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Biomedical subjects

K Nishi

Publications and source records attributed to K Nishi.

At least 19 recordsLinked to original sources
PubMed2005

Living-related small bowel transplantation: two cases experiences.

We have recently performed living-related small bowel transplantation for 2 patients. The first patient was a 14-year-old boy with total parenteral nutrition (TPN)-dependent short-bowel syndrome associated with hypoganglionosis of the entire intestine. He received a bowel graft from his 43-year-old mother. The second patient was a 27-year-old woman, who had massive enterectomy due to volvulus and developed vitamin deficiencies and severe metabolic disorders as a result of long-term TPN. She underwent living-related bowel transplantation from her 57-year-old mother. Blood types were ABO identical, cytotoxic cross matches were negative, and cytomegalovirus statuses were positive-to-positive in both cases. Up to one third of the donor bowel was harvested from the donor distal ileum more than 30 cm away from the ileocecal valve. The graft vessels were connected to infrarenal aorta, and inferior vena cava. The immunosuppressive regimen consisted of daclizumab, tacrolimus, and steroid. The graft surveillance was accomplished using zoom endoscopy and mucosal biopsy. The first patient developed progressive acute cellular rejection (ACR) on the 9th postoperative day (POD)-9 requiring OKT-3 therapy, which was effective. Two months after transplantation, he was weaned from TPN, tolerating oral intake with a fully functioning graft. The second patient experienced no episode of ACR and was weaned off TPN on POD-29 with a functioning graft. Her metabolic disorder dramatically improved after bowel transplantation. Both donors had no complication and were discharged from the hospital on POD-10. Living-related bowel transplantation is an extreme option of treatment for patients with short-bowel syndrome.

Adolescent↗
PubMed2004

The expression of intestinal CYP3A4 in the piglet model.

PURPOSE: In our previous study, the blood levels of tacrolimus were higher in the short bowel and small bowel transplantation models than those in controls. Metabolism by intestinal cytochrome p450 3A4 (CYP3A4) has been reported to influence the blood level of orally administered tacrolimus. We performed immunohistochemistry to examine the localization of intestinal CYP3A4. MATERIALS AND METHODS: Twenty-four piglets were divided into three groups: group 1 were controls (n = 11); group 2, ileal resection of 2/3 proximal small intestine (n = 5); and group 3, total small intestinal resection followed by 1/3 allotransplantation of ileum (n = 8). Tacrolimus was orally administered from postoperative days 3 to 7. On day 7, blood samplings were performed for the trough level and the calculation of area under the concentration time curve (AUC). Intestinal specimens from the jejunum, ileum, colon, and ileal graft were obtained on days 0 and 10 for immunohistochemistry of CYP3A4. RESULTS: The trough and AUC values in group 2 were significantly higher than those in group 1. Furthermore those measurements in group 3 animals were higher than in group 2 (trough levels: 2.5 +/- 1.7, 11.2 +/- 2.1, 16.3 +/- 2.7 ng/mL and AUC values: 126 +/- 90, 319 +/- 155, 546 +/- 117 ng. h/mL). The expression levels of CYP3A4 were, jejunum > ileum > ileal graft > colon. CONCLUSIONS: The intensity and extent of CYP3A4 staining diminished in the ileal graft showing an inverse correlation to the blood concentrations.

Animals↗
PubMed2004

The colon displays an absorptive capacity of tacrolimus.

PURPOSE: In our previous study, blood levels of orally administered tacrolimus were significantly higher in short bowel piglets than in control animals. It has been reported that the blood levels of tacrolimus are influenced by the metabolic activity of intestinal CYP3A4. If tacrolimus may be absorbed in the colon, direct administration of drug into this organ might be useful to augment bioavailability since the expression of CYP3A4 is low at this site. In the present study we evaluated the absorptive capacity of tacrolimus in the colon. MATERIALS AND METHODS: Piglets were divided into four groups: groups 1 and 2 were controls (n = 11 and 3, respectively); group 3 underwent resection of the entire small intestine (n = 8); and group 4 had a catheter placed in the cecum (n = 4). In groups 1 and 3, tacrolimus was administered orally; in group 2 it was given intravenously; and in group 4 it was injected into cecum through the catheter from postoperative days 3 to 7. On day 7, blood samples were obtained for drug measurements to calculate the area under the concentration time curve (AUC) values. RESULTS: The trough level and AUC values of tacrolimus in group 4 as well as in group 3 were significantly higher than those in group 1. In Group 4 animals showed a 60-minute time to peak concentration. CONCLUSIONS: Tacrolimus is absorbed by the colon. Since the blood levels were not influenced by the metabolic activity in the graft bowel, direct administration of tacrolimus into the colon might be useful in small intestinal transplantation.

Animals↗
PubMed2004

[Right ventricular myxoma with syncopal attach; report of a case].

Cardiac myxoma of right ventricle is rare. We report a 16-year-old girl who underwent an emergent surgical resection of right ventricular myxoma. She had syncopal attach in going to school and was referred to our hospital in emergency. There were no abnormal findings in brain computed tomography (CT) and electroencephalogram, but Levine IV/VI systolic ejection murmur was heard. Echocardiography and magnetic resonance imaging (MRI) revealed the presence of large mass in the right ventricle which was floating into the pulmonary artery. The tumor was removed completely through the both of main pulmonary artery and right atrium using cardiopulmonary bypass. The tumor was attached to the right ventricle free wall by a pedicle, which was 5 x 3 cm in size and was diagnosed as myxoma by histopathological examination.

Adolescent↗
PubMed2003

Correlation between periodontal status and biting ability in Chinese adult population.

This study investigated the relation between periodontal condition and biting ability in a Chinese population using the pressure-detecting sheet. A total of 142 subjects residing in Nanchang, Jiangxi province, China, participated in the study. The examination included probing pocket depth (PD), clinical attachment level (CAL), bleeding on probing and coronal caries teeth. Biting abilities per person, biting force, biting pressure and occlusal contact area were measured using the sheet. Number of teeth present showed positive correlation with biting force and occlusal contact area, but were negatively correlated with biting pressure. No significant correlation was observed between the mean PD, percentage of pocket > or = 4 mm, bleeding index and any of biting abilities. The mean CAL showed a significantly negative correlation with biting force and occlusal contact area. Multiple stepwise regression analysis selected the number of teeth present, sex and age as the significant factors affecting the biting ability. However, no periodontal indices were picked up as the significantly contributing factor. There appears to be little effect of periodontal condition on biting ability. Ageing was selected as a contributing factor to reduction in the Chinese adults, but not in the Japanese population.

Adult↗
PubMed2003

Raised plasma oxidised LDL in acute cerebral infarction.

BACKGROUND: The association between oxidised low density lipoprotein (OxLDL) and cerebral infarction is suspected but not established. OBJECTIVES: To determine whether plasma OxLDL is a useful marker for monitoring oxidative stress in stroke patients. METHODS: Plasma OxLDL concentrations were determined in 56 stroke patients with cerebral infarction (n = 45) or cerebral haemorrhage (n = 11), and in 19 age matched controls, using a novel sandwich enzyme linked immunosorbent assay. RESULTS: Compared with the controls (0.130 (0.007) ng/ micro g LDL, mean (SEM)), OxLDL was significantly raised in patients with cerebral infarction (0.245 (0.022); p < 0.0001) but not in those with haemorrhage (0.179 (0.023)). Patients with cortical ischaemic infarcts (n = 22) had higher OxLDL levels than either the controls (p < 0.0001) or the patients with non-cortical ischaemic infarcts (n = 23) (p < 0.001). Increased OxLDL concentrations in patients with cortical infarcts persisted until the third day after stroke onset. The National Institutes of Health stroke scales in patients with cortical infarction were higher than in those with non-cortical infarction (p < 0.01). CONCLUSIONS: There is a significant association between raised plasma OxLDL and acute cerebral infarction, especially cortical infarction. Plasma OxLDL may reflect oxidative stress in stroke patients.

Acute Disease↗
PubMed2003

Comparison of atopic cough with cough variant asthma: is atopic cough a precursor of asthma?

BACKGROUND: We have described a group of patients who present with isolated chronic bronchodilator resistant non-productive cough with an atopic constitution, eosinophilic tracheobronchitis, and airway cough receptor hypersensitivity without bronchial hyperresponsiveness, which we have termed "atopic cough". Although cough variant asthma (in which the cough responds to bronchodilators) is recognised as a precursor of typical asthma, it is not known whether atopic cough is also a precursor of asthma. METHODS: Eighty two patients with atopic cough were retrospectively examined for onset of typical asthma and compared with 55 patients with cough variant asthma (20 untreated patients and 35 treated with long term inhaled beclomethasone dipropionate (BDP), 218-467 micro g/day). The median follow up period for patients with atopic cough and cough variant asthma was 4.8 (1-11.5) years and 3.7 (1-12.4) years, respectively. RESULTS: Onset of typical asthma occurred in only one of the patients with atopic cough. In patients with cough variant asthma, typical asthma developed in two of 35 patients taking BDP and six of 20 untreated patients (difference 24.3%, 95% CI 2.8 to 45.8, p<0.02). CONCLUSIONS: These findings suggest that cough variant asthma is a precursor of typical asthma but that atopic cough is not. Treatment with inhaled steroids may prevent the transformation of cough variant asthma into typical asthma.

Administration, Inhalation↗
PubMed2001

LIGHT, a member of the TNF superfamily, induces morphological changes and delays proliferation in the human rhabdomyosarcoma cell line RD.

LIGHT is a member of the tumor necrosis factor (TNF) superfamily, which binds two known receptors, lymphotoxin-beta receptor (LTbetaR) and the herpesvirus entry mediator (HVEM)/TR2. We investigated the effects of LIGHT on the human rhabdmyosarcoma cell line RD. LIGHT delayed cell proliferation and induced morphological changes of the cells. These effects were not shown by other TNF family ligands such as TNFalpha and LTalpha, which induced the transcriptional activity of nuclear factor-kappaB (NF-kappaB) and NF-kappaB-responsible chemokine productions in the same manner as did LIGHT. LTalpha1beta2, another TNF family ligand for LTbetaR, was shown to have similar activities in RD cells as LIGHT. Both LIGHT and LTalpha1beta2 induced the expression of muscle-specific genes such as smooth muscle (SM) alpha-actin, while TNFalpha and LTalpha did not. These findings indicate that LIGHT may be a novel inducer of RD cell differentiation associated with SM alpha-actin expression through the LTbetaR.

Actins↗
PubMed2001

Subthalamo-pallido-striatal axis: a feedback system in the basal ganglia.

Systemic administration of a dopamine D2 receptor blocker, haloperidol, but not vehicle, significantly increased the number of c-Fos-immunoreactive neurons in the globus pallidus (GP) in rats. Dual immunohistochemistry, a combination of c-Fos immunohistochemistry and retrograde tracing experiments with cholera toxin B (ChB), revealed that a subset of the c-Fos-immunoreactive GP neurons was pallidostriatal feedback neurons. Lesioning of the subthalamic nucleus (STN) by local injection of ibotenic acid inhibited the haloperidol-induced c-Fos expression in the GP neurons, suggesting that the activation of GP neurons is a result of increased excitatory drives from the STN. Therefore, the present findings are evidence of the existence of the subthalamo-pallido-striatal axis as a feedback system in the internal circuits of the basal ganglia.

Animals↗
PubMed2001

Molecular monitoring of bleomycin-induced pulmonary fibrosis by cDNA microarray-based gene expression profiling.

Pulmonary fibrosis is a progressive disorder whose molecular pathology is poorly understood. Here we developed an in-house cDNA microarray ("lung chip") originating from a lung-normalized cDNA library. By using this lung chip, we analyzed global gene expression in a murine model of bleomycin-induced fibrosis and selected 82 genes that differed by more than twofold intensity in at least one pairwise comparison with controls. Cluster analysis of these selected genes showed that the expression of genes associated with inflammation reached maximum levels at 5 days after bleomycin administration, while genes involved in the development of fibrosis increased gradually up to 14 days after bleomycin treatment. These changes in gene expression signature were well correlated with observed histopathological changes. The results show that microarray analysis of animal disease models is a powerful approach to understanding the gene expression programs that underlie these disorders.

Animals↗
PubMed2001

Fluorescence intermittency in self-assembled InP quantum dots.

Fluorescence intermittency in InP self-assembled dots is investigated by means of far field imaging and single dot spectroscopy. Based on our observation that blinking dots are found in the vicinity of scratches and the blinking frequency is drastically enhanced under a near-infrared laser irradiation, we attribute the origin of the fluorescence intermittency to a local electric field due to a carrier trapped at a deep localized center in the Ga0.5In0.5P matrix. The validity of this explanation is confirmed by a thermal activation-type behavior of the switching rate and artificial reproduction of the blinking phenomenon by an external electric field.

Journal Article↗
PubMed2001

Pyrrolidine inhibitors of human cytosolic phospholipase A2. Part 2: synthesis of potent and crystallized 4-triphenylmethylthio derivative 'pyrrophenone'.

We synthesized a potent and crystallized human cytosolic phospholipase A2alpha inhibitor, pyrrophenone (6) which inhibits the isolated enzyme with an IC50 value of 4.2 nM. Pyrrophenone shows potent inhibition of arachidonic acid release, prostaglandin E2, thromboxane B2, and leukotriene B4 formation in human whole blood. The magnitudes of prostaglandin E2 and thromboxane B2 inhibition are the same as those of indomethacin.

Arachidonic Acid↗
PubMed2001

The cyclin-dependent kinase (CDK) inhibitor flavopiridol inhibits glycogen phosphorylase.

Flavopiridol has been shown to induce cell cycle arrest and apoptosis in various tumor cells in vitro and in vivo. Using immobilized flavopiridol, we identified glycogen phosphorylases (GP) from liver and brain as flavopiridol binding proteins from HeLa cell extract. Purified rabbit muscle GP also bound to the flavopiridol affinity column. GP is the rate-limiting enzyme in intracellular glycogen breakdown. Flavopiridol significantly inhibited the AMP-activated GP-b form of the purified rabbit muscle isoenzyme (IC50 of 1 microM at 0.8 mM AMP), but was less inhibitory to the active phosphorylated form of GP, GP-a (IC50 of 2.5 microM). The AMP-bound GP-a form was poorly inhibited by flavopiridol (40% at 10 microM). Increasing concentrations of the allosteric effector AMP resulted in a linear decrease in the GP-inhibitory activity of flavopiridol suggesting interference between flavopiridol and AMP. In contrast the GP inhibitor caffeine had no effect on the relative GP inhibition by flavopiridol, suggesting an additive effect of caffeine. Flavopiridol also inhibited the phosphorylase kinase-catalyzed phosphorylation of GP-b by inhibiting the kinase in vitro. Flavopiridol thus is able to interfere with both activating modifications of GP-b, AMP activation and phosphorylation. In A549 NSCLC cells flavopiridol treatment caused glycogen accumulation despite of an increase in GP activity, suggesting direct GP inhibition in vivo rather than inhibition of GP activation by phosphorylase kinase. These results suggest that the cyclin-dependent kinase inhibitor flavopiridol interferes with glycogen degradation, which may be responsible for flavopiridol's cytotoxicity and explain its resistance in some cell lines.

Adenosine Monophosphate↗
PubMed2001

Functional annotation of a full-length mouse cDNA collection.

The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.

Animals↗
PubMed2001

Both the conserved and the unique gene structure of stomach-specific calpains reveal processes of calpain gene evolution.

The proteins nCL-2 and nCL-2' are members of the Ca2+-dependent cysteine protease (calpain) superfamily, with stomach-specific expression. Like other typical calpains, nCL-2 has three distinct domains, a protease, a C2-like, and a 5EF-hand Ca2+-binding domain, as well as the N-terminal propeptide region. On the other hand, nCL-2' lacks the C2-like and 5EF-hand domains but is otherwise identical to nCL-2, except for the three C-terminal residues. To examine the stomach-specific and presumed alternative expression mechanisms of nCL-2 and nCL-2', we have cloned and characterized the mouse gene for nCL-2 and nCL-2'. The mouse nCL-2 gene contains at least 23 exons, spanning more than 50 kb, and possesses an exon specific for nCL-2' in the middle. Therefore, nCL-2 and nCL-2' are generated by alternative splicing of the same gene, Capn8. Capn8 shows the highly conserved gene organization of the other typical calpain large subunit genes, CAPN1, CAPN2, CAPN3, CAPN9, CAPN11, and Capn12, except for the unique exon between exon 9 and exon 10 of Capn8, which encodes the 3' half of the nCL-2' transcript. No such exon in the corresponding regions was found in CAPN1, CAPN2, CAPN3, CAPN9, or CAPN11. Gene and cDNA structures of a presumed human orthologue of mouse nCL-2, CAPN8, were determined, revealing that it overlaps human CAPN2, the gene for the m-calpain large subunit, in head-to-head orientation at 1q32-41. These features of Capn8 and CAPN8 illustrate a process of calpain gene evolution, i.e., the protease, C2-like, and 5EF-hand domains presumably functioned as independent genes, and the calpain superfamily has evolved by ordered fusions of these ancestral gene units, with subsequent amplifications.

Alternative Splicing↗