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Biomedical subjects

Z Zhuang

Publications and source records attributed to Z Zhuang.

At least 91 records · Page 5Linked to original sources
PubMed1999

[DNA damage in human peripheral blood lymphocyte caused by nickel and cadmium].

OBJECTIVE: To understand the different implication of various forms of DNA damage in genotoxicity of nickel and cadmium. METHODS: Human peripheral lymphocyte was exposed to nickel chloride and cadmium chloride in vitro. Levels of DNA single-and double-strand breaks and DNA-protein crosslinks in human peripheral lymphocyte were determined with single cell gel electrophoresis (SCGE). Activity of poly (ADP-ribose) polymerase (PARP) was determined by [(3)H]-NAD incorporating method. RESULTS: Levels of DNA single-and double-strand breaks and DNA-protein crosslinks in human peripheral lymphocyte treated with nickel and cadmium were significantly higher than those untreated, but dose-response relationship only showed in those treated with 0.10 - 10.00 micromol/L of nickel chloride and 0.16 - 20.00 micromol/L of cadmium. Low levels of the two kinds of metal (0.10 - 0.40 micromol/L of nickel and 0.16 micromol/L of cadmium) could induce the cleavage of DNA and activate PARP, and high levels of the two kinds of metal (2.00 - 10.00 micromol/L of nickel and 0.80 - 20.00 micromol/L of cadmium) could not induce the enzyme cleavage of DNA. CONCLUSION: Formation and cleavage of DNA double strand and blockage of activation of PARP can play an important role in carcinogenesis and mutagenesis.

Cadmium Chloride↗
PubMed1999

[Effects of anion ions on the structures of lanthanum glycine amino acid complex compounds].

Two lanthanum-glycine amino acid complexes, La(Gly)3 (ClO4)3 x H2O and La(Gly)3Cl3 x 3H2O, were synthesized with different anion ions. The infrared spectra of two complexes were characterized. The results show that the two complexes have different structures with different anion ions and the water molecules exit with different status in the two complexes. The results also indicate that one of the perchlorate ions is involved in the coordination in La(Gly)a(ClO4)3 x H2O.

Anions↗
PubMed1999

Telomerase activity in microdissected human gliomas.

Future improvements in the diagnosis and treatment of human gliomas might rely on obtaining more specific information concerning the biologic characteristics of individual tumor cells. Telomerase, a ribonucleoprotein that synthesizes telomeres, has been reported to be expressed in a majority of human tumors, including several subtypes of brain tumor. We hypothesized that a quantitative assay for telomerase activity, combined with selective microdissection of tumor or normal brain cells, might reveal telomerase gain-of-function to be important in the pathogenesis of gliomas and that telomerase levels might have prognostic significance. We used tissue microdissection for selective analysis of tumor cells obtained from eight patients with glioma, one with a meningioma, and one with a primary B-cell lymphoma of the central nervous system. Normal brain tissue microdissected from another patient was used as a control. Telomerase activity was screened by an electrophoretic method and then assayed by a quantitative ELISA method. All of the eight gliomas had positive telomerase activity, as did the lymphoma. The meningioma and normal brain were negative. Quantitative analysis of telomerase activity did not correlate with tumor grade nor predict outcome. Selective tissue microdissection, combined with qualitative and quantitative telomerase assays, permits rapid and reliable detection of telomerase activity in diverse brain tumor tissues. These preliminary findings suggest that telomerase reactivation is a frequent event in glioma tumorigenesis that can be sensitively and specifically detected in gliomas of all histologic grades. Furthermore, specific detection of telomerase reactivation represents another mechanism by which tumor formation and progression might become the target of novel therapeutics.

Adult↗
PubMed1998

Mutation of the uracil DNA glycosylase gene detected in glioblastoma.

Despite extensive characterization of genetic changes in gliomas, the underlying etiology of these tumors remains largely unknown. Spontaneous DNA damage due to hydrolysis, methylation, and oxidation is a frequent event in the brain. Failure of DNA repair following this damage may contribute to tumorigenesis of gliomas. Uracil DNA glycosylase (UDG), an enzyme which excises uracil from DNA, is an important component of the base excision repair pathway. The sequence of a human homologue of uracil DNA glycosylase gene (UNG) has been recently identified. We performed PCR-based SSCP mutational analysis of UNG in 11 sporadic gliomas (six glioblastomas, two anaplastic astrocytomas, and three oligodendrogliomas) and eight glioblastoma cell lines. One out of six sporadic glioblastomas had a point mutation in exon 3, which resulted in a missense mutation in codon 143. None of the eight glioblastoma cell lines or the five non-glioblastoma sporadic gliomas showed a mutation. Genetic alterations of UNG may play a role in the development of a subset of primary glioblastomas.

Adult↗
PubMed1998

Pluripotent tumor cells in benign pituitary adenomas associated with multiple endocrine neoplasia type 1.

Analysis of human tumor cells in vitro enhances the study of numerous neoplastic conditions. However, it has been difficult to establish long-term cultures of adenoma cells, especially those of neuroendocrine origin, because the endocrine cells survive only briefly in culture, and fibroblasts overgrow the culture dish in 1 or 2 weeks. We describe cells isolated from pituitary adenomas in two patients with multiple endocrine neoplasia type 1 in which cells with a mesenchymal phenotype evolved from pituitary tumor cells. It appears that these poorly differentiated cells arose from multipotent adenoma cells. This represents a path of cell differentiation not observed previously in humans and may help explain the diverse nature of the benign tumors in multiple endocrine neoplasia type 1.

Adenoma↗
PubMed1998

Endocrine tumors of the cervix: morphologic assessment, expression of human papillomavirus, and evaluation for loss of heterozygosity on 1p,3p, 11q, and 17p.

BACKGROUND: Cervical endocrine tumors are rare lesions, with a varied diagnostic nomenclature. A recent consensus meeting proposed a standardized terminology. This study evaluated: 1) applicability of histopathologic guidelines; 2) evidence of loss of heterozygosity (LOH) at selected sites; and 3) the presence of human papillomavirus (HPV) detected by nonisotopic in situ hybridization (ISH). METHODS: Thirty-eight cases (patient age range, 19-88 years; mean, 48 years) were retrieved. Outcome data were available for 32 patients. Classification was based on architectural and cytologic features. Tissue was available from 15 cases for LOH analysis with D3S1234(3p14), D3S1289(3p21), THRB(3p24), TP53(17p13), D1S468(1p36), and INT-2(11q13). In ten cases, tissue was analyzed by nonisotopic ISH with HPV probes for types 6/11, 16/18, and 31/33. RESULTS: Tumors were divided into four groups: small cell carcinoma (SCC) (n=25); large cell neuroendocrine carcinoma (LCNC) (n=5); SCC with focal LCNC differentiation (n=3), and carcinoid tumor (n=5). Tumors defined as exclusively or predominantly SCC had a particularly poor prognosis, with 20 patients dead of disease (<6 years after diagnosis) and 6 alive with disease (after <3 years of follow-up). LOH at various 3p loci (3p14, 3p21, and 3p24) was observed in eight cases. One patient demonstrated LOH on 17p(TP53). Eight of ten cases assessed by ISH showed nuclear staining using a combined HPV-16/18 probe. CONCLUSIONS: Cervical endocrine tumors are highly aggressive and can be subdivided into definable categories. LOH at 3p loci is a frequent finding, as is nuclear staining with a combined HPV-16/18 probe. LOH at 17p(TP53 locus) appears to be relatively uncommon, suggesting that p53 mutations may not be developmentally significant.

Adult↗
PubMed1998

cDNA sequencing and analysis of POV1 (PB39): a novel gene up-regulated in prostate cancer.

We recently identified a novel gene (PB39) (HGMW-approved symbol POV1) whose expression is up-regulated in human prostate cancer using tissue microdissection-based differential display analysis. In the present study we report the full-length sequencing of PB39 cDNA, genomic localization of the PB39 gene, and genomic sequence of the mouse homologue. The full-length human cDNA is 2317 nucleotides in length and contains an open reading frame of 559 amino acids which does not show homology with any reported human genes. The N-terminus contains charged amino acids and a helical loop pattern suggestive of an srp leader sequence for a secreted protein. Fluorescence in situ hybridization using PB39 cDNA as probe mapped the gene to chromosome 11p11.1-p11.2. Comparison of PB39 cDNA sequence with murine sequence available in the public database identified a region of previously sequenced mouse genomic DNA showing 67% amino acid sequence homology with human PB39. Based on alignment and comparison to the human cDNA the mouse genomic sequence suggests there are at least 14 exons in the mouse gene spread over approximately 100 kb of genomic sequence. Further analysis of PB39 expression in human tissues shows the presence of a unique splice variant mRNA that appears to be primarily associated with fetal tissues and tumors. Interestingly, the unique splice variant appears in prostatic intraepithelial neoplasia, a microscopic precursor lesion of prostate cancer. The current data support the hypothesis that PB39 plays a role in the development of human prostate cancer and will be useful in the analysis of the gene product in further human and murine studies.

Amino Acid Sequence↗
PubMed1998

Two North American families with hereditary papillary renal carcinoma and identical novel mutations in the MET proto-oncogene.

Hereditary papillary renal carcinoma (HPRC) is a newly recognized inherited disorder characterized by a predisposition to develop multiple bilateral papillary renal carcinomas. Individuals affected with HPRC have been shown to have germ-line mutations in the tyrosine kinase domain of the MET proto-oncogene. We identified a novel mutation in exon 16 of the MET gene in two large North American HPRC families. The H1112R MET mutation segregated with the disease, was not present in 320 normal chromosomes, and caused malignant transformation of NIH 3T3 cells. By examining individuals with the H1112R mutation, we determined the age-dependent penetrance of this mutation and identified additional nonrenal malignancies that occurred in mutation carriers. Affected members of the two families shared the same haplotype within and immediately distal to the MET gene, suggesting a founder effect. The identification of the H1112R mutation will facilitate predictive testing in HPRC and guide future studies of the MET gene in human neoplasia.

3T3 Cells↗
PubMed1998

Evidence of independent origin of multiple tumors from patients with prostate cancer.

BACKGROUND: In men with prostate cancer, the gland usually contains two or more widely separate tumors. A critical issue of prostatic carcinogenesis is whether these multiple tumors are independent in origin. Molecular analysis of microsatellite (i.e., highly repeated, short nucleotide sequences) alterations in the DNA from separate tumors in the same prostate can be used to determine whether or not these separate tumors arise independently. METHODS: Four microsatellite polymorphic markers (D8S133, D8S136, and D8S137, for a putative tumor suppressor gene on chromosome 8p, and D17S855, for the BRCA1 gene on chromosome 17q) were used to examine the pattern of allelic loss in prostate cancer from 19 patients who had two or more distantly separate tumors (i.e., located on contralateral sides or separated by at least half the anterior-posterior diameter of the prostate). Forty distantly separate tumors were microdissected, DNA samples were prepared from formalin-fixed, paraffin-embedded wholemount prostate tissue section, and the overall frequencies of loss of heterozygosity at the four loci were determined. RESULTS: The pattern of allelic loss was compatible with independent tumor origin in 15 of 18 informative cases. A random discordant pattern of allelic deletion was observed in distantly separate tumors, whereas the same allele was consistently lost in cells from different regions of the same tumor. For three patients, the results were compatible with either intraglandular dissemination or independent origin of prostate cancer. CONCLUSIONS: Our data suggest that multiple tumors in some patients with prostate cancer have independent origin.

Chromosome Deletion↗
PubMed1998

Loss of heterozygosity and somatic mutations of the VHL tumor suppressor gene in sporadic cerebellar hemangioblastomas.

Cerebellar hemangioblastoma is a benign central nervous system neoplasm with characteristic proliferation of vascular and stromal cells. There is increasing evidence that the stromal cell population may represent the neoplastic component of hemangioblastoma, whereas the vascular component may be composed of reactive, nonneoplastic cells. Therefore, successful genetic testing for loss of heterozygosity requires selective analysis of target cell populations. Here, tissue microdissection was used to selectively analyze the stromal cell component of 20 archival sporadic cerebellar hemangioblastomas for loss of heterozygosity at the Von-Hippel Lindau (VHL) gene and somatic VHL gene mutations. Allelic deletions at the VHL gene locus were detected in the stromal cell component with one or more markers (D3S1038, D3S1110, and/or 104/105) in 10 of 19 (52.6%) informative cases. In all cases, heterozygosity at the VHL gene locus was retained in the vascular component. In two cases, aberrant bands in exon 2 of the VHL gene were demonstrated in the stromal cells by PCR-based single-strand conformation polymorphism analysis, and somatic missense mutations were successfully characterized in two of the sporadic hemangioblastomas by direct sequencing. The results suggest that allelic losses and mutations of the VHL tumor suppressor gene play a role in sporadic cerebellar hemangioblastoma tumorigenesis. Furthermore, because the genetic changes were detected in selectively procured stromal cell areas, the data provide strong evidence that the stromal cell represents a neoplastic component of hemangioblastoma.

Adolescent↗
PubMed1998

Ultraviolet-induced acute histological changes in irradiated nevi are not associated with allelic loss.

BACKGROUND: Transformed melanocytes in atypical nevi, which are thought to be precursors of melanoma, are frequently deleted on chromosomes 1p, 9q, and 9p21 (p16 locus). Single UV irradiation induces histological changes that are similar to those of atypical nevi and, in part, of melanoma in situ. OBJECTIVE: To determine the effects of UV irradiation on benign melanocytic nevi in vivo. DESIGN: We investigated one half of a symmetric nevus 1 week after a single UV exposure with 4 times the patient's minimal erythema dose and compared it with the nonirradiated, shielded half of the same nevus. Two to 3 areas containing 5 to 30 melanocytes in 7 nevi were microdissected (a total of 18 areas in each nonirradiated and irradiated part), followed by a single-step DNA extraction. Extracted genomic DNA was amplified using a polymerase chain reaction with polymorphic markers D1S450 (1p), D9S12 (9q), IFNA, and D9S171 (9p21) and subjected to autoradiography. OBSERVATIONS: Two, 3, 2, and 2 of 18 areas were homozygous for D1S450, D9S12, IFNA, and D9S171, respectively. No allelic loss could be demonstrated in either nonirradiated or irradiated nevi. CONCLUSIONS: Acute histological changes demonstrated in melanocytic nevi after UV irradiation are not followed by allelic loss on identical chromosomal areas found in dysplastic melanocytes of atypical nevi. This finding supports the hypothesis that initial nonspecific genetic events may occur after UV irradiation, followed by an increase in various repair mechanisms potentially leading to specific genetic damage and loss of heterozygosity; however, loss of heterozygosity is not detectable at an early stage.

Cell Nucleus↗
PubMed1998

Analysis of recurrent germline mutations in the MEN1 gene encountered in apparently unrelated families.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder that manifests as varying combinations of tumors of endocrine and other tissues (parathyroids, pancreatic islets, duodenal endocrine cells, the anterior pituitary and others). The MEN1 gene is on chromosome 11q13; it was recently identified by positional cloning. We previously reported 32 different germline mutations in 47 of the 50 familial MEN1 probands studied at the NIH. Eight different germline MEN1 mutations were encountered repeatedly in two or more apparently unrelated families. We analyzed the haplotypes of families with recurrent MEN1 mutations with seven polymorphic markers in the 11q13 region surrounding the MEN1 gene (from D11S1883 to D11S4908). Disease haplotypes were inferred from germline DNA and also from tumors with 11ql3 loss of heterozygosity. Two different disease haplotype cores were shared by apparently unrelated families for two mutations in exon 2 (five families with 416delC and six families with 512delC). These two repeat mutations were associated with the two founder effects that we reported in a prior haplotype analysis. The disease haplotypes for each of the other six repeat mutations (seen twice each) were discordant, suggesting independent origins of these recurrent mutations. Most of the MEN1 germline mutations including all of those recurring independently occur in regions of CpG/CpNpG, short DNA repeats or single nucleotide repeat motifs. In conclusion, recurring germline mutations account for about half of the mutations in North American MEN1 families. They result from either founder effects or independent occurrence of one mutation more than one time.

CpG Islands↗
PubMed1998

11q13 allelotype analysis in 27 northern American MEN1 kindreds identifies two distinct founder chromosomes.

We analyzed constitutional and tumor DNA from 27 MEN1 kindreds not known to be related to each other. Disease allele haplotypes were constructed for each pedigree based on shared alleles from two or more affected members and from determination of allelic loss patterns in their tumors. Analysis of disease allele haplotypes showed unexpected linkage disequilibrium at marker PYGM. Further haplotype analysis indicated this could be explained by the presence of two founder chromosomes, one in four families, the other in three. A shared disease haplotype was not observed among two MEN1 kindreds with the prolactinoma phenotype of MEN1.

Alleles↗