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Biomedical subjects

T Mio

Publications and source records attributed to T Mio.

At least 73 records · Page 4Linked to original sources
PubMed1994

Involvement of cell wall beta-glucan in the action of HM-1 killer toxin.

HM-1 killer toxin secreted from Hansenula mrakii inhibits the growth of Saccharomyces cerevisiae cells by interfering with beta-1,3-glucan synthesis. We found that HM-1 killer toxin killed intact cells but not protoplasts. In addition, cells lacking the functional KRE6 allele (kre6 delta) became resistant to higher concentration of HM-1 killer toxin. As reported by Roemer and Bussey [(1991) Proc. Natl. Acad. Sci. 88 11295-11299], cells lacking functional KRE6 had a reduced level of the cell wall beta-1,6-glucan compared to that in cells harboring the normal KRE6. These results suggest that the cell wall beta-glucan is involved in the action of HM-1 killer toxin. Addition of HM-1 killer toxin with several kinds of oligosaccharides revealed that either beta-1,3- or beta-1,6-glucan blocked the cytocidal action of HM-1 killer toxin whereas alpha-1,4-glucan and chitin did not. Mannan also interfered with HM-1 killer toxin action, but this inhibitory effect was much weaker than that observed with beta-1,3- or beta-1,6-glucans. Thus, it appears that the cell wall beta-glucan interacts with HM-1 killer toxin, and that this toxin-beta-glucan commitment is required for the action of HM-1 killer toxin.

Cell Wall↗
PubMed1994

Emphysematous changes assessed by selective alveolobronchography and bronchodilator response in chronic airflow obstruction.

To investigate the relationship between the emphysematous changes and bronchodilator responses in patients with chronic airflow obstruction (CAO), we studied the correlation between bronchodilator response to 10 mg inhaled metaproterenol and the extent of emphysema, using selective alveolobronchogram (SAB). Fifty-one patients with CAO were classified into 3 groups by the extent of emphysematous changes detected by SAB. In group 1, no or mild emphysematous change was observed on SAB (n = 9); in group 2, there were significant emphysematous changes but the involved area was less than 75% (n = 17); in group 3, emphysematous change was extensive and covered more than 75% (n = 25). The post-bronchodilator forced expiratory volume in 1 sec (FEV1) of patients in group 3 was significantly lower than in groups 1 and 2. The mean value of changes of FEV1 as a percentage of predicted FEV1 of patients in group 3 was significantly lower than in groups 1 and 2. These results indicated that the extent of emphysematous change correlated positively with the severity of fixed airflow obstruction, and negatively with the bronchodilator response.

Bronchography↗
PubMed1994

Identification of four metabolites of 3-(phenylamino)alanine, a constituent in L-tryptophan products implicated in eosinophilia-myalgia syndrome, in rats.

3-(Phenylamino)alanine (PAA), a contaminant found in L-tryptophan tablets, has been discussed as a possible cause of eosinophilia-myalgia syndrome (EMS). We administered PAA (100 mg/kg) by gastric gavage to Wistar rats to determine its distribution and metabolism. We developed a purification procedure, using Bond Elut SCX cartridges followed by high performance liquid chromatography (HPLC) in order to determine levels of PAA. The level of PAA in blood was 4.22 micrograms/ml at 5 h and urinary excretion was 21.7 micrograms for 5 h and 84.6 micrograms between 5 and 24 h. The amount of PAA in the contents of the large intestine at 5 h was 0.76 microgram, indicating poor transfer of PAA to the large intestine. However, the highest concentration of PAA was 12.3 micrograms/g in the brain, indicating the passage of PAA through the blood-brain barrier. In addition to detecting PAA in the blood and organs, we also detected four metabolites of PAA in urine. We used gas chromatography mass spectrometry to identify PAA in rat liver, as well as N-(hydroxyphenyl)glycine, N-phenylglycine, 3-(pheylamino)lactic acid, and 3-(hydroxyphenylamino)-lactic acid in rat urine. These results suggest that the degradation pathway of PAA is similar to that of phenylalanine.

Administration, Oral↗
PubMed1994

Cloning of the Saccharomyces cerevisiae gene whose overexpression overcomes the effects of HM-1 killer toxin, which inhibits beta-glucan synthesis.

A gene whose overexpression can endow Saccharomyces cerevisiae cells with resistance to HM-1 killer toxin was cloned from an S. cerevisiae genomic library. This gene, designated HKR1 (Hansenula mrakii killer toxin-resistant gene 1), contains a 5.4-kb open reading frame. The predicted amino acid sequence of the protein specified by HKR1 indicates that the protein consists of 1,802 amino acids and is very rich in serine and threonine, which could serve as O-glycosylation sites. The protein also contains two hydrophobic domains at the N-terminal end and in the C-terminal half, which could function as a signal peptide and transmembrane domain, respectively. Hkr1p is found to contain an EF hand motif of the calcium-binding consensus sequence in the C-terminal cytoplasmic domain. Thus, Hkr1p is expected to be a calcium-binding, glycosylated type I membrane protein. Southern and Northern (RNA) analyses demonstrated that there is a single copy of the HKR1 gene in the S. cerevisiae genome, and the transcriptional level of HKR1 is extremely low. Gene disruption followed by tetrad analysis showed that HKR1 is an essential gene. Overexpression of the truncated HKR1 encoding the C-terminal half of Hkr1p made the cells more resistant to HM-1 killer toxin than the full-length HKR1 did, demonstrating that the C-terminal half of Hkr1p is essential for overcoming the effect of HM-1 killer toxin. Furthermore, overexpression of HKR1 increased the beta-glucan content in the cell wall without affecting in vitro beta-glucan synthase activity, suggesting that HKR1 regulates beta-glucan synthesis in vivo.

Amino Acid Sequence↗
PubMed1994

Bronchial responsiveness and acute bronchodilator response in chronic obstructive pulmonary disease and diffuse panbronchiolitis.

BACKGROUND: Diffuse panbronchiolitis (DPB) is characterised clinically by chronic airflow limitation and respiratory tract infection, and pathologically by chronic bronchiolar inflammation. To elucidate the functional differences between chronic obstructive pulmonary disease (COPD) and DPB the bronchial responsiveness to methacholine was compared in 64 patients with COPD and 32 patients with DPB, and the bronchodilator response was compared in 72 patients with COPD and 49 with DPB. METHODS: Bronchial responsiveness to methacholine was determined by the dosimeter method and expressed as PD20FEV1, and bronchodilator response was measured as the change in percentage predicted response with 5 mg nebulised salbutamol. RESULTS: Baseline FEV1 was similar in the two groups of patients. Patients with COPD were more responsive to methacholine than were those with DPB (geometric mean PD20FEV1 8.87 v 48.0 cumulative units). Reversibility of air flow obstruction, expressed as the difference between the percentage predicted postbronchodilator FEV1 and prebronchodilator FEV1, was significantly larger in patients with COPD than in those with DPB (7.87 (6.52)% v 4.16 (4.43)%). CONCLUSIONS: The observation that patients with DPB differ substantially in bronchial responsiveness from those with COPD is thought to reflect the difference in the mechanisms of these two diseases--that is, airway disease in DPB and more parenchymal disease in the group of patients with COPD. The nature of bronchiolar inflammation in COPD and DPB is also different, possibly explaining the difference in bronchial responsiveness. More fixed airflow limitation as a result of structural bronchiolar lesions in DPB will explain the smaller reversibility of airflow obstruction.

Aged↗
PubMed1993

Excitatory and inhibitory effects of toluene on neural activity in guinea pig hippocampal slices.

To investigate the effect of toluene and its derivatives on neural activity, postsynaptic field potential (population spike, PS) of granule cells as well as antidromic potential (AP) and presynaptic fiber potential (FP) (perforant path) were recorded in the guinea pig hippocampal slices. Toluene at the concentration of 0.2 ng/ml to 20 micrograms/ml in the perfusion medium increased the amplitude of PS to 109-150%. Toluene also increased the amplitude of FP and AP, although the most remarkable enhancement was observed in the PS. However, toluene at the concentrations over 1000 micrograms/ml completely depressed the PS, whereas it increased the amplitude of AP to 130% of the original level. These results indicate that toluene has excitatory and inhibitory biphasic effects on neurotransmission in the hippocampal slices according to concentration applied.

Animals↗
PubMed1993

Gastrin-releasing peptide-like immunoreactive substance in bronchoalveolar lavage of idiopathic pulmonary fibrosis and sarcoidosis.

The neuropeptide gastrin releasing peptide (GRP) is present in the lung, and functions as a modulator of tissue growth and repair in fibrotic processes, or as a modulator of cell movement and differentiation in various inflammatory processes, including granulomatous ones. In idiopathic pulmonary fibrosis (IPF), changes in the bronchoalveolar lavage (BAL) content of GRP can be expected. We measured GRP-like immunoreactive substances (GRP-IS) and another neuropeptide, vasoactive intestinal peptide (VIP)-IS in BAL by enzyme immunoassay. Our results showed a decrease in BAL GRP-IS in patients with IPF (26.5 +/- 5.5 pg.mg-1 protein) and sarcoidosis (35.9 +/- 9.2 pg.mg-1), compared to healthy nonsmokers (63.4 +/- 9.0 pg.mg-1). When data were expressed as pg.ml-1 BAL fluid recovered, a decrease was only seen in IPF, not in sarcoidosis. The levels of VIP-IS in BAL were not different between the groups studied. Increased protein levels in BAL had no correlation with the levels of GRP-IS or VIP-IS in BAL. Furthermore, BAL neutrophil percentages had no correlation with the levels of GRP-IS in BAL of patients with IPF. Using reversed phase high performance liquid chromatography (HPLC), several kinds of GRP-IS were detected in BAL. These findings suggest that the decreased level of GRP-IS in BAL may reflect a loss of GRP-producing cells due to chronic lung injury and fibrosis in patients with IPF.

Adult↗
PubMed1992

Proliferative characteristics of fibroblast lines derived from open lung biopsy specimens of patients with IPF (UIP).

We compared the doubling time of fibroblasts derived from idiopathic pulmonary fibrosis (usual interstitial pneumonia) (IPF [UIP]) lung tissues and control fibroblasts, cultured in usual growth medium, and examined the response of these fibroblasts to platelet-derived growth factor (PDGF) and prostaglandin E2 (PGE2). Ten fibroblast lines from open lung biopsy specimens of patients with IPF (UIP) and ten control fibroblast lines from surgically resected lung tissue of patients with limited lung diseases were established. The average doubling time of fibroblast lines was 32.0 +/- 6.0 h (mean +/- SD) in UIP and 33.2 +/- 10.4 h in controls, showing no difference between the two groups. To examine the responses of fibroblasts to PDGF and PGE2 and the differences between fibroblasts derived from fibrotic tissues with different intensity of fibrosis, lung specimens from five patients with IPF were subdivided into two groups, higher-intensity fibrotic lesions (H) and lower-intensity fibrotic lesions (L). The fibroblast lines were established separately. 3H-thymidine uptake with or without PDGF or PGE2 was examined. Results were expressed as the index of thymidine incorporation into the fibroblasts. There were no differences in the doubling times and the responses to PDGF and PGE2 between H and L. There were no differences between control and H regarding their response to PDGF. In response to PGE2, the growth inhibition for H was significantly decreased compared with the control (p less than 0.05). There was no difference in growth inhibition between H and L. The finding that PGE2 inhibits fibroblast proliferation less in UIP lung tissue suggests that fibroblasts from UIP were functionally altered cells or, to some extent, out of normal regulation. These results suggest an abnormal proliferation of fibroblasts observed in IPF (UIP).

Cell Division↗
PubMed1992

Response to oral corticosteroid in patients with chronic obstructive pulmonary disease.

We studied the effect of 30 mg of prednisolone on 29 Japanese patients with chronic obstructive pulmonary disease (COPD). The mean value of the baseline forced expiratory volume in one second (FEV1; mean +/- SEM) was 1.14 +/- 0.12 l (46.9 +/- 3.9% pred) and the FEV1 following the steroid trial was 1.30 +/- 0.12 l (53.7 +/- 4.3% pred). Post-trial FEV1--baseline FEV1/predicted FEV1 was 6.8 +/- 1.9%. Five patients (17%) had more than a 15% increase in FEV1 as a percentage of predicted FEV1. Post-trial FEV1/baseline FEV1 was 117.3 +/- 4.3%, and 12 patients (41%) had more than a 20% increase in FEV1 after the trial. Acute bronchodilator response to beta-agonist correlated positively with the response to corticosteroid. Baseline spirometries, blood eosinophil counts, serum IgE levels, sputum eosinophil counts, family history of asthma, and history of paroxysmal dyspnea did not vary across responders and non-responders. Patients with severe COPD should be treated to achieve the best possible pulmonary functions indicated by a steroid trial within the limit of acceptable levels of adverse effects.

Aged↗
PubMed1991

[Comparison of acute bronchodilator response between cases of diffuse panbronchiolitis and pulmonary emphysema].

Diffuse panbronchiolitis (DPB) is a disease characterized clinically by chronic airflow limitation, therefore patients with DPB are frequently treated with bronchodilators. However, there have been no reports on bronchodilator effects in patients with DPB. Because bronchodilator effects can be influenced by low baseline level of pulmonary function, we evaluated acute responses to inhaled metaproterenol (10 mg) in 31 patients with DPB and in 40 patients with pulmonary emphysema. Patients of both groups were clinically diagnosed, and, in addition, by usage of high-resolution computed tomography. All the subjects in both groups had a post-bronchodilator FEV1/FVC less than 0.7. There was no difference in baseline FEV1 between either group; FEV1 was 1.24 +/- 0.64 l (47.1 +/- 17.8% pred) in DPB vs. 1.24 +/- 0.64 l (51.0 +/- 19.0% pred) in pulmonary emphysema. Two indices, post FEV1/pre FEV1 and post FEV1-pre FEV1/predicted FEV1, were used for the judgement of bronchodilator response. Post FEV1/pre FEV1 was 110.3 +/- 9.3% in DPB and 119.9 +/- 17.1% in pulmonary emphysema. Post FEV1-pre FEV1/predicted FEV1 was 4.5 +/- 4.2% in DPB and 8.6 +/- 6.2% in pulmonary emphysema. Bronchodilator responses for both indices was larger in pulmonary emphysema than in DPB (both, p less than 0.01). It has been reported that post FEV1/pre FEV1 correlates negatively to baseline FEV1 and that post FEV1-pre FEV1/predicted FEV1 is positively correlated to baseline FEV1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1991

[Proliferative characteristics of fibroblast lines derived from open lung biopsy specimens of patients with the usual interstitial pneumonia form of idiopathic pulmonary fibrosis].

One form of idiopathic pulmonary fibrosis (IPF), usual intersitial pneumonia (UIP) is characterized pathologically by patchily distributed fibrotic areas in apparently normal parenchyma. Excessive accumulation of collagen and fibroblasts in fibrotic areas are shown histologically. Fibroblast proliferation is generally evaluated as a process following alveolitis. However, substantial alveolitis with increased inflammatory and immune cells were not observed in our UIP cases. To evaluate the possibility that fibroblasts in UIP are controlled by mechanisms other than normal paracrine regulation, proliferative features of lung fibroblast lines from UIP lung with regular growth medium, platelet derived growth factor (PDGF) and prostaglandin E2 (PGE2) were investigated. Ten fibroblast lines from open lung biopsy specimens of patients with IPF (UIP) and 10 control fibroblast lines from surgically resected lung tissues of patients with limited lung disease were established. The doubling time of fibroblast lines with regular growth medium was UIP:32.0 +/- 6.0 hrs. (mean +/- S.D.), normal control: 33.2 +/- 10.4 hrs. There was no difference between the groups. To examine growth promotion activity by PDGF and growth inhibition by PGE2, lung specimens from 4 patients with IPF were subdivided into tissue with high intensity fibrotic lesion (H) and low intensity fibrotic lesion (L), and the fibroblast lines were established separately. 3H-thymidine uptake with or without PDGF and PGE2 was examined, and results were expressed as the stimulation index. Growth promotion by PDGF was H: 1.97 +/- 1.19, L: 1.89 +/- 0.78, normal control: 2.29 +/- 0.55. There were no differences between groups. Growth inhibition by PGE2 was H: 0.88 +/- 0.24, L: 0.69 +/- 0.49, normal control: 0.44 +/- 0.33. Growth inhibition for H was significantly lower than control (p less than 0.05). Growth inhibition for L was lower than controls, but the difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Quantitative analysis of glutathione in human brain tumors.

Reduced glutathione (gamma-glutamylcysteinylglycine, GSH) plays an important role in the protection of cells against damage from free radicals and other electrophils and also influences cellular radiosensitivity, cellular response to hyperthermia, and cytotoxicity to some kinds of chemotherapeutic agents. The concentrations of GSH in 40 primary and metastatic brain tumors were quantitatively analyzed, and GSH was localized in these tumors by a novel o-phthalaldehyde histofluorescence method. The level of GSH was 195.2 +/- 57.1 micrograms/gm (mean +/- standard deviation) in glioblastomas multiforme, 444.1 +/- 105.1 micrograms/gm in normal brain tissues, and 614.4 +/- 237.4 micrograms/gm in meningiomas. The differences in GSH levels between glioblastomas and normal brain tissues and between glioblastomas and meningiomas were statistically significant (p less than 0.01). The mean GSH level in astrocytoma grades II and III was 321.9 +/- 11.8 micrograms/gm. The difference in the GSH level between glioblastomas and astrocytomas was statistically significant (p less than 0.05). Radiosensitive tumors, such as multiple myeloma, germinoma, and small-cell carcinoma, showed low GSH levels. These data suggest the possibility that the GSH may be a predictor for the efficacy of radiation therapy. The cytochemical study showed GSH localized in the cytoplasm; although it stained well in meningioma tissue, GSH was not well stained in sections of multiple myeloma. The endothelial proliferation did not stain well in glioblastoma, which seems to imply that this area is vulnerable to attack by free radicals from irradiation and/or chemotherapy.

Brain Neoplasms↗
PubMed1990

[Increased oxidant production by peripheral blood granulocytes in patients with idiopathic pulmonary fibrosis].

Oxidant production by peripheral granulocytes stimulated with phorbol myristate acetate (PMA) was investigated in 11 patients with idiopathic pulmonary fibrosis (IPF), 6 with interstitial pneumonia associated with collagen vascular disease (IP-CVD), 8 with sarcoidosis and 12 healthy subjects. Oxidant production was examined by flow cytometry using dichlorofluorescein diacetate. The reactivity of granulocytes to PMA was assessed according to the ratio between mean fluorescent intensity of granulocytes stimulated maximally with PMA and that without PMA, (stimulation index: S.I.). The concentration of PMA that induced half maximal fluorescent intensity of granulocytes (PC 1/2 max) was used as the index of sensitivity. The S.I. was 7.2 +/- 0.45 in IPF, 6.3 +/- 0.6 in IP-CVD, 6.0 +/- 0.71 in sarcoidosis, and 5.8 +/- 0.2 in healthy subjects. However differences between groups were not significant. PC 1/2 max was 7.3 +/- 2.1 ng/ml in IPF, 9.1 +/- 3.0 ng/ml in IP-CVD, 12 +/- 6.9 ng/ml in sarcoidosis and 16.1 +/- 5.8 ng/ml in healthy subjects. There was significant difference between IPF and healthy subjects (p less than 0.05) indicating that peripheral granulocytes in patients with IPF are more highly sensitive to PMA than healthy subjects.

Adult↗
PubMed1990

[Correlation of CT and pathologic findings of pulmonary lymphangioleiomyomatosis].

The X-ray CT findings of two cases of pulmonary lymphangioleiomyomatosis were reported. The correlation between high-resolution CT findings and inflated biopsy specimens was studied. The X-ray CT findings are 1) multiple low attenuation areas, 2) diffuse areas of slightly increased density and 3) irregular enlargement of pulmonary vascular images. Each low attenuation are turned out to correspond to emphysematous lesions. Slightly increased densities on CT images seemed to be caused by a summation of many small nodules of a proliferation of smooth muscle cells located in the wall of respiratory bronchioles and alveolar ducts, with or without intraalveolar hemosiderosis. Some nodular lesions in bronchiolar walls were so close to neighboring vessels that they could not be separated from vascular images on CT, so peripheral vascular images were irregularly thickened. X-ray CT reflected more actual pathological findings than routine chest radiographs. As low attenuation areas on CT images have been reported to be representative of pulmonary emphysema, it is thought that the above CT findings must be differentiated from those of pulmonary emphysema. While pulmonary vascular images were thin and stretched on the CT in patients with emphysema, they were irregularly thickened on the CT of patients with LAM. Furthermore, while CT of emphysema often revealed overinflation or decreased density, diffuse areas of slightly increased density were never found in emphysema.

Adult↗
PubMed1989

[BALF cell findings in patients with BOOP, particularly in comparison with UIP].

It is possible to differentiate to some degree to bronchiolitis obliterans organizing pneumonia (BOOP) of unknown etiology from idiopathic usual interstitial pneumonia (UIP) on the basis of clinical symptoms, chest X-ray findings, pulmonary function test and blood gas findings, but in certain patients it can be difficult. Cell findings in bronchoalveolar lavage fluids (BALF) were compared between 8 patients with BOOP and 28 patients with UIP, both diagnosed histologically by open lung biopsy. Findings characteristic of BOOP included (1) an increase in the percentage of lymphocytes, (2) an increase in the percentage of eosinophils, and (3) a decrease in the OKT4+/OKT8+ ratio. These findings provide useful information in making a clinical diagnosis of BOOP and in evaluating proper steroid treatment in patients who unable to undergo open lung biopsy.

Adult↗
PubMed1988

Measurement of inositol in uremic serum by selected ion monitoring.

A highly sensitive and specific quantitative assay for inositol in serum has been developed. Uremic serum, to which hexahydroxybenzene as an internal standard was added, was deproteined with trichloroacetate. The supernatant aqueous phase was taken after lipids in serum were removed with chloroform, and was lyophilized. The dried powder was converted to butylboronate derivatives by reaction with 5% n-butylboronate (pyridine solution). The reaction mixture was gas chromatographed on fused silica megabore column DB-1, and assayed by electron impact mass spectrometry using selected ion monitoring. Inositol was quantified by the internal standard method. It was possible to determine concentrations as low as 0.1 microgram/ml in 0.5 ml of serum sample with a relative standard deviation of less than 5%. The serum inositol concentration from fifteen fasting patients with chronic renal failure was 39.1 +/- 18.2 micrograms/ml, significantly higher than that of control subjects (5.1 +/- 2.1 micrograms/ml). In the fifteen fasting patients, serum inositol was linearly related to blood urea nitrogen (r = 0.96).

Adult↗