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Biomedical subjects

M Yamada

Publications and source records attributed to M Yamada.

At least 541 records · Page 30Linked to original sources
PubMed1999

Regulation of natural killer cell-mediated swine endothelial cell lysis through genetic remodeling of a glycoantigen.

The effect of remodeling of a glycoantigen such as the alpha-Gal epitope, Galalpha1,3Galbeta1,4GlcNAc-R, by the introduction of glycosyltransferase genes on natural killer (NK) cell-mediated direct cytotoxicity was investigated using human peripheral blood mononuclear cells (PBMC) or an NK-like cell line, YT cells, as an effector, and swine endothelial cells (SEC) as a target. Several SEC transfectants were established by transfection with the genes for beta1,4-N-acetylglucosaminyltransferase III, alpha2, 3-sialyltransferase and alpha1,2-fucosyltransferase. These transfections led to dramatic reductions in both direct and indirect NK cell-mediated cytotoxicity, by 72-94% in the case of PBMC and 27-72% in that of YT cells, in addition to an effective reduction in xenoantigenicity, which is substantially caused by the alpha-Gal epitope, to human natural antibodies. The NK cell-mediated direct cytotoxicity was remarkably blocked by an anti-alpha-Gal epitope monoclonal antibody or GSI lectin which preferentially binds to the epitope. Furthermore, treatment of the parental cells with alpha-galactosidase resulted in a significant reduction in cytotoxicity. These results suggest that the alpha-Gal epitope is involved not only in hyperacute rejection and acute vascular rejection, but also in NK cell-mediated direct cytotoxicity. Thus, the genetic remodeling of the alpha-Gal epitope and probably other glycoantigens as well can be expected to represent a new approach for overcoming not only indirect but also direct immunity to xenografts.

Animals↗
PubMed1999

Nuclear translocation of nuclear factor kappa B in early 1-cell mouse embryos.

Nuclear factor kappa B (NF-kappaB) is a transcription factor that controls the expression of a number of genes under cellular redox potential. It has recently been found that NF-kappaB plays a pivotal role in morphogenesis and embryonic development, e.g., in formation of Drosophila malanogaster ventral structures and chicken limb buds. However, the role of NF-kappaB in preimplantation development in mammals is not yet understood. In this study, we show that RelA, one of the subunits of NF-kappaB, is expressed in mouse eggs and embryos from the metaphase II (MII) oocyte to the blastocyst stage. Therefore, it is thought that RelA is maternally expressed and that it continues to be expressed during preimplantation development. Immunofluorescence analysis showed that RelA protein was mainly distributed in the cytoplasm of embryos, whereas nuclear translocation of RelA, evidence for NF-kappaB activation, was observed only at the early 1-cell stage. Finally we studied the effects of NF-kappaB inhibitors, pyrrolidine dithiocarbamate and N-acetyl-L-cysteine, on the preimplantation development of mouse embryos. When these inhibitors were added to the culture medium from the early 1-cell stage, subsequent development through the 2-cell stage was inhibited. However, little, if any, influence on the progression through the 2-cell stage was observed when the inhibitors were added at the late 1-cell or the 2-cell stage. Taken together, the results suggest that the activation of NF-kappaB at the early 1-cell stage is required for the development of mouse embryos beyond the 2-cell stage.

Acetylcysteine↗
PubMed1999

Varied appearance of cornea of patients with corneal dystrophy associated with R124H mutation in the BIGH3 gene.

PURPOSE: To evaluate the corneal phenotype of patients with corneal dystrophy and the R124H mutation in the BIGH3 gene. METHODS: We examined the corneas of 24 unrelated Japanese individuals who had an R124H mutation in the BIGH3 gene. Large, discrete, granular deposits were present in the anterior stroma of all patients. They were subdivided into two types according to the appearance of the cornea. Histologic examination of the cornea after Masson trichrome and Congo red staining also was performed in specimens from patients who underwent keratoplasty. RESULTS: The first and the most common type of corneal findings on slit-lamp examination (20 of 24 patients) were discrete granular deposits in the anterior stromal layer and star-shaped opacities in the mid-to-deep stroma. The central subepithelial diffuse opacity increased with age. Amyloid deposits were seen mainly in the mid-to-deep stroma in five of the seven such patients evaluated. The second type of corneal appearance (four of 24 patients) was the presence of diffuse subepithelial opacities in the anterior stroma predominantly, rather than granular or linear opacities. Amyloid deposits were present in the anterior cornea of three of these four patients. CONCLUSION: The corneal lesions documented in patients with the R124H mutation were not unique to that disease but could be divided into two types, which likely represent a disease continuum. The lesion location, amount of amyloid deposition, or an interaction between the granular materials and amyloid may influence the varied appearance of the corneal lesion in patients with this disease.

Aged↗
PubMed1999

Complement receptor type 3 plays an important role in development of protective immunity to primary and secondary Corynebacterium pseudotuberculosis infection in mice.

The present study was performed to investigate the role of CR3, the type 3 complement receptor, in host defense against primary and secondary Corynebacterium (C.) pseudotuberculosis infection in mice. Treatment of mice with 5C6, an anti-CR3 monoclonal antibody (mAb), resulted in unrestricted multiplication of bacteria in the organs and dramatically increased mortalities of the infected mice. Histological examinations showed the inflammation, degeneration and necrosis of organs and revealed that the infection-enhancing effect of 5C6 mAb was associated with the failure of mice to focus mononuclear phagocytes at sites of bacterial multiplication. These results suggest that CR3 plays an important role in host defense against primary as well as secondary C. pseudotuberculosis infection in mice.

Animals↗
PubMed1999

Gamma-irradiation deregulates cell cycle control and apoptosis in nevoid basal cell carcinoma syndrome-derived cells.

The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by nevi, palmar and plantar pits, falx calcification, vertebrate anomalies and basal cell carcinomas. It is well known in NBCCS that gamma-irradiation to the skin induces basal cell carcinomas or causes an enlargement of the tumor size, although the details of the mechanism remain unknown. We have established lymphoblastoid cell lines from three NBCCS patients, and we present here the first evidence of abnormal cell cycle and apoptosis regulations. A novel mutation (single nucleotide deletion) in the coding region of the human patched gene, PTCH, was identified in two sibling patients, but no apparent abnormalities were detected in the gene of the remaining patient. Nevertheless, the three established cell lines showed similar features in the following analyses. Flow cytometric analyses revealed that the NBCCS-derived cells were accumulated in the G2M phase after gamma-irradiation, whereas normal cells showed cell cycle arrest both in the G0G1 and G2M phases. The fraction of apoptotic cells after gamma-irradiation was smaller in the NBCCS cells. The level of p27 expression markedly decreased after gamma-irradiation in the NBCCS cells, although the effects of the irradiation on the expression profiles for p53, p21 and Rb did not differ in normal and NBCCS cells. These findings may provide a clue to the molecular mechanisms of tumorigenesis in NBCCS.

Adolescent↗
PubMed1999

Prevalence and risks of dementia in the Japanese population: RERF's adult health study Hiroshima subjects. Radiation Effects Research Foundation.

OBJECTIVES: To study the prevalence rate of dementia and its subtypes in Japan and to investigate the relationship of risk factors, such as demographic features and disease history, to the prevalence of Alzheimer's disease or vascular dementia. DESIGN: A prevalence study within a longitudinal cohort study. SETTING: The original Adult Health Study (AHS) cohort consisted of atomic-bomb survivors and their controls selected from residents in Hiroshima and Nagasaki using the 1950 national census supplementary schedules and the Atomic Bomb Survivors Survey. Since 1958, the AHS subjects have been followed through biennial medical examinations. PARTICIPANTS: Subjects were 637 men and 1585 women aged 60 years or older in the AHS cohort. Forty-eight subjects resided in hospitals and institutions. MEASUREMENTS: In addition to the biennial medical examinations ongoing since 1958, a screening test for cognitive impairment (CASI) was conducted by trained nurses between September 1992 and September 1996. The prevalence of dementia and its subtypes was assessed in 343 subjects suspected to have dementia and in 272 subjects with high CASI scores who were selected randomly. RESULTS: The prevalence of dementia based on DSM III/R criteria, using neurological examination, the IQCODE, and CDR > or = 1, was 7.2%. The prevalence of Alzheimer's disease was 2.0% in men and 3.8% in women, and the prevalence of vascular dementia was 2.0% in men and 1.8% in women. The relationship of risk factors to Alzheimer's disease or vascular dementia was investigated by the multivariate logistic linear regression analysis. Odds ratios of Alzheimer's disease for age (in 10-year increments), attained education (in 3-year increments), history of head trauma, and history of cancer are 6.3, 0.6, 7.4, and 0.3, respectively. Odds ratios of vascular dementia for age, history of stroke, and history of hypertension are 2.0, 35.7, and 4.0, respectively. Neither type of dementia showed any significant effect of sex or radiation exposure. CONCLUSION: This study is the first study of Japanese dementia rates carried out with a protocol similar enough to that of a US study to allow meaningful comparisons. The prevalence rates demonstrated are more similar to US rates than were found in many previous reports in Japan.

Aged↗
PubMed1999

Migration of neutrophils is dependent on mast cells in nonspecific pleurisy in rats.

To determine the role of mast cells in the recruitment of neutrophils and eosinophils, acute nonspecific pleurisy was induced by injecting isologous serum into normal +/+ and mast cell-deficient Ws/Ws rats. In +/+ rats, neutrophil infiltration peaked 4 h after serum administration, followed by influx of eosinophils after 24-48 h. The levels of neutrophil influx after 4 h as well as the activity of myeloperoxidase (MPO) in pleural lavage-cell extract were significantly lower in Ws/Ws rats than in +/+ rats. In contrast, numbers of eosinophils as well as activity of eosinophil peroxidase (EPO) did not differ significantly between Ws/Ws and +/+ rats. For local reconstitution of mast cells, +/+ rat peritoneal mast cells (PMC) or mesenteric lymph node cells (MLNC) as a control were transferred into the Ws/ Ws pleural cavity. Serum injection into animals with PMC transfer 7 days previously triggered augmented neutrophil influx by approximately 4.7-fold as compared to that in MLNC-transferred animals. Mast cells recovered from the pleural cavity of PMC-transferred rats showed histamine contents equivalent to 20% of that of freshly isolated PMC and retained the reactivity to compound 48/80. These results indicated that dependency of neutrophil recruitment on resident mast cells is greater than that of eosinophils in isologous serum-induced pleurisy.

Animals↗
PubMed1999

[The molecular epidemiological analysis of Shigella sonnei isolates from outbreak cases in Yokohama].

We conducted a molecular epidemiological analysis to evaluate the epidemiologic patterns of Shigella sonnei isolates from outbreak cases in Yokohama to clarify the epidemiologic linkages by contact tracing and sources of infection. In the first case (case A), all of the 6 isolates were the colicin 0 type and resistant to both streptomycin (SM) and trimethoprim/sulfamethoxazole (ST). The 5 isolates have plasmid of 230 kb. By RAPD analysis with 2 kinds of primers specific for Shigella, every 6 isolates showed the same pattern. But the DNA fingerprint analysis by PFGE that was performed according to 2 standardized restriction endonucleases revealed a discriminative pattern. However, the resemblance of all isolates, which was calculated by the UPGMA methods, was 0.90 or higher. In the second case (case B), all of the 14 isolates were the colicin 6 type and sensitive to 16 drugs. The serotype of 13 isolates was phase I. The 11 isolates have plasmids of 230 kb and 3 kb. The resemblance of all isolates, which was calculated by the UPGMA methods, was 0.89 or higher. The analysis with a combination of the plasmid, RAPD analysis and PFGE profiles may be effective in investigating detailed epidemiological features of isolates.

Disease Outbreaks↗
PubMed1999

An acoustical study of sound production in biphonic singing, Xöömij.

A theory that the high melody pitch of biphonic singing, Xöömij, is produced by the pipe resonance of the rear cavity in the vocal tract is proposed. The front cavity resonance is not critical to the production of the melody pitch. This theory is derived from acoustic investigations on several three-dimensional shapes of a Xöömij singer's vocal tract measured by magnetic resonance imaging. Four different shapes of the vocal tract are examined, with which the melody pitches of F6, G6, A6, and C7 are sung, along with the F3 drone of a specific pressed voice. The second formant frequency calculated from each tract shape is close to the melody pitch within an error of 36 cents. Sounds are synthesized by convolving a glottal source waveform provided by the Rosenberg model with transfer functions calculated from the vocal tract shapes. Two pitches are found to be successfully perceived when the synthesized sounds are listened to. In a frequency range below 2 kHz, their spectra have a strong resemblance to those of the sounds actually sung. The synthesized sounds, however, fail to replicate the harmonic clustering at 4-5 kHz observed in the actual sounds. This is speculated to originate from the glottal source specific to the "pressed" timbre of the drone.

Humans↗
PubMed1999

In vitro and in vivo activities of tea catechins against Helicobacter pylori.

The catechin epigallocatechin gallate showed the strongest activity of the six tea catechins tested against Helicobacter pylori (MIC for 50% of the strains tested, 8 microg/ml). It had bactericidal activity at pH 7 but not at pH </=5.0. In infected Mongolian gerbils, H. pylori was eradicated in 10 to 36% of the catechin-treated animals, with significant decreases in mucosal hemorrhage and erosion. Tea catechins, therefore, may have therapeutic effects on H. pylori infection.

Animals↗
PubMed1999

Characterization of the ssnA gene, which is involved in the decline of cell viability at the beginning of stationary phase in Escherichia coli.

When grown in rich medium, Escherichia coli exhibits a drastic reduction of the number of viable cells at the beginning of stationary phase. The decline of cell viability was retarded by disruption of the ssnA gene, which was identified as a gene subject to RpoS-dependent negative regulation. Moreover, ssnA expression was induced at the time of decline of cell viability at early stationary phase. The viability decline was augmented in the rpoS background, and this augmentation was suppressed by ssnA mutation. Cloning of the ssnA gene in a multicopy plasmid, pBR322, caused small colony formation and slow growth in liquid medium. Cells harboring the ssnA clone showed aberrant morphology that included enlarged and filamentous shapes. The gene product was identified as a 44-kDa soluble protein, but its function could not be deduced by homology searching. From these results, we conclude that ssnA is expressed in response to a phase-specific signal(s) and that its expression level is controlled by RpoS, by a mechanism which may contribute to determination of cell number in the stationary phase.

Amino Acid Sequence↗
PubMed1999

A novel growth- and cell cycle-regulated protein, ASK, activates human Cdc7-related kinase and is essential for G1/S transition in mammalian cells.

A novel human protein, ASK (activator of S phase kinase), was identified on the basis of its ability to bind to human Cdc7-related kinase (huCdc7). ASK forms an active kinase complex with huCdc7 that is capable of phosphorylating MCM2 protein. ASK appears to be the major activator of huCdc7, since immunodepletion of ASK protein from the extract is accompanied by the loss of huCdc7-dependent kinase activity. Expression of ASK is regulated by growth factor stimulation, and levels oscillate through the cell cycle, reaching a peak during S phase. Concomitantly, the huCdc7-dependent kinase activity significantly increases when cells are in S phase. Furthermore, we have demonstrated that ASK serves an essential function for entry into S phase by showing that microinjection of ASK-specific antibodies into mammalian cells inhibited DNA replication. Our data show that ASK is a novel cyclin-like regulatory subunit of the huCdc7 kinase complex and that it plays a pivotal role in G1/S transition in mammalian cells.

Amino Acid Sequence↗
PubMed1999

Dry eye after haematopoietic stem cell transplantation.

AIMS: To determine the incidence, natural course, and severity of dry eye occurring or worsening after haematopoietic stem cell transplantation (SCT). METHODS: At a tertiary care hospital, 53 patients undergoing allogeneic or autologous SCT followed by at least 180 days of follow up were studied prospectively. Examination included grading of symptoms of dry eye, evaluation of ocular surface, tear break up time, and Schirmer tests with and without nasal stimulation. Meibomian gland secretion was also examined using a slit lamp while applying steady digital pressure. RESULTS: Of the 53 patients, 44 received allografts. Half of these patients (22) developed dry eye or their pre-existing dry eye worsened after SCT, while none of nine autograft recipients did. Onset of dry eye was 171 (SD 59) days after SCT. Two types of dry eye occurred. One (n=10) was severe with ocular surface findings resembling Sjögren's syndrome and reduction of reflex tearing soon after onset. A mild type (n=12) had unimpaired reflex tearing. Meibomian gland dysfunction (MGD) was more frequent and severe in patients with dry eye and chronic graft versus host disease (GVHD), and overall severity of dry eye was greater in patients with MGD and chronic GVHD. CONCLUSIONS: Dry eye after SCT occurred only in allograft recipients, and was not evident in autograft recipients. The severe form of dry eye had a tendency to develop rapidly. Further study on the prediction and treatment of severe dry eye after SCT is necessary.

Adult↗
PubMed1999

Comparison of the levels of hepatocyte growth factor and vascular endothelial growth factor in aqueous fluid and serum with grades of retinopathy in patients with diabetes mellitus.

AIMS: To determine the relation between the stages of diabetic retinopathy (DR) and the levels of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) in aqueous fluid and serum. METHODS: Levels of HGF and VEGF in serum and aqueous humour obtained during ocular surgery were measured by enzyme linked immunosorbent assay in 58 diabetic patients with 32 non-diabetic patients (NDM) as controls. The patients with diabetes were classified into three groups according to the stage of DR: no DR (NDR; 15 cases), non-proliferative DR (NPDR; six cases), and proliferative DR (PDR; 37 cases). RESULTS: No significant differences were found between any of the groups in serum concentrations of HGF or VEGF. The aqueous HGF levels increased with the stage of DR: NDM, median 397 pg/ml, range 133-930 pg/ml; NDR, 371 pg/ml, 142-1536 pg/ml; NPDR, 455 pg/ml, 162-1007 pg/ml; and PDR, 638 pg/ml, 187-2222 pg/ml. The aqueous VEGF levels in PDR (median 212 pg/ml, range 14-1216 pg/ml) were significantly higher than in NDM (105 pg/ml, 9-203 pg/ml), but aqueous HGF concentrations were unrelated to those of VEGF. CONCLUSION: The results of the present study suggest that both HGF and VEGF present in the ocular tissues may play important roles in the progression of DR.

Adult↗
PubMed1999

Pattern of epitopic reactivity of the anti-Hu antibody on HuD with and without paraneoplastic syndrome.

Previous study has shown that the anti-Hu antibody titre of serum samples from patients with paraneoplastic encephalomyelitis/paraneoplastic sensory neuronopathy (PEM/PSN) was significantly higher than that from patients with small cell lung cancer without neurological disturbances (non-PEM/PSN). The aims of this study were (1) to identify the fine epitopes on HuD recognised by the anti-Hu antibody, (2) to determine if the pattern of epitopic reactivity differed between antibodies from patients with and without PEM/PSN, and (3) to determine if the pattern of epitopic reactivity correlated with the clinical features. Recombinant full length HuD and nine deletion fragments were constructed and immunoreacted by western blot analysis with 14 anti-Hu serum samples from eight patients with PEM/PSN and six without PEM/IPSN. All anti-Hu serum samples reacted with the deletion fragments containing amino acids (aa) 90-101 or aa 171-206. Some anti-Hu samples reacted with the deletion fragments containing aa 223-234, aa 235-252, or aa 354-373. There was no difference in the pattern of epitopic reactivity between patients with and without PEM/PSN. There was no correlation between the pattern of epitopic reactivity and the clinical features. The anti-Hu antibody titre from patients with PEM/ PSN was significantly higher than from patients without PEM/PSN, but there was overlap of their titre concentrations. In conclusion, aa 90-101 and aa 171-206 are the major epitopes with which all anti-Hu serum samples react, and aa 223-234, aa 235-252, and aa 354-373 are the minor epitopes with which only some anti-Hu serum samples react. The analyses suggested that the pattern of epitopic reactivity of the anti-Hu antibody on HuD was not a critical factor for the development or clinical features of PEM/PSN.

Antibodies↗