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Biomedical subjects

T Kawaguchi

Publications and source records attributed to T Kawaguchi.

At least 163 records · Page 9Linked to original sources
PubMed1998

[Langerhans cell histiocytosis in the hypothalamus: a case report].

A case of Langerhans cell histiocytosis (LCH) in the hypothalamus is presented. A 52 year old man with eosinophilic granuloma of the lung was referred to our hospital. He complained of headache, easy fatigability, high fever, and voiding large quantities of urine, but was otherwise asymptomatic. T1-weighted images demonstrated a small mass in the hypothalamus. After about six months, the mass had grown to 2 cm in diameter. Surgery was performed by a pterional approach and a biopsy specimen was collected. Light microscopic examination of sections of the biopsy specimen showed polymorphous cellular infiltration by histiocytic cells, eosinophils, neutrophils, and lymphocytes. Electron microscopy showed Langerhans cells and Birbeck granules in the cytoplasm. The histological diagnosis was LCH, multifocal type. After low-dose radiation therapy, the mass gradually decreased in size. The clinicopathological features, neuroradiological findings, and treatment are briefly discussed.

Combined Modality Therapy↗
PubMed1998

[Blood products use and related factors in Japan].

PURPOSES: To examine the use of blood products in Japan by prefectures and to determine the factors associated with the amount of blood products used. METHODS: The amounts of blood products used in November 1995 were surveyed in 8,723 hospitals throughout Japan. The survey also included whether the blood products in hospitals were stored and managed based on the guidelines for appropriate use of blood products. RESULTS: 1. 4,675(90.9%) of the 5,141 respondents used blood products in 1995. 2. The amount of use of each blood product was considerably different among the prefectures. Larger amounts of red blood products and plasma products were used in urban areas. 3. The amounts of use of red blood cell products, plasma products and platelet concentrates showed similar geographical distributions at a significant correlation (r > or = 0.6) each other. The amount of use of albumin products correlated significantly (r = 0.69) with that of immunoglobulin products. 4. Among the various blood products surveyed in this study, the amount of use of only red blood cell products was comparatively larger in the prefectures where blood products were appropriately stored and managed. 5. The number of surgical operations performed under general anesthetization correlated positively with the amount of use of red blood cell products, plasma products and platelet concentrates; a similar correlation was observed between the number of operations for malignant neoplasm and cardiac diseases. CONCLUSION: The amounts of use of blood products used were significantly different among the prefectures in Japan. The amount of use of red blood cell products possibly reflects demand and consumption of blood products as a whole.

Anesthesia, General↗
PubMed1998

[Stereotaxy during intravenous anesthesia with propofol].

A series of 30 patients, who underwent stereotactic surgery for movement disorder under intravenous propofol anesthesia between March, 1995 and December, 1997, was retrospectively reviewed. In 28 patients with Parkinson's disease including seven juvenile cases of parkinsonism, the postoperative motor and ADL scores on the Unified Parkinson's Disease Rating Scale significantly improved. In the other two patients, one of whom had severe posttraumatic tremor and the other had cerebral palsy, the stereotactic surgery produced considerable alleviation of their symptoms. We evaluated and discussed the usefulness of intravenous propofol anesthesia in stereotaxy. Except for one patient who had an allergic reaction against propofol, none of the patients complained of intraoperative pain postoperatively. Wake-up tests were performed to record neural noise levels in 26 cases. This recording was performed under propofol anesthesia in two cases with advanced Parkinson's disease and one with cerebral palsy. In these patients, neural noise levels were recorded and were useful for identifying the target. Although the tremor disappeared under propofol anesthesia in 17 patients presenting with moderate or severe tremor, it was presented again after discontinuation of propofol. Wake-up test, therefore, made a good evaluation of Vim thalamotomy for tremor. In juvenile parkinsonian patients, three presented with dopa-induced dyskinesia (DID) during propofol infusion. In two of them, the DID emerged immediately after posteroventral pallidotomy and continued 4 or 10 hours after stereotaxy. These findings suggest that propofol possibly has an anti-parkinsonian effect. Intravenous propofol anesthesia is a useful method to use with stereotactic surgery for movement disorders.

Adult↗
PubMed1998

Clinicopathologic features of local and metastatic recurrences in primary lung adenocarcinoma.

We attempted to construct the contour of recurrence in primary lung adenocarcinoma with clinicopathologic variables based on data of 131 patients with completely resected primary lung adenocarcinoma. In univariate analysis, tumor size (more or less 3 cm in diameter), p-T, p-N, pathological stage, differentiation, ly factor and v factor were chosen for prognostic predictors. In multivariate analysis, v factor and p-N were independent variables of local recurrence and metastatic recurrence, respectively. The examination of significant correlation among clinicopathologic variables in terms of 5-year survival rates of patients showed that tumor size, p-T, ly factor and v factor were profoundly related to local recurrence, whereas ly factor, differentiation and p-N were linked to distant metastasis. We therefore examined an additive effect of tumor size, differentiation and vascular invasion on recurrence. The results demonstrated that neither local nor metastatic recurrences were found in patients with well differentiated adenocarcinoma less than 3 cm in diameter if vascular invasion was negative. We conclude that vascular (ly factor and v factor) is central to lung adenocarcinoma recurrence. The vascular invasion is a powerful predictor of recurrence in less than 3 cm diameter, well differentiated adenocarcinoma of the lung.

Adenocarcinoma↗
PubMed1997

Purification and cloning of hepatocyte growth factor activator inhibitor type 2, a Kunitz-type serine protease inhibitor.

Hepatocyte growth factor (HGF) activator is a serine protease responsible for proteolytic activation of HGF in response to tissue injury and thus plays an important role in the regulation of biological functions of HGF in regenerating tissue. We previously purified an inhibitor of HGF activator (HGF activator inhibitor type 1, HAI-1) from the conditioned medium of a human stomach carcinoma cell line MKN45 and cloned its cDNA. HAI-1 is a novel member of the Kunitz family of serine protease inhibitors. In the present study, we purified a second type of HGF activator inhibitor (HAI-2) from the conditioned medium of MKN45 cells and molecularly cloned its cDNA. The cDNA sequence revealed that HAI-2 is derived from a precursor protein of 252 amino acids and contains two Kunitz domains, indicating that HAI-2 is also a member of the Kunitz family of serine protease inhibitors. The primary translation product of HAI-2 has a hydrophobic sequence in the COOH-terminal region, suggesting that, like HAI-1, HAI-2 is produced in a membrane-associated form and secreted in a proteolytically truncated form. Because HAI-2 and HAI-1 are potent inhibitors specific for HGF activator, they may be involved in regulation of proteolytic activation of HGF in injured tissues.

Amino Acid Sequence↗
PubMed1997

Chiral discrimination of 2'-deoxy-L-cytidine and L-nucleotides by mouse deoxycytidine kinase: low stereospecificities for substrates and effectors.

The effects of four kinds of 2'-deoxy-L-nucleoside 5'-triphosphates and L-ATP, which are enantiomers of natural D-dNTPs and D-ATP, on deoxycytidine kinase (dCK) partially purified from mouse leukemic P388 cells were investigated. Only L-dCTP did not act as a phosphate donor while other L-dNTPs and L-ATP showed 15-30% of the activity of the corresponding D-dNTP or D-ATP. L-dCTP inhibited dCK non-competitively with 2'-deoxycytidine (D-dCyd) and competitively with phosphate donor D-ATP. These inhibitory effects of L-dCTP on dCK were similar to the results of earlier studies using D-dCTP. Thus, L-dCTP was shown to be capable of serving as a feedback inhibitor for dCK instead of D-dCTP. Mouse dCK was also able to phosphorylate L-dCyd, as demonstrated in the case of human dCK. The present results suggest that the chirality of not only dCyd as the substrate but also nucleotides as the substrate or effector is not strictly discriminated by dCK.

Adenosine Triphosphate↗
PubMed1997

Apoptosis resistance of blood cells from patients with paroxysmal nocturnal hemoglobinuria, aplastic anemia, and myelodysplastic syndrome.

Bone marrow (BM) hypoplasia is a major cause of death in paroxysmal nocturnal hemoglobinuria (PNH). However, little is known about the molecular events leading to the hypoplasia. Considering the close pathologic association between PNH and aplastic anemia (AA), it is suggested that a similar mechanism operates in the development of their BM failure. Recent reports have indicated apoptosis-mediated BM suppression in AA. It is thus conceivable that apoptosis also operates to cause BM hypoplasia in PNH. If this is the case, PNH clones need to survive apoptosis and show considerable expansion leading to clinical manifestations. We report here that granulocytes obtained from 11 patients with PNH were apparently less susceptible than those from 20 healthy individuals to both spontaneous apoptosis without any ligands and that induced by anti-FAS (CD95) antibody in vitro. The patients' BM CD34+ cells were also resistant to apoptosis induced by treatment with tumor necrosis factor-alpha, interferon-gamma, and subsequently with anti-FAS antibody. In lymphocytes, the pathologic resistance was not discriminated from inherent resistance to apoptosis. Granulocytes from 13 patients with AA and 12 patients with myelodysplastic syndrome (MDS) exhibited similar resistance to apoptosis. CD34+ cells from MDS-BM also showed similar tendency. Thus, the comparative resistance to apoptosis supports the pathogenic implication of apoptosis in marrow injury of PNH and related stem cell disorders.

Adult↗
PubMed1997

Induction of cancer, actinic keratosis, and specific p53 mutations by UVB light in human skin maintained in severe combined immunodeficient mice.

To study the mechanism and risk of human skin cancer from solar light, we exposed human skin transplanted to severe combined immunodeficient mice to daily doses of UVB for periods of approximately 2 years. We have succeeded for the first time in inducing cancer and solar (actinic) keratosis in human skin by UVB. Of 18 normal skins exposed to doses of 7.3 x 10(5) to 1.8 x 10(6) J/m2, 14 actinic keratoses (77.8%) and 3 squamous cell carcinomas (16.7%) developed, whereas neither actinic keratosis nor cancer was observed in 15 human skins not exposed to UVB. Each human skin showed a different susceptibility, and skins sensitive for actinic keratosis were also sensitive for cancer induction. Among p53 mutations at various sites, mutation at codon 242 (C TGC --> C CGC; Cys --> Arg) was specifically observed in both skin cancers and actinic keratoses. Furthermore, double or triple mutations were induced in all UVB-induced skin cancers and in three of eight actinic keratoses. Most of the mutations (17 of 20) occurred at dipyrimidine sites.

Animals↗
PubMed1997

Hepatocyte growth factor activator inhibitor, a novel Kunitz-type serine protease inhibitor.

Hepatocyte growth factor (HGF) activator is a serine protease that is produced and secreted by the liver and circulates in the blood as an inactive zymogen. In response to tissue injury, the HGF activator zymogen is converted to the active form by limited proteolysis. The activated HGF activator converts an inactive single chain precursor of HGF to a biologically active heterodimer in injured tissue. The activated HGF may be involved in the regeneration of the injured tissue. In this study, we purified an inhibitor of HGF activator from the conditioned medium of a human MKN45 stomach carcinoma cell line and molecularly cloned its cDNA. The sequence of the cDNA revealed that the inhibitor has two well defined Kunitz domains, suggesting that the inhibitor is a member of the Kunitz family of serine protease inhibitors. The sequence also showed that the primary translation product of the inhibitor has a hydrophobic sequence at the COOH-terminal region. Inhibitory activity toward HGF activator was detected in the membrane fraction as well as in the conditioned medium of MKN45 cells. These results suggest that the inhibitor may be produced as a membrane-associated form and secreted by the producing cells as a proteolytically truncated form.

Amino Acid Sequence↗
PubMed1997

Soybean agglutinin binding as a useful prognostic indicator in stomach cancer.

Soybean agglutinin (SBA)-binding carbohydrate expression was studied immunohistochemically in 353 primary gastric carcinomas. The overall rate of positive SBA staining was 23% (81/353), and positive SBA staining was significantly correlated with tumor size, macroscopic tumor type, depth of invasion, lymph node metastasis, and venous invasion (P < 0.05). Moreover, patients with tumors that were immunoreactive for SBA demonstrated significantly higher survival (P < 0.01). From these findings we conclude that careful follow-up and intense postoperative therapy are required for patients with gastric cancers that lack immunoreactivity for SBA.

Adenocarcinoma↗
PubMed1997

Genetic immobilization of cellulase on the cell surface of Saccharomyces cerevisiae.

We tried genetically to immobilize cellulase protein on the cell surface of the yeast Saccharomyces cerevisiae in its active form. A cDNA encoding FI-carboxymethylcellulase (CMCase) of the fungus Aspergillus aculeatus, with its secretion signal peptide, was fused with the gene encoding the C-terminal half (320 amino acid residues from the C terminus) of yeast alpha-agglutinin a protein involved in mating and covalently anchored to the cell wall. The plasmid constructed containing this fusion gene was introduced into S. cerevisiae and expressed under the control of the glyceraldehyde-3-phosphate dehydrogenase promoter from S. cerevisiae. The CMCase activity was detected in the cell pellet fraction. The CMCase protein was solubilized from the cell wall fraction by glucanase treatment but not by sodium dodecyl sulphate treatment, indicating the covalent binding of the fusion protein to the cell wall. The appearance of the fused protein on the cell surface was further confirmed by immunofluorescence microscopy and immunoelectron microscopy. These results proved that the CMCase was anchored on the cell wall in its active form.

Aspergillus↗
PubMed1997

Changes in the noradrenaline and acetylcholine content of three major salivary glands and in the salivation and protein component patterns of whole saliva in chronically isoprenaline-administered mice.

One group of mice was injected subcutaneously with 20 mg/kg body wt isoprenaline each day for 10 days; another group (control) was injected with saline. Half the animals of each group were kept untreated for a further 10 days for restoration. Chronic administration of isoprenaline caused enlargement of parotid (4-fold) and submandibular glands (1.7-fold) but had no effect on sublingual glands. Concomitantly, noradrenaline and acetylcholine contents were, in parallel, increased in parotid, decreased in sublingual, and unchanged in submandibular glands. Under these conditions, pilocarpine- or isoprenaline-induced salivation was not affected but phenylephrine-induced salivation was augmented; the protein component patterns of saliva characteristic of the three sialogogues were also changed. In addition, secretory proteins whose synthesis was induced by isoprenaline were found to be secreted by stimulation with different types of sialogogues. Most changes were reversible. These results indicate that continued beta-adrenoceptor stimulation not only causes broadly altered forms of saliva, probably by involving, in part, alpha-adrenoceptor hypersensitivity, but also changes the activities of both sympathetic and parasympathetic nerves to salivary glands in parallel, though the extent differs among the three glands.

Acetylcholine↗
PubMed1997

Increased levels of nitric oxide derivatives in induced sputum in patients with asthma.

BACKGROUND: Nitric oxide (NO) plays an important role as an inflammatory mediator in the airways. However, because direct measurement of endogenous NO has been difficult in vivo, the exact pathologic roles of NO in human airway inflammation have remained unclear. OBJECTIVE: This study was designed to determine whether NO may be harmful by amplifying allergic inflammation in asthmatic airways. METHODS: In this study we examined the concentration of stable end products of NO, nitrite and nitrate, in induced sputum in 18 patients with asthma and 10 normal control subjects and evaluated the relationship between levels of NO derivatives in sputum and cellular and biochemical profiles, the degree of airflow obstruction, and the cytotoxic activities for epithelial cells. RESULTS: The concentration of NO derivatives in induced sputum was significantly higher in patients with asthma than in normal control subjects (1086 +/- 325 mumol/L, 577 +/- 115 mumol/L; p < 0.05). Percentages of eosinophil counts and eosinophil cationic protein levels in sputum were also significantly higher in patients with asthma. Moreover, percentages of eosinophil counts and eosinophil cationic protein levels in sputum in patients with asthma were significantly correlated with the concentration of NO derivatives in sputum (r = 0.63, p < 0.01; r = 0.56, p < 0.05, respectively). In addition, we found that the concentration of NO derivatives in sputum in patients with asthma was significantly correlated with the degree of airflow obstruction (FEV1/forced vital capacity) (r = -0.62, p < 0.01) and with percentages of shedding epithelial cells (r = 0.61, p < 0.01). CONCLUSION: We have shown that a higher concentration of NO derivatives was found in induced sputum of patients with asthma as compared with normal subjects. The clinical implication of our findings is that measurement of NO derivatives in induced sputum may be useful for assessing allergic inflammation in airways.

Adult↗
PubMed1997

Markedly high plasma erythropoietin and granulocyte-colony stimulating factor levels in patients with paroxysmal nocturnal hemoglobinuria.

In patients with paroxysmal nocturnal hemoglobinuria (PNH), we measured plasma concentrations of endogenous hematopoiesis-regulatory cytokines to characterize bone marrow (BM) hypoplasia which is a major cause of death. Contrary to 10 healthy individuals, all 14 patients with PNH showed increases of erythropoietin (Epo) and granulocyte-colony stimulating factor (G-CSF). There were no signs of infection, renal dysfunction or hypoxia. The lower the hemoglobin level and granulocyte count, the higher the plasma Epo and G-CSF levels. In contrast, marked differences were not found in the levels of interleukin-3 (IL-3), tumor necrosis factor-alpha (TNF-alpha), stem cell factor (SCF), granulocyte/macrophage-colony stimulating factor (GM-CSF), or interferon-gamma) (IF-gamma). The cytokine profiles of PNH patients were quite similar to those of patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS). The cytokine profiles may support a pathological relationship between PNH and these stem cell disorders.

Adolescent↗
PubMed1997

Estimation of obesity in schoolchildren by measuring skinfold thickness.

To determine whether skinfold thickness is correlated with degree of overweight, serum levels of cholesterol, and blood pressure in children, 161 boys and 167 girls aged 9 and 10 y underwent physical examinations at three elementary schools in Japan. Triceps skinfold thickness was positively correlated with degree of overweight, atherosclerosis index, and systolic blood pressure, and was negatively correlated with levels of high-density lipoprotein (HDL) cholesterol. Among children who were highly overweight (> or = 30%), those with low triceps skinfold thickness (< 11.2 mm) have lower levels of HDL cholesterol, a higher atherosclerosis index, and higher systolic blood pressure than those with greater triceps skinfold thickness (> or = 11.2 mm). The ratio of degree of overweight to triceps skinfold thickness was significantly correlated with levels of HDL cholesterol in girls but not in boys. These results suggest that, in overweight schoolchildren, skinfold thickness may reflect the risk of future hypercholesterolemia and hypertension. Measurement of triceps skinfold thickness and determination of degree of overweight may be useful for the estimation of obesity in children.

Blood Pressure↗
PubMed1997

Recombinant thermostable cycloinulo-oligosaccharide fructanotransferase produced by Saccharomyces cerevisiae.

A truncated fragment of the cycloinulo-oligosaccharide fructanotransferase (CFTase) gene of Bacillus circulans MCI-2554 was fused to the prepro secretion sequence of the alpha-factor and expressed in Saccharomyces cerevisiae under the control of the 5' upstream region of the isocitrate lyase gene of Candida tropicalis (UPR-ICL). Efficiently secreted recombinant CFTase protein (yeast CFTase) was purified. Yeast CFTase consisted of three protein molecules, each of which had CFTase activity (yeast CFTase 1 [116 kDa], yeast CFTase 2 [117 kDa], and yeast CFTase 3 [116 kDa]). Yeast CFTase 2 was the major product of the expression system employed and was shown to be N glycosylated by endoglycosidase H treatment. Yeast CFTase 1 was N glycosylated but had a short truncation at its N terminus, while yeast CFTase 3 did not contain an N-glycosylated carbohydrate chain(s). Yeast CFTase 2 showed an optimum pH, an optimum temperature, and a pH stability similar to those of CFTase purified from B. circulans but exhibited a significant increase in thermostability. Production of yeast CFTase by the strain which had two copies of the CFTase gene integrated into its chromosomes reached 391 U per liter of culture at 120 h, which corresponded to 8.40 mg of protein per liter, by shake-flask cultivation.

Amino Acid Sequence↗
PubMed1997

Pial arteriolar constriction to alpha 2-adrenergic agonist dexmedetomidine in the rat.

Dexmedetomidine (Dex) is an alpha 2-adrenergic agonist that decreases cerebral blood flow (CBF) when administered systemically. It is unclear whether cerebral vasoconstriction is mediated by a local effect on cerebral vessels or by a remote neural mechanism. In the present study, we compared the pial arteriole responses to locally and systemically administered Dex with and without local application of the specific alpha 2-adrenergic antagonist atipamezole. Six groups of male rats (n = 7 each) were anesthetized with isoflurane and prepared for measurements of small (20-39 microns), medium (40-59 microns), and large (60-79 microns) pial arteriole diameter by intravital microscopy or for regional CBF measurement by the radiolabeled-microsphere method. Local application of Dex caused dose-dependent constriction that was significant starting at 10(-8) M for small and medium-sized arterioles and at 10(-7) M for large arterioles. Constriction to 10(-5) M in small [21 +/- 2% (SE)], medium (21 +/- 2%), and large (15 +/- 1%) arterioles was almost completely blocked by local application of 10(-4) M atipamezole. Intravenous administration of Dex at 1 microgram/kg decreased CBF and caused modest arteriolar constriction that began to resolve 8 min after administration. A dose of 10 micrograms/kg constricted arterioles of all sizes with constriction beginning to resolve after approximately 10 min. Local application of atipamezole (10(-4) M) slightly blunted the response to 1 micrograms/kg of intravenous Dex but did not substantially limit constriction after 10 micrograms/kg. These data demonstrate that pial arterioles are capable of substantial constriction to Dex by a local alpha 2-adrenergic mechanism. However, the inability of locally applied atipamezole to substantially inhibit the vasoconstrictor response to systemically administered Dex suggests that Dex might also cause vasoconstriction indirectly through actions at other sites in the central nervous system.

Adrenergic alpha-Agonists↗