Biomedical subjects

K Kasahara

Publications and source records attributed to K Kasahara.

At least 19 recordsLinked to original sources

PubMed2004

Observation by an air-shower array in Tibet of the multi-TeV cosmic-ray anisotropy due to terrestrial orbital motion around the Sun.

We report on the solar diurnal variation of the galactic cosmic-ray intensity observed by the Tibet III air shower array during the period from 1999 to 2003. In the higher-energy event samples (12 and 6.2 TeV), the variations are fairly consistent with the Compton-Getting anisotropy due to the terrestrial orbital motion around the Sun, while the variation in the lower-energy event sample (4.0 TeV) is inconsistent with this anisotropy. This suggests an additional anisotropy superposed at the multi-TeV energies, e.g., the solar modulation effect. This is the highest-precision measurement of the Compton-Getting anisotropy ever made.

Journal Article↗

PubMed2004

Quantification of telomerase activity of regions unstained with iodine solution that surround oral squamous cell carcinoma.

The aim of this study was to analyze the iodine-unstained region expanding around oral squamous cell carcinoma (SCC) by quantification of telomerase activity. The epithelial dysplasia often observed around SCC is considered to cause local recurrence or a second primary cancer. However these areas are hard to distinguish from normal mucosa. To clear the border of the expanding epithelial dysplasia around SCC, we stained with 3% iodine solution, and then decided the surgical margin. We measured quantification of telomerase activity in tumor, in epithelial dysplasia, and also in normal epithelium. Thirty-three primary cases of oral SCC which have iodine-unstained region around lesions were investigated. Fluorescense-based TRAP was applied to obtain quantification of telomerase activity. We obtained the following results: histological examination confirmed that every patient's unstained region consisted of various degrees of epithelial dysplasia. The quantified telomerase activities for squamous cell carcinoma, epithelial dysplasia and normal epithelium were 53.9, 39.6 and 2.7 U/microgP, respectively, and there was a significant difference between carcinoma and normal areas, and between dysplasia and normal epithelium. Therefore, these findings suggest that the areas of epithelial dysplasia unstained by iodine consist of cells that are nearly cancerous and excessively proliferative, and that epithelial dysplasia around SCC should be resected together with the tumor. Vital staining with iodine is useful for identifying epithelial dysplasia around SCC.

Adult↗

PubMed2004

Characteristics of coated copper wire specimens using high frequency ultrasonic complex vibration welding equipments.

Welding characteristic of thin coated copper wires were studied using 40, 60, 100 kHz ultrasonic complex vibration welding equipments with elliptical to circular vibration locus. The complex vibration systems consisted of a longitudinal-torsional vibration converter and a driving longitudinal vibration system. Polyurethane coated copper wires of 0.036 mm outer diameter and copper plates of 0.3 mm thickness and the other dimension wires were used as welding specimens. The copper wire part is completely welded on the copper substrate and the insulated coating material is driven from welded area to outsides of the wire specimens by high frequency complex vibration.

Journal Article↗

PubMed2004

RNA editing of interleukin-12 receptor beta2, 2451 C-to-U (Ala 604 Val) conversion, associated with atopy.

BACKGROUND: The production of IgE in B lymphocytes is down-regulated by IFN-gamma. IL-12 induces IFN-gamma production by T lymphocytes and natural killer cells by binding to its specific receptor. RNA editing is a post-transcriptional modification. OBJECTIVE: Here we show that the RNA editing of IL-12 receptor (R) beta2 is associated with atopy. METHODS: Atopic patients and non-atopic healthy controls were studied. Fragments of IL-12R beta2 cDNA and genomic DNA were amplified and sequenced. Furthermore, the function of the IL-12R beta2 chain was investigated. RESULTS: Sequence analysis of the cDNA clones representing IL-12R beta2 mRNA transcripts revealed a C-to-U conversion at nucleotide 2451 (Ala 604 Val) on exon 13 in some atopic patients. Surprisingly, sequence analysis of their genomic DNA showed no 2451 C-to-T (Ala 604 Val) mutation. We concluded that the observed C-to-U mismatch in the cDNA clone is due to a post-transcriptional modification, RNA editing. The C-to-U conversion was observed in 21 (20.6%) of 102 atopic patients, whereas this conversion was observed in only 4 (3.8%) of 104 non-atopic subjects (P<0.001). IFN-gamma production by peripheral blood mononuclear cells (PBMCs) stimulated with IL-12 in the subjects with the C-to-U conversion was significantly lower than that in the subjects without the C-to-U conversion. In atopic patients with the C-to-U conversion, PBMCs faintly showed the tyrosine phosphorylation of Stat4, and the IgE production by PBMCs was not suppressed by IL-12 whereas it was suppressed by IFN-gamma. CONCLUSIONS: The RNA editing of IL-12R beta2, 2451 C-to-U (Ala 604 Val) conversion causes impairment of the IL-12 signal cascade and the subsequent reduction in IFN-gamma production, resulting in the impaired down-regulation of IgE production. This is the first report indicating that atopy is associated with RNA editing.

Case-Control Studies↗

PubMed2004

Molecular analysis of B-cell differentiation in selective or partial IgA deficiency.

Selective IgA deficiency is the most common form of primary immunodeficiency, the molecular basis of which is unknown. To investigate the cause of selective IgA deficiency, we examined what stage of B-cell differentiation was blocked. DNA and RNA were extracted from three Japanese patients with selective IgA deficiency and three with a partial IgA deficiency. In selective IgA deficiency patients, Ialpha germline transcript expression levels decreased and alpha circle transcripts were not detected. Stimulation with PMA and TGF-beta1 up-regulated Ialpha germline and alpha circle transcripts. In some patients, IgA secretion was induced by stimulation with anti-CD40, IL-4 and IL-10. In partial IgA deficiency patients, Ialpha germline, alpha circle transcripts and Calpha mature transcripts were detected in the absence of stimulation. Our findings suggest that the decreased expression level of Ialpha germline transcripts before a class switch might be critical for the pathogenesis of some patients with selective IgA deficiency. However, in patients with a partial IgA deficiency, B-cell differentiation might be disturbed after a class switch.

Adolescent↗

PubMed2004

Identification of somatic and germline mosaicism for a keratin 5 mutation in epidermolysis bullosa simplex in a family of which the proband was previously regarded as a sporadic case.

Epidermolysis bullosa simplex (EBS) is an autosomal-dominant inherited blistering skin disease characterized by intraepidermal blistering due to mechanical stress-induced degeneration of basal keratinocytes. EBS is caused by mutations in either keratin 5 or keratin 14, the major keratins expressed in the basal layer of the epidermis. We experienced a unique EBS-affected family. The proband had a heterozygous 1649delG mutation in the keratin 5 gene and had been reported as a case of de novo mutation, because the mutations were not detected in the parents' DNA from blood samples. However, the proband's younger sister was revealed to have the same disease at birth and we found the same mutation in her. We reinvestigated the familial segregation of the 1649delG mutation and it was shown that the mother's DNA from hair bulb and buccal cell samples had the 1649delG mutation heterozygously, but her DNA from blood samples did not. A careful check on the mother's history disclosed that she had migratory circinate pigmentation in her skin in childhood, which means maternal somatic and germline mosaicism. The demonstration of somatic and gonadal mosaicism in the keratin 5 gene is important for accurate genetic counselling of families with sporadic cases of EBS.

Base Sequence↗

PubMed2003

Characteristics of pulmonary Mycobacterium avium-intracellulare complex (MAC) infection in comparison with those of tuberculosis.

To clarify the clinical features of pulmonary Mycobacterium avium-intracellulare complex (MAC) infection, we retrospectively evaluated clinical manifestations, laboratory data, chest and maxillary sinus computed tomographic scans and induced sputum findings in 26 with MAC infection in comparison with 104 patients with tuberculosis (TB) infection. We found that carbohydrate antigen 19-9 (CA 19-9) and immunoglobulin A (IgA) in the serum and percentage of neutrophils in the sputum were significantly higher, and sinusitis was significantly more frequent in patients with MAC compared with patients with TB. MAC infection might be more strongly associated with impaired upper and lower airway defense mechanism in comparison with TB.

Aged↗

PubMed2003

Semiquantitative evaluation of mRNAs for the membranous form of immunoglobulin heavy chain is useful for investigating the etiology in CVID.

Common variable immunodeficiency (CVID) is a primary antibody deficiency syndrome characterized by defective B-cell maturation and antibody formation resulting in low serum antibody levels of all immunoglobulin (Ig) isotypes. To investigate the pathogenesis of CVID, we developed a set of competitive polymerase chain reaction for membrane-bound Ig heavy chain (mHC) mRNAs for IgM, IgG and IgA. Data on three children with CVID in group A of Bryant's classification were analysed. All the three mHC mRNA levels in Patient 1 were almost same as those in healthy controls. In Patient 2, mHC mRNA for IgM was detected at a level similar to that in controls, but mHC mRNAs for IgG and IgA heavy chains were not detected. In Patient 3, all the three mHC mRNAs were undetectable. Our data suggest that a different molecular basis exists in these patients with CVID even though all belong to group A of Bryant's classification. Use of our method facilitates a better understanding of molecular events in CVID patients and may be useful for precise classifications of CVID.

Child↗

PubMed2003

[Experience of off-pump coronary artery bypass grafting with starfish heart positioner].

Recent advances in off-pump coronary artery bypass (OPCAB) technique have demonstrated that multivessel coronary revascularization can be safely performed in selected patient without cardiopulmonary bypass. Numerous positioning technique and devices have been developed to assist access to coronary vessels during OPCAB, such as deep pericardial suture, surgical pads, and cardiac positioning device and stabilizers. We used new cardiac positioning device Starfish heart positioner (Medtronic Corporation) for 2 case of OPCAB. Starfish heart positioner was very useful to successfully perform multivessel coronary bypass on all walls of the beating heart. Starfish heart positioner will facilitate and expand the ability to easily and consistently perform OPCAB.

Aged↗

PubMed2002

A chronic toxicity study of josamycin in F344 rats.

The chronic toxicity of josamycin was examined in Fischer 344 (F344) rats. Groups of 10 males and 10 females were given the test compound in the diet at concentrations of 0 (control), 0.02, 0.1, 0.5 or 2.5% for 52 weeks. Daily intake of josamycin was 0, 10, 50, 260 and 1310 mg/kg body weight in males and 0, 10, 60, 290 and 1460 mg/kg body weight in females, respectively. Body weight gain was significantly (P<0.05) reduced in the male 2.5% group but no noticeable changes were found in food intake. In hematological examination, the platelet count was significantly (P<0.01) lower in the male groups given 0.02% or more of josamycin and in the 2.5% female group as compared with the control group values in a dose-dependent manner. In serum biochemical examination, blood urea nitrogen was significantly (P<0.05 and P<0.01, respectively) higher in males given 0.5 and 2.5% and total bilirubin was significantly (P<0.05) higher in females receiving 2.5% as compared with those of the control group. No death occurred at any dose levels during the dosing period. At necropsy, with the exception of cecal enlargement in the groups given more than 0.1% josamysin and a significant (P<0.01) increase in the relative liver weight of females in the 2.5% group, no particular findings related to the administration were observed. Histopathologically, the incidence and severity of liver bile duct proliferation in female 2.5% group were significantly (P<0.01) greater than those of the control group. Other histological changes found in the treated and control groups were similar to the spontaneous lesions in this strain of rats in terms of the incidence and severity. Interestingly, the josamycin treatment reduced the development of altered liver cell foci in females in a dose-dependent manner. Thus, it is concluded that, under the present experimental conditions, josamycin induces bile duct proliferation in female F344 rats at a high dose of 1460 mg/kg body weight. Based on the decrease of platelet count found in males given 10 mg/kg body weight or more, the no-observed-adverse-effect level (NOAEL) was estimated to be less than 10 mg/kg body weight.

Animals↗

PubMed2002

A recurrent case of odontogenic ghost cell tumour of the mandible.

Odontogenic ghost cell tumour (OGCT), also referred to as dentinogenic ghost cell tumour, is an extremely rare tumour classified as a neoplastic variant of calcifying ondontogenic cyst (COC). To date, only 13 cases of OGCT arising in the maxilla or mandible have been reported. We describe an OGCT that recurred after segmental resection of the mandible in a 59-year-old man. Histopathological examination revealed tumour invasion of the surrounding cortical bone, areas containing numerous calcifying flaky cell nests, and dentinoid matrix near epithelial cell nests. No atypical mitosis was found. There has been no evidence of recurrence or metastasis in the 4 years after operation.

Dentin↗

PubMed2002

Correlation between the bronchial subepithelial layer and whole airway wall thickness in patients with asthma.

BACKGROUND: The epithelial reticular basement membrane (Rbm) of the airway wall thickens in patients with asthma. However, whether the thickening parallels whole airway wall thickening, which limits airflow, is unknown. The aim of this study was to examine the correlation between the bronchial Rbm thickening and whole airway wall thickening in asthma. In addition, the association of Rbm and whole wall thickening with airflow obstruction was examined. METHODS: Forty nine patients with asthma and 18 healthy control subjects took part in the study. The Rbm thickness was measured in bronchial biopsy specimens and whole airway wall thickness was assessed with high resolution computed tomographic (HRCT) scanning after pretreatment with oral steroids for 2 weeks and inhaled beta2 agonist to minimise reversible changes of the airway walls. The percentage airway wall area (WA%; defined as (wall area/total airway area) x 100) and percentage airway wall thickness (WT%; defined as [(ideal outer diameter - ideal luminal diameter)/ideal outer diameter] x 100) were determined from HRCT scans to assess whole airway wall thickness. Spirometric tests were also performed. RESULTS: WA% and WT% were higher in patients with asthma than in healthy subjects. Both WA% and WT% were strongly correlated with Rbm thickness. Moreover, these three indices of airway wall thickness were inversely correlated with the percentage of predicted forced expiratory volume in 1 second in patients with asthma. CONCLUSIONS: These findings indicate that Rbm thickening parallels whole airway wall thickening which can cause irreversible airflow obstruction in patients with asthma.

Asthma↗

PubMed2001

Effects of oral steroids on blood CXCR3+ and CCR4+ T cells in patients with bronchial asthma.

Corticosteroids are widely used in bronchial asthma, but their mechanism of action is not fully understood. The in vitro studies have proposed that human T helper cells, type 1 (Th1) favor expression of CXCR3, whereas Th2 cells favor CCR4. In this study we investigated whether oral prednisolone modulates the balance of peripheral blood CXCR3+ and CCR4+ T cells. We analyzed the T-cell subsets in 28 patients with stable atopic asthma and 13 normal control subjects before and after 2 wk of treatment with prednisolone, 20 mg/d, or placebo in a randomized, double-blind, parallel group study. The numbers of CXCR3+ and CCR4+ memory T cells were measured with a flow cytometer, and expressed as percentages in CD4+/CD45RO+ memory T cells. In the steroid-treated asthma group, there was a decrease in CCR4+ T cells (from 29.3% to 20.3%, p < 0.0001), and an increase in CXCR3+/ CCR4+ ratio (from 1.86 to 2.89, p = 0.0047), whereas there was no change in CXCR3+ T cells. However, the percentages of CCR4+ cells did not change after steroid therapy in normal control subjects. These results suggest that short-term oral corticosteroid modulates the balances of CXCR3+ and CCR4+ cells in patients with asthma.

Administration, Oral↗

PubMed2001

Simplified method of heterotopic rat heart transplantation using the cuff technique: application to sublethal dose protocol of methotrexate on allograft survival.

Rodent heterotopic heart transplantation (HHT) models have been developed for the study of transplantation immunology. Most of these transplantations are performed by hand-suture techniques, requiring several months of training. We describe a modified technique of rat HHT in the neck, using a cuff method that can be mastered by beginners within a few weeks. Our main modification of the rat HHT in the neck is that the right superior vena cava of the graft is chosen as an outflow duct, while the pulmonary artery has been taken as an effluent drainage in the ordinary HHT models. The aorta of the donor is anastomosed with the carotid artery of the recipient. Donation can be completed within 5 min and vascular connections in the recipient done within 3 min, resulting in a minimum of ischemia time. Using this minimum surgical intervention model, we tested the immunosuppressive effect of a sublethal dose of methotrexate (MTX), which has been widely used in cancer therapy. Our results showed that high doses of MTX severely suppressed the recipient bone marrow, but prolonged heart allografts for more than 365 days after HHT. In conclusion, the new model simplified the rat HHT procedure and made it possible for the beginner of rodent transplantation to master this skill within a few weeks. Using this minimized intervention technique, we found that the high doses of MTX can significantly prolong the survival of fully mismatched DA heart graft in PVG/c recipient.

Animals↗

PubMed2001

Fatal acute hepatic failure induced by danazol in a patient with endometriosis and aplastic anemia.

We describe a 47-year-old woman with severe aplastic anemia with genital bleeding who developed acute severe hepatitis after the administration of danazol while she was receiving cyclosporin. She had been diagnosed with severe aplastic anemia 1 year previously and, while hospitalized, had received methyl prednisolone pulse therapy, which was not successful. She was then referred to our hospital. She was treated with antithymocyte globulin, cyclosporin, granulocyte colony-stimulating factor, and methyl prednisolone; a good response was achieved after 3 months of this therapy. Subsequently, oral administration of cyclosporin was continued, but she was readmitted to our hospital when pancytopenia gradually developed and the genital bleeding recurred. Danazol was administered for pancytopenia and endometriosis. Four days after the first administration of danazol, epigastric pain occurred, and the danazol was stopped. Eighteen days after the first danazol administration, very severe hepatic injury occurred abruptly. The patient died of hepatic failure. Postmortem examination revealed centrilobular massive necrosis of the liver. Danazol was implicated as the agent responsible for causing the hepatic failure. Drug interactions between danazol and cyclosporin may cause adverse effects.

Anemia, Aplastic↗

PubMed2001

Follicle-stimulating hormone receptor gene mutations are rare in Japanese women with premature ovarian failure and polycystic ovary syndrome.

OBJECTIVE: To determine whether the known inactivating FSH receptor gene mutations are present in Japanese women with secondary amenorrhea because of premature ovarian failure (POF) and polycystic ovary syndrome (PCOS). DESIGN: Clinical and molecular studies. SETTING: An outpatient clinic in a university hospital. PATIENT(S): Fifteen women with idiopathic POF, 38 women with PCOS, and three normal controls. INTERVENTION(S): Extraction of DNA from blood samples for subsequent polymerase chain reaction (PCR). MAIN OUTCOME MEASURE(S): PCR fragments digested with MunI, BsmI, and HhaI were compared in patients and controls. PCR fragments were also analyzed by denaturing gradient gel electrophoresis (DGGE) and direct sequencing. RESULT(S): No inactivating mutations reported thus far in exons 6, 7, 9, and 10 of the FSH receptor gene were identified in Japanese women with POF and PCOS. DGGE analysis of PCR fragments of exon 10 also revealed no FSH receptor gene mutations in this region. CONCLUSION(S): Although we cannot exclude the presence of point mutations in other regions of the FSH receptor gene, the described FSH receptor mutations may be uncommon in Japanese patients with POF and PCOS.

Adult↗

PubMed2001

Characterization of increased cough sensitivity after antigen challenge in guinea pigs.

Increased sensitivity of cough reflex is a fundamental feature of bronchodilator resistant non-productive cough associated with eosinophilic tracheobronchitis. Our hypothesis is that cough sensitivity is increased by airway allergic reaction characterized by airway eosinophilic inflammation. The aim of this study was to elucidate the hypothesis and clarify the characteristics of the increased cough sensitivity. Number of coughs elicited by inhalation of increasing concentrations of capsaicin (10-8, 10-6 and 10-4 M) was counted 24 h after an aerosolized antigen or saline in actively sensitized or non-sensitized (naive) conscious guinea pigs and then bronchoalveolar lavage was performed. The cough response was also measured 1 day before and 1, 2, 3, 5 and 7 days after an aerosolized antigen challenge in sensitized or naive animals. In addition, effect of procaterol (0.1 mg/kg), atropine (1 or 10 mg/kg), phosphoramidon (2.5 mg/kg) given intraperitoneally 30 min before the capsaicin challenge or capsaicin desensitization on the cough response was examined. Furthermore, the thromboxane A2 (TXA2) receptor antagonist S-1452 in a dose of 0.01 or 0.1 mg/kg or vehicle (saline) was given intraperitoneally at 24 and 1 h before the measurement of cough response. Number of coughs caused by capsaicin was extremely increased 24 h after an antigen challenge in sensitized guinea pigs compared with a saline or an antigen challenge in naive animals or a saline challenge in sensitized animals. The increased cough response disappeared at 3-7 days after the antigen challenge. Eosinophils in bronchoalveolar lavage fluid obtained after the measurement of capsaicin-induced coughs, which was performed 24 h after the antigen challenge, were significantly increased in sensitized guinea pigs. The eosinophil count was significantly correlated to the number of capsaicin-induced coughs. Procaterol or atropine did not alter the antigen-induced increase of cough sensitivity, whereas atropine did reduce the cough response in naive animals. Phosphoramidon increased the number of capsaicin-induced coughs in naive guinea pigs but not in sensitized and antigen-challenged animals. Capsaicin desensitization decreased the cough response in both antigen-challenged sensitized guinea pigs and naive animals. S-1452 reduced the antigen-induced increase of cough response in sensitized guinea pigs, but not in naive animals. Airway allergy accompanied with airway eosinophilia induces transient increase in cough sensitivity, which is not mediated by bronchoconstriction. The increased cough sensitivity may result in part from inactivation of neutral endopeptidase and TXA2, one of the inflammatory mediators.

Allergens↗

PubMed2001

IFN-gamma production in response to IL-18 or IL-12 stimulation by peripheral blood mononuclear cells of atopic patients.

BACKGROUND: Several studies have shown that interleukin (IL)-4 and interferon-gamma (IFN-gamma) are important for the regulation of immunoglobulin E (IgE) production and that IL-18 and IL-12 induce IFN-gamma. OBJECTIVE: IFN-gamma production in response to IL-18 or IL-12 stimulation was investigated in peripheral blood mononuclear cells (PBMCs) of atopic patients with various levels of serum IgE. METHODS: Cytokine production from PBMCs was measured following stimulation with a non-specific stimulator (phytohemagglutinin: PHA), IL-18 or IL-12 in 12 healthy controls and 26 atopic patients with various serum IgE levels. RESULTS: IFN-gamma production by IL-18-stimulated PBMCs was positively correlated with IFN-gamma production by IL-12-stimulated PBMCs (P < 0.05). However some atopic patients showed discrepancy between the levels of IFN-gamma production stimulated by IL-12 and by IL-18. CONCLUSIONS: The results shown here suggest the presence of abnormalities in the IL-12 and/or IL-18 signalling pathways, such as genetic defects in the atopic patients.

Adolescent↗