Biomedical subjects

T Tokuyama

Publications and source records attributed to T Tokuyama.

At least 19 recordsLinked to original sources

PubMed1999

Occurrence and significance of decahydroquinolines from dendrobatid poison frogs and a myrmicine ant: use of 1H and 13C NMR in their conformational analysis

Structures for 2,5-disubstituted decahydroquinolines (DHQs) are reported for the two diastereomeric pairs cis-275B (14) and cis-275B' (15) and 5-epi-trans-269AB (18) and trans-269AB (19), all isolated from skin extracts of dendrobatid frogs, and for 5-epi-cis-275B' (16) and 5-epi-trans-275B (17) found in the extracts of virgin queens of a myrmicine ant [Solenopsis (Diplorhoptrum) azteca]. Detection of such DHQs in an ant, their first reported occurrence, strengthens a dietary hypothesis for the origin of the approximately 30 DHQs that have been detected in extracts of frog skin. NMR data on the two conformers of cis-decahydroquinoline permit assignment of ring conformations and stereochemistry to cis-DHQs of the "N-endo" type or the "N-exo" type. These conformations are also assigned on whether H-8a is equatorial or axial as determined with E-COSY or 1D-HOHAHA spectra.

Journal Article↗

PubMed1999

Biodegradation of cyclohexylamine by Brevibacterium oxydans IH-35A.

A bacterial strain capable of growing on cyclohexylamine (CHAM) was isolated by using enrichment and isolation techniques. The strain isolated, strain IH-35A, was classified as a member of the genus Brevibacterium. The results of growth and enzyme studies are consistent with degradation of CHAM via cyclohexanone (CHnone), 6-hexanolactone, 6-hydroxyhexanoate, and adipate. Cell extracts obtained from this strain grown on CHAM contained CHAM oxidase, and the model for CHAM oxidation by this enzyme was similar to the model for deamino oxidation of amine by amine oxidase.

Biodegradation, Environmental↗

PubMed1998

Estimation of regional lung function in interstitial pulmonary disease using 99mTc-technegas and 99mTc-macroaggregated albumin single-photon emission tomography.

For quantitative evaluation of the regional lung function in patients with interstitial pulmonary disease (IP) in the sitting position, 99mTc-Technegas and 99mTc-macroaggregated albumin (MAA) single-photon emission tomography (SPET) studies were performed in 12 healthy controls (HC) and 42 IP patients. Four transverse images were prepared from the data obtained and designated as slices no. 1-4 from the top downward. Regions of interest (ROIs) were determined in the anterior and posterior parts of the lung in each slice, and the ratio of the count per voxel in the ROIs to the count in the entire lung was calculated as the regional Technegas index (T). The regional perfusion index (Q) was calculated by a similar procedure using the data of 99mTc-MAA SPET. The ratios between T and Q (T/Q) in the anterior and posterior regions of the lung, and the ratios of T and Q between the anterior and posterior regions of the lung (Tp/Ta and Qp/Qa) were examined. In the HC group, T/Q decreased but Tp/Ta and Qp/Qa increased from the upper to the lower lung fields. When IP patients were classified into (I) those in whom T/Q decreased from the upper to the lower lung fields, (II) those in whom it was similar in all slices, (III) those in whom it increased from slice 3 to slice 4, and (IV) those in whom it increased from slice 2 to slices 3 and 4, this classification was more closely correlated with %VC than with %DLCO or PaO2. When the patients were classified according to Tp/Ta and Qp/Qa into (A) those in whom the values were greater in the lower than the upper lung field, (B) those in whom the values were similar in all slices, and (C) those in whom the values were smaller in lower than in upper lung fields, categories B and C were observed frequently even in patients whose %VC was in the normal range. This method is considered to be an effective means to evaluate the progression and pathology of IP and to detect early impairment of lung function.

Adult↗

PubMed1998

Effect of plasma colloid osmotic pressure on intraocular pressure during haemodialysis.

BACKGROUND: In a previous case report, it was shown that an increase in plasma colloid osmotic pressure induced by the removal of fluid during haemodialysis was instrumental in decreasing intraocular pressure. The relation between changes in intraocular pressure, plasma osmolarity, plasma colloid osmotic pressure, and body weight before and after haemodialysis is evaluated. METHODS: Intraocular pressure, plasma osmolarity, plasma colloid osmotic pressure, and body weight were evaluated before and after haemodialysis in 36 patients. RESULTS: Intraocular pressure and plasma osmolarity both decreased significantly after haemodialysis (p < 0.0001). Plasma colloid osmotic pressure increased significantly after haemodialysis (p < 0.0001). Body weight decreased significantly because of the removal of fluid during haemodialysis (p < 0.0001). No significant correlation was found between the change in intraocular pressure and that in plasma osmolarity (r = -0.206, p = 0.2297), whereas the change in intraocular pressure was correlated with the change in plasma colloid osmotic pressure (r = -0.510, p = 0.0012) and the change in body weight (r = 0.534, p = 0.0006). A significant correlation was found between the change in plasma colloid osmotic pressure and that in body weight (r = -0.756, p < 0.0001). CONCLUSION: The change in intraocular pressure was inversely correlated with the increase in plasma colloid osmotic pressure caused by the removal of fluid during haemodialysis.

Adult↗

PubMed1998

[Energy expenditure in patients with pulmonary emphysema].

We evaluated resting energy expenditure (REE) using canopy mode indirect calorimetry in 21 ambulatory, clinically stable outpatients with pulmonary emphysema (age: 69.3 +/- 8.4, %IBW: 79.3 +/- 12.5, FEV1: 0.98 +/- 0.36) and compared it with that of a 14 age-matched healthy controls (age: 71.1 +/- 6.0, %IBW: 94.5 +/- 13.4). We also compared REE in malnourished patients (%IBW < 90; 73.0 +/- 7.6, N = 14) and normonourished patients (%IBW > or = 90; 92.0 +/- 5.6, N = 7). We examined the relation ship between %REE (REE/REEpred. x 100) and measurements of lung function tests in 21 emphysema patients using single regression analysis. The REE of the patient group was significantly higher than that of the control group (%REE; 115.9 +/- 12.0 vs 86.5 +/- 8.7, p < 0.01). The REE of the malnourished patient subgroup was significantly higher than that of the normonourished patient subgroup (%REE; 121.9 +/- 7.9 vs 109.9 +/- 9.2, p < 0.01). There were no significant differences in FEV1(L), RV/TLC(%), TLC(pred.%) or DLco/VA (pred.%) between the two patient subgroups. The REE of the normonourished subgroup was significantly higher than that of control group (%REE; 109.1 +/- 9.2 vs 86.5 +/- 8.7, p < 0.01). There were significant relations hips among %REE and FEV1, %FVC, FEV1% G, %DLco/VA and RV/TLC (p < .05). These findings suggest that elevated REE may have a significant relation ship with abnormal lung function, and that elevated REE may be a cause of malnutrition in clinically stable patients with pulmonary emphysema.

Aged↗

PubMed1997

Expression of human islet amyloid polypeptide/amylin impairs insulin secretion in mouse pancreatic beta cells.

Non-insulin-dependent diabetes mellitus (NIDDM) is associated histopathologically with islet amyloid deposits of which a major component is islet amyloid polypeptide (IAPP)/amylin. We examined whether endogenous IAPP controls insulin secretion via a local effect within pancreatic islets and whether overexpression of this peptide contributes to pancreatic beta-cell dysfunction in this disease. Transgenic mice expressing human IAPP in pancreatic beta cell were used in this study. Human IAPP expression did not influence the mouse proinsulin mRNA level and insulin content. Glucose-induced insulin secretion was decreased in the isolated pancreatic islets of transgenic mice. MIN6, a glucose-responsive pancreatic beta-cell line, was transfected with human IAPP cDNA by a lipofectin method. Human IAPP expression was confirmed by RNA blot and immunohistochemical analysis. In two transfectants expressing the largest amount of human IAPP, insulin secretion was increased in response to glucose stimulation; however, the magnitude of the insulin response in cells transfected with human IAPP was smaller than in control clones. Insulin content was not influenced by the expression. We conclude that endogenous IAPP inhibits insulin secretion via an autocrine effect within pancreatic islets, and that the impaired insulin secretion in this disease may be partly caused by overexpression of IAPP.

Amyloid↗

PubMed1997

Structure and expression of the human SM22alpha gene, assignment of the gene to chromosome 11, and repression of the promoter activity by cytosine DNA methylation.

To investigate the molecular mechanisms that control expression of smooth muscle cell (SMC) differentiation genes, we have isolated the human SM22a gene, which is composed of five exons and four introns, spanning an approximately 6-kilobase (kb) genomic DNA at chromosome region 11q23.2. Expression of the SM22a messenger RNA was detected in serum-stimulated cell cultures including SMC, undifferentiated skeletal muscle-lineage cells, and fibroblasts, and it was down-regulated in SMC of balloon-injured atheromatous human vessels. A major transcription start site of the SM22alpha gene is located at 75 base-pairs (bp) upstream of the ATG start codon. Analysis of the 2.6 kb 5'-upstream sequence demonstrated that two CArG/SRF-boxes and two GC-box/Sp1-binding sites were present at bp -147 and -274, and at bp -233 and -1635, respectively. The nucleotide sequences of the two CArG/SRF-boxes and the proximal GC-box/Sp1 binding site are 100% conserved with those of the murine SM22alpha genes [Solway, J., Seltzer, J., Samaha, F.F., Kim, S., Alger, L.E., Niu, Q., Morriesey, E.E., Ip, H.S., and Parmacek, M.S. (1995) J. Biol. Chem. 270, 13460-13469; Kemp, P.R., Osbourn, J.K., Grainger, D.J., and Metcalf, C. (1995) Biochem. J. 310, 1037-1043]. Cell transfection assays using a luciferase reporter gene construct containing the 455-bp 5'-flanking region (positions -26 to -480) showed that methylation of the CpG dinucleotides within this segment reduces its transcriptional activity. The results imply a novel mechanism for transcriptional control of the SMC differentiation-specific gene promoter.

Amino Acid Sequence↗

PubMed1997

Airway inflammation in COPD assessed by sputum levels of interleukin-8.

STUDY OBJECTIVE: To assess the characteristics of airway inflammation in patients with COPD. METHODS: We measured the sputum concentration of interleukin-8 (IL-8), a chemokine involved in the migration and activation of neutrophils and eosinophils. We also measured myeloperoxidase (MPO) as a parameter of neutrophil activity and eosinophil cationic protein (ECP) as a parameter of eosinophil activity. Spontaneous sputum samples were obtained from 33 patients with stable COPD and 30 patients with asthma. Induced sputum samples were obtained from 12 normal control subjects. RESULTS: The sputum concentration of IL-8 was significantly higher in the patients with COPD than in the patients with asthma or in the control subjects (p<0.0001). Concentrations of MPO and ECP were significantly higher in the patients with COPD than in the control subjects but did not differ significantly between the patients with COPD and those with asthma. In the patients with COPD, the sputum concentration of IL-8 was significantly correlated with the concentration of MPO (r=0.55, p<0.001) and of ECP (r=0.53, p<0.01). The sputum concentration of IL-8 was negatively correlated with FEV1/FVC (r=-0.78, p<0.0001) in the COPD group. CONCLUSIONS: Results suggest the activation of both neutrophils and eosinophils in the airways of patients with COPD. It appears that IL-8 plays a primary role in this activation. The sputum concentration of IL-8 appeared to be closely associated with the degree of airflow obstruction in patients with COPD and may serve as a marker in evaluating the severity of airway inflammation, which is a risk factor for COPD.

Adult↗

PubMed1997

[Cytokine producing ability of peripheral blood mononuclear cells in the clinical course of pulmonary tuberculosis].

Interferon-gamma (IFN-gamma) and interleukin-10 (IL-10)-producing ability of peripheral blood plastic-dish adherent cells and non-adherent cells obtained from patients with active pulmonary tuberculosis (N = 17) and healthy controls (N = 14) upon stimulation with purified protein derivatives (PPD) were assessed. Adherent cells and non-adherent cells were obtained two times from each patient with active pulmonary tuberculosis without any underlying diseases, on admission before the initiation of administering anti-tuberculous drugs and 2 months later from the negative conversion of Mycobacterium tuberculosis in sputum culture. ELISA was performed to measure IFN-gamma and IL-10 levels in culture media of adherent cells and non-adherent cells stimulated with PPD. IFN-gamma levels produced by non-adherent cells on admission were significantly higher than that of healthy controls (p < 0.001). Elevated IFN-gamma levels on admission was reduced after treatment for tuberculosis (p < 0.03), but still remained higher than that in healthy controls. IL-10 levels of non-adherent cells of patients were lower than those of healthy controls, although the difference was not significant. IL-10 levels produced by non-adherent cells on admission correlated with the time needed for negative conversion of bacilli in sputum culture (p < 0.05). IL-10 level produced by adherent cells from nutritionally normal patients were significantly higher than that of healthy controls (p < 0.05), and elevated IL-10 level was significantly reduced after therapy (p < 0.05). In the normonourished patients, the time needed for negative conversion of the bacilli in sputum culture of patients kept higher level of IL-10 of non-adherent cells (N = 5) was significantly longer than that of patients reduced IL-10 level after therapy. These results suggest that IL-10 produced by monocytes may diminish the TH1 responses of patients with pulmonary tuberculosis.

Acute Disease↗

PubMed1997

[A case of Mycobacterium intracellulare infection associated with sinobronchial syndrome].

The patient was 71-year-old male with a history of sinobronchial syndrome since 8 years ago. He has been suffering from cough, sputum and upper abdominal discomfort since January 1994. He was diagnosed as an early gastric cancer by endoscopy, and his chest X-ray film showed an infiltrative shadow in the right upper lung field. A smear of the sputum specimen was positive for acid fast bacilli, which were later identified as Mycobacterium intracellulare. In this case, before the Mycobacterium intracellulare infection, it was confirmed that his mucociliary transport was severely impaired by using aerosol inhalation cine-scintigraphy. This case suggests that an impairment of the local defence mechanisms may play an important role in the pathogenesis of Mycobacterium intracellulare infection.

Aged↗

PubMed1997

[Tissue polypeptide antigen as a biological marker of malignant pleural mesothelioma].

To evaluate the role of tissue polypeptide antigen (TPA) as a biological marker of malignant pleural mesothelioma (MPM), we used immunohistochemical techniques to detect TPA in tumor cells, and we measured the content of TPA in serum from patients with MPM. In 14 of 16 patients with MPM, TPA was detected in the cytoplasm of tumor cells. Epithelial-type cells from 11 of 12 patients were stained positively (91.7%), and sarcomatous-type cells from 7 of 8 patients were stained positively (87.5%). Serum TPA levels were abnormally high in 7 of 9 patients. Two of three patients with stage-I disease had normal serum TPA levels, and all patients whose disease was at stage II or higher had abnormal serum TPA levels. Serum TPA levels increased as MPM progressed. These results suggest that the serum TPA level can be used as a biological marker of MPM.

Adult↗

PubMed1997

[Photomicrographs of a pleural biopsy specimen, showing malignant mesothelioma and necrosis--malignant pleural mesothelioma in a patient with sarcoidosis].

A 45-year-old woman was admitted to Nara Medical University Hospital because of right-sided chest pain. Both a chest X-ray film and a chest CT scan revealed bilateral hilar and mediastinal lymphadenopathy and right pleurisy. She underwent fiberoptic bronchoscopy and mediastinoscopy. Biopsy specimens of the lung and mediastinal lymph nodes showed non-caseous epithelioid cell granulomas. After on ophthalmologic examination, she was given a diagnosis of sarcoidosis with a pleural lesion and uveal involvement. The pleurisy become less severe and the lymph nodes shrank without any treatment. About one year later, she complained of right-sided chest pain again and a chest X-ray film revealed diffuse thickening of the pleural on the right side. Examination of pleural biopsy specimens revealed malignant mesothelioma. We know of no previous report from Japan of malignant pleural mesothelioma in a patient with sarcoidosis.

Biopsy↗

PubMed1997

[The relation between diabetes mellitus and IFN-gamma, IL-12 and IL-10 productions by CD4+ alpha beta T cells and monocytes in patients with pulmonary tuberculosis].

Diabetics are prone to bacterial infection in part, due to polymorphonuclear neutrophil dysfunction, but the precise mechanism is not yet fully explained. Of many complications, diabetes mellitus (DM) is one of the most common diseases, which causes pulmonary tuberculosis. To elucidate the mechanism of susceptibility to tuberculosis infection in patients with diabetes mellitus, we measured IFN-gamma, IL-12 and IL-10 productions by CD4+ alpha beta T cells and autologous monocytes stimulated with live BCG in patients with pulmonary tuberculosis complicated with DM (TB + DM) or without DM (TB) and healthy controls. The levels of IFN-gamma and IL-12 production in TB patients were significantly lower than those in the control. These cytokine productions were also lower in TB + DM patients than in TB patients significantly. The level of IL-10 production in TB patients were highest among these three groups. The production of this cytokine in TB + DM patients was lowest. The level of IFN-gamma production was significantly lower in TB + DM patients under poor DM control than in those patients under good DM control and showed a significant negative correlation to HbA1c, an indicator of diabetic control. The period for negative conversion of culture finding in TB + DM patients under poor control was prolonged when compared with those in TB patients. These results demonstrated the difference in cytokines secretion profile between TB patients and TB + DM patients, and suggest that the immunological mechanism underlying pathogenesis of tuberculosis might work differently between these two patients groups.

Adult↗

PubMed1997

[A study on the prognosis of patients with asbestos pleurisy].

We investigated the outcome of patients with asbestos pleurisy. The mean follow-up period of 12 patients was 6.5 +/- 3.7 years. Recurrence occurred in 5 patients (41.7%). Six of the cases recurred contralateral to the original lesion, while one recurred ipsilaterally. The mean period from onset to recurrence was 2.8 +/- 2.8 years. Five of the cases ended in death, and the mean period from onset to death was 5.0 +/- 3.1 years. Two patients died from pneumonia, 2 died from respiratory failure due to progressive pleural fibrosis, and 1 died from lung cancer. One of the 2 patients with progressive pleural fibrosis had leukopenia. It has been reported that the majority of cases of asbestos pleurisy resolve spontaneously, with a good prognosis. However, because of the possible mortality associated with respiratory failure caused by progressive pleural fibrosis, it seems prudent to follow patients with asbestos pleurisy closely.

Aged↗

PubMed1997

[CD4+ alpha beta T cell and gamma delta T cell responses to BCG in patients with pulmonary tuberculosis--comparison with healthy controls].

We demonstrated that CD4+ alpha beta (CD4+) and gamma delta T cell subsets from healthy donors had similar effector functions (cytotoxicity and cytokine production) in response to mycobacterial antigens, despite differences in the antigens recognized. To elucidate the pathogenesis of pulmonary tuberculosis, this study was undertaken to compare T cell functions between patients with pulmonary tuberculosis with no complications and healthy controls. Both resting and activated CD4+ and gamma delta T cells from the patient group proliferated in response to live BCG at a significantly lower rate than those from the control group. The cytotoxicity of BCG-pulsed monocytes and IFN-gamma production in both the CD4+ and gamma delta T cells from patients was significantly lower than those of controls. In contrast to IFN-gamma, significantly higher IL-10 production by both CD4+ and gamma delta T cells from patients was detected. The proliferative responses to BCG by CD4+ and gamma delta T cells from patients after antituberculous therapy were partially restored, but remained at lower levels compared with controls. These results suggest that not only a general deterioration in CD4+ and gamma delta T cells effector functions, but also suppressive factors (such as IL-10) might be responsible for the pathogenesis of pulmonary tuberculosis, and that the low response to BCG by both CD4+ and gamma delta T cells in patients with tuberculosis is in part attributable to patient predisposition.

Aged↗

PubMed1996

The mouse zic gene family. Homologues of the Drosophila pair-rule gene odd-paired.

The mouse Zic gene, which encodes a zinc finger protein, is expressed in the developing or matured central nervous system in a highly restricted manner. We identified two novel Zic-related genes (Zic2, Zic3) through genomic and cDNA cloning. Both genes are highly similar to Zic(1), especially in their zinc finger motif. A comparison of genomic organization among the three Zic genes showed that they share common exon-intron boundaries and belong to the same gene family . Zic1, Zic2, and Zic3 were determined to mouse chromosome 9, 14, and X using an interspecific backcross panel. Northern blotting and ribonuclease protection showed that Zic2 and Zic3 are expressed in a restricted manner in the cerebellum at the adult stage. However, the temporal profile of the mRNA expression in the developing cerebella differ in the three Zic genes. Furthermore, we found that the Drosophila pair-rule gene, odd-paired is highly homologous to the Zic gene family. The similarity was not only the zinc finger motif, but also the exon-intron boundary was the same as those of mouse Zic gene family. These findings suggest that the Zic gene family and Drosophila odd-paired are derived from a common ancestral gene.

Amino Acid Sequence↗

PubMed1996

[Interleukin-8 in sputum from patients with pulmonary emphysema].

We measured concentrations of interleukin-8 (IL-8) in sputum from 38 patients with pulmonary emphysema, from 30 patients with bronchial asthma, and in induced sputum from 10 healthy subjects. Concentrations of IL-8 were significantly higher in sputum from patients with emphysema than in sputum from patients with asthma (mean +/- SE: 22,961 +/- 1,412 pg/ml and 9,135 +/- 1,590 pg/ml, respectively, p<0.0001) and were also higher than in sputum from healthy subjects (3,253+/-687 pg/ml, p<0.0001). Concentrations of IL-8 in sputum from patients with emphysema were unrelated to whether the patient was a current smoker or an ex-smoker, and did not correlate with concentrations of IL-8 in serum. Concentrations of IL-8 in sputum from patients with emphysema correlated significantly with FEV1% (r=-0.78, p<0.0001) and with %RV/TLC (r=0.63, p<0.01). These data suggest that IL-8 is mainly involved in chronic airway inflammation and that concentrations of IL-8 in sputum are closely related to airflow obstruction in patients with pulmonary emphysema.

Female↗

PubMed1996

[Study on correlation between chest X-P course findings and change in antinuclear antibody in asbestos plant employees].

In order to investigate the correlation between a course of chest radiograms and changes in antinuclear antibody (ANA), 140 asbestos workers who had a chest radiogram and measurement of ANA in 1987 and had been working in the same plant were given the same examination again in 1992. In the group who showed a change in ANA to positive, the progression of pulmonary asbestosis was significantly higher than in the group who remained negative. Progression in pleural lesions was not significantly correlated.

Antibodies, Antinuclear↗