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Biomedical subjects

M Yao

Publications and source records attributed to M Yao.

At least 181 records · Page 10Linked to original sources
PubMed1995

[Combination therapy with interferon-alpha and continuous infusion of 5-fluorouracil for advanced renal cell carcinoma].

Between May 1990 and April 1994, eleven patients with metastatic renal cell carcinoma received a combination therapy with interferon-alpha (IFN alpha) and 5-fluorouracil (5FU). IFN was administered intramuscularly six or ten million units three times per week for 4 weeks and 300 mg/m2 of 5FU was administered by continuous intravenous infusion daily for 4 weeks. Of 8 evaluable patients, two had a partial response (25%) two had a minor response (25%), and two had a stable disease (25%). The common side effects of the regimen were flu-like symptoms (91%), mucositis (64%) and leukopenia (75%). Three patients refused this therapy because of severe mucositis or stomatitis. Although the combination of IFN and 5FU in patients with metastatic renal cell carcinoma had some efficacy, this regimen had severe toxicity especially for the gastrointestinal (GI) tract. None of the patients could be administered the initially scheduled dosage of 500 mg/m2 of 5FU. The dose limiting factor of this regimen is considered to be GI symptoms.

Aged↗
PubMed1995

Effect of antihydatid drugs on carbohydrate metabolism of metacestode of echinococcus granulosus.

A biochemical some enzymes of glycolysis and a partial reversed tricarboxylic acid cycle together with hydrolytic enzymes in the cyst wall of Echinococcus granulosus was carried out. Lactate dehydrogenase (LDH), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), and adenosine triphosphatase (ATPase) showed their high level of activity, suggesting that the proliferation of E. granulosus cyst wall is an energy-dependent process and the major pathways for glucose metabolism is glycolysis. Treatment of E. granulosus-infected mice with mebendazole and albendazole resulted in marked inhibition of PK, PEPCK and ATPase of E. granulosus cyst wall, whereas praziquantel had no effect, indicating that PK, PEPCK, and ATPase might be chemotherapeutic targets and the differences in the inhibitory effects might account for the efficacy of the three antihydatid drugs.

Adenosine Triphosphatases↗
PubMed1995

Infrequent somatic mutations of the p16 and p15 genes in human bladder cancer: p16 mutations occur only in low-grade and superficial bladder cancers.

A recently identified gene, p16, located on chromosome 9p21, has been shown to be deleted and/or mutated in various types of human cancers. To investigate structural alterations of p16 and a neighboring gene, p15, we examined human bladder cancers for mutations in the entire coding region of these genes using polymerase chain reaction and single-strand conformational polymorphism analysis. Of 50 samples obtained from patients with bladder cancer, 3 (6%), all low-grade and superficial tumors, were found to have p16 gene alterations. The alterations included 1 missense mutation and 2 single-base deletions. We found no p15 gene mutations in these 50 bladder cancers. Our results suggested that p16 gene mutations, although they occurred at low frequency, are involved in some low-grade and early stage bladder cancers.

Base Sequence↗
PubMed1994

Strand-specific cleavage of mismatch-containing DNA by deoxyinosine 3'-endonuclease from Escherichia coli.

A deoxyinosine-specific endonuclease, deoxyinosine 3'-endonuclease (Yao, M., Hatahet, Z., Melamede, R. J., and Kow, Y. W. (1994) J. Biol. Chem. 269, 16260-16268), from Escherichia coli was found to recognize mismatches in DNA. Using DNA duplexes containing a unique mismatch, the enzyme was found to hydrolyze the second phosphodiester bond 3' to the mismatch. The cleavage efficiency of deoxyinosine 3'-endonuclease on mismatch-containing DNA was affected by the nature of the mismatches. The cleavage activity was also affected by the sequence context surrounding the mismatches. The presence of a G/C or C/G pair immediately 3' or 5' to the mismatch substantially reduced the ability of the enzyme to nick the mismatch-containing DNA. The presence of two G/C pairs, one 5' and the other 3' to the mismatch, abolishes the ability of the enzyme to recognize the mismatch. Interestingly, deoxyinosine 3'endonuclease showed strong strand specificity on DNA containing mismatches, and only one strand of the mismatch-containing DNA was nicked by the enzyme. This strand specificity of mismatch cleavage was not affected by the nature of the mismatch. Preliminary data suggest that the strand specificity is terminus dependent; the enzyme cleaves the strand with the mismatch closer to its 5' terminus. However, when DNA duplexes containing deoxyinosine were used as substrates, deoxyinosine 3'-endonuclease cleaved exclusively the strand containing deoxyinosine. Deoxyinosine 3'-endonuclease also cleaved single-stranded DNA containing deoxyinosine, but not DNA containing normal deoxynucleotides or deoxynebularine, suggesting the enzyme uses different mechanisms of recognition for deoxyinosine and mismatches in DNA.

Apurinic Acid↗
PubMed1994

Somatic mutations of the von Hippel-Lindau tumor suppressor gene in sporadic central nervous system hemangioblastomas.

Hemangioblastoma is one of the benign tumors in the central nervous system. It is often associated with the von Hippel-Lindau (VHL) disease, a well known hereditary tumor syndrome. It is believed that inactivation of both alleles of VHL tumor suppressor gene is essential in the tumorigenic processes in hemangioblastomas associated with VHL disease. The molecular basis for the development of sporadic hemangioblastomas is not known. Here, we analyzed 13 cases of primary sporadic hemangioblastomas for somatic mutations of VHL gene with single strand conformational polymorphism analyses of the tumor DNAs. We detected abnormal single strand conformational polymorphism pattern in 7 tumors (54%). Of these 7 possibly mutated tumors, we successfully characterized 3 tumors by direct sequencing. We were unable to sequence 4 tumors because of the poor quality of DNA obtained from paraffin blocks. Somatic mutations in the 3 tumors were 2 missense mutations and 1 microdeletion. These mutations were observed in 1 tumor in exon 1 and 2 tumors in exon 2. Our results suggest that mutations of VHL tumor suppressor gene are involved in the development of at least 20% of sporadic central nervous system hemangioblastomas.

Base Sequence↗
PubMed1994

Purification and characterization of a novel deoxyinosine-specific enzyme, deoxyinosine 3' endonuclease, from Escherichia coli.

We have purified a novel endonuclease from Escherichia coli that recognizes deoxyinosine, a deamination product of deoxyadenosine in DNA. This activity, which we named deoxyinosine 3' endonuclease, is different from the known hypoxanthine DNA N-glycosylases which have been partially characterized in E. coli and other organisms. The enzyme was purified 24,800-fold to apparent homogeneity. SDS- and activity PAGE analyses indicate that the enzyme has an apparent molecular mass of 25 kDa. Deoxyinosine 3' endonuclease recognized deoxyinosine in both single- and double-stranded DNA but exhibited a 4-fold preference for double stranded over single-stranded DNA. In addition to deoxyinosine, the enzyme recognized urea residues and AP sites. Deoxyinosine 3' endonuclease has an obligatory requirement for Mg2+, but other cations such as Co2+ and Mn2+ could partially replace Mg2+. The optimal pH for deoxyinosine 3' endonuclease was around 7.5. In contrast to most of the known repair enzymes, deoxyinosine 3' endonuclease makes an incision at the second phosphodiester bond 3' to a deoxyinosine or AP site, leaving behind the intact lesion on the nicked DNA. Therefore, deoxyinosine 3' endonuclease recognizes, but does not remove, the lesion from the DNA molecule. The biological significance of this novel activity is discussed with reference to other repair activities in E. coli.

Base Sequence↗
PubMed1994

One-megabase yeast artificial chromosome and 400-kilobase cosmid-phage contigs containing the von Hippel-Lindau tumor suppressor and Ca(2+)-transporting adenosine triphosphatase isoform 2 genes.

We have isolated and ordered yeast artificial chromosomes (YACs) and cosmids surrounding the von Hippel-Lindau (VHL) tumor suppressor and plasma membrane Ca(2+)-transporting ATPase isoform 2 (PMCA-2) genes on chromosome 3p25-26. The YAC contig consists of six YACs and covers a region of 1 megabase. A cosmid-phage contig around VHL and PMCA-2 genes (400 kilobases) was established and integrated into the YAC map. Using these clones, we generated an EcoRI map of the 400-kilobase region. PMCA-2 and VHL complementary DNA were positioned entirely within the cosmid-phage contig as well as two polymorphic markers (D3S601 and D3S1317). This physical map of the cloned region will allow a detailed analysis of both the PMCA-2 and VHL genes. Some of the genomic clones may be useful for isolation of the full-length VHL complementary DNA.

Base Sequence↗
PubMed1994

Differential expression of protooncogenes in human germ cell tumors of the testis.

BACKGROUND: It has been suggested that tumorigenesis of the germ cell tumor of the testis includes abnormal and developmentlike differentiation of primordial germ cells to several mature type tumors. METHODS: To clarify roles of protooncogenes in the unique tumorigenic mechanism in the human germ cell tumor, the authors examined the expression of 15 protooncogenes in human primary germ cell tumors of the testis with Northern blot analyses. RESULTS: Fifteen (94%) of 16 seminomas and 5 (83%) of 6 embryonal carcinomas had a significant levels of N-myc expression, whereas they did not express two receptor type protooncogenes, c-erbB-1 and c-erbB-2. In contrast, some immature teratomas had a high level of c-erbB-1 expression, and an advanced case showed a significant level of c-erbB-2 expression. Immature teratomas did not show N-myc expression. Higher levels of c-mos expression were observed in several cases of seminomas and embryonal carcinomas. Expression of c-Ki-ras or N-ras was observed in all histologic subgroups and normal testes. CONCLUSION: A significant level of N-myc expression may be essential for undifferentiated tumors including seminoma and embryonal carcinoma, whereas c-erbB-1 and possibly c-erbB-2 may have important roles in the differentiated tumors such as immature teratoma. These results suggest that some of the protooncogene expression may be switched critically during the differentiation from seminomas or embryonal carcinomas to the more differentiated-type tumor.

Biomarkers, Tumor↗
PubMed1994

From embryonal carcinoma cells to neurons: the P19 pathway.

The differentiation of mammalian neurons during development is a highly complex process involving regulation and coordination of gene expression at multiple steps. The P19 mouse embryonal carcinoma cell line is a suitable model system with which to analyze regulation of neuronal differentiation. These multipotential cells can be maintained and propagated in tissue culture in an undifferentiated state. Exposure of aggregated P19 cells to retinoic acid results in the differentiation of cells with many fundamental phenotypes of mammalian neurons. Undifferentiated P19 cells are amenable to genetic manipulations such as transfection and establishment of stable clonal cell lines expressing introduced genes. Proteins that play a key role in the neuronal differentiation of P19 cells are beginning to be identified. These include retinoic acid receptors, the epidermal growth factor receptor and the transcription factors Oct-3 and Brn-2. The biological and technical advantages of this system should facilitate deeper analysis of the activities of proteins that play a role in neuronal differentiation.

Animals↗
PubMed1994

Clinicopathological spectrum of haemophagocytic syndrome in Epstein-Barr virus-associated peripheral T-cell lymphoma.

Haemophagocytic syndrome (HS) is frequently observed in Epstein-Barr virus-associated peripheral T-cell lymphoma (EBV-PTCL) and represents a major cause of death. In this communication we have further analysed the spectrum of HS in 12 patients with EBV-PTCL. The patients could be divided into three groups according to the time of onset of HS during the clinical course of PTCL. Group I patients (four cases) had HS as the initial clinical manifestation. All four patients were initially suspected to have malignant histiocytosis (MH) but a MH-like PTCL was later diagnosed. Group II patients (six cases) developed HS at the time of lymphoma relapse. Four of them belonged to the angioinvasive type PTCL. Group III patients (two cases) developed HS at clinical remission; both were angioinvasive type PTCL. Nine patients had serological evidence suggesting active EBV infection. The clinical course after the onset of HS was generally fulminant in each group with a median survival of only 44d despite combination chemotherapy and/or empirical therapy with high-dose immunoglobulin and corticosteroids in six patients. In conclusion, HS represents a severe complication of EBV-PTCL. Although most patients develop HS at a time of active lymphoma, the syndrome may occur when the lymphoma is in remission. Because of the poor outcome, early diagnosis and a new modality of treatment for HS associated with EBV-PTCL should be pursued in future.

Adult↗
PubMed1994

[Effect of artemether on glycogen, protein, alkaline phosphatase and acid phosphatase of Schistosoma japonicum].

When mice infected with Schistosoma japonicum for 32-35 d were treated ig with artemether (Art) at a single dose of 300 mg.kg-1 for 24 h, the glycogen content of female and male schistosomes decreased significantly with reduction rates of about 50%. 72 h after medication, the glycogen reduction rates were 64.1-77.9%. Meantime, the protein content of female and male worms was also decreased, the reduction rates being 68.1% and 49.3%, respectively. In infected mice treated ig with Art at the same dosage for 24 h, the inhibition rates of alkaline phosphatase (AKP) activity in female and male worms were 30% and 25%, respectively. 72 h later, the AKP activity of female worm was further inhibited to 62.3% as compared with the control. Besides, the inhibitory effect of Art on acid phosphatase (ACP) activity of female worm was also more apparent than that of male worm. 72 h after medication, the respective inhibition rates of ACP activity in female and male worms were 75.7% and 47.6%. The results indicated that Art might exert its effect on both carbohydrate and protein metabolism of schistosomes.

Acid Phosphatase↗
PubMed1994

[Infection of acid-fast bacterial L-forms].

One hundred and fifty five cases which pathological diagnosis were chronic lymphadenitis were studied in order to detect infection of acid-fast bacterial L-forms by Ziehl-Neelsen (ZN), intensified kinyoun (IK) and immunohistochemical staining (PAP). The results showed that the expression of M-tuberculosis antibody was positive in 106 cases (68.4%). Among them, 94 cases (60.6%) were positive in IK staining. The positive rate of acid-fast bacillus was 0.6% (1 case), of L-forms was 60% (93 cases). L-forms are higher pleomorphic, spherical bodies, giant bodies or long filaments were shown. The L-forms mostly localised within macrophages, only a few distributed sporadically. The possible causes of misdiagnosis physician and pathologist were discussed. The prognostic value was also suggested.

Antibodies, Bacterial↗
PubMed1994

[M-VAC chemotherapy for advanced urothelial cancer--side effects and their management].

Since the M-VAC (methotrexate, vinblastine, doxorubicin, cisplatin) regimen was reported by Sternberg in 1985, it has been widely accepted for the treatment of metastatic transitional cell carcinoma. This regimen has a significantly high response rate, but bone marrow suppression and gastrointestinal (GI) symptoms are inevitable. To complete this M-VAC regimen, preventive therapy for side effects is necessary. From November 1986 to March 1993, a total of 72 patients were admitted and received M-VAC therapy at our hospital. All of them had metastatic or invasive transitional cell carcinoma and they received a total of 163 complete courses of M-VAC therapy. We examined the side effects of this M-VAC regimen, and evaluated the effectiveness of colony-stimulating factor for prevention of granulocytopenia or granisetron for prevention of GI symptoms. Twenty-three patients (39 courses) were given recombinant colony-stimulating factor. This cytokine prevented the nadir of neutropenia and shortened the period to reach the nadir and period that the neutrophil count was below 1,000/mm3. Twelve patients (26 courses) were given granisetron, with significant reduction of the incidence of GI symptoms. These findings suggest that M-VAC therapy is effective and safe when used in combination with these drugs.

Adult↗
PubMed1993

Identification of the von Hippel-Lindau disease tumor suppressor gene.

A gene discovered by positional cloning has been identified as the von Hippel-Lindau (VHL) disease tumor suppressor gene. A restriction fragment encompassing the gene showed rearrangements in 28 of 221 VHL kindreds. Eighteen of these rearrangements were due to deletions in the candidate gene, including three large nonoverlapping deletions. Intragenic mutations were detected in cell lines derived from VHL patients and from sporadic renal cell carcinomas. The VHL gene is evolutionarily conserved and encodes two widely expressed transcripts of approximately 6 and 6.5 kilobases. The partial sequence of the inferred gene product shows no homology to other proteins, except for an acidic repeat domain found in the procyclic surface membrane glycoprotein of Trypanosoma brucei.

Amino Acid Sequence↗
PubMed1993

von Hippel-Lindau syndrome: cloning and identification of the plasma membrane Ca(++)-transporting ATPase isoform 2 gene that resides in the von Hippel-Lindau gene region.

We have isolated and analyzed full-length complementary DNA clones encoded by a 200-kilobase gene encompassing the D3S601 locus that resides in the von Hippel-Lindau (VHL) gene region. The deduced amino acid sequence shows 99% identity with the published sequence of the rat plasma membrane Ca(++)-transporting ATPase isoform 2 complementary DNA, implying that we have cloned and positioned the human plasma membrane Ca(++)-transporting ATPase isoform 2 gene within the VHL critical region. The gene is expressed in VHL target tissues and should be considered a potential candidate gene for the VHL disease.

Amino Acid Sequence↗
PubMed1993

von Hippel-Lindau disease: identification of deletion mutations by pulsed-field gel electrophoresis.

Von Hippel-Lindau disease (VHL) is an inherited multisystem neoplastic disorder. We prepared a 2.5-megabase (Mb) restriction map of the region surrounding the VHL gene and identified and characterized overlapping deletions in three unrelated patients affected with VHL. The smallest nested deletion (100 kb) was located within a 510-kb NruI fragment detected by 19-63'. The rearrangements detected will be useful in isolating and evaluating candidate cDNAs for the VHL gene. The detailed physical map will be useful in studying the organization and structure of genes in the VHL region.

Adult↗