young, and four of eight old mice. Among the ischemic groups, it was found in 12 of 17 young and 11 of 11 old mice. Moreover, the percentage of total mtDNA containing deletions was 22% for the old non-ischemic group, 37% for the young ischemic group, and 69% for the old ischemic group. In addition, PCR analysis detected two other deletions of 3,726 bp and 4,236 bp in 4 of the 11 old ischemic cerebrums. The results indicate that mtDNA deletions are associated with aging, that ischemia increases the incidence of mtDNA deletions, and that mtDNA deletions resulting from ischemia are more likely to occur in old mice than in young mice.

Age Factors↗

Msx2 gene dosage influences the number of proliferative osteogenic cells in growth centers of the developing murine skull: a possible mechanism for MSX2-mediated craniosynostosis in humans.

Throughout its complex morphogenesis, the vertebrate skull must at once protect the brain and expand to accommodate its growth. A key structural adaptation that allows this dual role is the separation of the bony plates of the skull with sutures, fibrous joints that serve as growth centers and allow the calvarial bones to expand as the brain enlarges. Craniosynostosis, the premature fusion of one or more calvarial bones with consequent abnormalities in skull shape, is a common developmental anomaly that disrupts this process. We found previously that a single amino acid substitution in the homeodomain of the human MSX2 gene is associated with the autosomal dominant disorder craniosynostosis, Boston type. This mutation enhances the affinity of Msx2 for its target sequence, suggesting that the mutation acts by a dominant positive mechanism. Consistent with this prediction, we showed that general overexpression of Msx2 under the control of the broadly expressed CMV promoter causes the calvarial bones to invade the sagittal suture. Here we use tissue-specific overexpression of Msx2 within the calvarial sutures to address the developmental mechanisms of craniosynostosis and skull morphogenesis. We demonstrate that a segment of the Msx2 promoter directs reporter gene expression to subsets of cells within the sutures. In late embryonic and neonatal stages, this promoter is expressed in undifferentiated mesenchymal cells medial to the growing bone. By P4, promoter activity is reduced in the suture, exhibiting a punctate pattern in undifferentiated osteoblastic cells in the outer margin of the osteogenic front. Overexpression of Msx2 under the control of this promoter is sufficient to enhance parietal bone growth into the sagittal suture by P6. This phenotype is preceded by an increase in both the number and the BrdU labeling of osteoblastic cells in the osteogenic fronts of the calvarial bones. These findings suggest that an important early event in MSX2-mediated craniosynostosis in humans is a transient retardation of osteogenic cell differentiation in the suture and a consequent increase in the pool of osteogenic cells.

Animals↗

Determination of trace elements in tissue of human uterine cancer by instrumental neutron activation analysis.

In this article, the low-temperature freeze-drying pretreated technique and instrumental neutron activation analysis were used to determine 29 trace elements in samples of human uterine cancer tissue. The content of these trace elements in uterine cancer tissue was compared with that in cervicitis tissue and in healthy tissue, respectively. Preliminary results indicated that significant differences in contents of Au, I, and Se were observed in these tissues.

Female↗

[Implication of mutation of hepatitis C virus 1b interferon sensitivity determining region(NS5A aa 2209-2248) response to interferon alpha therapy in patients with chronic hepatitis C].

Hepatitis C virus (HCV) isolates from 12 patients with chronic hepatitis C underwent the sequence analysis. Among the 12 patients, 9 obtained a complete response (CR), 2 partial response (PR) and 1 non--response (NR) after the treatment with IFN-alpha. The results showed that only single amino acid (aa) substitution in iIFN sensitivity determining region (ISDR) (aa 2213 and aa 2218) in 6 cases with CR was observed, while 3 cases of CR and all PR and NR cases had no aa mutation of ISDR. It is suggested that the ISDR in HCV NS5A was yet not identified by our patients.

Adult↗

An azoospermic man with a de novo point mutation in the Y-chromosomal gene USP9Y.

In humans, deletion of any one of three Y-chromosomal regions- AZFa, AZFb or AZFc-disrupts spermatogenesis, causing infertility in otherwise healthy men. Although candidate genes have been identified in all three regions, no case of spermatogenic failure has been traced to a point mutation in a Y-linked gene, or to a deletion of a single Y-linked gene. We sequenced the AZFa region of the Y chromosome and identified two functional genes previously described: USP9Y (also known as DFFRY) and DBY (refs 7,8). Screening of the two genes in 576 infertile and 96 fertile men revealed several sequence variants, most of which appear to be heritable and of little functional consequence. We found one de novo mutation in USP9Y: a 4-bp deletion in a splice-donor site, causing an exon to be skipped and protein truncation. This mutation was present in a man with nonobstructive azoospermia (that is, no sperm was detected in semen), but absent in his fertile brother, suggesting that the USP9Y mutation caused spermatogenic failure. We also identified a single-gene deletion associated with spermatogenic failure, again involving USP9Y, by re-analysing a published study.

Base Sequence↗

Cloning of karyopherin-alpha3 from Drosophila through its interaction with the nuclear localization sequence of germ cell-less protein.

The D. melanogaster germ cell-less (gcl) gene has previously been shown to play a key role in the establishment of the germ cell lineage during fly embryogenesis. To identify other molecules that function with Gcl in this process, we have conducted a yeast two-hybrid screen that utilized Gcl protein as bait. A predominant class of Gcl-interacting clones encodes a species of importin-alpha from Drosophila (karyopherin-alpha3; kap-alpha3), a nuclear-localization sequence binding protein previously shown to act in the transport of proteins from the cytoplasm to the nucleus. The expression of kap-alpha3 is widespread both temporally and spatially throughout the embryo during development, as judged by Northern blotting and whole-mount in situ hybridization to Drosophila embryos, suggesting that it functions at multiple stages of development. Studies of the Gcl/Kap-alpha3 interaction have identified a functional nuclear-localization sequence in Gcl protein which is necessary for an in vivo interaction and for nuclear entry of Gcl, making it likely that one role for Kap-alpha3 is to deliver Gcl protein to the nucleus. The identification of Kap-alpha3 and an in vivo substrate will allow for further characterization of the basis for specificity between importin-alpha molecules and their binding substrates.

Amino Acid Sequence↗

[The clinical and pathology study of HBV precore mutant infection in chronic HBV patients].

OBJECTIVE: To elucidate the clinical feature, pathological change and IFN therapy of HBV pre-c mutant(1,896 G-->A point mutation). METHODS: Mutation specific PCR was employed for detecting precore mutation from 108 serum and/or liver samples of patients with chronic hepatitis B infection. Liver damage was evaluated with Knodell's histology activity index(HAI) in 46 patients. RESULTS: HBV precore mutant existed popularly in different e systems status, but the detective rate of HBV precore mutant or mutant prevailing over wild type in HBeAb+ group(14.29%, 46.23%) was significantly higher than that in HBeAg+(0%, 6.45%)group. Mutant infection was associated with the severity of liver diseases, the detective rate in severe chronic hepatitis group was significantly higher(13.64%, 40.91%) than that in chronic asympotamatic carriers groupe(0%, 15.62%). 5 precore mutant positive patients with IFN treatment showed either response or nonresponse to IFN therapy. There was no significant difference of liver pathological change between mutant type and wild type infection in patients with mild chronic hepatitis. CONCLUSION: HBV precore mutant infection existed commonly in patients with chronic hepatitis B, despite of the e system status, though it was more prevalent in patients with HBeAb positive. Further study is needed in the pathogenicity and the treatment of HBV precore mutation.

Adolescent↗

[Screening and early diagnosis of primary liver cancer].

OBJECTIVE: To investigate the value of screening for early diagnosis of primary liver cancer (PLC). METHODS: A total of 18,816 persons, who were high-risk population of PLC, were divided randomly to allocated screening group and control group. In the screening group every individual was checked up by serum AFP test and ultrasound every 6 months but those in the control group were not. RESULTS: Eighty-six patients with PLC were detected in the screening group, while 51 patients with PLC occurred in the control group. In patients from the screening group 60.5% were in the early stage, 45.3% of them were with small liver cancer. However, in the control group the figures were 0 and 0 respectively. In the screening group, 57 patients with PLC were detected by follow-up screening every 6 months, 77.2% patients of this series were in the early stage. However in the screening group the other 29 patients with PLC were detected by screening but they were not followed up every 6 months. Early-stage patients were only 27.6% in this series. CONCLUSION: This suggests mass screening, especially continual screening every 6 months in fixed population can diagnose PLC early.

Humans↗

[Expressions of the metastasis-associated factors of a new human hepatocellular carcinoma cell line with highly metastatic potential].

OBJECTIVE: To explore the expressions of some metastasis-related factors in a new human hepatocellular carcinoma cell line with a highly metastatic potential by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. METHODS: A human hepatocellular carcinoma (HCC) cell line (MHCC97) was established derived from subcutaneous xenograft of a metastatic model of human HCC in nude mice (LCI-D20) by means of alternating cell culture in vitro and grown in nude mice. RT-PCR and immunohistochemistry were performed on this line and its intrahepatic xenografts and metastatic lesions to explore the expressions of metastasis-related factors. RESULTS: The tumorigenicity and metastatic rate to lungs of MHCC97 cell line was 100% by orthotopic inoculation. RT-PCR products for integrin alpha 5 and beta 1, uPAR, VEGF and nm23-H1 mRNA from MHCC97 cell line were positive. Immunostaining showed strongly positive for c-Met, uPAR in both of xenografts and lung metastatic lesions, and also positive in xenografts, but negative in lung metastatic lesions for integrin alpha 5 and beta 1. E-cadherin was not expressed either in xenografts or in the metastatic lesions. The PCR productions for HBsAg and HBxAg were positive, and negative for HBcAg. CONCLUSIONS: MHCC97 cell line has a ability to express some metastasis-associated factors. DNA for virus hepatitis B may be integrated into the genome of MHCC97 cells.

Animals↗

[Randomized controlled prospective study of secondary prevention for primary liver cancer].

OBJECTIVE: To evaluated the effectiveness of secondary prevention for primary liver cancer (PLC). METHODS: This is a randomized controlled study. 18,816 Shanghai urban residents, aged 35-55, with serum evidence of HBV infection or chronic hepatitis were randomly assigned into the screening group (9,373) or the control group (9,443). In the screening group, participants were tested with serum AFP and real time ultrasound every 6 months, while in the control group, participants were not informed about the study and received no screening. Participants with positive results underwent a diagnostic evaluation, and all patients diagnosed as PLC were treated appropriately and followed up. RESULTS: After 5 years of study, there were 22,631.5 person-years screened. 86 patients with PLC were detected. 51 patients were detected in the control group within 32,944 person-years. In the screened group, 60.5% (52/86) of patients were in stage I, and 45.3% (40/86) with small liver cancer. However, there were no patients in stage I or with small liver cancer in the control group. The resection rates were 46.5% in the screened group, and 7.8% in the control group. The 1 to 5 years survival rates of PLC patients in the screening group were 65.0%, 65.0%, 52.7%, 52.7% and 52.7%, respectively, and in the control group were 30.0%, 6.5%, 0%, 0% and 0%, respectively. CONCLUSION: Screening can detect PLC in the early stage, and improve the prognosis of PLC, indicating that secondary prevention can decrease the mortality of PLC.

Adult↗

Surgical treatment of hepatocellular carcinoma and related basic research with special reference to recurrence and metastasis.

OBJECTIVE: To summarize the progress of surgical treatment of hepatocellular carcinoma (HCC) and related basic research at the Liver Cancer Institute of Shanghai Medical University in the recent years, with special reference to recurrence and metastasis. METHODS: Published and unpublished update clinical and experimental data in the above-mentioned areas are summarized. RESULTS: Surgical resection has played an important role in improving prognosis of HCC, the 5-year survival were 63.4% for small HCC resection (n = 806), 39.6% for large HCC resection (n = 1061), 64.7% for cytoreduction (using hepatic artery cannulation and ligation) and sequential resection of initially unresectable HCC (n = 93), 56.0% for cytoreduction using transcatheter arterial chemoembolization (TACE) and followed by resection (n = 65), and 22.4% for hepatic resection with removal of tumor thrombi in portal vein (n = 103). Unfortunately, the 5-year recurrent rate after curative resection of HCC was up to 61.5%, which was mainly a result of intrahepatic "metastasis" and multicentric origin of HCC. Clinically, re-resection of subclinical recurrence yielded 56% of 5-year survival (n = 202); prevention of recurrence by transcatheter arterial chemoembolization (TACE) + Interferon, or LAK/IL-2 therapy have decreased 3-year recurrent rate from 33% to 11%-18%. In experimental aspect, metastatic human HCC model in nude mice (LCI-D20) and HCC cell line with metastatic potential (MHCC97) have been established; studies on HCC invasiveness in the molecular level revealed similar results that reported in other solid cancers, and small HCC showed slightly better biological characteristics as compared with large HCC; microvessel density (MVD) that reflecting angiogenesis adversely correlated with 5-year survival of small HCC; experimental interventions using antisense H-ras, bispecific antibody, BB94, as well as anti-angiogenic agents (TNP470, suramin, CAI, heparin, antisense VEGF, etc.) have been demonstrated to inhibit tumor growth and lung metastasis in nude mice model. CONCLUSIONS: Recurrence and metastasis are the major obstacle to further improve prognosis of HCC, studies should be conducted both in clinical and experimental aspects, "HCC invasiveness" will be the major target to be studied, particularly in the molecular level, and anti-angiogenesis will be one of the important approach.

Angiogenesis Inhibitors↗

Significance of anti-neutrophil cytoplasmic antibodies in patients with pauci-immune crescentic glomerulonephritis.

OBJECTIVE: To evaluate the significance of serum antineutrophil cytoplasmic antibodies (ANCAs) and the effects of immune suppressive treatments on its activity in patients with pauci-immune crescentic glomerulonephritis (PICGN). METHODS: Serum ANCAs and myeloperoxidase (MPO)-ANCA were detected by indirect immunofluorescence and enzyme-linked immunosorbent assay (ELISA) methods respectively, and the renal tissues infiltrating cells including CD4+, CD8+, CD68+ and PCNA+ cells were determined by four-layer peroxidase-antiperoxidase (PAP) method. The clinical manifestations, pathologic features and immune pathologic changes in patients with positive ANCAs were compared with that in patients with negative ANCAs. The effects of immune suppressive therapy on clinic and pathologic changes as well as ANCAs activity were also investigated in ANCAs positive and ANCAs negative patients. RESULTS: Both of clinic active manifestations such as the degree of hematuria, rapidly progressive renal failure and pathologic active features including segmental capillary necrosis and vasculitis were much common in patients with positive ANCAs as compared with that in patients with negative ANCAs. The number of infiltrating cells in renal tissue, especially CD4+ cells, was markedly higher in ANCAs positive patients than that in ANCAs negative patients. The effects of immune suppressive therapy were also much better in patients with positive ANCAs than that in patients with negative ANCAs. CONCLUSION: Serum ANCAs is not only a marker for diagnosis of systemic vasculitis, but also a sensitive predictor for evaluation of diseases' activity and treatment in patients with PICGN. The good effect of immune suppressive treatments on patients with PICGN is partially associated with the degree of ANCAs activity.

Adolescent↗

[Combination therapy of murine liver cancer with IL-12 gene and HSV-TK gene].

OBJECTIVE: To investigate the synergistic antitumor effects of murine IL-12 gene and HSV-TK gene therapy in mice bearing liver cancer. METHODS: Mouse liver cancer MM45T. Li (H-2d) cells were transfected with retroviral vector containing IL-12 gene or HSV/TK gene insert. Gene-modified liver cancer cells, MM45T. Li/IL-12 and MM45T. Li/TK, with stable expression of IL-12 and TK were obtained. Balb/c mice were inoculated subcutaneously with 2 x 10(5) MM45T. Li Cells. When the tumor reached a size of 0.5-1.0 cm, a mixture of MM45T. Li/TK cells and 60Co-irradiated MM45T. Li/IL-12 cell were injected intratumoraly. Ganciclovir (GCV) was injected i.p. (40 mg.kg-1.d-1) for 10 days. Intratumoral injection of 60Co-irradiated MM45T. Li/IL-12 cells was repeated twice in one week apart. Mice with distant tumors were treated according to the same protocol. CTL activity of spleen cells was measured by 51Cr-release assay and phenotype of tumor infiltrating lymphocytes by immunohistochemical staining. RESULTS: In mice treated with MM45T. Li/IL-12 or MM45T. Li/TK + GCV individually led to moderate reduction in tumor growth, but neither could eradicate the tumor completely, while in 60% of mice treated with a mixture of MM45T. Li/IL-12 and MM45T. Li/TK cells plus GCV, complete tumor regression was observed, with no tumor recurrence for two months. The growth of distant tumor was also inhibited significanty in mice similarly treated. Most of the mice received combined gene therapy plus GCV had abundant CD4+, CD8+ T lymphocyte infiltration. Their CTL activity was significantly higher than in mice received single gene therapy. CONCLUSION: Combination therapy with IL-12 gene and HSV-TK gene + GCV is effective for mouse liver cancer.

Animals↗

[Hepatic resection with removal of tumor thrombi for hepatocellular carcinoma with tumor thrombi in portal vein and curative analysis].

OBJECTIVE: To study the therapeutic effects of surgical treatment for hepatocellular carcinoma (HCC) with tumor thrombi in the main trunk or the first branch of the portal vein (PVTT) and factors affecting prognosis. METHODS: 111 HCC patients with PVTT underwent hepatic resection with removal of tumor thrombi in the first left or the right branch of the portal vein or removal of tumor thrombi by direct opening of the main trunk of the portal vein. Hepatic artery infusion and/or portal vein infusion were performed after hepatic resection with removal of tumor thrombi for HCC with PVTT in 22 of the patients. Among 111 patients, 32 received postoperative transhepatic arterial chemoembolization and/or portal vein chemotherapy. Conservative treatment and surgical exploration or hepatic artery ligation (HAL) and infusion (HAI) and/or portal vein infusion (PVI) were performed in other 14 and 20 HCC patients with PVTT, respectively. RESULTS: The 1-, 2-, 3-, 4- and 5- year survival rates were 61.7%, 36.2%, 32.3%, 24.4% and 22.4% in the resected group, respectively, whereas 14 HCC patients with PVTT treated conservatively died in three months and the 1-, 2- year survival rates were 6.0% and 0 in the 20 patients with surgical exploration or HAL and HAI and/or PVI respectively. CONCLUSIONS: Hepatic resection with removal of tumor thrombi for HCC with PVTT should be encouraged for the prolongation of life span and quality of life.

Adult↗

[Retrospective analysis of severe infection complicated with acute respiratory distress syndrome in children confirmed by autopic reports].

A retrospective review was made on 9 children (7-day to 14-month old) suffering from serious pneumonia complicated with acute respiratory distress syndrome and septicemia. The main clinical manifestation was continuous and serious hypoxemia, which was hard to treat, but PaCO2 was not increased obviously. The failure of multiple organs is not only a common complication, but also is a common cause of death. Consecutive observation of chest X-ray photograph is helpful to the diagnosis as the disease gets worse. Autopsy is still an important way to improve the knowledge of diseases in clinical diagnosis.

Female↗

[The comparison of component contents and pharmacological actions between two kinds of processed products of Pinellia rhizoma prepared by ginger juice and alum].

OBJECTIVE: To compare the component contents in Pinellia Rhizoma processed with ginger separately on orthogonal technology and pharmaceutical technology stipulated in pharmacopoeia, and study the action of the two differently processed products on animals. METHOD: Using gravimetric method and acid dye colorimetry to determine the total alkaloids, et al. RESULT AND CONCLUSION: The experiment has shown that the contents of total alkaloids of product of Pinellia Rhizoma processed by orthogonal technology are higher than those processed by pharmaceutical technology, but the contents of digged substances of the latter are higher than those of the former, and the toxicity of decoction of the latter is also higher than that of the former. Compared with raw Pinellia Rhizoma, the two products of Pinellia Rhizoma prepared by different technologies all have shown promoting action on PGE2 contents and activity of gastric proteinase in rat gastric juice. The experimental results also have shown that on the above mentioned items. There are no obvious differences between the product of Pinellia Rhizoma processed by orthogonal technology and the product processed by pharmaceutical technology. However, the component contents of raw Pinellia Rhizoma are lower than those of the above mentioned two processed products and help inhibit PGE2 contents and activity of gastric proteinase in rat gastric juice.

Alkaloids↗