To assess the contribution of the HLA class I region to susceptibility to and heterogeneity of type 1 diabetes, we investigated the association of polymorphism of MHC class I chain-related gene A (MICA) with age-at-onset as well as susceptibility to type 1 diabetes. One hundred one Japanese patients and 110 healthy control subjects were studied. The frequency of A4 allele was significantly higher and that of A6 allele was significantly lower in patients than in control subjects. The frequency of A5.1 allele was highest in early-onset patients (23.0%), intermediate in intermediate-onset patients (9.2%) and lowest in late-onset patients (7.7%) (trend chi-squared test, p = 0.0098). A5. 1 allele was strongly associated with HLA-B7 and Cw7, suggesting that MICA*A5.1-B7-Cw7 haplotype contains a gene responsible for age-at-onset. A4 allele was associated with a susceptible haplotype, DR4-DQB1*0401, and A6 allele was associated with a protective haplotype, DR2-DQB1*0601, suggesting that the association of MICA with type 1 diabetes susceptibility may be due to linkage disequilibrium with class II haplotypes. These data suggest that MICA gene is associated with age-at-onset and that a gene (or genes) responsible for age-at-onset of type 1 diabetes is located in the HLA class I region, probably near the region of MICA-B-C.

Adolescent↗

PubMed2000

NO-mediated MaxiK(Ca) channel activation produces relaxation of guinea pig aorta independently of voltage-dependent L-type Ca(2+) channels.

The role of L-type Ca(2+) channels in the relaxation to nitric oxide (NO)-mediated MaxiK(Ca) channel activation was examined in guinea pig aorta. Acetylcholine (ACh) produced an endothelium-dependent relaxation of guinea pig aorta precontracted with noradrenaline (NA), which was abolished by an NO synthase inhibitor, N(G)-nitro-L-arginine (L-NNA). Both endothelium-dependent relaxation by ACh and endothelium-independent relaxation by an NO donor, (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide (NOR3), were strongly suppressed by a soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4]-oxadiazolo-[4,3-a]-quinoxalin-1-one (ODQ), suggesting that increased intracellular cGMP plays the key role in both responses. ACh- and NOR3-induced relaxations were significantly suppressed by iberiotoxin (IbTX), a selective blocker of MaxiK(Ca) channels. ACh- and NOR3-induced relaxations were greatly attenuated when arteries were precontracted with high KCl instead of NA, supporting the idea that K(+) channel activation mediates the relaxant responses. (6) NOR3-induced relaxations were not affected by a L-type Ca(2+) channel blocker, diltiazem. Furthermore, endothelium-independent relaxation by a K(ATP) channel opener, (+)-7,8-dihydro-6, 6-dimethyl-7-hydroxy-8-(2-oxo-1-piperidinyl)-6H-pyrano[2,3-f] benz-2,1, 3-oxadiazole (NIP-121) was not affected by diltiazem and nicardipine. These findings suggest that blockade of L-type Ca(2+) channels is not a major mechanism responsible for the vascular relaxation due to NO-mediated MaxiK(Ca) channel activation in guinea pig aorta.

Acetylcholine↗

PubMed2000

Evaluation of Abdominal Tumors with

Purpose: The purpose of this study was to evaluate the diagnostic usefulness of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET).Procedures: We performed FDG-PET in 22 patients with suspected primary or recurrent cancer (23 cases). The FDG-PET findings were compared with the final diagnosis, which was obtained by histological examination of resected, or biopsy specimens and the clinical course.Results: In all patients, the sensitivity, specificity, and the accuracy of FDG-PET were 93.8%, 85.7%, 91.3%, respectively. In the patients with colo-rectal cancer, the sensitivity, specificity, and accuracy were 92.9%, 100%, 94.4%, respectively.Conclusions: FDG-PET was considered to be clinically useful for the detection of primary or recurrent malignant tumors, and for differentiating recurrent tumors from inflammatory scars.

Journal Article↗

PubMed2000

Possibility of Differential Diagnosis of Small Polypoid Lesions in the Gallbladder Using FDG-PET.

Purpose: We discuss three cases of patients with small polypoid lesions of gallbladder in which we successfully differentiated the malignancy or benignity preoperatively using positron emission tomography (PET) scanning with 18F-labelled deoxyglucose (FDG).Methods and Results: The first case involves a 47-year-old woman who had a 15 x 10 mm polypoid lesion of the gallbladder. FDG-PET was performed and revealed no FDG uptake. The histopathological diagnosis was a cholesterol polyp. The second case is a 56-year-old woman who had a 22 x 8 mm polypoid lesion in the neck of the gallbladder and wall-thickening of the fundus. FDG-PET was performed and no FDG uptake was found. The postoperative diagnosis was pseudo-tumorous sludge in the neck and adenomyomatosis of the fundus. The third case is a 77-year-old man who had a 15 x 15 mm polypoid lesion in the gallbladder. PET revealed a focus of FDG uptake at the site of the gallbladder. The histopathologic diagnosis was adenocarcinoma. Focal FDG uptake was the sole indicator of a malignant tumor of the gallbladder.Conclusions: FDG-PET may become one of the most useful tools for the accurate preoperative diagnosis of gallbladder carcinoma.

Journal Article↗

PubMed2000

Amino-acid replacements in an internal region of tropomyosin alter the properties of the entire molecule.

Two isoforms of lobster muscle tropomyosin, a fast muscle type, fTm, and a slow muscle type, sTm1, are identical except for 15 residues within the region of amino acids 39-80, which corresponds to exon 2 of the tropomyosin genes of many phyla. Although the difference in the sequence does not include the terminal regions, the two isoforms are extremely different in viscosity, which is a good measure of the head-to-tail interaction strength and should be dependent on the conformation of the terminal 7-9 residues. To determine the influence of amino-acid replacements in the internal region on the overall conformation and the functional properties of the molecule, we compared the physical properties of the two isoforms and their interactions with other proteins, such as actin and myosin subfragment 1 (S1). Limited proteolysis by trypsin and chymotrypsin showed that sTm1 is more susceptible than fTm at the sites outside the region with the replaced residues. Compared with fTm, sTm1 showed higher viscosity, had a higher actin affinity, and inhibited acto-S1 ATPase to a greater extent. Finally, the binding isotherm of S1-ADP to actin-sTm1 is less sigmoidal than that to actin-fTm. These results indicate that the amino-acid replacements in the internal region alter the conformation and the physical properties of the entire molecule as well as its interactions with actin and myosin.

Actins↗

PubMed2000

Adhesion of dermatophytes to healthy feet and its simple treatment.

At several public baths, we isolated dermatophytes from the soles of healthy volunteers by a new direct isolation method (foot-press culture method). We confirmed that a public bath is one of major sources of infection of dermatophytes. We showed that simple treatments such as (i) wiping the sole with a towel; (ii) washing with soap; (iii) 100 steps on another mat; and (iv) holding the foot up for an hour, significantly reduced the fungi on the soles of six healthy volunteers. These treatments may be effective for prevention of tinea pedis.

Adult↗

PubMed2000

Flow-cytometric separation and enrichment of hepatic progenitor cells in the developing mouse liver.

Stem cells responsible for tissue maintenance and repair are found in a number of organs. However, hepatic stem cells assumed to play a key role in liver development and regeneration remain to be well characterized. To address this issue, we set up a culture system in which primitive hepatic progenitor cells formed colonies. By combining this culture system with fluorescence-activated cell sorting (FACS), cells forming colonies containing distinct hepatocytes and cholangiocytes were identified in the fetal mouse liver. These cells express both CD49f and CD29 (alpha6 and beta1 integrin subunits), but do not mark for hematopoietic antigens such as CD45, TER119, and c-Kit. When transplanted into the spleen, these cells migrated to the recipient liver and differentiated into liver parenchymal cells. Our data demonstrate that hepatic progenitor cells are enriched by FACS and suggest approaches to supplanting organ allografting and improving artificial-organ hepatic support.

Animals↗

PubMed2000

The effectiveness of the visual analogue scale 8 in measuring health-related quality of life for COPD patients.

The Visual Analogue Scale 8 (VAS8), consisting of eight linear scales, has been developed to measure health-related quality of life (HRQoL) in chronic obstructive pulmonary disease (COPD) patients. The purpose of this study was to examine the validity and responsiveness of the VAS8. First, HRQoL was assessed in a cross-sectional study with the VAS8 and the St George's Respiratory Questionnaire (SGRQ) in 46 COPD patients. Relationships between the VAS8 and various physiological parameters were examined. Second, in a longitudinal study, changes in HRQoL scores after pulmonary rehabilitation were evaluated in 29 COPD patients. The total VAS8 scores showed a weak correlation with vital capacity and maximal inspiratory pressure and a moderately strong correlation with 6-min walking distance and dyspnoea rating. The total VAS8 score showed a significant correlation with each SGRQ score. Furthermore, almost every VAS8 and SGRQ score improved significantly after pulmonary rehabilitation. The change in the total VAS8 value showed a strong correlation with that of the SGRQ. The VAS8 is well-suited to assess HRQoL in COPD patients. Visual analogue scales are generally useful in measuring HRQoL in COPD patients, and the VAS8 is particularly beneficial because of its ease of use.

Aged↗

PubMed2000

Interleukin 5 and granulocyte-macrophage colony-stimulating factor levels in bronchoalveolar lavage fluid in interstitial lung disease.

The purpose of this study was to evaluate the role of several eosinophil growth factors including interleukin (IL)-5, interleukin (IL)-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the pathogenesis of interstitial lung disease with eosinophilia. IL-5, IL-3 and GM-CSF in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA) in patients with eosinophilic pneumonia (EP), bronchiolitis obliterans organizing pneumonia (BOOP), idiopathic pulmonary fibrosis (IPF), sarcoidosis and healthy volunteers. IL-5 in BALF was high only in patients with EP. IL-3 in BALF was undetectable in the majority of patients with these diseases. GM-CSF in BALF was detectable in 30-67% of each group of patients. In patients with BOOP and IPF, the number of eosinophils in BALF was higher in patients with detectable GM-CSF than in patients in whom GM-CSF was below the detection limit. Eosinophil cationic protein (ECP) was detected in all patients with EP and some with BOOP and IPF. There was a significant correlation between ECP levels and percentage or number of eosinophils in BALF. The results suggest the possibility that interleukin 5 in eosinophilic pneumonia, and granulocyte-macrophage colony-stimulating factor in bronchiolitis obliterans organizing pneumonia and idiopathic pulmonary fibrosis may play important roles in eosinophil recruitment in the lung. Activation of eosinophils in the lung is likely to be induced by both interleukin 5 and granulocyte-macrophage colony-stimulating factor.

Adult↗

PubMed2000

DMPO-Alkyl radical spin trapping: an in situ radiolysis steady-state ESR study.

Short-lived free radicals formed in the reaction of 11 substrates and radiolytically produced hydroxyl radicals were trapped successfully with 5, 5-dimethyl-1-pyrroline-N-oxide (DMPO) in dilute aqueous solution. The in situ radiolysis steady-state ESR spectra of the spin adducts were analyzed to determine accurate ESR parameters for these spin adducts in a uniform environment. Parent alkyl radicals include methyl, ethyl, 1-propyl and 2-propyl (1-methylethyl). Hydroxyalkyl parent radicals were hydroxymethyl, hydroxyethyl, 2-hydroxy-2-propyl (1-methyl-1-hydroxyethyl), 1-hydroxypropyl and 2-hydroxy-2-methylpropyl. Carboxyl radical (carbon dioxide anion, formate radical) and sulfite anion radical were the sigma radicals studied. The DMPO spin adduct of 1-propyl was identified for the first time. For most spin adducts, g factors were also determined for the first time. In DMPO spin adducts of hydroxyalkyl radicals, nitrogen and C(2)-proton hyperfine coupling constants are smaller than those of alkyl radical adducts; the hydroxyalkyl spin adducts possess larger g values than their unsubstituted counterparts. These changes are ascribed to the spread of pi conjugation to include the hydroxyl group. Strong evidence of spin addend-aminoxyl group interaction can be seen in the asymmetrical line shapes in the hydroxyethyl and the hydroxypropyl spin adducts.

Cyclic N-Oxides↗