Biomedical subjects
T Azuma
Publications and source records attributed to T Azuma.
IgE antibodies against midge and moth found in Japanese asthmatic subjects and comparison of allergenicity between these insects.
The specific IgE antibodies to moth (Bombyx mori) and midge (Chironomus yoshimatsui) were measured by the Pharmacia CAP system in 51 house-dust-mite-sensitive asthma patients. None of these patients had definite histories of exposure to these insects or apparent evidence of insect-induced asthma symptoms. The RAST-inhibition assay was performed to investigate cross-allergenicity between these two insects. Furthermore, IgE immunoblotting was done to study the IgE-binding components in moth and midge extracts. Thirty (59%) of these patients showed positive IgE antibodies to moth, while 25 (49%) showed positive IgE antibodies to midge. Those frequencies of positivity were similar to that for Japanese cedar pollen, which is well known to cause allergy. A significant correlation (r = 0.863) was observed between IgE antibody titers of these two insects. The results from the RAST-inhibition assay indicated cross-allergenicity between these insects and also the existence of species-specific allergens. Fifteen IgE-binding components in moth extract were observed. The most frequent IgE-binding protein was the 79-kDa (84.2%), followed by the 72-kDa (78.9%), the 82-kDa (57.9%), and the 76-kDa (57.9%) proteins. Those were considered to be major allergens in moth. Twenty-four IgE-binding components in midge extract were observed. However, no IgE-binding protein to which over 50% of patient sera reacted was observed. These results suggest that these two insects may be considered to bear important allergens and that there is cross-allergenicity between these insects as well as species-specific allergens.
Analysis and typing of the vacA gene from cagA-positive strains of Helicobacter pylori isolated in Japan.
Approximately 50% of Helicobacter pylori strains produce a cytotoxin that is encoded by vacA and that induces vacuolation of eukaryotic cells. Mosaicism in vacA alleles was reported, and there are three different families of vacA signal sequences (s1a, s1b, and s2) and two different families of middle-region alleles (m1 and m2). In addition, the vacA genotype of a strain is associated with its cytotoxin phenotype and its capacity to induce peptic ulceration. To clarify the strain diversity of H. pylori in Japan, 87 Japanese clinical isolates of H. pylori (40 from patients with chronic atrophic gastritis, 25 from patients with duodenal ulcer, 16 from patients with gastric ulcer, 3 from patients with both duodenal and gastric ulcers, and 3 from patients with intestinal type gastric cancer) were characterized by vacA typing by PCR and DNA sequencing. Eighty-four of the 87 isolates were s1a/m1, one was s1b/m1, and two could not be typed. Moreover, all isolates in this study were cagA positive. There were no distinct differences between the cytotoxin-producing strains and cytotoxin-nonproducing strains within the 0.73-kb middle region. Japanese strains were highly homologous, with more than 96% identity in this region, in which maximum divergence has been reported. In addition, there were no associations between the specific vacA types and the level of in vitro cytotoxin activity or the clinical consequences. These results indicate that the cagA-positive, s1a/m1-type strains are common in Japan, regardless of the vacA phenotype or clinical outcome.
Effects of Helicobacter pylori eradication therapy on hyperammonaemia in patients with liver cirrhosis.
BACKGROUND AND AIMS: Helicobacter pylori has strong urease activity. Ammonia produced by H pylori in the stomach can be a source of systemic ammonia in patients with hepatic dysfunction. The effect of the eradication of H pylori on hyperammonaemia was examined in patients with liver cirrhosis. SUBJECTS AND METHODS: Ammonia concentrations in blood and gastric juice were analysed in 50 patients with liver cirrhosis and hyperammonaemia. All patients were first treated with a low protein diet, kanamycin, lactulose, and branched chain enriched amino acid solution. Hyperammonaemia remained in 18 patients. These 18 patients were divided into three groups according to the status of H pylori infection; those with a diffuse distribution of H pylori in the stomach (group I), those with a regional distribution (group II), and those without H pylori (group III). These patients were given 30 mg iansoprazole, 1000 mg amoxicillin, and 400 mg clarithromycin or 500 mg metronidazole for two weeks to eradicate H pylori. RESULTS: In group I ammonia concentrations in blood and gastric juice were significantly reduced after H pylori eradication. The blood ammonia concentration at 12 weeks after the eradication was still significantly lower than that before eradication. In groups II and III the ammonia concentrations in blood and gastric juice were not significantly reduced after eradication therapy. CONCLUSIONS: The diffuse distribution of H-pylori in the stomach contributes partly to hyperammonaemia in patients with liver cirrhosis, and the eradication of H pylori is effective in patients with hyperammonaemia with diffuse H pylori infection in the stomach.
Association between genetic polymorphism of the pepsinogen C gene and gastric body ulcer: the genetic predisposition is not associated with Helicobacter pylori infection.
BACKGROUND AND AIMS: The genetic trait plays a part in the pathogenesis of peptic ulcer disease. To identify a DNA marker for peptic ulcer disease, the association between the restriction fragment length polymorphism (RFLP) of the pepsinogen C (PGC) gene and peptic ulcer disease was investigated. PATIENTS AND METHODS: One hundred and seventy seven unrelated controls, 75 patients with gastric ulcer, and 70 with duodenal ulcer were studied. PGC-RFLP was analysed by polymerase chain reaction (PCR), and the association between PGC-RFLP and peptic ulcer disease was examined. The relation between the genetic association of PGC polymorphism with peptic ulcer and Helicobacter pylori infection was also examined. RESULTS: Four alleles, 480 (allele 1), 450 (allele 2), 400 (allele 3), and 310 bp (allele 4), were detected by PCR. The frequency of allele 4 was significantly higher in patients with gastric body ulcer than in controls (chi (2) = 9.92, p < 0.005). Genotypes containing allele 4 were significantly more frequent in patients with gastric body ulcer than in controls and patients with gastric angular or antral ulcer. The relative risk of gastric body ulcer associated with the presence of allele 4, compared with its absence, was 4.63 and was statistically significant (chi (2) = 14.84, p < 0.005). There were no significant differences in the allelic frequencies between H pylori positive and H pylori negative groups in controls, patients with gastric body ulcer, or patients with gastric angular or antral ulcer. Both in H pylori negative and H pylori positive cases, there was an increased frequency of allele 4 in patients with gastric body ulcer compared with controls. CONCLUSIONS: These results suggest that there is a significant association between this genetic polymorphism at the PGC gene locus and gastric body ulcer. There are differences in the genetic aetiology between gastric body ulcer and gastric angular or antral ulcer. PGC-RFLP may be used as a genetic marker for a genetic predisposition to gastric body ulcer; this genetic predisposition is not associated with H pylori infection.
NSAID-induced gastrointestinal damage. Epidemiology, risk and prevention, with an evaluation of the role of misoprostol. An Asia-Pacific perspective and consensus.
The problem of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal toxicity was reviewed by members of the Asia Pacific League of Associations for Rheumatology (APLAR) in a consensus conference in September 1992. This paper by the participants presents the consensus conclusions incorporating knowledge from recent publications. There had been a high level of concern that much of the toxicity had resulted from extensive and indiscriminate prescribing of NSAIDs. The implementation of evidence-based guidelines was considered likely to be able to effect a substantial reduction in toxicity without significant loss of overall therapeutic benefit. The evidence from which such guidelines could be developed is critically appraised.
[Effects of fibronectin on the monokine production by cultured-human monocytes].
The effect of fibronectin (FN) on IL-1 alpha, IL-1 beta, TNF-alpha, and IL-6 production was investigated with cultured monocytes isolated from human peripheral blood. Monokine concentrations were determined by ELISA. FN markedly stimulated the secretion of IL-1 alpha, IL-1 beta, TNF-alpha, and IL-6 from cultured monocytes. Northern blot analysis revealed the up-regulated expression of mRNA specific for each monokine on exposure of monocytes to FN. GM-CSF, IFN-gamma, and LPS synergistically enhanced FN-induced IL-1 alpha production. We further investigated the signal transduction pathways involved in FN-stimulated monokine secretion. FN-stimulated TNF-alpha secretion was markedly inhibited by either herbimycin A or genistein, inhibitors of protein tyrosine kinase (PTK), but was not affected by staurosporin, a inhibitor of protein kinase C (PKC). The results suggest that PTK is required for FN-stimulated TNF-alpha secretion. In contrast, LPS-stimulated TNF-alpha secretion was markedly inhibited by not only herbimycin A or genistein, but also staurosporin. Therefore, both PTK and PKC may be involved in LPS-stimulated TNF-alpha secretion. We also demonstrated that, in monocytes, cytoplasmic proteins of about 70 and 240 kDa were phosphorylated after FN stimulation. Our results indicate that FN may contribute to the inflammatory response of monocyte by inducing monokine production.
[Adverse reaction of drugs in the field of orthopaedic surgery].
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Lazaroid U-74500A for warm ischemia and reperfusion injury of the canine small intestine.
BACKGROUND: Although lazaroids have been shown to protect various organs from ischemia/reperfusion injury, results obtained in the small intestine have been conflicting. STUDY DESIGN: The canine small intestine was made totally ischemic for 2 hours by occluding the superior mesenteric artery and the superior mesenteric vein with interruption of the mesenteric collateral vessels. A lazaroid compound, U74500A, or a citrate vehicle was given intravenously to each of the six animals for 30 minutes before intestinal ischemia. Intestinal tissue blood flow, lipid peroxidation, neutrophil infiltration, adenine nucleotides and their catabolites, and histologic changes after reperfusion were determined. RESULTS: Lazaroid treatment attenuated decline of the mucosal and serosal blood flow after reperfusion. Accumulation of lipid peroxidation products and neutrophils in mucosal tissues was markedly inhibited by the treatment. Postischemic energy resynthesis was also augmented by lazaroid. Morphologically, mucosal architectures were better preserved with lazaroid treatment after reperfusion, and recovered to normal by postoperative day 3 in the treated group and by postoperative day 7 in control animals. CONCLUSIONS: Lazaroids protect the canine small intestine from ischemia/reperfusion injury by inhibiting lipid peroxidation and neutrophil infiltration. Dogs are tolerant of 2-hour normothermic complete intestinal ischemia.
[Late phase II clinical study of M-5011C on osteoarthritis--a multi-institutional double-blind, three group comparative, dose finding study].
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[Late phase II clinical study of M-5011C on rheumatoid arthritis--a multi-institutional double-blind, three group comparative, dose finding study].
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[Management of anorectal malformations and Hirschsprung's disease].
Anorectal malformations include various type of anomalies resulting from abnormal development of hindgut, allantois and Müllerian duct. It is essential for the successful construction of new anorectum to know the correct anatomy of pelvic muscles. Peña and deVries proposed a new concept of pelvic muscles, the surgical entities "muscle complex". Based on new anatomical understanding, posterior sagittal anorectoplasty (PSARP) was described by Peña and deVries and has gained a wide acceptance in the world. This approach may lead us a better understanding of surgical anatomy and change our therapeutic concept. Hirschsprung's disease is known to be congenital disorder characterized by the absence of enteric nervous system. Recently, gene mutations associated with Hirschsprung's disease have been widely investigated and gene mutations of RET, glial cell line-derived neutrophic factor (GDNF), endothelin receptor B (EDNRB) and endothelin-3 (EDN3) have been identified in patients with Hirschsprung's disease. These results suggest a role of gene mutations in the migration and differentiations of neural crest-derived neuroblasts. One-stage endorectal pull-through procedure in the neonate and a primary laparoscopic pull-through procedure has been shown to be feasible.
Expression of cathepsin E in pancreas: a possible tumor marker for pancreas, a preliminary report.
Ductal cancers of the pancreas frequently express markers of gastrointestinal epithelial cells. Cathepsin E (CTSE) is a non-secretory, intracellular, but non-lysosomal proteinase found in the highest concentration in the superficial epithelial cells of the stomach. The aims of our study were to examine the expression of CTSE in the pancreas, to establish an assay system of CTSE and to evaluate the diagnostic usefulness of CTSE in the pancreatic juice. Eleven patients with pancreatic ductal adenocarcinoma, 10 with mucin-producing adenoma, 3 with intraductal papillary hyperplasia and 43 with chronic pancreatitis were examined. Surgically resected pancreatic tissues were subjected to immunohistochemistry for CTSE. Pancreatic juice was collected from the patients and subjected to sandwich ELISA and Western analysis for detecting CTSE. Positive staining for CTSE was observed in pancreatic ductal adenocarcinoma by immunohistochemistry. CTSE was also expressed in mucin-producing adenoma, intraductal papillary hyperplasia and mucinous hyperplasia. CTSE in the pancreatic juice was present in 8 of 11 patients with pancreatic ductal adenocarcinoma, 5 of 10 patients with mucin-producing tumor, 1 of 3 patients with intraductal papillary hyperplasia and 4 of 43 patients with chronic pancreatitis. The detection frequency of CTSE in the pancreatic juice was significantly higher in the patients with pancreatic ductal adenocarcinoma than in the patients with chronic pancreatitis. Our findings suggest that the expression of CTSE is associated with the pathogenesis of pancreatic ductal adenocarcinoma, that CTSE in the pancreatic juice seems to be a useful marker for a definitive diagnosis and that CTSE may be expressed at a relatively early stage of multistep carcinogenesis in pancreatic lesions.
Change in cognitive function in idiopathic Parkinson disease.
OBJECTIVE: To study the effects of Parkinson disease (PD) on cognitive function by determining the frequency and amount of change in Mini-Mental State Examination (MMSE) performance. DESIGN: During a 4-year period, 77 patients with idiopathic PD and 43 normal elders were administered a neuropsychological test battery twice at 2 years apart. RESULTS: A 4-point score difference on the MMSE was the amount that was statistically calculated to be a significant difference at the .05 probability level. Using this metric, 17 (22%) patients with PD had a change in their MMSE performance during a 2-year period. Fifteen individuals performed poorer, and 2 individuals improved. Using the same metric, no normal subjects changed in their MMSE performance. The groups of patients with PD who had a change and did not have a change in their MMSE performance were not characterized by significant differences in their years of education, duration of illness, age at onset, age at test time 1, estimated premorbid intelligence, Hamilton Psychiatric Rating Scale for Depression score at test time I, or Unified Parkinson's Disease Rating Scale score. The singular difference was the higher frequency of change that was found in subjects who were taking dopamine agonists at the second test time. CONCLUSION: A change in cognitive function in patients with PD, as measured by a change of 4 points or more in their MMSE performance, was observed in only 22% of a sample of 77 patients with idiopathic PD during a 2-year period.
Interactions between gramicidin S and its producer, Bacillus brevis.
Gramicidin S (GS) inhibition of germination outgrowth of Bacillus brevis spores was reversed completely by a short pretreatment with sodium dodecyl sulfate, moderately by ethanol or by incubation at pH 10 but not by incubation at pH 4. Of five metal ions tested (Na+, Mg2+, Fe2+, Cu2+, Ca2+), only Ca2+ reversed GS inhibition. When Ca2+ (but not the other four metal ions) was added to the growth medium, there was a considerable portion of the biosynthesized GS found in the extracellular fluid. These findings are interpreted in terms of the binding of GS to the external layers of the B. brevis spore.
Transvenous biopsy of a right atrial tumor under transesophageal echocardiographic guidance.
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Nitric oxide (NO)-releasing pathway of FK409 in the presence of sulfhydryl-bearing compounds.
PURPOSE: We have recently reported that degradation of FK409 with generation of NO is spontaneous and is accelerated in the presence of sulfhydryl-bearing compounds, such as L-cysteine (Cys) and glutathione (GSH). The purpose of the present study is to investigate the NO-releasing pathway of FK409 in the presence of sulfhydryl-bearing compounds. METHODS: The degradation process of FK409 in the presence of Cys or GSH was investigated by means of 1H-nuclear magnetic resonance (NMR) spectroscopy and high-performance liquid chromatography (HPLC). RESULTS: The degradation of FK409 in the presence of Cys was dependent on concentration of Cys, and showed pH-dependency, accelerating with an increase in pH. The 1H-NMR spectra of FK409 with Cys suggested that time-dependent elimination of the hydrogen atom at the alpha-position of the nitro moiety (5-position) was accelerated by Cys in weakly alkaline solution. Cys and GSH were transformed readily, concomitant with FK409 degradation, to give their oxidized forms and probably S-nitrosothiols. CONCLUSION: The effect of sulfhydryl-bearing compounds on FK409 degradation is due to the acceleration of deprotonation of the hydrogen atom at the 5-position by thiolate anion as well as hydroxyl ion. Sulfhydryl-bearing compounds reacted with the released NO resulting in formation of disulfides via intermediate S-nitrosothiols.
Biochemical properties of the monomeric mutant of human cathepsin E expressed in Chinese hamster ovary cells: comparison with dimeric forms of the natural and recombinant cathepsin E.
Cathepsin E (CE) is the only known aspartic proteinase that exists as a homodimer consisting of two fully catalytically active monomers, which are covalently bound by a disulfide bond between two cysteine residues at the NH2-terminal region (Cys43 in human pro-CE). To understand the physiological significance of the dimer formation, the monomeric mutant of human CE was constructed by site-directed mutagenesis (Cys43 ->Ser43) and expressed in Chinese hamster ovary (CHO) cells. Immunolocalization of the mutant protein at both the light and electron microscopic levels revealed the monomeric CE to be associated predominantly with the endoplasmic reticulum and the non-lysosomal endocytic organelles. The cellular localization of the monomeric protein was compatible with that of the wild-type (dimeric form) of recombinant human CE expressed in the same cells. The monomeric protein was generated primarily as the 46-kDa pro-CE with a high-mannose-type oligosaccharide chain in the cells. In addition to the maximal activation at around pH 3.5, a substantial proportion of the monomeric pro-CE was converted to the mature form by incubation at pH 7 and 37 degrees C for 5 min. In contrast, the dimeric pro-CE was scarcely activated by treatment at pH7. Although catalytic properties of the in vitro-activated monomeric CE appeared to be indistinguishable from those of the dimeric forms of natural and recombinant CE, the monomeric form was more unstable to pH and temperature changes than these dimeric forms. These results indicate that the dimerization of CE is not necessarily required for proper folding to express activity, correct intracellular localization and carbohydrate modification, but that it may be essential to structurally stabilize the molecule in vivo.