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Biomedical subjects

A Yamada

Publications and source records attributed to A Yamada.

At least 127 records · Page 7Linked to original sources

[A case treated surgically through anterior axillary thoracotomy for recurrent right spontaneous pneumothorax after repeated video-assisted thoracoscopic surgery].

A 21-year-old male who had thoracoscopic surgery for right spontaneous pneumothorax was admitted to our hospital complaining of dyspnea due to the recurrence. There was no bulla in right apex but empysematous change in visceral pleura at re-thoracoscopic surgery. Two bulla in right S6 were removal using endo-stapler. Three years after the second thoracoscopic surgery, the recurrence of right pneumothorax was recognized. Chest CT revealed a new bulla in right apex. Therefore the third operation was carried out through anterior axillary thoracotomy. A new bulla was resected with endo-stapler and pleurodesis using argon laser was also applied to prevent of recurrence of pneumothorax. The patient is now doing well without recurrence 6 months after the third operation.

Adult↗

A case of mixed connective tissue disease (MCTD) complicated with MPO-ANCA-related necrotizing glomerulonephritis.

Renal diseases of mixed connective tissue disease (MCTD) are not unusual. Although most of them are SLE-like renal impairment with immune complex deposits, systemic sclerosis- (SSc) like renal impairments with intimal thickening of interlobular arteries or arterioles are also encountered. Several cases of SSc complicated with MPO-ANCA-related necrotizing glomerulonephritis (nGN) are reported. Here we report a case which developed MPO-ANCA-related nGN 16 years after the diagnosis of MCTD. She exhibited pauci-immune focal nGN and significantly high titer of MPO-ANCA. She was successfully treated with prednisolone and cyclophosphamide. We believe this is the first case in which MPO-ANCA-related nGN was demonstrated in a patient with MCTD.

Antibodies, Antineutrophil Cytoplasmic↗

[Human tumor-rejection antigens and peptides from genes to clinical research].

One of the most significant advances in the field of modern tumor immunology is the identification of genes encoding tumor-rejection antigens that are recognized by human leukocyte antigen (HLA) class I-restricted and tumor-specific cytotoxic T lymphocytes (CTLs). Several peptides encoded by these genes are now under clinical trial as cancer vaccines, and major tumor regression has been observed in some melanoma patients. These results indicate that identification of the peptides capable of inducing CTLs may provide a new modality of cancer therapy. We investigated tumor-rejection antigens from epithelial cancers, and reported 7 genes encoding tumor-rejection antigens and peptides available for specific immunotherapy of HLA-A26 or -A24 patients with epithelial cancers. Furthermore, we identified more than 10 genes encoding tumor-rejection antigens and peptides available for specific immunotherapy of HLA-A2 patients with epithelial cancers. Therefore these new antigens and peptides could be applicable to the treatment of numerous epithelial cancer patients worldwide. Phase I clinical trials of cancer vaccine with these peptides for epithelial cancer patients are in progress at our university. Basic and clinical research will provide new insights for a better understanding of the molecular basis of T cell-mediated recognition of cancer cells and be important for the development of cancer vaccines.

Antigens, Neoplasm↗

Tacrolimus (FK506) treatment of CD34+ hematopoietic progenitor cells promote the development of dendritic cells that drive CD4+ T cells toward Th2 responses.

The macrolide lactone, tacrolimus (FK506), is utilized in bone marrow transplantation (BMT) to prevent graft-versus-host disease (GVHD). In the current study, we evaluated the ability of FK506 to modify the function of dendritic cells (DCs) derived from CD34+ hematopoietic progenitor cells (HPCs). Comparable to DCs obtained in the absence of FK506, DCs cultured in the presence of FK506 (FK-DCs) had higher expression of CD1a+ and formed a greater number of DC colonies. Despite the same expression of costimulatory molecules, FK-DCs displayed a reduced capacity to stimulate an allogeneic T cell response, and showed significantly lower interleukin (IL)-12 production. While normal DCs pulsed with the exogenous antigen, keyhole limpet hemocyanin (KLH) induced specific Th1-like interferon-gamma(IFN-gamma) producing CD4+ T cell line, FK-DCs induced Th2-like interleukin-4 (IL-4) producing CD4+ T cell line. These data demonstrate the ability of FK506 to induce Th2-promoting function in developing DCs.

Antigens, CD34↗

Distinct parameters are involved in controlling the number of rounds of cell division in each tissue during ascidian embryogenesis.

We counted cell numbers during embryogenesis of the ascidian, Halocynthia roretzi, every hour. Cell numbers were determined by counting the numbers of nuclei in squashed embryos. The cell number of a larva just after hatching was approximately 3000. Our study addresses the question of what factors control the number of rounds of cell division during development. Three kinds of egg fragments were prepared by cutting unfertilized eggs to alter the volume of cytoplasm and the amount of DNA. After the egg fragments were fertilized, the cell numbers were estimated at the hatching stage. The cell numbers of the resulting larvae differed from those of normal larvae. Precursor blastomeres of various tissues were then isolated from normal and manipulated embryos, and cultured as partial embryos. The cell numbers of the resulting partial embryos were counted to estimate the number of cell divisions in each larval tissue. The results suggested that the number of cell divisions is controlled by a distinct mechanism in each tissue. We propose that the number of rounds of cell division during ascidian embryogenesis is controlled by three mechanisms: the first depending on the volume of cytoplasm; the second on the nucleo-cytoplasmic ratio; and the third depending on neither of these parameters. J. Exp. Zool. 284:379-391, 1999.

Animals↗

The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta.

Xeroderma pigmentosum variant (XP-V) is an inherited disorder which is associated with increased incidence of sunlight-induced skin cancers. Unlike other xeroderma pigmentosum cells (belonging to groups XP-A to XP-G), XP-V cells carry out normal nucleotide-excision repair processes but are defective in their replication of ultraviolet-damaged DNA. It has been suspected for some time that the XPV gene encodes a protein that is involved in trans-lesion DNA synthesis, but the gene product has never been isolated. Using an improved cell-free assay for trans-lesion DNA synthesis, we have recently isolated a DNA polymerase from HeLa cells that continues replication on damaged DNA by bypassing ultraviolet-induced thymine dimers in XP-V cell extracts. Here we show that this polymerase is a human homologue of the yeast Rad30 protein, recently identified as DNA polymerase eta. This polymerase and yeast Rad30 are members of a family of damage-bypass replication proteins which comprises the Escherichia coli proteins UmuC and DinB and the yeast Rev1 protein. We found that all XP-V cells examined carry mutations in their DNA polymerase eta gene. Recombinant human DNA polymerase eta corrects the inability of XP-V cell extracts to carry out DNA replication by bypassing thymine dimers on damaged DNA. Together, these results indicate that DNA polymerase eta could be the XPV gene product.

Alleles↗

Effects of exogenous human heparin-binding epidermal growth factor-like growth factor on DNA synthesis of hepatocytes in normal mouse liver.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been reported to stimulate DNA synthesis of the hepatocytes in culture and highly express in regenerating rat liver after partial hepatectomy. We examined mitogenic effects and activation of transcription factors caused by exogenous human HB-EGF (hHB-EGF) in mouse liver. The mean labeling index in hepatocytes of hHB-EGF-injected mice was 2.6%, a significant increase over that in saline-injected controls (under 0.01%). By exogenous hHB-EGF injection, activation of transcription factors such as nuclear factor (NF)-kappaB and activator factor (AP)-1 was observed in the liver. By Northern blot analysis, hepatocyte growth factor (HGF) gene expression in the liver was found to be induced in the hHB-EGF-injected mice. In conclusion, intravenously injected hHB-EGF showed a limited but definite effect on the DNA synthesis of hepatocytes in the mice liver. HB-EGF may serve as a hepatotrophic factor in vivo.

Animals↗

Xeroderma pigmentosum variant (XP-V) correcting protein from HeLa cells has a thymine dimer bypass DNA polymerase activity.

Xeroderma pigmentosum variant (XP-V) represents one of the most common forms of this cancer-prone DNA repair syndrome. Unlike classical XP cells, XP-V cells are normal in nucleotide excision repair but defective in post-replication repair. The precise molecular defect in XP-V is currently unknown, but it appears to be a protein involved in translesion synthesis. Here we established a sensitive assay system using an SV40 origin-based plasmid to detect XP-V complementation activity. Using this system, we isolated a protein from HeLa cells capable of complementing the defects in XP-V cell extracts. The protein displays novel DNA polymerase activity which replicates cyclobutane pyrimidine dimer-containing DNA templates. The XPV polymerase activity was dependent on MgCl2, sensitive to NEM, moderately sensitive to KCl, resistant to both aphidicolin and ddTTP, and not stimulated by PCNA. In glycerol density gradients, the activity co-sedimented with a 54 kDa polypeptide at 3.5S, indicating that the monomeric form of this polypeptide was responsible for the activity. The protein factor corrected the translesion defects of extracts from three XPV cell strains. Bypass DNA synthesis by the XP-V polymerase occurred only in the presence of dATP, indicating that it can incorporate only dATP to bypass a di-thymine lesion.

Aphidicolin↗

Novel Preparation Method for Nano-Sized Gold Particles by Using NH2-Terminated Polyethyleneoxide.

Nano-sized gold particles dispersed in a composite were prepared by using NH2-terminated polyethyleneoxide (PEO-NH2) as a matrix. Gold was vapor-deposited onto a melt of PEO-NH2. Gold was smoothly dispersed into the interior of PEO-NH2 to form nano-sized gold particles. After cooling the melt to room temperature, a stable solid composite was obtained. The composite readily dissolved in water or various kinds of organic solvents to produce a stable colloidal solution. The mean size of the gold particles was 3.4 nm, and the content of gold was ca. 5 wt%. Copyright 1999 Academic Press.

Journal Article↗

Molecular cloning of a glycosylphosphatidylinositol-anchored molecule CDw108.

CDw108, also known as the John-Milton-Hagen human blood group Ag, is an 80-kDa glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein that is preferentially expressed on activated lymphocytes and E. The molecular characteristics and biological function of the CDw108 were not clarified previously. In this manuscript, we identify the cDNA clone containing the entire coding sequence of the CDw108 gene and report its molecular characteristics. The 1998-base pairs of the open reading frame of the cloned cDNA encoded a protein of 666 amino acids (aa), including the 46 aa of the signal peptide and the 19 aa of the GPI-anchor motif. Thus, the membrane-anchoring form of CDw108 was the 602 aa, and the estimated molecular mass of the unglycosylated form was 68 kDa. The RGD (Arg-Gly-Asp) cell attachment sequence and the five potential N-linked glycosylation sites were located on the membrane-anchoring form. Flow cytometric and immunoprecipitation analyses of the CDw108 cDNA transfectants confirmed that the cloned cDNA encoded the native form of CDw108. The CDw108 mRNA was expressed in activated PBMCs as well as in the spleen, thymus, testis, placenta, and brain, but was not expressed in any other tissues tested. Radiation hybrid mapping indicated that the CDw108 gene was located in the middle of the long arm of chromosome 15 (15q23-24). This molecular information will be critical for understanding the biological function of the CDw108 Ag.

Amino Acid Sequence↗

Post marketing surveillance of 13 products: safety and effectiveness.

We surveyed the safety and effectiveness of 13 drug products under the reexamination system in Japan. Until the time of reexamination, a total of 106,328 case reporting forms were collected in the drug use investigations, while 1340 adverse drug reactions (ADRs) were reported in the spontaneous case reporting on ADRs. In the drug use investigations, the data were primarily obtained on the incidence of unexpected ADRs and the incidence of ADRs in special patient populations. The spontaneously reported ADR provided the data on serious and unexpected ADRs. We established proper use of the 13 products by examining the data for significant risk factors for serious ADRs, including agranulocytosis, jaundice, hypotension, and QT prolongation. We revised the package inserts of the 13 products with the new safety information a total of 50 times and passed on the revisions to health care professionals. We also assessed the safety and effectiveness of the 13 products compared with that before marketing. We summarized the data and submitted them to the Japanese Ministry of Health and Welfare (JMHW). For all 13 products, the same indications and dosage and administration as those approved previously were approved at the reexamination.

Journal Article↗

Phosphate depletion enhances tissue-nonspecific alkaline phosphatase gene expression in a cultured mouse marrow stromal cell line ST2.

Alkaline phosphatases (ALP) are highly ubiquitous enzymes present in the majority of animals from bacteria to higher vertebrate. Although their wide distribution in nature has suggested that these enzymes should perform important biological functions, their detailed roles or natural substrates remain unknown. In Escherichia coli, the extracellular phosphate (Pi) limitation induces the ALP gene, indicating the role of extracellular Pi in ALP gene regulation. However, little is known about the similar mechanisms in mammalian cells. This study was designed to examine the effect of low Pi medium on the ALP activity and its expression in the mouse stromal cell line ST2. The enzymatic property was classified into tissue-nonspecific ALP (TNSALP). After treatment by Pi starvation for 3 days, there was a 2-fold increase in the specific activity of TNSALP. RT-PCR analysis revealed that the mRNA of the TNSALP gene was highly stimulated. These results indicated that the effect of Pi depletion on ALP activity was regulated at the TNSALP transcriptional level, suggesting that the possible role of the Pi sensing system for biological functions of ALP might have been conserved in evolution. Our findings also made it possible to discuss the physiological roles of ALP in vivo.

Alkaline Phosphatase↗

Reduced plasma transforming growth factor-beta1 levels in patients with chronic hepatitis C after interferon-alpha therapy: association with regression of hepatic fibrosis.

BACKGROUND/AIM: Transforming growth factor-beta1 is involved in liver fibrosis. Our aim was to examine the association of plasma transforming growth factor-beta1 levels with the degree of liver fibrosis. METHODS: We analyzed plasma transforming growth factor-beta1 levels in 43 patients with chronic hepatitis C treated with interferon-alpha using a transforming growth factor-beta1 ELISA. The content of transforming growth factor-beta1 in liver tissue obtained by needle biopsy (n=13) was also analyzed. The degree of liver fibrosis was assessed histologically and morphometrically. RESULTS: Plasma transforming growth factor-beta1 levels were significantly correlated with transforming growth factor-beta1 content in liver tissue (r=0.83, p<0.001), indicating that plasma levels correspond with tissue cytokine. Plasma transforming growth factor-beta1 levels in patients (8.1+/-1.1 ng/ml) before interferon-a therapy were significantly higher than in controls (1.9+/-0.3 ng/ml) (p<0.01). Plasma levels were significantly correlated with the degree of fibrosis (p<0.01). Plasma transforming growth factor-beta1 levels were significantly decreased in sustained responders (from 5.2+/-1.0 ng/ml to 2.9+/-0.7 ng/ml), relapsed patients (from 9.8+/-2.0 ng/ml to 3.4+/-0.6 ng/ml), and nonresponders (from 9.3+/-2.1 ng/ml to 3.9+/-0.9 ng/ml) at the end of therapy (p<0.05 for all comparisons). Significant regression of liver fibrosis after therapy was observed in both sustained responders and nonresponders (p<0.05 for both). CONCLUSIONS: These observations suggest that plasma transforming growth factor-beta1 levels appear to be associated with the degree of liver fibrosis.

Aged↗

Oral administration of hot water extracts of Chlorella vulgaris reduces IgE production against milk casein in mice.

Hot water extract of Chlorella vulgaris (CVE) is a biological response modifier (BRM) which enhances resistance to Listeria monocytogenes through augmentation of helper T cell type 1 (Thl) responses producing gamma-interferon (gammaIFN). We show here that oral administration of CVE in mice suppressed the production of immunoglobulin (Ig)E against casein antigen accompanied by increased gammaIFN and IL-12 mRNA expression. Oral administration of CVE enhanced Thl response to casein in the spleen of casein immunized mice. CVE may be useful for prevention of allergic diseases with a predominant Th2 response.

Administration, Oral↗

Transcatheter renal arterial embolization therapy on a patient with polycystic kidney disease on hemodialysis.

We report a patient with autosomal dominant polycystic kidney disease (ADPKD) undergoing long-term hemodialysis who underwent transcatheter arterial embolization (TAE) of the renal arteries to shrink enlarged kidneys. In 1983, the patient started hemodialysis because of chronic renal failure secondary to ADPKD. However, renal size continued to increase. In January 1997, he was admitted to our hospital with abdominal distension and anorexia, in addition to progression of anemia. Upper gastroendoscopy showed an esophageal ulcer and severe external compression of the stomach. Renal angiography using the Seldinger technique showed stretched and deformed segmental renal arteries with massive enlargement of the kidneys. TAE with stainless steel coils was performed on both renal arteries. With a rapid and progressive decrease in kidney size, anorexia and anemia were improved, and the gastrointestinal compression was eliminated. In some patients with ADPKD, renal size continues to increase even after the initiation of dialysis. In about 10 years, patients develop gastrointestinal complications, such as dysphagia, ileus, severe constipation, and intestinal perforation. Surgical procedures such as nephrectomy are not satisfactory. This report shows that TAE is a safe and effective therapy for patients with ADPKD with massively enlarged kidneys.

Angiography↗