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Biomedical subjects

Akira Watanabe

Publications and source records attributed to Akira Watanabe.

At least 73 records · Page 4Linked to original sources
PubMed2003

An opposing view on WWOX protein function as a tumor suppressor.

WW domain-containing oxidoreductase (WWOX) is a candidate tumor suppressor gene. Because mutation or deletion in the coding region of WWOX is rarely found, it is speculated that the appearance of aberrant transcripts affects progression of various cancers. However, little is known about the role in these cancers of the WWOX protein. To characterize endogenous WWOX proteins, we analyzed WWOX expression using newly generated monoclonal antibodies. In immunoblot analysis of 49 cancer cell lines, only the normal form of the protein was detectable, although some of cell lines exhibited aberrant WWOX RNA transcripts. Accumulation of truncated proteins was observed by inhibiting proteasomal degradation with MG-132, whereas expression level of normal protein did not change, suggesting truncated proteins may be subjected to rapid degradation through proteasomal machinery. Immunohistochemistry for cancer cells demonstrated that WWOX protein levels are not decreased but rather elevated in gastric and breast carcinoma, challenging the notion of WWOX as a classical tumor suppressor. In noncancerous cells, WWOX was observed only in epithelial cells, including hormone-regulated cells such as Leydig cells, follicular cells, prostate epithelium, and mammary glands. Interestingly, restricted staining in nuclei was observed in some mammary gland cells while other epithelial cells exhibited localization of WWOX in cytoplasm. Nuclear localization of WWOX was also confirmed in confluent human fibroblast KMS-6, whereas WWOX was associated mainly with mitochondria before reaching confluence, indicating that WWOX shuttles between cytoplasm and nuclei. These findings provide novel insights into aspects of human WWOX function in both normal and malignant cells.

Animals↗
PubMed2003

Three Drosophila EXT genes shape morphogen gradients through synthesis of heparan sulfate proteoglycans.

The signaling molecules Hedgehog (Hh), Decapentaplegic (Dpp) and Wingless (Wg) function as morphogens and organize wing patterning in Drosophila. In the screen for mutations that alter the morphogen activity, we identified novel mutants of two Drosophila genes, sister of tout-velu (sotv) and brother of tout-velu (botv), and new alleles of tout-velu (ttv). The encoded proteins of these genes belong to an EXT family of proteins that have or are closely related to glycosyltransferase activities required for biosynthesis of heparan sulfate proteoglycans (HSPGs). Mutation in any of these genes impaired biosynthesis of HSPGs in vivo, indicating that, despite their structural similarity, they are not redundant in the HSPG biosynthesis. Protein levels and signaling activities of Hh, Dpp and Wg were reduced in the cells mutant for any of these EXT genes to a various degree, Wg signaling being the least sensitive. Moreover, all three morphogens were accumulated in the front of EXT mutant cells, suggesting that these morphogens require HSPGs to move efficiently. In contrast to previous reports that ttv is involved exclusively in Hh signaling, we found that ttv mutations also affected Dpp and Wg. These data led us to conclude that each of three EXT genes studied contribute to Hh, Dpp and Wg morphogen signaling. We propose that HSPGs facilitate the spreading of morphogens and therefore, function to generate morphogen concentration gradients.

Amino Acid Sequence↗
PubMed2003

Immunosuppressive substances in Aspergillus fumigatus culture filtrate.

Invasive aspergillosis has become a serious problem in clinical practice, but the actual factor that confers virulence on the fungus has not been thoroughly elucidated. To identify and isolate the immunosuppressive substances produced by the fungus, the bioactivity of culture filtrates was assessed, and analyses of the culture filtrates were carried out. Culture filtrates from different strains of Aspergillus fumigatus were assessed for their effect on human polymorphonuclear leukocytes and murine macrophages. To assess their activities in vivo, their effect on the survival of mice infected by the fungus was also studied. Subsequently, the composition of the culture filtrates was analyzed by gas chromatography-mass spectrometry. The analyses revealed that the culture filtrates contained gliotoxin at concentrations of 3 to 4 microgram/ml, and some other unidentified compounds. The bioactivities of the culture filtrates were similar to those of gliotoxin. The fungal culture filtrate reduced the survival of infected mice, but the filtrate itself did not cause the death of mice. However, all the bioactivities could not be accounted for by gliotoxin itself. These results indicate that gliotoxin in the culture filtrates may be responsible for part of the immunosuppressive activity, but some other components produced by A. fumigatus contribute, in an additive or synergistic manner, to the virulence of the fungus.

Animals↗
PubMed2003

Primary squamous cell carcinoma of the brain. A rare autopsy case.

In the present study, a rare autopsy case of primary squamous cell carcinoma of the brain is described. The patient was a 49-year-old man who showed brainstem symptoms and signs. These included oculomotor, abducens and facial palsies, dysphagia, dysarthria, and long tract signs such as quadriplegia with Babinski's signs during the 3-year and 6-month course of his illness. Neuropathologically, poorly differentiated squamous cell carcinoma was seen in the pons, medulla oblongata, part of the midbrain and spinal cord, the base of the cerebellum, the hypothalamus, the optic chiasm, and the left parahippocampal gyrus. The base of the pons and medulla oblongata were extensively destroyed by tumor cells. The relevant literature regarding primary squamous cell carcinomas of the brain was reviewed, and the characteristic features of this rare condition were discussed.

Brain Neoplasms↗
PubMed2003

Predictors of first-onset major depressive episodes among white-collar workers.

Major depression is a multifactorial disorder. Previous studies have mainly evaluated work stress to determine the risk factors for depression among workers. The present study aimed to determine factors predictive of the first depressive episode 1 year later among white-collar workers, and to examine whether work 'stress' is associated with an elevated risk of depression. A 5 year open-cohort study was carried out in a Japanese company. The odds ratios (OR) of the development of depression 1 year later were calculated. Ninety-eight first-onset cases were compared with 1267 never-ill cases. Forward stepwise multiple logistic regression indicated that the first onset of depression was associated with a past history of panic attack (OR: 5.14; 95% confidence interval (CI): 1.64-16.10), neuroticism (OR: 3.59; 95%CI: 2.06-6.26), perceived overprotection (OR: 2.75; 95%CI: 1.66-4.55), poor support (OR: 2.55; 95%CI: 1.58-4.10), and low care (OR: 2.23; 95%CI: 1.23-4.04). First-onset cases were more likely to have had objective work events (OR: 1.50; 95%CI: 1.18-1.90) but they did not differ from never-ill cases in subjective job stress. The development of major depression in white-collar workers is associated with multiple factors, as is depression in the community.

Adult↗
PubMed2003

Free perforator flap for the treatment of defects after resection of huge arteriovenous malformations in the head and neck regions.

The authors report two cases of huge arteriovenous malformations in the head and neck regions treated successfully with preoperative superselective transarterial embolization and resection followed by a free perforator flap transfer. Based on the authors' previous cases, en block mass resection of the malformation was possible with bleeding of less than 150 ml. The massive defects could be repaired with free perforator flaps using an anterolateral thigh flap and a deep inferior epigastric artery perforator flap. One patient who lost facial muscle underwent reconstruction by simultaneous muscle transfer, and both patients regained acceptable cosmetic appearance and dynamic facial function. Now, more than 4 to 7 years after surgery, the patients have shown no reexpansion of the malformation. The important points of this treatment are complete embolization to accomplish total resection with minimal bleeding, free flap transfer to prevent postoperative reexpansion or recurrence of arteriovenous malformations, and the selection of recipient vessels because of arterial embolization in part of the lesion.

Adult↗
PubMed2003

[Evaluation of rapid identification method for Mycobacterium tuberculosis complex using the immunochromatographic slide test kit].

Capilia TB, a lateral flow immunochromatographic slide test kit for directly identifying Mycobacterium tuberculosis complex (MTC), was evaluated by using culture-positive specimens from Mycobacteria Growth Indicator Tubes (MGIT). Sputum specimens from patients suspected of having tuberculosis were treated with NALC-NaOH and cultivated in MGIT960. Liquid specimens were collected from the positive tubes and directly inoculated with Capilia TB. Liquid specimens were also directly tested with AccuProbe. Of the organisms isolated from the 100 MGIT positive tubes, M. tuberculosis complex was identified in 49 (49%) tubes with Capilia TB and not identified in 51 (51%) with Capilia TB. Mycobacterium avium-intracellulare complex (MAC) was identified in 46 (46%) with AccuProbe MAC and other acid-fast bacteria were identified in 5 (5%) by DNA-DNA hybridization method. There were one tube in which M. tuberculosis complex was detected with Capilia TB and M. tuberculosis complex was not detected with AccuProbe MTC, but no tubes in which M. tuberculosis complex was detected with AccuProbe MTC and M. tuberculosis complex was not detected with Capilia TB. Capilia TB is excellent in sensitivity and specificity and very suitable for rapid diagnosis of tuberculosis and is considered to contribute to public health intervention measures taken for the tuberculosis control in Japan.

Bacteriological Techniques↗
PubMed2003

Survey of high- and low-level mupirocin-resistant strains of methicillin-resistant Staphylococcus aureus in 15 Japanese hospitals.

BACKGROUND: The extent of mupirocin-resistant methicillin-resistant Staphylococcus aureus (MRSA) in countries using mupirocin only for the eradication of nasal carriage of MRSA is unknown. METHODS: During 1997, 1998, 1999, 2000, and 2001, 1368 strains of MRSA were isolated from 15 general hospitals in the Tohoku area of Japan and tested for susceptibility to mupirocin. RESULTS: The isolation of low-level mupirocin resistance was 0.8% in 1997, 1.1% in 1998, 0.7% in 1999, 4.0% in 2000, and 2.4% in 2001. For the first 3 years it was about 1%. However, the isolation rate of low-level mupirocin resistance in MRSA increased dramatically in 2000. High-level mupirocin resistance was not detected during these years. CONCLUSION: Most patients from whom low-level mupirocin resistant MRSA were found in 2000 and 2001 had previously received mupirocin treatment for eradicating nasal carriage of MRSA, and these strains were isolated from sputum or the pharynx. This result indicates that mupirocin treatment is likely to be one of the causes of mupirocin resistance and, therefore, the development of low-level mupirocin resistance in MRSA isolated from sputum or the pharynx should be considered when using mupirocin in order to improve the control of the spread of MRSA in hospitals.

Anti-Bacterial Agents↗
PubMed2003

Cerebrovascular response to cognitive tasks and hyperventilation measured by multi-channel near-infrared spectroscopy.

We assessed the cerebral blood volume response in the bilateral frontal area in 10 healthy subjects during the design fluency task, verbal fluency task, and hyperventilation measured by 24-channel near-infrared spectroscopy. Oxygenated and total hemoglobin increased during the design fluency task and verbal fluency task and decreased during hyperventilation bilaterally, while deoxygenated hemoglobin did not change. The test-retest reliability examined in five subjects was acceptable to assess the cerebrovascular response to cognitive tasks and hyperventilation.

Adult↗
PubMed2003

Ischemia in the territory of the first major septal perforator branch anomalously originating from the first diagonal branch leads to a transient leftward shift of the QRS axis in the frontal plane: a case report.

A patient with non-Q wave myocardial infarction had severe luminal narrowing in the first major septal perforator branch, which arose anomalously from the first diagonal branch. In this case, an exercise ECG showed a transient leftward QRS axis shift.

Angioplasty, Balloon, Coronary↗
PubMed2003

Purification, amino acid sequence, and cDNA cloning of trypsin inhibitors from onion (Allium cepa L.) bulbs.

Three protease inhibitors (OTI-1-3) have been purified from onion (Allium cepa L.) bulbs. Molecular masses of these inhibitors were found to be 7,370.2, 7,472.2, and 7,642.6 Da by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), respectively. Based on amino acid composition and N-terminal sequence, OTI-1 and -2 are the N-terminal truncated proteins of OTI-3. All the inhibitors are stable to heat and extreme pH. OTI-3 inhibited trypsin, chymotrypsin, and plasmin with dissociation constants of 1.3 x 10(-9) M, 2.3 x 10(-7) M, and 3.1 x 10(-7) M, respectively. The complete amino acid sequence of OTI-3 showed a significant homology to Bowman-Birk family inhibitors, and the first reactive site (P1) was found to be Arg17 by limited proteolysis by trypsin. The second reactive site (P1) was estimated to be Leu46, that may inhibit chymotrypsin. OTI-3 lacks an S-S bond near the second reactive site, resulting in a low affinity for the enzyme. The sequence of OTI-3 was also ascertained by the nucleotide sequence of a cDNA clone encoding a 101-residue precursor of the onion inhibitor.

Amino Acid Sequence↗
PubMed2003

Role of the Nh (Non-hair) mutation in the development of dermatitis and hyperproduction of IgE in DS-Nh mice.

The DS-Nh (DS Non-hair) mouse is a spontaneous hairless mutant of the DS mouse. The inheritance mode of the Nh mutation is autosomal dominant, and the Nh locus is mapped to Chromosome 11. The roles of the Nh mutation in spontaneous dermatitis and IgE hyperproduction were studied using an Nh congenic strain with a genetic background from the BALB/c mouse. In contrast to DS-Nh (Nh/+) mice, BALB/c-Nh (Nh/+) mice under conventional conditions showed a marked increase in serum IgE, without the development of dermatitis. These results suggest that IgE hyperproduction is regulated by the Nh mutation, while other genetic factor(s) are also involved in the development of dermatitis.

Animals↗
PubMed2003

Spontaneous development of dermatitis in DS-Nh mice under specific pathogen-free conditions.

Spontaneous development of dermatitis in DS-Nh mice under specific pathogen-free conditions was examined to verify the hypothesis [Exp. Anim. 46: 225-229, 1997] that Stapylococcus aureus (S. aureus) infection is causally associated with the dermatitis. Observation of the mice up to 28 weeks of age indicated that obvious dermatitis does occur under S. aureus-free conditions, though the incidence was low (six of 42 females and two of 90 males). Skin lesions in the absence of this bacterium showed histological changes very similar to those that can be observed under conventional conditions. In addition, hyperproduction of serum IgE was demonstrated in the dermatitis-positive mouse. These findings suggested that the dermatitis is triggered by IgE-mediated allergic reactions.

Animals↗
PubMed2003

[Q fever].

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4-Quinolones↗