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Biomedical subjects

S Kohno

Publications and source records attributed to S Kohno.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effects of pranlukast on aspirin-induced bronchoconstriction: differences in chemical mediators between aspirin-intolerant and tolerant asthmatic patients.

BACKGROUND: Aspirin inhibits cyclooxygenase activity and modifies production of the arachidonate cascade in aspirin-induced asthma. The aim of the present study was to examine the effects of leukotriene (LT) receptor antagonist on aspirin challenge on eosinophil activity and chemical mediators released into the airway of asthmatic patients. METHODS: Aspirin oral provocation test was performed in aspirin-intolerant asthmatic patients (AIA; N = 7) and aspirin-tolerant asthmatic patients (ATA; N = 7). In AIA, LT receptor antagonist (pranlukast) was administered orally 2 hours before the test, and its inhibitory effects on sputum LTC4+C4, eosinophil cationic protein (ECP), eosinophil count, urinary LTE4/creatinine (Cr), 11-dehydrothromboxane (11-dhTX) B2/Cr, serum LTC4+D4, ECP, and peripheral blood eosinophil count were compared with the findings in ATA subjects. RESULTS: In AIA, aspirin induced an immediate reaction associated with increased urinary LTE4/Cr and sputum ECP and a fall in urinary 11-dhTXB2/Cr. Pranlukast inhibited the bronchial reaction and an increase in sputum ECP after threshold dosed of ASA, but failed to change aspirin-induced LT production in sputum and urine. In ATA, aspirin challenge was only associated with a fall in urinary 11-dhTXB2. CONCLUSIONS: Our results indicated that aspirin-induced asthma is associated with overproduction of LT with a shift to the 5-lipoxygenase series of the arachidonate cascade and that leukotriene receptor antagonist are useful for AIA through inhibition of production of LT and eosinophilic inflammation in the airway.

Adult↗
PubMed2001

Correlation between airway hyperresponsiveness and airway inflammation in a young adult population: eosinophil, ECP, and cytokine levels in induced sputum.

BACKGROUND: Eosinophil counts and eosinophil cationic protein (ECP) levels in the airway are elevated in asthmatic patients. However, few studies have examined the correlation between various cytokines in the sputum and airway hyperresponsiveness (AHR) in young adults with or without asthma. OBJECTIVE: We examined the correlation between AHR and eosinophil counts or ECP, and levels of several cytokines in the sputum. METHODS: We studied 120 nonsmoker students (group 1: intermittent mild asthmatic patients; group 2: subjects with history of childhood asthma; group 3: subjects sensitized by Dermatophagoides farinae with atopic disease; group 4: normal subjects sensitized by D. farinae; group 5: subjects with cedar pollinosis; and group 6: normal subjects). In each subject, AHR and lung function tests were measured, together with eosinophil count, ECP, granulocyte-macrophage colony-stimulating factor, TNF-alpha, IL-5, and interleukin-1beta in induced sputum. RESULTS: AHR in groups 1 and group 2 were high, in groups 5 and 6 low, and in groups 3 and 4 lower than in groups 1 and 2 but higher than groups 5 and 6. Percentages of eosinophils, ECP, and TNF-alpha in induced sputum in groups 1 and 2 were high, those in groups 5 and 6 were below detection limits, and those in groups 3 and 4 were lower than the percentages in groups 1 and 2. Granulocyte-macrophage colony-stimulating factor in the sputum was elevated only in group 1. The correlations between AHR and sputum eosinophil count, ECP, and TNF-alpha were significant, with the strongest correlation with TNF-alpha. CONCLUSIONS: Our results suggest that TNF-alpha levels in the sputum play an important role in determining the severity of AHR in young individuals. Further once AHR develops, it does not disappear, and the severity of airway inflammation influences the extent of AHR.

Adult↗
PubMed2001

Breadth of the mandibular condyle affected by disturbances of the sex hormones in ovariectomized and orchiectomized mice.

It is well known that the size of the condyle is different between males and females in humans. It has also been documented that ovariectomy (OVX) and orchiectomy (ORX) influence the remodeling of the condylar head in experimental animals. However, influences of sex hormones on the condyle in terms of its breadth have not been examined. With these considerations, this study was designed to examine the breadth of the mandibular condyle in OVX and ORX mice by histomorphometry 8 weeks after surgery. In the OVX mice, the condylar breadth was significantly larger than in the controls, while no significant differences in the breadth were found between the ORX mice and the controls. The thickness of the condylar cartilage layers exhibited similar findings to the breadth of the condyle. On the contrary, the trabecular bone volume was significantly smaller in the OVX and ORX mice than in the corresponding controls, and the difference was more substantial in female mice than in the males. These findings emphasize that a reduction of sex hormone levels, induced by OVX and ORX, significantly influences condylar morphogenesis.

Journal Article↗
PubMed2001

Hammerhead ribozyme against gamma-glutamylcysteine synthetase sensitizes human colonic cancer cells to cisplatin by down-regulating both the glutathione synthesis and the expression of multidrug resistance proteins.

Multidrug resistance in cancer cells is often associated with an elevation in the concentration of glutathione (GSH) and the expression of gamma-glutamylcysteine synthetase (gamma-GCS), a rate-limiting enzyme for GSH. We constructed a hammerhead ribozyme against a gamma-GCS heavy subunit (gamma-GCSh) mRNA transcript and transfected it to human colonic cancer cells (HCT8DDP) resistant to cisplatin (CDDP). The effect of the ribozyme transfection on the drug resistance of cancer cells was studied. (a) Transfection of the ribozyme decreased the GSH level and the efflux of CDDP-GSH adduct, resulting in higher sensitivity of the cells to CDDP. (b) The transfection suppressed the expression of ATP-binding cassette (ABC) family of transporters such as MRP1, MRP2, and MDR1, and stimulated the expression of mutant p53. (c) An electrophoretic mobility shift assay showed that mutant p53 suppresses the SP1-DNA binding activity, suggesting that this mutant p53 is functional and it, in turn, suppresses the expression of ABC transporters. Collectively, transfection of anti-gamma-GCSh ribozyme reduced the synthesis of GSH and the expression of ABC transporters, which causes an increase in the sensitivity of cancer cells to anticancer drugs. Suppression of the SP1-DNA binding activity by p53 may be a factor of down-regulation of ABC transporters.

Antineoplastic Agents↗
PubMed2001

Elevated IL-5 levels in pleural fluid of patients with paragonimiasis westermani.

To investigate the pathogenic mechanisms of eosinophilic pleural effusion in patients with paragonimiasis, we measured the levels of IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) in pleural effusions. Samples were obtained from 11 patients with Paragonimus westermani infection. In addition, samples from 12 patients with pleural transudates, 16 with tuberculous pleurisy, seven with empyema and 20 with lung cancer were also examined. Eosinophilia was remarkable in peripheral blood (range 4-34%, median 23.4%) and pleural fluid (range 0-95%, median 71%) of paragonimiasis patients. IL-5 concentrations in pleural effusions of paragonimiasis were markedly higher than those in other groups. Although marked elevation of GM-CSF and IFN-gamma levels was observed in pleural effusion of empyema and tuberculosis patients, it was marginal in the pleural effusion of paragonimiasis patients. In paragonimiasis patients, IL-5 levels in the pleural effusion correlated well with the percentage of eosinophils in peripheral blood and pleural fluid. Such a correlation was not observed between GM-CSF levels in pleural effusion and percentages of eosinophils in pleural fluid or peripheral blood. Our findings suggest that in paragonimiasis IL-5 in the local inflammatory site is particularly important in mediating eosinophilia in peripheral blood and pleural effusion.

Adult↗
PubMed2001

Characterization of CD44 expressed on alveolar macrophages in patients with diffuse panbronchiolitis.

Interleukin (IL)-8 may play an important role in neutrophil infiltration in the airways of patients with diffuse panbronchiolitis (DPB). Furthermore, alveolar macrophages could produce IL-8 subsequent to CD44-hyaluronic acid (HA) interaction. The purpose of this study was to evaluate the contribution of CD44 expressed on alveolar macrophages to the pathogenesis of DPB. We examined the concentration of soluble CD44 (sCD44) in bronchoalveolar lavage fluid (BALF) and CD44 expression on macrophages in BALF from patients with DPB before and after low-dose, long-term macrolide therapy. We also assessed the HA-binding ability of alveolar macrophages as a functional analysis of the CD44 molecule. The sCD44 concentration in BALF was significantly lower in patients with DPB than in healthy volunteers. Percentages of alveolar macrophages expressing low CD44 (CD44 low(+)) and HA-nonbinding alveolar macrophages were higher in patients with DPB compared with healthy volunteers. Furthermore, macrolide therapy normalized CD44 expression and HA-binding ability of macrophages in BALF from DPB patients. Our findings suggest that alveolar macrophage dysfunction could result from abnormalities of CD44 expression in patients with DPB and that these events could contribute to the pathogenesis of DPB.

Adult↗
PubMed2001

Functional-rhythmical coupling of head and mandibular movements.

It is known that small head movements accompany the movements of the jaw during mastication; however, it is unknown whether these movements occur rhythmically and synchronously. The objective of this study was to determine whether there exists a functional coupling between the head and mandibular movements. Four healthy male adults (mean age 25.5) with normal occlusion and without TMD history were selected as subjects. Using the Trimet system, we measured tridimensionally both the movement of the head and the mandible by tracking upper and lower incisal points, respectively, during tapping movements with different opening range and frequency, then analysed the vertical component of these movements. The upper incisal point moved in opposite direction to the mandible in all tapping strokes in all subjects, during opening the head moved in a cranial direction and during closing in a caudal direction; the incidence rate for this concomitant movement was 98%, implying that the head moves periodically and rhythmically, as the mandible does. The cycle time of these coincident movements showed a correlation coefficient of 0.94. Moreover, the vertical range of head movement was within 10% of the jaw's movement. From these results we concluded that, at least during teeth tapping, the head moves in rhythmical coordination with mandibular movement.

Adult↗
PubMed2001

Rotational head motion concurrent to rhythmical mandibular opening movements.

We have previously demonstrated the existence of a functional-rhythmical coupling between the head and the mandible using maxillary and mandibular incisal tracking points. However, that data did not provide information neither on the movement of the head as a whole nor on the location of its instantaneous centre of rotation. Thus, the objective of the present study was to determine whether the head undergoes a rotational motion during mouth opening and to locate its putative instantaneous centre of rotation. The same 6 d.f. (degree of freedom) measuring device employed in our previous studies was used again to analyse data from five male adults (age range: 26-29 years old) chosen as subjects. Concomitant head and mandibular movements were assessed in the sagittal plane by allocating several reference points in the head (upper incisor, cranial base, occipital and parietal points) and a mandibular incisor point during maximal mouth open-close movements. Then, the magnitude and inclination of the vectors of motion in each reference point during the opening phase were calculated. The instantaneous centre of rotation was defined as the point showing the least amount of motion in a determined area around each head reference point. The mandibular incisal point and the maxillary incisal point showed concomitant movements; that is, during opening the mandibular point moved downwards and the maxillary incisor point upwards. Making a large jaw opening movement caused an inferior-anterior displacement in the O point, a posterior-inferior displacement of the P point, and an anterior-superior displacement in the C point in all subjects. During jaw closing all points followed a trajectory opposite to that described above. In other words, during opening the head moved clockwise and counter-clockwise during closing, at least in the sagittal plane of the subjects' left side. These results suggest that the head undergoes a rotation-like sagittal movement during mouth opening whose rotation centre seems to be located above the cranial base point, which was set close to the centre of mass of the head. However, its location varies according to the magnitude of mouth opening.

Adult↗
PubMed2001

Changes in titers of antimitochondrial and antinuclear antibodies during the course of primary biliary cirrhosis.

A case of primary biliary cirrhosis (PBC) in whom a complete biochemical (serum bilirubin, transaminases and alkaline phosphatase) remission was noted after combination treatment with ursodeoxycholic acid (UDCA) and corticosteroid is reported. The antimitochondrial antibody (AMA) detected by indirect immunofluorescence was initially positive, and the antinuclear antibody (ANA) was negative, but these two antibodies subsequently fluctuated independently (AMA-positive/ANA-negative, AMA-negative/ANA-negative, AMA-negative/ANA-positive, AMA-positive/ANA-positive, and again AMA-negative/ANA-positive) in spite of a lack of histopathological improvement in the liver after treatment. The clinical presentation in our case suggests that in some cases the diagnosis of PBC or so-called autoimmune cholangitis (AIC) might depend on the 'phase' of the same disease. Our results also suggest that detailed immunoreactive profiles against 2-oxo-acid dehydrogenase complex (2-OADC) enzymes by using immunoblotting, together with a serial histological examination, should provide more precise information for a diagnosis of PBC.

Adult↗
PubMed2001

Enhanced expression of complement C5a receptor mRNA in human diseased kidney assessed by in situ hybridization.

BACKGROUND: Anaphylatoxin C5a mediates inflammatory responses through interaction with a specific C5a receptor (C5aR), the expression of which is thought to be restricted to peripheral blood leukocytes. Although the presence of C5aR on cultured mesangial cells and tubular epithelial cells has recently been documented, the tissue distribution of C5aR in diseased kidney has not yet been determined. METHODS: Immunohistochemistry and nonradioactive in situ hybridization for C5aR were performed in 34 tissue samples of kidneys from patients with various renal diseases, including 4 with minimal change nephrotic syndrome (MCNS), 5 with membranous nephropathy (MN), and 25 with mesangial proliferative glomerulonephritis (mesGN; 15 patients with IgA nephropathy, 5 with non-IgA mesGN, and 5 with lupus nephritis). Normal portions of surgically resected kidney served as the control. RESULTS: In normal kidneys, C5aR protein was detected in tubular epithelial cells, while C5aR mRNA was detected in a few glomerular cells, tubular epithelial cells, and vascular endothelial and smooth muscle cells. In MCNS, the distribution of C5aR protein and mRNA was similar to that in normal kidneys. In MN and mesGN, C5aR protein and mRNA were detected in mesangial cells, glomerular epithelial and endothelial cells, Bowman's capsule cells, tubular cells, infiltrating cells, and vascular endothelial and smooth muscle cells. The glomerular expression of C5aR mRNA and protein correlated positively with the degree of mesangial hypercellularity and mesangial matrix expansion in mesGN. In the tubulointerstitium, interstitial expression of C5aR mRNA correlated positively with the degree of tubular atrophy and interstitial broadening in mesGN. Furthermore, the interstitial expression of C5aR mRNA correlated positively with the level of serum creatinine. CONCLUSIONS: Our results indicate that renal cells produce C5aR and that activation of C5a/C5aR pathway on renal cells may be involved in tissue injury in mesGN.

Adolescent↗
PubMed2001

Screening for acetaldehyde dehydrogenase 2 genotype in alcohol-induced asthma by using the ethanol patch test.

BACKGROUND: We have previously reported that alcohol-induced asthma in Japanese patients is caused by increased blood acetaldehyde concentration resulting from abnormalities of acetaldehyde dehydrogenase 2 (ALDH2) enzyme activity on the basis of ALDH2 genotype differences. OBJECTIVES: The purpose of the present study was to determine whether the ethanol patch test could predict the ALDH2 genotype in Japanese asthmatic subjects. METHODS: An ethanol patch test on the upper arm and a questionnaire survey addressing the past history of alcohol-induced asthma were administered to 148 adult Japanese asthmatic subjects. The ALDH2 genotypes in these 148 subjects were also determined by means of PCR. RESULTS: The genotype distribution of ALDH2 determined by PCR in 68 subjects with positive ethanol patch test results was 4 (5.9%), 56 (82.4%), and 8 (11.8%) for genotypes NN (normal homozygote), NM (mutant heterozygote), and MM (mutant homozygote). The ALDH2 genotype in 80 subjects with a negative test result was only NN. The distribution of ALDH2 genotype in 78 (52.7%) subjects who had experienced alcohol-induced asthma symptoms on the basis of the questionnaire was 27 (34.6%), 44 (56.4%), and 7 (9.0%) for genotypes NN, NM, and MM, respectively. On the other hand, 70 subjects had never experienced alcohol-induced asthma symptoms. In these subjects the ALDH2 genotype was NN in 51 (72.9%), NM in 18 (25.7%), and MM in 1 (1.4%). CONCLUSIONS: Our results indicate that the results of ethanol patch testing correlate well with ALDH2 genotype, as determined by means of PCR, suggesting that the ethanol patch test is useful for the screening of alcohol-induced asthma.

Adult↗
PubMed2001

Increased oxysterols associated with iron accumulation in the brains and visceral organs of acaeruloplasminaemia patients.

Acaeruloplasminaemia is characterized by excessive neurovisceral iron accumulation due to mutation of the caeruloplasmin gene. Excess iron functions as a potent catalyst of biological oxidation, and increased iron concentration is associated with the products of lipid peroxidation in the serum and cerebrospinal fluid. We investigated whether the amount of iron accumulated paralleled lipid peroxidation levels in acaeruloplasminaemia tissues, examining brains and visceral organs of two affected patients at autopsy for iron and copper content, and oxysterols, including 7-hydroxycholesterol and 7-ketocholesterol, which are directly produced from cholesterol by active oxygen species. The amount of iron accumulated in various tissues was correlated with the levels of the oxysterols. These findings suggest that lipid peroxidation produced by the intracellular accumulation of iron is involved in the pathogenesis of acaeruloplasminaemia.

Aged↗
PubMed2001

Clinical and endoscopic features of adult T-cell leukemia/lymphoma with duodenal involvement.

We describe three cases of adult T-cell leukemia/lymphoma (ATLL) with duodenal involvement and provide a review of the literature. The first case, a 74-year-old woman with acute subtype of ATLL, had multiple polypoid lesions from the bulbus extending into the descending portion of the duodenum. The second case, a 70-year-old man with lymphoma subtype of ATLL, had a polypoid tumor in the descending portion of the duodenum and multiple protruded lesions in the small and large intestines. The third case, a 67-year-old man with lymphoma subtype of ATLL, had a flat-elevated lesion in the descending portion of the duodenum, as well as a gastric ulcerated lesion. Biopsies from these lesions showed mucosal invasion of ATLL cells in each case. All patients received combination chemotherapy, which was successful in the first and third cases, accompanied by the disappearance of gastroduodenal lesions.

Adult↗
PubMed2001

Autoantibody to heat shock protein Hsp40 in sera of lung cancer patients.

Heat shock protein Hsp40 is a stress protein with chaperone activity and has a cooperative function with Hsp70 in mammalian cells. We examined the possible expression of Hsp40 in lung tumor tissues using immunoblotting and immunohistochemistry, and established an enzyme-linked immunosorbent assay (ELISA) method to detect IgG antibody to Hsp40 in the serum using purified human Hsp40. Sera were obtained from 130 normal subjects and 50 patients with lung cancer. Lung tumor tissues and cells specifically overexpressed Hsp40, and no such expression was detected in normal lung tissues. Compared with normal sera, significantly higher levels of autoantibody to Hsp40 were present in patients with lung cancer. The present study is the first to demonstrate overexpression of Hsp40 in human tumor tissue and the associated presence of autoantibody to Hsp40 in the serum. These results suggest that overexpression of Hsp40 in tumor cells may be recognized as a self-antigen.

Adenocarcinoma↗