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Biomedical subjects

Takeshi Ogura

Publications and source records attributed to Takeshi Ogura.

12 recordsLinked to original sources

Resistance of B16 melanoma cells to CD47-induced negative regulation of motility as a result of aberrant N-glycosylation of SHPS-1.

The adhesion receptor SHPS-1 activates the protein-tyrosine-phosphatase SHP-2 and thereby promotes integrin-mediated reorganization of the cytoskeleton. SHPS-1 also contributes to cell-cell communication through association with CD47. Although functional alteration of SHPS-1 is implicated in cellular transformation, the role of the CD47-SHPS-1 interaction in carcinogenesis has been unclear. A soluble SHPS-1 ligand (CD47-Fc) has now been shown to bind to Melan-a non-tumorigenic melanocytes but not to syngeneic B16F10 melanoma cells. Treatment of B16F10 cells with 1-deoxymannojirimycin, which prevents N-glycan processing, restored the ability of SHPS-1 derived from these cells to bind CD47-Fc in vitro, indicating that aberrant N-glycosylation of SHPS-1 impairs CD47 binding in B16F10 cells. CD47-Fc inhibited the migration of Melan-a cells but not that of B16F10 cells. However, a monoclonal antibody that reacts with SHPS-1 on both Melan-a and B16F10 cells inhibited the migration of both cell types similarly. CD47 binding induced proteasome-mediated degradation of SHPS-1 in a tyrosine phosphorylation-independent manner. Furthermore, overexpression of SHPS-1 reduced the level of tyrosine phosphorylation of focal adhesion kinase, and this effect was reversed by CD47 binding. These results suggest that CD47 binds to and thereby down-regulates SHPS-1 on adjacent cells, resulting in inhibition of cell motility. Resistance to this inhibitory mechanism may contribute to the highly metastatic potential of B16 melanoma.

Animals↗

Rapid serodiagnosis of active pulmonary Mycobacterium tuberculosis by analysis of results from multiple antigen-specific tests.

We have prospectively analyzed three antigens for serodiagnosis of tuberculosis (TB). These antigens were tuberculous glycolipid antigen, lypoarabinomannan polysaccharide antigen, and antigen 60 (A60), which was derived from purified protein derivatives. Of the 131 patients with active pulmonary TB, 57 were both smear and culture negative and 14 had chronic active pulmonary TB that remained smear positive for >12 months of chemotherapy. One hundred twenty healthy adults were controls. The percentages of patients positive in all three tests were 58.8% for smear-positive active pulmonary TB and 71.4% for chronic active pulmonary TB. When the results of the three serodiagnostic tests were evaluated in combination, the sensitivity increased to 91.5% in patients with active pulmonary TB and to 86.0% in smear- and culture-negative patients. The false-positive rate of the three-test combination was 12.5% in the healthy control groups. In conclusion, it was not possible to detect all of the antibodies against antigenic substances in the cell walls of the tuberculous bacilli in the sera of all TB patients by using available serodiagnostic tests. However, the combined use of tests with three separate antigens maximizes the effectiveness of serodiagnosis.

Antigens, Bacterial↗

[Direct detection of rifampicin resistant Mycobacterium tuberculosis in sputum by line probe assay (LiPA)].

OBJECTIVES: To examine the direct detection of rifampicin (RFP)-resistant Mycobacterium tuberculosis in sputum by Line Probe Assay (LiPA). MATERIALS AND METHODS: We collected 130 sputa and analyzed both by LiPA and the Amplicor M.tuberculosis assay. For culture-positive samples, RFP resistance testing was performed and compared with the results by LiPA. RESULTS: Eighty two out of 84 M. tuberculosis samples were detected by LiPA and all of 10 Mycobacteria other than M. tuberculosis (MOTT) samples and 36 negative samples were negative by LiPA. The detection rate is same as Amplicor. For culture-positive samples, LiPA showed mutation pattern for all of 22 RFP-resistant strains and wild type pattern for 19 of 20 RFP-sensitive strains. The one remaining showed mixed pattern of wild type and mutation pattern. CONCLUSION: The use of LiPA for sputum coould enable early detection of RFP-resistant tuberculosis and seems to be useful for the control of tuberculosis.

Antibiotics, Antitubercular↗

Ubiquitination-mediated regulation of biosynthesis of the adhesion receptor SHPS-1 in response to endoplasmic reticulum stress.

Misfolding of proteins during endoplasmic reticulum (ER) stress results in the formation of cytotoxic aggregates. The ER-associated degradation pathway counteracts such aggregation through the elimination of misfolded proteins by the ubiquitin-proteasome system. We now show that SHP substrate-1 (SHPS-1), a transmembrane glycoprotein that regulates cytoskeletal reorganization and cell-cell communication, is a physiological substrate for the Skp1-Cullin1-NFB42-Rbx1 (SCF(NFB42)) E3 ubiquitin ligase, a proposed mediator of ER-associated degradation. SCF(NFB42) mediated the polyubiquitination of immature SHPS-1 and its degradation by the proteasome. Ectopic expression of NFB42 both suppressed the formation of aggresome-like structures and the phosphorylation of the translational regulator eIF2alpha induced by overproduction of SHPS-1 as well as increased the amount of mature SHPS-1 at the cell surface. An NFB42 mutant lacking the F box domain had no such effects. Our results suggest that SCF(NFB42) regulates SHPS-1 biosynthesis in response to ER stress.

Amino Acid Sequence↗

Prognostic predictors for survival in patients with COPD using cardiopulmonary exercise testing.

We studied the relationship between physiologic parameters in cardiopulmonary exercise testing (CPET) and prognosis in terms of survival time in patients with chronic obstructive pulmonary disease (COPD) in order to accurately assess the severity of the disease. From a group of 195 patients with COPD who had consecutively undergone CPET between July 1989 and October 1997, we enrolled 120 subjects (mean age 67.6 years, 104 males) with exertional dyspnoea into a cohort protocol. Of these subjects, 34 (28.3%) died during the 3-5-year follow-up period after CPET. By univariate analysis, the following factors were significantly associated with survival time: age, body mass index, %FVC, %FEV1, FEV1%, PaCO2 at rest, severity of exercise-induced hypoxemia evaluated by DeltaPaO2/DeltaVO2 (PaO2-slope), oxygen uptake, ventilation, tidal volume, PaCO2 and oxygen pulse at maximum exercise, as well as prescribing long-term oxygen therapy. By multivariate analysis, age and the PaO2-slope showed significance as independent prognostic factors, and the PaO2-slope was most closely associated with the survival time. These results reveal that CPET is a useful technique to accurately assess the relationship between the functional impairments and the prognosis of patients with COPD.

Aged↗

Prospective clinical evaluation of the serologic tuberculous glycolipid test in combination with the nucleic acid amplification test.

We have conducted a prospective controlled multicenter study to evaluate differences in the levels of clinical utility of the tuberculous glycolipid (TBGL) serodiagnostic test and the nucleic acid amplification test in patients with smear-negative active pulmonary tuberculosis (TB). The TBGL test and the PCR test were individually not so useful for the rapid diagnosis of smear-negative active pulmonary TB. However, clinical utility was considerably improved by using the TBGL test and the PCR test in combination, especially in patients with smear-negative and culture-negative active pulmonary TB and in patients with minimally advanced lesions.

DNA, Bacterial↗

Exercise-induced electrocardiographic changes in patients with chronic respiratory diseases: differential diagnosis by 99mTc-tetrofosmin SPECT.

UNLABELLED: Evaluation of possible cardiac complications is essential for safe and effective respiratory rehabilitation of patients with chronic respiratory diseases (CRDs). The aim of this study is to clarify the pathophysiology of electrocardiographic (ECG) changes during exercise and the prevalence of coronary artery disease (CAD) in CRD patients without a history of myocardial ischemia. METHODS: We studied 42 CRD patients with exercise-induced ST depression by cardiopulmonary exercise testing (CPET). They were selected from 249 consecutive CRD patients without any history of CAD who underwent CPET between January 1999 and December 2001. Thirty-three patients without respiratory diseases who had positive ST depression during exercise were selected as disease control subjects. Exercise myocardial SPECT was performed to evaluate myocardial ischemia and right ventricular (RV) overload as measured by increased RV uptake. RESULTS: Among the 249 consecutive CRD patients without any history of CAD, positive ST depression during exercise was found in 42 (16.9%). Only 2 of the 42 patients (4.8%) had an ST depression other than in II, III, or aVF leads. The incidence of myocardial ischemia by perfusion SPECT was significantly lower in CRD patients (26.2%) than in disease control subjects (78.8%). The most common finding in the CRD patients during exercise was RV overload but without ischemia (26 cases; 61.9%). Ischemia was found in 11 patients (26.2%), with 10 of these patients also having RV overload. Neither ischemia nor RV overload was found in 5 patients (11.9%); these patients were eventually diagnosed as normal. CONCLUSION: The incidence of myocardial ischemia as determined by perfusion SPECT was low in CRD patients with positive exercise-induced ECG changes. On the other hand, RV overload was observed in most such cases. Cardiac perfusion SPECT is a useful technique to evaluate cardiac ischemia and RV overload simultaneously. CPET with 12-lead ECG monitoring is necessary in CRD patients before respiratory rehabilitation. Further examination for ischemia should be done if positive ST depression is found.

Aged↗

[Lung cancer].

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History, 20th Century↗

Serodiagnosis of pulmonary disease due to Mycobacterium avium complex with an enzyme immunoassay that uses a mixture of glycopeptidolipid antigens.

It is difficult to distinguish pulmonary disease due to Mycobacterium avium complex (MAC) from that due to other mycobacteria, such as Mycobacterium tuberculosis and Mycobacterium kansasii. We developed an enzyme immunoassay (EIA) for diagnosis of MAC pulmonary diseases that uses glycopeptidolipid (GPL) antigens specific for MAC, and we used it for diagnosis in immunocompetent patients. The mean optical densities (+/- standard deviation) of serum immunoglobulin G antibodies to GPLs in patients with MAC disease, MAC colonization, M. kansasii disease, and tuberculosis and in healthy subjects were 0.778+/-0.784, 0.042+/-0.035, 0.059+/-0.035, 0.071+/-0.035, and 0.030+/-0.027, respectively. A significant increase in the level of anti-GPL antibodies was detected in patients with MAC disease. The level of anti-GPL antibodies reflected disease activity, because the level was decreased in culture-negative patients who had conversion of culture results. When a cutoff level of seropositivity (0.119) was defined, the sensitivity of EIA for diagnosis of MAC disease was 92.3%, and the specificity was 96.7%. Measurement of serum anti-GPL antibodies is useful for both the diagnosis of and assessment of activity in MAC disease.

Adolescent↗

Synchronous optic and pineal pilocytic astrocytomas in a paediatric patient with neurofibromatosis type 1.

A 12-year-old girl with neurofibromatosis type 1 presented with headache, visual acuity and visual field disturbance. Computed tomography and magnetic resonance imaging revealed an enhanced solid mass involving her right optic nerve and optic chiasm, and a cystic lesion in the pineal region that had resulted in obstructive hydrocephalus. An open biopsy of the right optic nerve tumour was performed, and it was histologically identified as a pilocytic astrocytoma. Local irradiation of 50 Gy to the optic pathway tumour was performed, and the tumour has remained stable for more than 29 months. On the contrary, the pineal cystic mass that was also histologically identified as a pilocytic astrocytoma showed marked enlargement within 5 months after a subtotal resection. Chemotherapy with cisplatin and vincristine was performed after a second surgery, and the pineal tumour has not re-grown in 18 months. To our knowledge, this is the first case report to describe synchronous optic and pineal pilocytic astrocytomas associated with neurofibromatosis type 1.

Astrocytoma↗