Search PubMed⌕ Search

Biomedical subjects

N Kawamura

Publications and source records attributed to N Kawamura.

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

Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 8). Effects of daily subcutaneous administration of reserpine on spermatogenesis for 2 and 4 weeks.

To obtain information on the validity and the limitations of 2-weeks repeated-dose toxicity studies to detect effects on the male genital organs of rats, reserpine was administered daily at 0.05 and 0.1 mg/kg by subcutaneous injection to Crj:CD(SD)IGS male rats for 2 and 4 weeks (2-weeks and 4-weeks studies). In the 2-weeks study, suppression of body weight gain was observed in the reserpine 0.1 mg/kg group. In the 4-weeks study, suppression of body weight gain and a decrease in prostate weight were observed in the reserpine 0.1 mg/kg group. Slight to moderate retention of step 19 spermatids in the seminiferous tubules (stages IX-XI) was observed in a few animals of both the reserpine 0.05 and 0.1 mg/kg groups in both the 2- and 4-weeks studies. However, seminiferous tubule atrophy with degeneration of germ sells was observed sporadically not only in the reserpine groups but also in the control group, and this change might have been the cause of the spermatid retention. Therefore, we were unable to reach a clear conclusion with regard to whether it is possible to detect reserpine toxicity on spermatogenesis in rats after 2-weeks administration.

Animals↗
PubMed2000

Unmyelinated nerve fiber analysis of the human oculomotor nerve.

Unmyelinated nerve fibers of the oculomotor nerve have occasionally been observed in experimental animals with the use of electron microscopes, but no details concerning normal oculomotor nerves in humans have been published. We measured and analyzed unmyelinated nerve fibers in the human oculomotor nerve with an image analyzer and a computer, using a new staining method, the Luxol fast blue-periodic acid-Schiff-hematoxylin (LPH) discriminative staining method which is the only one suitable for morphometric research on nervous tissues. We studied the numbers and transverse areas of unmyelinated fibers of the oculomotor nerve in 20 cadavers. The number of unmyelinated axons did not change with age, but the mean transverse area decreased with age. These fibers were distributed diffusely in the transverse area of the oculomotor nerve, not localized in any part of the nerve. These findings may be important for the analysis of clinical and neurological signs in relation to aging and ophthalmologic functions.

Adult↗
PubMed2000

Mutation analysis of the p53 tumor suppressor gene using paraffin-embedded specimens of human transitional cell carcinomas by the direct sequencing method.

A very small quantity of DNA was extracted from paraffin sections of 25 bladder and 2 ureteral cancer cases, and exons 5-8 of the p53 gene were amplified by the polymerase chain reaction. Mutations were detected by direct sequencing, and their relationships to clinicopathological factors were assessed. Point mutations of the p53 gene were observed in 2 of 27 specimens of transitional cell carcinoma. One was a novel nonsense mutation. The prognosis of patients with p53 gene mutations was poorer than those of patients without mutations. Analysis of the data showed that assessment of the potential malignancy of bladder cancer, combined with a conventional pathological diagnosis, allows a more precise prognosis. Direct sequencing of tissue specimens enables swift prognostic evaluation and prompt decisions concerning treatment.

Adult↗
PubMed2000

[Small epidermoid induced trigeminal neuralgia unrecognized by conventional CT and MRI for over 25 years].

A 65-year-old woman had been conservatively treated as idiopathic trigeminal neuralgia for over 25 years, because conventional computed tomography (CT) and magnetic resonance imaging(MRI) showed no abnormality in the cerebello-pontine(CP) angle cistern. She received a detailed MRI by constructive interference in steady state and diffusion weighted image(DWI) sequences. Those sequences on MRI well demonstrated a epidermoid tumor in the CP angle cistern, and the removal of the tumor completely resolved the neuralgia. Since a small epidermoid in the CP angle cistern seems to be unrecognized by conventional CT and MRI, detailed evaluation by DWI sequence, which has been widespread recently, is required for patients with trigeminal neuralgia.

Aged↗
PubMed2000

[Genetic analysis of two patients with adenosine deaminase (ADA)-deficiency: detection of three novel mutations and characterization of two paradoxical carriers].

Genetic basis of two patients (AT, MT) with ADA deficiency was studied. We identified three novel mutations (119 Q-->Stop, 235 R-->Q, one base deletion in Exon 4) from the patients. 119 Q-->Stop was detected in AT and her father. Deletion of one base in Exon 4 which would change the reading frame after codon 105 H, was detected in MT, her father and brother. There was no relation between the two families, however, 235 R-->Q was also detected in both the patients and their mothers. Extremely low ADA activity of PBMCs was revealed in healthy MT's mother and brother just as MT, although their dAXP levels of RBCs showed significantly lower than that of MT. We defined that they shared an additional mutation (310 M-->T) together with the mutation described above, respectively. EBV-transformed B-cell line (EBV-B) were established from the carriers. To our surprise, ADA activity of their lines was 1/10-1/5 of normal. The result of heat treatment studies using the EBV-B showed that the mutant ADA rapidly lose its enzyme activity without degradation of the protein. It suggests that 310 M-->T mutant ADA rapidly lost its enzyme activity due to conformational change of the catalytic site of ADA.

Adenosine Deaminase↗
PubMed1999

Two types of aggregate in the cerebral cortex of a seizure-sensitive strain of the Mongolian gerbil.

A 70-kDa protein, P70, found mostly in the pyramidal cells of the cerebral cortex of cobalt-induced epileptogenic rats, has been implicated in epileptogenesis. The presence of a P70-like substance was searched for immunohistochemically in the cerebral cortex of MGS/ldr, a seizure-sensitive strain of the Mongolian gerbil (Meriones unguiculatus) that we previously established. Immunoreactive aggregates were observed in the pyramidal neurons of the motor cortex and the primary somatosensory cortex. Analysis using confocal laser scanning microscopy revealed that the aggregates were often colocalized with a second type of aggregate with red autofluorescence at the marginal zone of the cell somata. Both aggregates appeared and increased before the appearance of generalized tonic-clonic convulsion. These may be involved in some change of physiological function of the cerebral cortex but their presence itself is not enough to determine the occurrence of epileptic seizure because the gerbils that showed no such seizure had both aggregates.

Animals↗
PubMed1999

In vivo kinetics of transduced cells in peripheral T cell-directed gene therapy: role of CD8+ cells in improved immunological function in an adenosine deaminase (ADA)-SCID patient.

We previously reported successful peripheral T cell-directed gene therapy in a boy with adenosine deaminase (ADA)-SCID. In the present study, to better understand the reconstitutive effect of this gene therapy on his immunological system, we investigated the in vivo kinetics and functional subsets of T cells in PBL. Apparent immunological improvements were obtained after infusion of transduced cells at more than 4 x 108 cells/kg/therapy/3 mo. Frequency of ADAcDNA-integrated cells in PBL, ADA activity in PBL and clinical improvement showed good correlation, even though CD8+ cells gradually became predominant in PBL. On the basis that polyethylene glycol (PEG)-ADA was maintained at the same dosage as before gene therapy, we consider that his immunological improvement resulted from the gene therapy itself. Most CD3+ cells in PBL after gene therapy expressed TCRalphabeta. Analysis of TCR repertoire based on TCR V region usage revealed no expansion of limited clones in his PBL. The T cell subset cells CD8+CDw60+ and CD8+CD27+CD45RA-, which are reported to provide substantial help to B cells, were maintained throughout the gene therapy. Furthermore, his reconstituted peripheral T cells helped normal B cells to produce substantial IgG in vitro. Expression of both Th1- and Th2-type cytokine genes was induced in his reconstituted T cells at the same comparably high level as in normal subjects. Collectively, these results provide evidence of persistent and distinct functions of transduced cells in this patient's PBL after gene therapy.

Adenosine Deaminase↗
PubMed1999

The alkaline single cell gel electrophoresis assay with mouse multiple organs: results with 30 aromatic amines evaluated by the IARC and U.S. NTP.

The genotoxicity of 30 aromatic amines selected from IARC (International Agency for Research on Cancer) groups 1, 2A, 2B and 3 and from the U.S. NTP (National Toxicology Program) carcinogenicity database were evaluated using the alkaline single cell gel electrophoresis (SCG) (Comet) assay in mouse organs. We treated groups of four mice once orally at the maximum tolerated dose (MTD) and sampled stomach, colon, liver, kidney, bladder, lung, brain, and bone marrow 3, 8 and 24 h after treatment. For the 20 aromatic amines that are rodent carcinogens, the assay was positive in at least one organ, suggesting a high predictive ability for the assay. For most of the SCG-positive aromatic amines, the organs exhibiting increased levels of DNA damage were not necessarily the target organs for carcinogenicity. It was rare, in contrast, for the target organs not to show DNA damage. Organ-specific genotoxicity, therefore, is necessary but not sufficient for the prediction of organ-specific carcinogenicity. For the 10 non-carcinogenic aromatic amines (eight were Ames test-positive and two were Ames test-negative), the assay was negative in all organs studied. In the safety evaluation of chemicals, it is important to demonstrate that Ames test-positive agents are not genotoxic in vivo. Chemical carcinogens can be classified as genotoxic (Ames test-positive) and putative non-genotoxic (Ames test-negative) carcinogens. The alkaline SCG assay, which detects DNA lesions, is not suitable for identifying non-genotoxic carcinogens. The present SCG study revealed a high positive response ratio for rodent genotoxic carcinogens and a high negative response ratio for rodent genotoxic non-carcinogens. These results suggest that the alkaline SCG assay can be usefully used to evaluate the in vivo genotoxicity of chemicals in multiple organs, providing for a good assessment of potential carcinogenicity.

Amines↗
PubMed1999

Dorsum sellae meningioma mimicking pituitary macroadenoma: case report.

BACKGROUND: A dorsum sellae meningioma is a rare occurrence. It is difficult to evaluate dorsum sellae meningiomas preoperatively from the viewpoint of neuroimaging. We report a rare case of dorsum sellae meningioma mimicking pituitary macroadenoma in a 73-year-old woman. CASE PRESENTATION: The patient presented with bitemporal hemianopsia and panhypopituitarism. Magnetic resonance imaging demonstrated a bright, homogeneously enhancing intra- and suprasellar mass and a hypointense region in this mass, which was interpreted as a dorsum sellae. Transsphenoidal extirpation was used because of a suspicion of nonsecreting pituitary macroadenoma. Histopathologically, the tumor was diagnosed as a meningioma. Superselective external carotid angiography before the second surgery revealed that the mass was supplied by the left accessory middle meningeal artery and appeared to originate from dorsum sellae. After preoperative embolization, the patient developed hyponatremia. The tumor was subtotally removed via a transcranial route, and the attachment to the dorsum sellae was coagulated extensively. She did well after a second surgical procedure. CONCLUSION: These radiologic findings may be useful in differentiating dorsum sellae meningioma from pituitary macroadenoma.

Adenoma↗
PubMed1999

Production of IL-4 and expression of CD40 ligand by human CD8 T cells.

BACKGROUND: The role of CD8(+) T cells in IgE synthesis remains unclear. OBJECTIVE: The aim of this study was to investigate IL-4 production and CD40 ligand expression by human CD8(+) T cells. METHODS: We conducted functional and phenotypic analyses of human T cells in peritoneal washings from severe combined immunodeficiency mice reconstituted with PBMCs from normal and atopic human donors. We also examined the expression of IL-4 and CD40 ligand by CD8(+) T cells from a patient with adenosine deaminase deficiency who received autologous T cell-directed gene therapy. RESULTS: Transfer of atopic cells into the mice caused production of IgE and IgG with increased expression of IL-4 and CD40 ligand mRNA. In addition, both intracellular IL-4 and cell surface CD40 ligand were detected in CD8(+) and in CD4(+) T cells. CD8(+) T-cell lines generated from the patient's T cells carrying the adenosine deaminase gene expressed not only IL-4 mRNA and protein but also CD40 ligand mRNA and protein after being stimulated with an anti-CD3 mAb. After anti-CD3 stimulation and paraformaldehyde fixation, CD8(+) T cells induced IgE synthesis by normal human B cells in the presence of recombinant IL-4. CONCLUSION: Taken together, these results demonstrate that IL-4-producing and CD40 ligand-expressing CD8(+) cells are detectable among human T cells and suggest that such cells may promote IgE production by B cells under some conditions.

Adenosine Deaminase↗
PubMed1999

Risk factors for the development of Escherichia coli O157:H7 associated with hemolytic uremic syndrome.

Verotoxin-producing Escherichia coli (VTEC) O157:H7 is a major cause of hemorrhagic colitis that is often associated with the development of hemolytic uremic syndrome (HUS). In July, 1996, a severe mass outbreak of VTEC O157 infection occurred in Sakai city, Osaka. The present study investigates the risk factors which may contribute to the development of HUS in the early stages of the VTEC O157 infection. There was no significant difference between HUS-developed and non-HUS-developed groups with respect to sex, age, rates of clinical manifestations, such as fever, abdominal pain and bloody stool, use of anti-diarrheal agents, anti-motility agents, and/or antibiotic agents, and serum sodium concentrations at the early stage of VTEC O157 infection. Thus, these factors did not appear to be risk factors associated with the development of HUS. In contrast, leukocyte counts and C-reactive protein levels in the early stage of VTEC O157 infection were significantly higher in the HUS-developed group (P < 0.001), suggesting that these are risk factors associated with the development of HUS.

Bacterial Toxins↗
PubMed1999

PTEN/MMAC1 mutations in hepatocellular carcinomas: somatic inactivation of both alleles in tumors.

Allelic loss of loci on chromosome 10q occurs frequently in hepatocellular carcinomas. Somatic mutations of the PTEN/MMAC1 gene on this chromosome at 10q23 were recently identified in sporadic cancers of the uterus, brain, prostate and breast. To investigate the potential role of PTEN/MMAC1 gene in the genesis of hepatocellular carcinomas, we examined 96 tumors for allelic loss on 10q and also for subtle mutations anywhere within the coding region of PTEN/MMAC1 gene. Allelic loss was identified in 25 of the 89 (27%) tumors that were informative for polymorphic markers in the region. Somatic mutations were identified in five of those tumors: three frameshift mutations, a 1-bp insertion at codon 83-84 in exon 4 and two 4-bp deletions, both at codon 318-319 in exon 8; two C-to-G transversion mutation, both at -9 bp from the initiation codon in the 5' non-coding region of exon 1. No missense mutation was observed in this panel of tumors. In most of the informative tumors carrying intragenic mutations of one allele, we were able to detect loss of heterozygosity as well. These findings suggest that two alleles of the PTEN/MMAC1 gene may be inactivated by a combination of intragenic point mutation on one allele and loss of chromosomal material on the other allele in some of these tumors.

Alleles↗
PubMed1999

Distribution of beta-lactamases in actinomycetes.

The distribution of beta-lactamase activities in a collection of actinomycete strains was surveyed. Six of 127 strains were found to produce beta-lactamase. This low frequency was in contrast to the case with Streptomyces species. The producing strains were not related phylogenetically. MICs of benzylpenicillin did not correlate with beta-lactamase production.

Actinomycetales↗