Search PubMed⌕ Search

Biomedical subjects

A Yamada

Publications and source records attributed to A Yamada.

At least 109 records · Page 6Linked to original sources
PubMed2000

FD-891, a structural analogue of concanamycin A that does not affect vacuolar acidification or perforin activity, yet potently prevents cytotoxic T lymphocyte-mediated cytotoxicity through the blockage of conjugate formation.

FD-891 belongs to a group of 18-membered macrolides, and is a structural analogue of a specific inhibitor of vacuolar type H+-ATPase, concanamycin A (CMA). In our previous work, we have shown that CMA specifically inhibits perforin-dependent cytotoxic T lymphocyte (CTL)-mediated cytotoxicity through the degradation and inactivation of perforin, although CMA does not affect Fas ligand (FasL)-dependent cytotoxicity. Here, we show that FD-891 potently prevents not only perforin-dependent but also FasL-dependent CTL-mediated killing pathways by blocking CTL-target conjugate formation. In contrast to CMA, FD-891 was unable to inhibit vacuolar acidification and only slightly decreased the perforin activity in lytic granules. FD-891 blocked granule exocytosis in response to anti-CD3, mainly owing to the lack of CTL binding to immobilized anti-CD3. The conjugate formation was markedly inhibited only when effector cells were pretreated with FD-891. Consistent with these observations, fluorescence-activated cell sorter (FACS) analysis for cell surface receptors revealed that FD-891 significantly reduced the expression of the T-cell receptor (TCR)/CD3 complex. These data suggest that the blockage of conjugate formation and subsequent target cell killing might be at least partly owing to FD-891-induced down-regulation of the TCR/CD3 complex.

Animals↗
PubMed2000

Intramuscular haemangioma of the anterior chest wall.

Intramuscular haemangiomas of the chest wall are rare. We present the case of a 33-year-old man with an intramuscular haemangioma of the left side of the anterior chest wall located in the left sixth intercostal space. We resected the tumour and surrounding tissue. Histopathological examination of the tumour demonstrated an intramuscular haemangioma of small-vessel type. The patient has been free of recurrence for 5 years after surgery.

Adult↗
PubMed2000

Treatment of hypoglossia-hypodactyly syndrome without extremeity anomalies.

Three cases of hypoglossia-hypodactyly syndrome without limb deformities are reported. All exhibited different degrees of tongue hypoplasia, micrognathia, retrognathia with a very narrow space between the left and right halves of the mandible, constricted isthmus, and only one lower incisor. Bone lengthening for the midline mandibular hypoplasia and orthodontic treatment were performed in the three cases with satisfactory results.

Bone Lengthening↗
PubMed2000

Differences in the recognition of glucan elicitor signals between rice and soybean: beta-glucan fragments from the rice blast disease fungus Pyricularia oryzae that elicit phytoalexin biosynthesis in suspension-cultured rice cells.

Partial acid/enzymatic hydrolysis of the beta-(1-->3, 1-->6)-glucan from the cell walls of the rice blast disease fungus Pyricularia oryzae (Magnaporthe grisea) released elicitor-active fragments that induced phytoalexin biosynthesis in suspension-cultured rice cells. From the digestion of the glucan by an endo-beta-(1-->3)-glucanase, one highly elicitor-active glucopentaose was purified as a reduced compound, tetraglucosyl glucitol. The structure of this tetraglucosyl glucitol as well as two other related tetraglucosyl glucitols was elucidated as follows: (1) Glcbeta(1-->3)Glcbeta(1-->3)(Glcbeta(1-->6)) Glcbeta(1-->3)Glucitol (most active fragment); (2) Glcbeta(1-->3)(Glcbeta(1-->6))Glcbeta(1-->3)Glcbeta (1-->3)Glucitol; and (3) Glcbeta(1-->6) Glcbeta(1-->3)Glcbeta(1-->3)Glcbeta(1-->3)Glucitol. However, a synthetic hexa-beta-glucoside, known as a minimal structural element for the phytoalexin elicitor for soybean cotyledon cells, did not induce phytoalexin biosynthesis in the rice cells. Conversely, the beta-glucan fragment from P. oryzae did not induce phytoalexin biosynthesis in the soybean cotyledon cells, indicating differences in the recognition of glucooligosaccharide elicitor signals in these two plants. Because rice cells have been shown to recognize chitin fragments larger than pentamers as potent elicitors, these results also indicate that the rice cells can recognize at least two types of oligosaccharides from fungal cell walls as signal molecules to initiate defense response.

Carbohydrate Sequence↗
PubMed2000

Mouse homologue of the human SART3 gene encoding tumor-rejection antigen.

We recently isolated a human SART3 (hSART3) gene encoding a tumor-rejection antigen recognized by HLA-A2402-restricted cytotoxic T lymphocytes (CTLs). The hSART3 was also found to exist as an RNA-binding nuclear protein of unknown biological function. In this study, we cloned and analyzed the homologous mouse SART3 (mSART3) gene in order to understand better the function of hSART3, and to aid in establishing animal models of specific immunotherapy. The cloned 3586-bp cDNA encoded a 962-amino acid polypeptide with high homology to hSART3 (80% or 86% identity at the nucleotide or protein level, respectively). Nonapeptides recognized by the HLA-A2402-restricted CTLs and all of the RNA-binding motifs were conserved between hSART3 and mSART3. The mSART3 mRNA was ubiquitously expressed in normal tissues, with low level expression in the liver, heart, and skeletal muscle. It was widely expressed in various organs from as early as day 7 of gestation. mSART3 was mapped to chromosome 5, a syntenic region for human chromosome 12q23-24, and its genomic DNA extended over 28-kb and consisted of 19 exons. This information should be important for studies of the biological functions of the SART3 protein and for the establishment of animal models of specific cancer immunotherapy.

Amino Acid Sequence↗
PubMed2000

Establishment and epitope analysis of allo-specific cytotoxic T lymphocytes at a tumor site recognizing a spouse's HLA-A0206 molecule.

PROBLEM: The molecular basis of allo-reactivity in reproductive immunity has not been fully clarified. METHOD OF STUDY: Cytotoxic T lymphocytes (CTLs) were established from tumor-infiltrating lymphocytes (TILs). The allo-reactivity of the CTLs against various tumor cell lines or human leukocyte antigen (HLA)-A allele-transfected COS-7 cells was measured by 51Cr-release or interferon-gamma production assay. RESULTS AND CONCLUSIONS: We have established CTLs reacting to an HLA-A0206 molecule that matched a spouse's HLA-A allele from the TILs of a 68-year-old multiparous patient with gastric cancer. The amino acids at positions 66 and 88 in the alpha1 domain of HLA-A0206, both of which were common in the other HLA-A2 subtypes, were involved in the recognition by the CTLs. Endogenous peptides in the groove were not involved in the recognition. These results suggest the presence of long-lasting memory CTLs raised by the reproduction process, and may facilitate a better understanding of the molecular basis of allo-recognition during reproduction.

Aged↗
PubMed2000

In vitro activities of a new lipopeptide antifungal agent, FK463, against a variety of clinically important fungi.

The in vitro antifungal activity and spectrum of FK463 were compared with those of amphotericin B, fluconazole, and itraconazole by using a broth microdilution method specified by National Committee for Clinical Laboratory Standards document M27-A (National Committee for Clinical Laboratory Standards, Wayne, Pa., 1997). FK463 exhibited broad-spectrum activity against clinically important pathogens including Candida species (MIC range, <==0.0039 to 2 microg/ml) and Aspergillus species (MIC range, <==0.0039 to 0.0313 microg/ml), and its MICs for such fungi were lower than those of the other antifungal agents tested. FK463 was also potently active against azole-resistant Candida albicans as well as azole-susceptible strains, and there was no cross-resistance with azoles. FK463 showed fungicidal activity against C. albicans, i.e., a 99% reduction in viability after a 24-h exposure at concentrations above 0.0156 microg/ml. The minimum fungicidal concentration (MFC) assays indicated that FK463 was fungicidal against most isolates of Candida species. In contrast, the MFCs of FK463 for A. fumigatus isolates were much higher than the MICs, indicating that its action is fungistatic against this species. FK463 had no activity against Cryptococcus neoformans, Trichosporon species, or Fusarium solani. Neither the test medium (kind and pH) nor the inoculum size greatly affected the MICs of FK463, while the addition of 4% human serum albumin increased the MICs for Candida species and A. fumigatus more than 32 times. Results from preclinical in vitro evaluations performed thus far indicate that FK463 should be a potent parenteral antifungal agent.

Antifungal Agents↗
PubMed2000

marY1, a member of the gypsy group of long terminal repeat retroelements from the ectomycorrhizal basidiomycete Tricholoma matsutake.

We cloned an intact copy of a long terminal repeat retroelement designated marY1 from the ectomycorrhizal basidiomycete Tricholoma matsutake. The reverse transcriptase domain is found in T. matsutake and Tricholoma magnivelare worldwide. This finding suggests that retroelements associate with ectomycorrhizal basidiomycetes and may be useful as genetic markers for identification, phylogenetic analysis, and mutagenesis of this fungal group.

Basidiomycota↗
PubMed2000

An intron 4 gene polymorphism in endothelial cell nitric oxide synthase might modulate volume-dependent hypertension in patients on hemodialysis.

Nitric oxide (NO) has some relevance to the pathophysiology of hypertension. We examined the distribution of endothelial nitric oxide synthase (ecNOS4) gene polymorphism in patients with essential hypertension (n = 107) in comparison with healthy subjects (n = 362), and then studied the possibility that ecNOS4 gene polymorphism affects changes in blood pressure (BP) due to water load in hemodialysis patients. Though the NO metabolite (NOx) level in subjects with the a allele (31.2 +/- 1.76 micromol/l) was significantly lower than in those without the a allele (35.6 +/- 0.90 micromol/l) (p = 0.0263), we found no association between this gene polymorphism and essential hypertension. However, there still remains the possibility that the NO response to elevation of BP might be suppressed in patients with hypertension. In order to examine the association between ecNOS4 gene polymorphism and volume-dependent hypertension, 181 hemodialysis patients with complete anuria were recruited. Depending on the increase in mean BP (mm Hg) divided by percent increase in body weight (deltaBP/deltaBW), patients were divided into high responders (High-R: deltaBP/deltaBW >2.0 mm Hg; n = 90) and low responders (Low-R: deltaBP/deltaBW <2.0 mm Hg; n = 91). In the High-R group, the frequencies of a/a, b/a and b/b genotypes were 1.1, 32.1 and 66.8%, respectively, and in the Low-R group, these frequencies were 1.1, 9.4 and 89.5%, respectively. The relative risk for those in the High-R group conferred by the ecNOS4 a allele (b/a + a/a) was 3.64 (95% confidence intervals: 1.60-8.24, p = 0.0089). This study did not show a strong involvement of ecNOS4 gene polymorphism, at least in the basal NO production in patients with essential hypertension, however, it indicated that ecNOS4 gene polymorphism might modulate changes in BP due to water load in patients on hemodialysis, thus indicating that these polymorphisms may be involved in the pathophysiology of volume-dependent hypertension.

Alleles↗
PubMed2000

The role of CD154-CD40 versus CD28-B7 costimulatory pathways in regulating allogeneic Th1 and Th2 responses in vivo.

We used signal transducer and activator of transcription 4 (STAT4) and STAT6 gene knockout (-/-) mice as recipients of fully mismatched cardiac allografts to study the role of T-cell costimulatory pathways in regulating allogeneic T-helper 1 (Th1) versus Th2 responses in vivo. STAT4(-/-) mice have impaired Th1 responses, whereas STAT6(-/-) mice do not generate normal Th2 responses. Cardiac allografts from C57BL/6 mice were transplanted into normal wild-type (WT), STAT4(-/-), and STAT6(-/-) BALB/c recipients. STAT4(-/-) and STAT6(-/-) mice rejected their grafts with the same tempo as untreated WT recipients. CD28-B7 blockade by a single injection of CTLA4Ig induced long-term engraftment and donor-specific tolerance in all three groups of recipients. CD154 blockade by a single injection of MR1 was effective in prolonging allograft survival and inducing tolerance in STAT4(-/-) mice but was only marginally effective in STAT6(-/-) recipients and WT controls. In addition, a similar protocol of MR1 was ineffective in prolonging graft survival in CD28(-/-) BALB/c recipients, suggesting that the lack of efficacy seen in WT and STAT6(-/-) mice is not due to the presence of a functional CD28-B7 pathway. Furthermore, there was a similar differential effect of CD28-B7 versus CD154-CD40 blockade in inhibiting immune responses in animals immunized with ovalbumin and complete Freund's adjuvant. These novel data indicate that Th1 and Th2 cells are differentially regulated by CD28-B7 versus CD154-CD40 costimulation pathways in vivo and may have potential implications for the development of therapeutic strategies such as T-cell costimulatory blockade in humans.

Animals↗
PubMed2000

An FGF signal from endoderm and localized factors in the posterior-vegetal egg cytoplasm pattern the mesodermal tissues in the ascidian embryo.

The major mesodermal tissues of ascidian larvae are muscle, notochord and mesenchyme. They are derived from the marginal zone surrounding the endoderm area in the vegetal hemisphere. Muscle fate is specified by localized ooplasmic determinants, whereas specification of notochord and mesenchyme requires inducing signals from endoderm at the 32-cell stage. In the present study, we demonstrated that all endoderm precursors were able to induce formation of notochord and mesenchyme cells in presumptive notochord and mesenchyme blastomeres, respectively, indicating that the type of tissue induced depends on differences in the responsiveness of the signal-receiving blastomeres. Basic fibroblast growth factor (bFGF), but not activin A, induced formation of mesenchyme cells as well as notochord cells. Treatment of mesenchyme-muscle precursors isolated from early 32-cell embryos with bFGF promoted mesenchyme fate and suppressed muscle fate, which is a default fate assigned by the posterior-vegetal cytoplasm (PVC) of the eggs. The sensitivity of the mesenchyme precursors to bFGF reached a maximum at the 32-cell stage, and the time required for effective induction of mesenchyme cells was only 10 minutes, features similar to those of notochord induction. These results support the idea that the distinct tissue types, notochord and mesenchyme, are induced by the same signaling molecule originating from endoderm precursors. We also demonstrated that the PVC causes the difference in the responsiveness of notochord and mesenchyme precursor blastomeres. Removal of the PVC resulted in loss of mesenchyme and in ectopic notochord formation. In contrast, transplantation of the PVC led to ectopic formation of mesenchyme cells and loss of notochord. Thus, in normal development, notochord is induced by an FGF-like signal in the anterior margin of the vegetal hemisphere, where PVC is absent, and mesenchyme is induced by an FGF-like signal in the posterior margin, where PVC is present. The whole picture of mesodermal patterning in ascidian embryos is now known. We also discuss the importance of FGF induced asymmetric divisions, of notochord and mesenchyme precursor blastomeres at the 64-cell stage.

Actins↗
PubMed2000

Diabetes mellitus associated with rapidly progressive glomerulonephritis with perinuclear antineutrophil cytoplasm antibodies.

A 55-year-old woman who had been treated for diabetes mellitus for twenty-five years developed interstitial pneumonia and rapidly progressive glomerulonephritis (RPGN). The findings of light microscopy revealed fibrocellular crescent formation in all glomeruli and infiltration of lymphoid cells in interstitium. There were no deposits in the intracapillary area and mesangial area on both immunofluorescence and electron microscopy. Her interstitial pneumonia improved with pulse therapy of methylprednisolone and her hematuria disappeared with mix treatment of cyclophosphamide and double filtration plasmapheresis (DFPP). Her serum creatinine level improved from 2.2 mg/dl to 1.5 mg/dl. Interstitial pneumonia and hematuria did not recur at twelve months after the first hospitalization. This report presents a rare case with RPGN associated with diabetes mellitus who recovered with combination therapy of cyclophosphamide, steroid and DFPP.

Acute Kidney Injury↗
PubMed2000

[Dilated form of hypertrophic cardiomyopathy].

To clarify pathological features of dilated form of hypertrophic cardiomyopathy (d-HCM), 14 autopsied hearts with d-HCM were studied. Prognosis of 23 cases with dHCM confirmed by myocardial biopsy specimens were evaluated. Pathological study revealed marked myocardial fibrosis(14/14), moderate to severe disarray(14/14), fibro-fatty degeneration of the outer layer of the left ventricle(13/14) and sclerosis of the intramural coronary arteries(mild, 5; moderate, 4). Degeneration of LV outer layer is an unique pathology in patients with d-HCM. Prognosis of 23 patients with d-HCM is longer than usually supposed(Ten-year-survival rate from the initial symptoms: 78%).

Adult↗