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Biomedical subjects

H Nagata

Publications and source records attributed to H Nagata.

At least 55 records · Page 3Linked to original sources
PubMed2001

Patterns of age-dependent changes in the numbers of lymph follicles and germinal centres in somatic and mesenteric lymph nodes in growing C57Bl/6 mice.

The timing of the first appearance of lymph follicles and germinal centres in various lymph nodes, and the ways in which numbers of these and IgM-synthesising cells increase within the nodes, were investigated in male and female C57Bl/6N mice aged from 4 d to 16 wk. The lymphoid organs examined were the Peyer's patches, spleen, somatic (submandibular, deep cervical, brachial, axillary, inguinal and popliteal) and visceral (mesenteric and lumbar) lymph nodes. Primary follicles appeared in most somatic lymph nodes 6 d after birth. The number of follicles per node then increased rather sharply in larger lymph nodes and slowly in smaller nodes, up to 28 d of age, reaching a level which varied according to the location of the node. Thereafter, the number of follicles in the somatic lymph nodes increased only slightly to moderately, reaching a peak or plateau at 8-12 wk. In the mesenteric (ileocaecal) nodes, primary follicles first appeared at 12 d, then increased linearly during the suckling period and after weaning to reach a plateau at 8 wk of age. Germinal centres appeared in the submandibular and mesenteric nodes at 28 d and their numbers increased consistently in the latter, while remaining low in the former. The impact of possible 'natural' exogenous antigen stimulation of the various lymph nodes was estimated from the presence of IgM-synthesising cells and germinal centres. Differences between the patterns of age-dependent changes in the numbers of lymph follicles observed in the somatic and mesenteric lymph nodes during their ontogeny are discussed in relation to differences in the magnitude of the exogenous antigen stimulatory effect. We also found that the variations in the numbers of lymph follicles produced in somatic lymph nodes at different locations during the first 28 d after birth reflected differences in the dimensions of the body regions drained by a particular somatic lymph node at this stage of development.

Aging↗
PubMed2001

In vitro effect of gelatins on murine cell proliferation.

Porcine skin (PS) gelatin suppressed proliferation of a murine hepatic cell carcinoma cell line, MH134, a murine fibrosarcoma cell line, Meth A and a murine T cell lymphoma cell line, RL Male 1. The magnitude of suppression of the proliferation by cold water fish skin (CWFS) or bovine bone (BB) gelatin was lower than that by PS gelatin. On the other hand, BB gelatin stimulated proliferation of murine spleen cells. The magnitude of stimulation of the proliferation by CWFS gelatin was lower than that by BB gelatin. PS gelatin slightly suppressed proliferation of murine spleen cells. PS gelatin induced apoptosis but not necrosis of MH134 tumor cells. CWFS gelatin induced weaker apoptosis of the cells than PS gelatin. DNA histogram indicated that PS and CWFS gelatins acted on MH134 tumor cells to increase ratios of G2 + M-phase.

Animals↗
PubMed2001

In situ demonstration of intraepithelial lymphocyte adhesion to villus microvessels of the small intestine.

The recirculation of lymphocytes through the intestinal mucosa is important for specific immune defense, but the origin and differentiation of intraepithelial lymphocytes (IEL) are not fully understood. The present study therefore used intravital microscopy to investigate the migration of IEL to the villus mucosa and Peyer's patches of the small intestine. IEL were separated from inverted murine small intestine and mesenteric lymph node (MLN) T cells were also isolated. The adhesion of fluorescence-labeled lymphocytes to postcapillary venules (PCV) of Peyer's patches and arcade microvessels of small intestinal villi was observed after injection. In some experiments, the effect of antibodies against adhesion molecules on cell kinetics were investigated. IEL time-dependently accumulated in villus microvessels of the small intestine, whereas few MLN cells did. Few IEL adhered to the PCV of Peyer's patches. IEL were shown to express alpha(E)beta(7)-integrin but not L-selectin. The accumulation of IEL in villus archade was significantly inhibited by antibody against beta(7)-integrin or mucosal addressin cell adhesion molecules (MAdCAM)-1, but not by alpha(E)-integrin. The combined blocking of beta(7)-integrin and MAdCAM-1 further attenuated the sticking of IEL in this area, although it did not entirely block the IEL adherence. The adherence of CD4(+) or TCRalphabeta IEL to villus microvessels was significantly greater than that of CD4(-) or TCRgammadelta IEL. It was demonstrated in situ for the first time that IEL adhered selectively to the villus microvessels of the small intestine partly via beta(7) and MAdCAM-1.

Animals↗
PubMed2001

(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assays showed a lack of toxicity of ganciclovir (GCV), C.OXTs, and their derivatives, to TaY(OK) cells at 1 microM. Therefore we compared the antiviral potencies of these drugs at 1 microM by monitoring the viral loads produced during a 1-day period during the course of the drug treatment. Among the drugs tested, 3'-fluorocarbocyclic oxetanocin A (3'F-C.OXT-A) was the most effective for inhibiting the virus production, and at concentrations ranging from 0.5 microM to 10 microM, the inhibition of the viral production was dose-dependent. A comparison of the chemical structures of the derivatives with that of C.OXT-A, which is the parental molecule, suggested that the 3'-fluorine-modification might account for the higher anti-HHV-6 activity and lower cytotoxicity.

An infection of TaY cells, which originated from an adult T-cell leukemia, with an HHV-6B OK isolate resulted in a chronically infected culture, termed TaY(OK). Cell cloning analysis revealed that the TaY(OK) culture consisted of a mixture of cells permissive and refractory to the infection, and that the permissive cells were continuously produced from the refractory cell population. Since the chronically infected culture has been maintained for over 2 years without the addition of uninfected TaY cells, we used it for an evaluation of the antiviral potency of nucleoside analogs, especially carbocyclic oxetanocins (C.OXTs).

Adenine↗
PubMed2001

Ataxic form of chronic inflammatory demyelinating polyradiculoneuropathy: clinical features and pathological study of the sural nerves.

We investigated clinical and pathological features of the sural nerves of 5 patients with the ataxic form of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and compared these features with those of chronic ataxic neuropathies due to other causes. The CIDP patients presented with slowly progressive ataxia with deep sensory impairment. The durations of the symptoms from onset were relatively short in CIDP (4-8 months) and cancer (3 and 10 months), but long in chronic idiopathic ataxic neuropathy (24-260 months). Corticosteroid therapy elicited a good response in all the patients with CIDP, but a poor response in the patients with other ataxic neuropathies. Sural nerve biopsy of CIDP patients showed a slight or moderate loss of myelinated fiber. This report suggests that ataxic form of CIDP is a steroid-responsive ataxic neuropathy, and large myelinated fibers of the sural nerves in ataxic form of CIDP were better preserved than those in nerves with other chronic ataxic neuropathies.

Adult↗
PubMed2001

Enhancement of submicroscopic damage of the nasal epithelium by topical allergen challenge in patients with perennial nasal allergy.

The purposes of this study were to clarify whether damage of the nasal epithelium exists in patients with nasal allergy, and how the morphology of the epithelium changes after topical allergen challenge. Electron microscopy revealed 2 characteristic features in the nasal epithelium of patients with perennial nasal allergy--an increase in the number of epithelial cells with cytoplasmic vacuoles, and markedly widened intercellular spaces--although these changes were unclear under light microscopy. The density of vacuolated cells significantly increased 24 hours after allergen challenge. Further, the number of eosinophils that were associated with vacuolated cells was significantly higher in patients with nasal allergy than in controls. These morphological changes, thus, were considered to be types of damage to the nasal epithelium associated with nasal allergy. Such changes may be among the causes of nasal hyperreactivity, which is an important feature of nasal allergy.

Administration, Topical↗
PubMed2001

Judgments of grammaticality of Japanese bitransitive sentences with a differing number of arguments.

This study explored the linguistic intuition of Japanese speakers when they judged the grammaticality of isolated simple bitransitive sentences. The role of the number of arguments and the manner of presenting sentences-whether or not the number of arguments increased across judgment trials-in determining the judged grammaticality was examined. Findings showed that the speakers tended to judge even sentences lacking arguments as grammatical. A direct object was most influential in determining judged grammaticality, an indirect object next most influential, and a subject least influential. The manner of presenting sentences had an almost negligible effect. The findings suggest that speakers' judgments of sentences are graded as contrasted to linguists' judgments. Osgood's Naturalness Principle of 1980 was interpreted as providing a good explanation for the findings.

Adolescent↗
PubMed2001

Analysis of the p53 gene in parotid gland cancers: a relatively high frequency of mutations in low-grade mucoepidermoid carcinomas.

Mutations and overexpression of the p53 gene and protein were analyzed in 40 cases with various types of parotid gland cancers. Mutations were found in 12 cases (30%), and low-grade mucoepidermoid carcinomas (43%) and highly malignant carcinomas including adenocarcinoma, salivary duct carcinoma, and undifferentiated carcinoma (56%) showed a relatively high frequency of mutations. Overexpression of the protein was observed in 11 cases (28%) and 4 of the 11 cases also had p53 mutations. These results suggest that mutations of the p53 gene have significance in certain types of parotid cancers irrespective of the aggressiveness of a tumor type.

Carcinoma, Mucoepidermoid↗
PubMed2001

Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in Japanese population.

We analyzed genetic alterations in BRCA1 and BRCA2 genes among 82 ovarian cancer families in Japan. The clinical characteristics of BRCA-associated ovarian cancer patients were compared with cases carrying no mutations as well as with population controls. Using a direct sequencing method, 45 of the 82 ovarian cancer families were found to carry BRCA1 or BRCA2 germ-line mutations (40 with BRCA1 and 5 with BRCA2). In 24 independent mutations of BRCA1, 5 recurrent mutations were found and 2 of them, the L63X and Q934X mutations, were detected in seven and eight independent families, respectively. In addition, 16 mutations of BRCA1 and 3 mutations of BRCA2 have never been described previously. In consideration of clinicopathological features, there was a significantly higher proportion of tumors with serous adenocarcinoma and of cases of advanced stages in the BRCA1 or BRCA2 cases than in those of the controls. On the other hand, there were no differences of mean age at diagnosis between patients with BRCA1 or BRCA2 mutation and those of the controls. Our results indicate that the features of BRCA-associated ovarian cancer in Japan appear to be similar to those in Western countries, and the L63X and Q934X mutations of BRCA1 appear to be common founder mutations unique to the Japanese population.

Adolescent↗
PubMed2001

Virtual reality system using force feedback device for molecular modeling.

We designed two new concept of computer aided molecular modeling system using virtual reality technologies. Although it is still a prototype, the most characteristic function of the system is enabling its user to "touch" and feel the electrostatic potential field of a protein or a drug molecule. User can scan surface of a protein using a globular probe, which is given an electrostatic charge, controlled by a force feedback devise. The electrostatic force between the protein and the probe is calculated in real time, and immediately fed back into the force feedback device. The user can easily search interactively for positions where the probe is strongly attracted to the force field. Such positions can be regarded as candidate sites where small chemical groups corresponding to the probe, functional parts of lead compounds, can bind to the target protein. We also developed a binding simulator which we can bind a small molecule (drug) to a large molecule (protein). In this system, we placed a camera, so that we can not only "feel" but also "see" how drug fits into the binding site. Our prototype system has the potential to serve as a new application method as well as being applicable to conventional VR technologies, especially to force feedback technologies.

Computer Simulation↗
PubMed2001

Intercellular cell adhesion molecule-1 regulates lymphocyte movement into intestinal microlymphatics of rat Peyer's patches.

The objective of this study was to determine whether specific adhesion molecules modulate lymphocyte movement from Peyer's patches into intestinal microlymphatics. The fluorochrome acridine orange was injected via a micropipette into Peyer's patches to fill lymphatics. The flux of labeled lymphocytes into intestinal microlymphatics was monitored with intravital fluorescence microscopy. The lymphatic microvessels in the perifollicular area of Peyer's patches were filled with lymphocytes, most of which remained within the lymphatics. Some lymphocytes became detached and were drained into intestinal lymph. Administration of antibodies directed against ICAM-1 significantly increased lymphocyte flux into interfollicular lymphatics. The immunohistochemical study showed intense ICAM-1 expression on the lymphocytes densely packed in the lymphatics surrounding follicles in Peyer's patches. A large number of lymphocytes are normally sequestered in the lymphatic network of Peyer's patches. This sequestration of lymphocytes is largely mediated by ICAM-1-dependent cell-cell interactions.

Animals↗
PubMed2000

Evaluation of the validity of the 1997 International Union Against Cancer TNM classification of major salivary gland carcinoma.

BACKGROUND: The TNM classification (International Union Against Cancer) of salivary gland carcinoma was revised in 1997. In this study, the authors have evaluated the validity of this new TNM classification and clinical staging in 1683 patients with parotid gland carcinoma. METHODS: Reclassification was conducted according to the new classification based on the clinical data of 1683 patients registered to the salivary gland division of the Japanese Joint Committee on TNM classification. The 5- and 10-year survival rates according to TNM classification were calculated for 1074 patients whose prognosis could be followed up. Finally, the distribution of the total patient population was analyzed using the new staging and the survival curves for each disease stage. RESULTS: The variance of the patients for T1 to T4 was appropriate using the new T classification. The 5- and 10-year survival rates corresponded well to the degree of progression of TNM. However, there were only nine patients with Stage III, and marked nonuniformity in the staging was observed. The separation of the survival curves for each stage was not clear, and no significant differences between the survival curves of Stages II and III and Stages III and IV were observed. When the authors classified T1N1M0, T2N1M0, T3N1N0, and T4N0M0, which have 5- and 10-year survival rates similar to Stage III, distribution of patients and separation of the survival curves in each stage improved markedly. CONCLUSIONS: The results of the current study confirm that the new TNM classification system is valid. However, a significant problem was observed with respect to the new clinical staging. The authors propose that T1N1M0, T2N1M0, T3N1M0, and T4N0M0 be classified as Stage III.

Disease-Free Survival↗
PubMed2000

Isolation and characterization of murine orthologue of PTP-BK.

We isolated and characterized a murine orthologue of PTP-BK, a receptor-type protein tyrosine phosphatase expressed in brain and kidney. The deduced amino acid sequences showed 89, 95, and 92% identities with human, rabbit, and chicken homologues of PTP-BK. Mouse PTP-BK encodes a polypeptide of 1,226 amino acids with calculated molecular weight of 138,598 Da. The mature form of PTP-BK constitutes of 3 domain structures including extracellular, transmembrane, and a single intracellular PTPase domain. Western blot analysis indicated that anti-PTP-BK antibody specifically immunoreacted to 2 distinct molecules of 200 kDa and 220 kDa in COS cells, possibly due to differential glycosylation. The recombinant PTP-BK showed the phosphatase activity specific for the phosphotyrosine, but not for the phosphoserine residue of phosphopeptides in vitro. Radiation hybrid panel assigned mouse PTP-BK gene to 5.02cR distal to from the marker D6Mit339 on chromosome 6. Mouse PTP-BK was classified in PTPRO family in novel nomenclature. We discuss here the diversity and physiological functions of PTPRO family of PTP.

Amino Acid Sequence↗
PubMed2000

Precise measurements of the gamma-ray emission probabilities of 186Re and 188Re.

Gamma-ray emission probabilities of 186Re and 188Re are important in nuclear medicine, and have been precisely measured by 4pibeta-gamma coincidence using a live-timed two-dimensional data-acquisition system. The gamma-ray emission probabilities of the 137.2 keV for 186Re and 155.1 keV for 188Re were 0.09487+/-0.00029 and 0.15425+/-0.00072, respectively.

Gamma Rays↗
PubMed2000

Relation of motility of subgingival microflora as a clinical parameter to periodontal disease status in human subjects.

BACKGROUND/AIMS: The purpose of this study was to evaluate the possible relationship between the motility of subgingival microflora and 5 clinical parameters commonly used in dental clinics. METHOD: The clinical parameters were pocket depth, gingival inflammation, plaque accumulation, bleeding on probing and pus discharge. The motility of human subgingival microflora was estimated as the number of pixels remaining after subtraction of serial video frames using a high speed shutter camera and image analysis system, and was defined as the sum of pixels of 10 successive subtractions per sample over a 10-s time period. RESULTS: The bacterial motility showed significant positive, moderate or low associations with the five clinical parameters. The highest correlation was observed between the bacterial motility and pocket depth (r=0.36, p=0.0001). Furthermore, clinically defined periodontal healthy and diseased sites were significantly different with respect to the bacterial motility (p<0.0001). To determine whether the bacterial motility was dependent or independent of the other clinical variables, the data were analyzed based on common factor analysis. Three factors were extracted and explained about 75% of the variance of the original 6 clinical parameters. Only the bacterial motility had a positive coefficient for all these three factors. The plot of bacterial motility was placed separately from those of other variables in the scatterplot of the loadings of factor 2 versus factor 1 and factor 2 versus factor 3. CONCLUSIONS: This suggests that bacterial motility may be an independent variable among the clinical parameters. Taken together, these data indicate that bacterial motility provides unique information about the clinical periodontal condition and may be a useful tool for the monitoring of subgingival plaque in relation to periodontal disease.

Adolescent↗
PubMed2000

Production of fibrogenic cytokines by cord blood-derived cultured human mast cells.

BACKGROUND: Mast cells are a potential source of cytokines, but their contribution to nonallergic inflammatory conditions, such as fibrosis, remains unclear. OBJECTIVE: We investigated whether cord blood-derived cultured human mast cells could produce fibrogenic cytokines by IgE-mediated activation. METHODS: Mast cells were obtained from human cord blood mononuclear cells by culture with stem cell factor and IL-6. The mast cells were incubated with human myeloma IgE and were activated with anti-IgE. The expression of messenger RNA for fibrogenic cytokines was examined by the reverse-transcription polymerase chain reaction, and cytokine protein was assayed by enzyme-linked immunosorbent assay, or bioassay. RESULTS: Cultured human mast cells constitutively expressed mRNA for transforming growth factor-beta(1), and its expression was not increased by anti-IgE stimulation. The cells released this factor into the culture medium spontaneously, which showed bioactivity after heat treatment. The mast cells also expressed mRNA for platelet-derived growth factor A, which was enhanced with a peak at 3 hours by stimulation with anti-IgE. Conditioned medium from nonactivated mast cells did not contain basic fibroblast growth factor, but this cytokine was released into the medium in a time-dependent manner after stimulation with anti-IgE. CONCLUSION: Human mast cells activated by IgE-mediated stimulation show production of fibrogenic cytokines that varies depending on the cytokine, which suggests possible involvement of mast cell cytokines in the development of fibrosis.

Cells, Cultured↗
PubMed2000

Evaluation of outcome and QOL in patients with craniofacial resection for malignant tumors involving the anterior skull base.

The purpose of this study was to retrospectively evaluate the effectiveness of anterior craniofacial resection in the treatment of nasal and paranasal malignant tumors involving anterior skull base. Between 1992 and 1998, 13 patients with nasal or paranasal malignant tumors underwent this surgical procedure. The site and time of metastasis or recurrence, and survival outcome were retrospectively surveyed. Current status of long-surviving patients and their subjective assessment of the surgical treatment were also evaluated through questionnaires. Median follow-up period was 52 months. Nine patients (69%) were alive with no evidence of disease. Of these patients, eight had survived for more than three years. Recurrence or metastasis occurred in four patients (31%). The mean time interval between surgery and recurrence or metastasis was 11 months. According to the results of questionnaires to long-surviving patients, 89% patients had some complaints. In particular, complaints of unsightly appearance were manifested by all these patients. When the patients themselves evaluated their current conditions resulting from this surgical treatment, 63% were dissatisfied. These results suggest that this surgical treatment is valid for selected patients in regard to survival outcome. When the effectiveness of this treatment is evaluated, however, psychological and functional issues should not be taken lightly.

Adolescent↗