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Biomedical subjects

Akira Watanabe

Publications and source records attributed to Akira Watanabe.

At least 91 records · Page 5Linked to original sources

[Relapsing polychondritis with idiopathic hypoparathyroidism].

A 49-year-old man who had been treated with vitamin D since idiopathic hypoparathyroidism (IPH) was diagnosed at age 15 was referred to our hospital because of progressive wheezing. The same condition was also diagnosed in his sister at age 19. Chest radiography and computed tomography (CT) showed diffuse tracheal stenosis to a diameter of 6-8 mm. Laryngoscopy revealed no abnormality in the patient's epiglottis or vocal cords. No intact parathyroid hormone was detected in his sera but a brain CT scan showed calcification of the basal ganglia, which was compatible with IPH. Steroid therapy relieved his wheezing occasionally, but with little improvement of the narrowing of his trachea. He died of respiratory failure accompanied by lung abscess 15 weeks later. Autopsy revealed tracheal stenosis, thickening of the tracheal wall with marked fibrosis, and slight infiltration of inflammatory cells, which supported a diagnosis of relapsing polychondritis. This is the first report of relapsing polychondritis associated with IPH. Since both diseases are associated with autoimmune activity, this case may provide some insight into the pathogeneses of both diseases.

Autoimmune Diseases↗

[Successful treatment of bronchiolitis obliterans organizing pneumonia with cyclosporin and steroids].

A 71-year-old woman with fever and dry cough was admitted to our hospital. Chest computed tomography, bronchoalveolar lavage and transbronchial lung biopsy were performed, and bronchiolitis obliterans organizing pneumonia (BOOP) was diagnosed. The patient was treated with corticosteroid, and marked improvement was noted. However, when the dosage was tapered, the BOOP recurred. We increased the dosage of corticosteroid and also put the patient on a daily regimen of cyclosporin. The cyclosporin was administered orally, and was effective, so that we could gradually decrease the dosage of corticosteroid. We concluded that cyclosporin may be useful in the treatment of refractory BOOP.

Aged↗

[Evidence of indications of influenza vaccine and its efficacy--including Guillain-Barré syndrome as an adverse reaction(?)].

With respect to the indications of influenza vaccine, the US CDC guidelines are the most rational. All people aged not less than 50 years old, patients with pulmonary diseases, cardiac diseases and metabolic diseases such as diabetes mellitus, residents in old-age homes, high-risk subjects such as pregnant women, medical professionals at the position liable to infect the populations with influenza, employees of institutions, persons in charge of home care, and lodgers with high-risk patients are the subjects recommended for vaccination. There are many evidences of the efficacy of influenza vaccine in the world, and recently, it has been reported that vaccination has significantly reduced hospitalization and death due to not only influenza and pneumonia but also other diseases such as cerebrovascular diseases and cardiac diseases. Since Guillain-Barré syndrome which has been considered an adverse reaction of influenza vaccine was attributable to the swine influenza vaccine (swine type virus vaccine) used in the USA in the season from 1976 to 1977 and no incidence in the syndrome has been reported with subsequent vaccines, this syndrome does not become a reason for avoidance from vaccination in the subjects other than those with a history of the syndrome.

Age Factors↗

[Results of survey of adult community-acquired pneumonia utilizing flow chart of diagnostic guideline for management of respiratory infections].

We performed a nationwide survey of 1,258 patients to assess the treatment of community-acquired pneumonia in Japan. Cases were classified as bacterial pneumonia in which the causal organism was unknown (Type A) or presumed (Type B), atypical pneumonia (Type C), severe pneumonia (Type D), or pneumonia in certain specific morbid states (Type E). Our objectives were to assess the actual use of antimicrobials and to determine the usefulness of the "Guidelines on Respiratory Infections--Basic Concepts in the Medical Care of Community-Acquired Pneumonia in Adults", developed by the Guideline-Drafting Committee of the Japanese Respiratory Society (JRS), in differentiating these categories of patients. We also hoped to elicit constructive opinions that would contribute to future revisions of these guidelines. The findings showed that pneumonia was classified as "bacterial pneumonia in which the causal organism was unknown" in approximately half (50.2%) of the patients studied. The next most common classification was "severe pneumonia", followed by "atypical pneumonia", "bacterial pneumonia in which the causal organism was presumed", and "pneumonia in certain specific morbid states", in that order. Our results suggest that the JSR guidelines, including the methods for differentiating between bacterial pneumonia and atypical pneumonia, are useful and appropriate, and that antimicrobial agents were generally selected in accordance with the guidelines. We also identified a number of issues to be addressed in future updates of the guidelines, including criteria for physiological assessment, handling of cases in which physical findings and laboratory test results are not in agreement, age-related issues (especially the treatment of patients 65 years of age and older), the differentiation between bacterial pneumonia and atypical pneumonia, the weighing of underlying diseases and complications, and guidelines regarding the use of adjuvant therapy.

Adolescent↗

Acetylcholinesterase distribution and refractory constipation - a new criterion for diagnosis and management.

To describe manifestations of acetylcholinesterase (AchE) activity in the bowel of patients presenting with refractory constipation and correlate them with outcome, rectal biopsy specimens (RBS) from 165 patients who presented with refractory constipation between 1988 and 1999 were examined. Age at biopsy ranged from 4 days to 17 years; 45 subjects were excluded because they satisfied diagnostic criteria for Hirschsprung's disease, intestinal neuronal dysplasia, or hypoganglionosis. Thirty-five autopsy subjects were used as controls. All RBS were compared and AchE activity was assessed in the lamina propria (LP), muscularis mucosae (MM), and around the submucosal vessels (V). Variations in AchE distribution were classified as grade I (no AchE-positive nerve fibers in the LP or MM), grade II (some positive fibers in the LP or MM), grade III (moderate positive fibers in the LP or MM), grade IV (many positive fibers in the LP, MM, or V), or grade V (fibrillar, foamy, or amorphous staining for AchE). All grade I (11/120) and V (12/120) subjects achieved normal bowel control with laxatives alone and all grade II subjects (58/120) did with laxatives and enemas. Grade III subjects (34/120) required addition of cisapride. All grade IV subjects (5/120) were unresponsive to conservative management and 4/5 were found to have a megarectum, which was treated surgically. AchE distribution correlated well with eventual outcome and requirement for surgery. AchE distribution could also be used to classify bowel motility disorders, and we suggest the term AchE-positive disease be used to describe them.

Acetylcholinesterase↗

Reaction mechanism of alanine racemase from Bacillus stearothermophilus: x-ray crystallographic studies of the enzyme bound with N-(5'-phosphopyridoxyl)alanine.

The crystal structures of alanine racemase bound with reaction intermediate analogs, N-(5'-phosphopyridoxyl)-L-alanine (PLP-L-Ala) and N-(5'-phosphopyridoxyl)-D-alanine (PLP-D-Ala), were determined at 2.0-A resolution with the crystallographic R factor of 17.2 for PLP-L-Ala and 16.9 for PLP-D-Ala complexes. They were quite similar not only to each other but also to the structure of the native pyridoxal 5'-phosphate (PLP)-form enzyme; root mean square deviations at Calpha among the three structures were less than 0.28 A. The side chains of the amino acid residues around the PLP-L-Ala and PLP-D-Ala were virtually superimposable on each other as well as on those around PLP of the native holoenzyme. The alpha-hydrogen of the alanine moiety of PLP-L-Ala was located near the OH of Tyr(265)', whereas that of PLP-D-Ala was near the NZ of Lys(39). These support the previous findings that Tyr(265)' and Lys(39) are the catalytic bases removing alpha-hydrogen from L- and D-alanine, respectively. The prerequisite for this two-base mechanism is that the alpha-proton abstracted from the substrate is transferred (directly or indirectly) between the NZ of Lys(39) and the OH of Tyr(265'); otherwise the enzyme reaction stops after a single turnover. Only the carboxylate oxygen atom of either PLP-Ala enantiomer occurred at a reasonable position that can mediate the proton transfer; neither the amino acid side chains nor the water molecules were located in the vicinity. Therefore, we propose a mechanism of alanine racemase reaction in which the substrate carboxyl group directly participates in the catalysis by mediating the proton transfer between the two catalytic bases, Lys(39) and Tyr(265)'. The results of molecular orbital calculation also support this mechanism.

Alanine↗

Formation of active oxygen species and lipid peroxidation induced by hypochlorite.

Hypochlorite or its acid, hypochlorous acid, may exert both beneficial and toxic effects in vivo. In order to understand the role and action of hypochlorite, the formation of active oxygen species and its kinetics were studied in the reactions of hypochlorite with peroxides and amino acids. It was found that tert-butyl hydroperoxide and methyl linoleate hydroperoxide reacted with hypochlorite to give peroxyl and/or alkoxyl radicals with little formation of singlet oxygen in contrast to hydrogen peroxide, which gave singlet oxygen exclusively. Amino acids and ascorbate reacted with hypochlorite much faster than peroxides. Free radical-mediated lipid peroxidation of micelles and membranes in aqueous suspensions was induced by hypochlorite, the chain initiation being the decomposition of hydroperoxides by hypochlorite. It was suppressed efficiently by ebselen which reduced hydroperoxides and by alpha-tocopherol, which broke chain propagation, but less effectively by hydrophilic antioxidants present in the aqueous phase. Cysteine suppressed the oxidation, but it was poorer antioxidant than alpha-tocopherol. Ascorbate also exerted moderate antioxidant capacity, but it acted as a synergist with alpha-tocopherol. Taken together, it was suggested that the primary target of hypochlorite must be sulfhydryl and amino groups in proteins and that the lipid peroxidation may proceed as the secondary reaction, which is induced by radicals generated from sulfenyl chlorides and chloramines.

Amino Acids↗

The effects of benzodiazepines on event-related potential indices of automatic and controlled processing in schizophrenia: a preliminary report.

The effects of benzodiazepines on cognitive function in schizophrenic patients were investigated using event-related potential (ERP) measurement during an auditory selective attention task. In this study, the authors compared the mismatch negativity (MMN) and N2b components between two subgroups of schizophrenic patients: one is comprised of patients who received no benzodiazepines (NT group, n = 7) and the other is comprised of those administered benzodiazepines in the daytime (T group, n = 7). There were no significant differences in MMN and N2b amplitudes between the two subgroups, whereas the N2b latency was significantly prolonged in the T group relative to the NT group. This suggested that benzodiazepines induce delayed stimulus classification processing in schizophrenic patients.

Adolescent↗

Breed differences in growth hormone and insulin secretion between lactating Japanese Black cows (beef type) and Holstein cows (dairy type).

This study was performed to clarify the levels of growth hormone (GH) and insulin (INS) secretions and the glucose response to INS during lactation in a representative beef breed in Japan, Japanese Black cows, and to compare them with their counterparts in a dairy breed, Holstein cows. Six Japanese Black and seven Holstein primiparous cows received a single intravenous injection of GH-releasing factor (GRF; 0.25 microg/kg), glucose (112.5 mg/kg), or INS (0.2 U/kg) from late pregnancy (2 weeks antepartum) to mid-lactation (6 months postpartum). Japanese Black cows had one-tenth of the total milk yield of Holstein cows during lactation, and significantly lower GRF-induced GH and higher glucose-induced INS secretions than Holstein cows at all stages. In Japanese Black cows, even with lactation, these secretions remained essentially unchanged, whilst Holstein cows showed higher GH and lower INS secretions after the onset of lactation as compared with cows in late pregnancy. Both breeds had similar glucose response to INS at the respective stages. These results suggest that, during lactation, Japanese Black cows may minimize the catabolic effects of GH and sustain the anabolic effects of INS, in contrast with Holstein cows, but have similar ability to inhibit INS-mediated glucose utilization in peripheral tissues to Holstein cows.

Animals↗

Identification of a novel gene HYS1/CPR5 that has a repressive role in the induction of leaf senescence and pathogen-defence responses in Arabidopsis thaliana.

We isolated two allelic mutants of Arabidopsis thaliana that showed an early senescence phenotype under light/dark and continuous dark photo regimes, and designated the mutant hypersenescence1 (hys1). The hys1 mutants decreased chlorophyll and protein content, lowered the efficiency of photosystem II, and accumulated several senescence upregulated gene transcripts earlier than the wild-type plants. In addition to these senescence features, the hys1 seedlings responded more intensely to exogenously applied sugars than did wild-type seedlings in sugar-induced growth inhibition and sugar-mediated transcript accumulation, both of which are known to be regulated by the sugar sensor hexokinase. The hys1 mutant also had abnormal trichomes. Map-based cloning of the HYS1 gene identified a novel gene that encodes a protein with a potential nuclear localization signal in the amino-terminal region, and five putative transmembrane domains in the carboxyl-terminal region. Furthermore, we found that the constitutive expressor of pathogenesis-related genes 5 (cpr5) mutant, which shows spontaneous pathogen-defence responses and abnormal trichomes, has a point mutation in the HYS1 gene, suggesting that these independently isolated mutants are allelic to each other. Although no definite conclusion can be drawn from these results, we suggest that altered sensitivity to sugars and/or enhanced efficiency of sugar signalling in the hys1/cpr5 mutant may have important roles in the initiation processes of leaf senescence and pathogen-defence responses in Arabidopsis.

Alleles↗

A delayed leaf senescence mutant is defective in arginyl-tRNA:protein arginyltransferase, a component of the N-end rule pathway in Arabidopsis.

We have isolated a delayed-leaf-senescence mutant, designated dls1, from an Arabidopsis T-DNA line. Leaf senescence progresses more slowly in the dls1 mutant than in the wild-type plant in both age-dependent and dark-induced senescence. Genetic analysis revealed that the dls1 is a monogenic recessive mutation that cosegregated with the T-DNA insertion. Isolation of DNA flanking the T-DNA revealed that the T-DNA was inserted into the fourth intron of the AtATE1 gene, which encodes arginyl-tRNA:protein arginyltransferase (EC. 2.3.2.8, R-transferase), a component of the N-end rule proteolytic pathway in yeast and mammals that transfers arginine to the N-terminus of proteins with N-terminal glutamyl or aspartyl residues. AtATE1 transcripts were not detectable in the dls1 mutant by RT-PCR analysis. Introduction of a wild-type AtATE1 gene into the dls1 mutant complemented the dls1 phenotype. We also showed using a transient expression assay system, that the dls1 mutation results in a decreased degradation of proteins with Asp or Glu at their N-termini, and that the introduction of the wild-type AtATE1 gene reverses this deficiency. These results suggest that the normal progression of leaf senescence requires R-transferase activity, and that proteolysis by the N-end rule pathway has an important physiological function in the progress of leaf senescence in plants.

Aminoacyltransferases↗