Search PubMed⌕ Search

Biomedical subjects

M Yamakawa

Publications and source records attributed to M Yamakawa.

At least 37 records · Page 2Linked to original sources
PubMed2001

Correlation between p21(waf1) and p16(INK4a) expression in hepatocellular carcinoma.

Background: The cyclin dependent kinase p21(waf1) plays a crucial role in the regulation of cell cycle. The family of p53 proteins has the ability to induce p21(waf1), whereas p16(INK4a) modulates post-transcriptionally the expression of p21(waf1). Methods: Total 36 hepatocellular carcinomas (HCCs) and 24 paired adjacent liver tissues were evaluated for the following: (1) expression of p21(waf1) and p16(INK4a); (2) that of p21(waf1), p73 and p63 mRNAs; (3) genomic mutations and the loss of heterozygosity of p73 and p53; and (4) frequency of methylation in the 5'CpG promoter region of p16(INK4a). Results: In HCCs compared with the adjacent non-cancerous liver tissues, the expression of p21(waf1) and p16(INK4a) was reduced. Indeed, p21(waf1) was not detected in 36% (8/22) of HCCs in spite of the presence of p21(waf1) mRNA: among them, mutations of p53 gene were found in 50%, whereas a lack of p16(INK4a) expression in all of them. p21(waf1) and p16(INK4a) were reduced in proportion to the degree of methylation in p16(INK4a) gene. p73 did not mutated, and p63 did not expressed in HCCs. Conclusion: Methylation status of p16(INK4a) gene will play a part for reducing constitutive expression of p16(INK4a) and of p21(waf1) coordinately in HCCs.

Journal Article↗
PubMed2001

Truncated mutant B subunit for factor XIII causes its deficiency due to impaired intracellular transportation.

Two Japanese patients were newly diagnosed as having B subunit (XIIIB) deficiency of factor XIII (former type I deficiency). Both patients have a previously described one-base deletion at the boundary between intron A/exon II in the XIIIB gene, heterozygously or homozygously. A founder effect was proposed for this mutation because 3 unrelated patients with XIIIB deficiency also share 2 3'-polymorphisms. In one patient heterozygous for the above mutation, a novel mutation was also identified: a deletion of guanosine in exon IX (delG) of the XIIIB gene. To understand the molecular and cellular pathology of the delG mutation, expression studies were performed using a cultured mammalian cell line. Pulse-chase experiments showed that a resultant truncated XIIIB remained inside the cells and could not be secreted into the culture medium. Furthermore, immunocytochemical examinations by epifluorescence, confocal, and electron microscopes indicated impaired intracellular transportation of the truncated XIIIB from the endoplasmic reticulum to the Golgi apparatus. No mutations in the gene for the A subunit (XIIIA) were identified in this patient. Therefore, secretion of the truncated XIIIB must also be impaired in vivo, leading to a secondary XIIIA deficiency. These results support a previous conclusion that genetic defects of XIIIB are the basis for the former type I factor XIII deficiency.

Amino Acid Sequence↗
PubMed2001

Accumulation of 67Ga citrate in early pregnancy.

A 26-year-old pregnant woman complained of chest pain and dyspnea and was diagnosed with malignant lymphoma of the mediastinum. To determine the stage of malignant lymphoma, tumor scintigraphy with 67Ga citrate was performed. 67Ga scintigraphy revealed an abnormal accumulation in the center of the pelvic cavity. An artificial abortion was performed, and the early pregnancy obtained from the abortion showed a prominent uptake of 67Ga citrate ex vivo. 67Ga citrate re-examination, which was performed immediately after the abortion, showed no abnormal accumulation in the pelvic cavity. To our knowledge, this is the first medical report on an aborted tissue investigated ex vivo to determine whether it demonstrated increased uptake of 67Ga citrate.

Abortion, Induced↗
PubMed2001

High-dose radiation therapy for elderly patients with inoperable or unresectable non-small cell lung cancer.

PURPOSE: To evaluate definitive radiation therapy delivering doses in excess of 60 Gy for elderly patients aged 75 years or over with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The treatment results for 97 patients aged 75 years or older (mean age 78 years; elderly group) with inoperable or unresectable NSCLC were retrospectively analyzed and compared with those for 206 patients younger than 75 year old (mean age 64 years; younger group). The elderly patients were classified into two groups; 67 patients aged 75-79 years (the elderly A) and 30 patients aged 80 years or older (the elderly B). Most of all patients were treated with a total dose of 60 Gy or more in 2 Gy daily standard fractionation. RESULTS: The overall 2 and 5 year survival rates were 32 and 13% for the elderly A group, and 28 and 4% for the elderly B group, respectively, compared with 36 and 12% for the younger group. There was not a statistically significant difference in survival rates among three groups. In stage I-II NSCLC patients there was also no significant difference in survival curves among the three groups. In patients with stage III disease, however, the survival curve of the elderly B was inferior to those of the younger group and the elderly A group, although the difference was not statistically significant. After the treatment the deterioration rate of the performance status was only 5% in the younger group and 8% in the elderly group. Only three younger and two elderly patients died of late pulmonary insufficiency associated with high-dose irradiation to the proximal bronchus. No other treatment-related event was observed except for mild acceptable acute complications in the elderly groups. CONCLUSIONS: Definitive radiation therapy is recommended to the elderly aged 75 years or older with inoperable or unresectable NSCLC, especially early stage disease, as an acceptable choice of treatment.

Aged↗
PubMed2001

Synthesis of (-)-[4-3H]epigallocatechin gallate and its metabolic fate in rats after intravenous administration.

Because a great deal of attention has been focused on the metabolism of (-)-epigallocatechin gallate (EGCg), quantitative analysis of this compound is required. For this purpose we developed a method of chemical synthesis of [4-(3)H]EGCg. Synthesized [4-(3)H]EGCg showed 99.5% radiochemical purity and a specific activity of 13 Ci/mmol. To clarify the excretion route of EGCg, the radioactivity levels of bile and urine were quantified after intravenous administration of [4-(3)H]EGCg to bile-duct-cannulated rats. Results showed that the radioactivity of the bile sample excreted within 48 h accounted for 77.0% of the dose, whereas only 2.0% of the dose was recovered in the urine. The excretion ratio of bile to urine was calculated to be about 97:3. These results clearly showed that bile was the major excretion route of EGCg. Time-course analysis of the radioactivity in blood was also performed to estimate the pharmacokinetic parameters following intravenous administration of [4-(3)H]EGCg. In addition, EGCg metabolites excreted in the bile within 4 h after the intravenous dose of [4-(3)H]EGCg were analyzed by HPLC. The results showed that 4',4"-di-O-methyl-EGCg was present in the conjugated form and made up about 14.7% of the administered radioactivity.

Animals↗
PubMed2001

Metabolic fate of (-)-[4-(3)H]epigallocatechin gallate in rats after oral administration.

After oral administration of [4-(3)H]EGCg to rats, the radioactivity in blood, major tissues, urine, and feces was measured over time. The radioactivity in blood and most tissues remained low for 4 h postdose, began to increase after 8 h, peaked at 24 h, and then decreased. Major urinary excretion of radioactivity occurred in the 8-24 h period, and the cumulative radioactivity excreted by 72 h was 32.1% of the dose. The radioactivity in the feces was 35.2% of the dose within 72 h postdose. In the case of rats pretreated with antibiotics (antibiotic-pretreated rats), the radioactivity levels of the blood and urine were definitely lower than those in rats not pretreated with antibiotics (normal rats). The radioactivity recovered in the antibiotic-pretreated rat urine was estimated to be only (1)/(100) of that in the normal rat urine. These results clearly demonstrated that the radioactivity detected in the blood and urine of normal rats mostly originated from degradation products of EGCg produced by intestinal bacteria. Furthermore, a main metabolite in the normal rats was purified and identified as 5-(5'-hydroxyphenyl)-gamma-valerolactone 3'-O-beta-glucuronide (M-2). In feces of the normal rats, EGC (40.8% of the fecal radioactivity) and 5-(3',5'-dihydroxyphenyl)-gamma-valerolactone (M-1, 16.8%) were detected. These results suggested that M-1 was absorbed in the body after degradation of EGCg by intestinal bacteria, yielding M-1 with EGC as an intermediate. Furthermore, M-2 was thought to be formed from M-1 in the intestinal mucosa and/or liver, then to enter the systemic circulation, and finally to be excreted in the urine. Taking into account all of the above findings, a possible metabolic route of EGCg orally administered to rats is proposed.

Administration, Oral↗
PubMed2001

Purification, characterization and gene expression of a glycine and proline-rich antibacterial protein family from larvae of a beetle, Allomyrina dichotoma.

Two structurally related antibacterial proteins were isolated from larvae of a beetle, Allomyrina dichotoma, immunized with Escherichia coli. The two proteins were designated A. dichotoma (A. d.) coleoptericin A and B. The mature portion of A. d. coleoptericins deduced from nucleotide sequences of the cDNAs consists of seventy-two amino acids without cysteine residues and is rich in glycine (11.1%) and proline (11.1%). Comparison of the amino acid sequences of the A. d. coleoptericins revealed that these antibacterial proteins have 94%, 75%, 50% and 43% similarity to rhinocerosin, holotricin 2, coleoptericin and acaloleptin A1. Recombinant A. d. coleoptericin A and B showed strong antibacterial activity against Staphylococcus aureus, methicillin resistant S. aureus (MRSA) and Bacillus subtilis. Recombinant A. d. coleoptericin A and B were shown to not form pores through bacterial membranes of E. coli, but to hamper cell division. Results of Northern blotting showed that A. d. coleoptericin genes are inducible by bacteria and are expressed strongly in the fat bodies and haemocytes, and weakly in the Malpighian tubules. Analysis of the evolutionary relationship of amino acid sequences among A. d. coleoptericins and other antibacterial proteins suggests that A. d. coleoptericins, rhinocerosin and holotricin 2 are closely related and form a gene family.

Amino Acid Sequence↗
PubMed2001

Tissue-engineered vascular autograft: inferior vena cava replacement in a dog model.

Tissue-engineered vascular autografts (TEVAs) were made by seeding 4-6 x 10(6) of mixed cells obtained from femoral veins of mongrel dogs onto tube-shaped biodegradable polymer scaffolds composed of a polyglycolid acid (PGA) nonwoven fabric sheet and a copolymer of L-lactide and caprolactone (n = 4). After 7 days, the inferior vena cavas (IVCs) of the same dogs were replaced with TEVAs. After 3, 4, 5, and 6 months, angiographies were performed, and the dogs were sacrificed. The implanted TEVAs were examined both grossly and immunohistologically. The implanted TEVAs showed no evidence of stenosis or dilatation. No thrombus was found inside the TEVAs, even without any anticoagulation therapy. Remnants of the polymer scaffolds were not observed in all specimens, and the overall gross appearance similar to that of native IVCs. Immunohistological staining revealed the presence of factor VIII positive nucleated cells at the luminal surface of the TEVAs. In addition, lesions were observed where alpha-smooth muscle actin and desmin positive cells existed. Implanted TEVAs contained a sufficient amount of extracellular matrix, and showed neither occlusion nor aneurysmal formation. In addition, endothelial cells were found to line the luminal surface of each TEVA. These results strongly suggest that "ideal" venous grafts with antithrombogenicity can be produced.

Animals↗
PubMed2001

The cadherin-catenin superfamily in endocrine tumors.

It has been well-known that the cadherin-catenin complexes bind with intracellular skeleton actin, which result in stabilization of cellular structure and tissue organization. Therefore, the cadherin-catenin family has been considered prerequisite for normal cell function and the preservation of tissue integrity. In human malignancies especially colon cancers, dysfunction and/or decrease of expression of these proteins have been proposed to prevent differentiation of tumors and to increase invasiveness and poor prognosis. However, recent studies also revealed that a member of this superfamily, beta-catenin, may play an important role in Wnt/wingless intracellular signaling pathway. Decreased expression of this protein or somatic mutation of the beta-catenin gene has been also reported in human carcinomas including various endocrine tumors. Mutant beta-catenin is associated with abnormal nuclear accumulation in tumor cells and subsequently to activate other transcription factors such as Tcf/Lef. This activation eventually results in which upregulation of mRNA and protein levels of various cell growth mediators in these endocrine tumors. Therefore, dysfunction of the cadherin-catenin system is considered to be closely correlated with tumorigenesis and development in human endocrine tumors.

Animals↗
PubMed2001

[Pyogenic sacroiliitis in pregnancy].

Pyogenic sacroiliitis is an extremely rare disease in the field of obstetrics and gynecology, and especially for the cases discovered and treated during pregnancy, only five cases can be found in literature. We experienced one case of the disease in which the patient needed urgent hospitalization due to dysbasia caused by fever and pain at the left hip at the 27th week of her pregnancy. The patient was a 31-year-old primipara presenting typical clinical symptoms of pyogenic sacroiliitis along with evidence of severe infection as represented by fever of 39.7 degrees C and CRP of 12.6 mg/dl. She showed a good response to meropenem (MEPM) at 1 g twice a day for 8 days and then at 0.5 g twice a day for 2 days, followed by faropenem (FRPM) at 200 mg three times a day for 12 days, which successfully improved her subjective and objective findings as well as her laboratory test values, resulting in a complete cure. The definitive diagnosis of the disease in the patient was made on the basis of MRI findings, but no pathogen was identified. The patient was found to have marginal placenta previa as a complication, but she had an uneventful trans-vaginal delivery at the 37th week of her pregnancy and left hospital after both she and her baby showed favorable post-delivery progress. The case reported here is the first case of pyogenic sacroiliitis that has ever been discovered and treated during pregnancy in Japan.

Adult↗
PubMed2000

Transgenic expression of cecropin B, an antibacterial peptide from Bombyx mori, confers enhanced resistance to bacterial leaf blight in rice.

The short persistence of cecropin B peptide in plants, due to post-translational degradation, is a serious impediment in its effective utilization for developing bacterial resistance transgenic plants. Two DNA constructs encoding the full-length precursor of cecropin B peptide and the mature sequence of cecropin B peptide preceded by a signal peptide derived from rice chitinase gene were transformed in rice. The differences in the transcriptional levels in independent transgenic lines showed moderate to high expression of cecropin B gene that correlated well with the differences in cecropin B accumulation observed by Western blot analysis. The development of lesions resulting from infection by Xanthomonas oryzae pv. oryzae was significantly confined in the infected leaflet of transgenic lines, when compared with the control plants.

Animals↗
PubMed2000

Absence of interleukin-4 enhances germinal center reaction in secondary immune response.

The germinal center (GC) is a compartment for B cell differentiation and proliferation. Interleukin (IL)-4 has been considered essential for GC functioning. To define the role of IL-4 in GC reaction, immunohistology of draining lymph nodes (LNs) of IL-4 gene-targeted (IL-4(-/-)) mice was performed during secondary immune response. IL-4(-/-) mice were immunized with ovalbumin emulsified in Freund' complete adjuvant. Final antigen challenge was done 4 weeks later. IL-4(-/-) mice had a higher production of IgG2a and IgG2b and a lower production of IgG1 than those in wild-type (WT) mice. In comparison with WT mice, LNs of IL-4(-/-) mice on days 4 and 7 after final antigen challenge were larger and contained a markedly greater number of GCs, which showed marked size variations with a large number of small GCs and a small number of markedly large GCs. By day 14, the number of GCs decreased to the same level as that in WT mice. However, the LN size in IL-4(-/-) mice was still larger than that in WT mice due to the presence of markedly large GCs. Although well-developed complement receptor(+) follicular dendritic cell (FDC) networks were present in GCs of IL-4(-/-) mice, no FDCs of mature phenotype (CD23(+)) were observed in many of the small GCs. In conclusion, the absence of IL-4 enhanced GC reaction and specific antibody response of Th1-type. IL-4 may play an important role in inducing the appropriate magnitude of humoral immune response.

Animals↗
PubMed2000

Preferential infection of neuronal and astroglia cells by Akabane virus in primary cultures of fetal bovine brain.

Akabane virus is a member of the genus Bunyavirus; it is pathogenic for ruminants and transmitted by arthropod vectors. Infection of adult cattle and sheep causes a transient viremia without obvious clinical signs, while infection of pregnant animals often causes fetal abnormalities including hydranencephaly, poliomyelitis and arthrogryposis. Infectious virus or viral antigens is present in the brain, spinal cord and skeletal muscle of infected fetuses. To understand the interaction between Akabane virus and bovine brain cells, we investigated the viral tropism using primary cultures of fetal bovine brain. The cultured neuronal cells, astroglia cells and microglia cells were distinguished by cell type specific antisera. Akabane virus was found to infect neuronal cells and astroglia cells, which led to degenerative death. No microglia cells were found infected. In some brain cultures, we observed different sensitivities of the cells to two Akabane virus strains: an attenuated strain infected and spread more readily than wild type virus. This difference was not observed in a hamster fibroblast cell line. Both viral and host determinants might be involved in the different susceptibility of brain cells to Akabane virus infection.

Animals↗
PubMed2000

Treatment of superficial esophageal cancer by external radiation therapy alone: results of a multi-institutional experience.

PURPOSE: To assess the effectiveness and toxicity of external radiation therapy for superficial esophageal cancer. METHODS AND MATERIALS: During the period from March 1979 to November 1996, 78 patients with superficial esophageal cancer received radiation therapy without intracavitary irradiation at nine radiotherapy institutions in Japan. All patients had histologically-proven squamous cell carcinoma. Endoscopic ultrasonography was performed in 34 patients to discriminate mucosal from submucosal cancer. Most of the patients had received radiation therapy using conventional fractionation at an average dose of 65.5 Gy. RESULTS: The survival rates at 1, 2, and 5 years were 88%, 73%, and 45%, respectively. The local control rates at 1, 2, and 5 years were 85%, 79%, and 66%, respectively. Although the difference was not significant, the survival rate of cancer patients with a tumor invading the submucosa was lower than that of the other patients. In 6 mucosal cancer patients, local recurrence was observed in 1 patient with extensive cancer. Regional lymph node recurrence and distant failure were not observed in mucosal cancer patients, while in 28 submucosal cancer patients, the 5-year survival rate and relapse free rate were only 49% and 43%, respectively. Univariate and multivariate analysis identified age as the only significant prognostic factor. Severe late injury, such as esophageal ulcer, perforation, and bleeding, was not observed. CONCLUSION: External radiation therapy is effective for mucosal cancer. However, further investigation is needed to establish a better standard treatment protocol for submucosal cancer.

Aged↗
PubMed2000

Radiation therapy for elderly patient with squamous cell carcinoma of the uterine cervix.

OBJECTIVE: The purpose of this study was to profile cervical squamous cell carcinoma in elderly patients undergoing radiation therapy and to study the treatment outcome and side effects of therapy. MATERIALS AND METHODS: A retrospective analysis was carried out from the records of 380 patients with squamous cell carcinoma of the uterine cervix who had been given radiation therapy between 1970 and 1994. The patients were divided into three age groups: under 70 years (youngest group; n = 215), 70 to 79 years (intermediate group; n = 124), and 80 years or older (oldest group; n = 41). Radiation therapy was performed by a combination of external beam therapy and three brachytherapy fractions using low-dose-rate sources. RESULTS: The 5-year overall survival rates in the youngest, intermediate, and oldest groups were 58, 50, and 33%, respectively, while cause-specific survival rates were 68, 70, and 65%, respectively. For the patients with stage III, the 5-year overall survival rates in the youngest, intermediate, and oldest groups were 59, 48, and 36%, respectively, while cause-specific survival rates were 72, 70, and 70%, respectively. There was no statistical significance in the 5-year intrapelvic recurrence rates among the three groups. Grade 3 or 4 complications occurred in 6.5% of the youngest, 11.3% of the intermediate, and 7.3% of the oldest groups. CONCLUSION: Radiation therapy with external beam combined with three fractions of low-dose-rate brachytherapy proved both highly effective and safe for senior patients with cervical squamous cell carcinoma.

Adult↗
PubMed2000

Genetic diversity of RNA segments 5, 7 and 9 of the Palyam serogroup orbiviruses from Japan, Australia and Zimbabwe.

Reverse transcriptase-polymerase chain reaction (RT-PCR) methods, based on the sequences of RNA segments 5, 7 and 9 of Chuzan virus, were established for specific detection and molecular characterization of the Palyam serogroup orbiviruses. Nucleotide sequences obtained from the amplified cDNA fragments of these three genes of 24 isolates were analyzed and compared individually to determine the intra-serogroup phylogenetic relationship of Japanese, Australian and Zimbabwean isolates. It seems that Chuzan virus isolates in Japan are genetically stable. Interestingly, mutations have occurred almost simultaneously on these three genes of Chuzan virus. In all cases, isolates from the same geographical area were closely related to each other at the molecular level, irrespective of serotype. The data suggested that the Palyam serogroup viruses can be differentiated into geographically distinct groups and that the viruses evolve independently in the different gene pools. A strain KY-115 was considered to be produced by reassortment of genome segments between different groups. Restriction fragment length polymorphism (RFLP) analysis of these PCR products is useful for rapid discrimination of isolates and for detection of genetic mutations.

Animals↗