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Biomedical subjects

T Oguma

Publications and source records attributed to T Oguma.

At least 55 records · Page 3Linked to original sources
PubMed1998

[Pulmonary emphysematous changes associated with Pneumocystis carinii pneumonia in an AIDS patient].

A 60-year-old man was admitted to our hospital complaining of non-productive cough. He had worked in Africa and received a blood transfusion after a traffic accident in 1985. On admission, the patient had remarkable hypoxemia and a decreased CD4+ lymphocyte count. A serological test for human immuno-deficiency virus (HIV)-1 was positive. His chest radiographs showed diffuse reticular and linear opacities, and broncoalveolar lavage findings established a diagnosis of Pneumocystis carinii pneumonia (PCP). A high-resolution CT of the chest revealed peripheral infiltrates and low attenuation areas (LAA) consistent with severe emphysematous alterations. We administered high-dose methylprednisolone and trimethoprim-sulphamethoxazole (TMP-SMX). Because of marked eosinophilia, TMP-SMX was discontinued, and the patient was given inhaled pentamidine isothiocyanate. Although there was a striking clinical improvement, the emphysema-like lesion on chest CT remained unaltered. LAA on CT had been modest in 1994, but had markedly enlarged during the three years thereafter, leading us to speculate that most of the LAA lesions recognized on admission might have developed in association with PCP. Pulmonary function tests showed an obstructive ventilatory defect and impaired diffusing capacity. Although PCP classically presents with diffuse ground-glass or fine granular opacities, thin-walled cavities or other atypical findings have recently been reported, especially in AIDS patients. There have been several reports about emphysema-like lesions associated with PCP. It was suggested that these lesions might be due to lung parenchyma destruction induced by HIV itself or increased elastase release from HIV-infected macrophages. This is the first report of PCP with pulmonary emphysematous lesions in Japan.

AIDS-Related Opportunistic Infections↗
PubMed1997

Alteration of hepatic microcirculation by oxethazaine and some vasoconstrictors in the perfused rat liver.

We previously reported that, in isolated perfused rat livers in a constant flow system, oxethazaine (OXZ) rapidly increased portal pressure (PP) accompanied by inhibition of oxygen uptake and the subsequent metabolic effects. In this study, hemodynamic changes were studied by using an indicator dilution technique and by microscopic observation of post-fixed liver samples stained with acridine orange or trapped fluorescence microspheres (FMSs). During the increase in PP induced by OXZ, the mean transit times of both red blood cells and azoalbumin were shortened markedly, and the vascular and extravascular albumin spaces decreased to 55 and 18% of the controls, respectively. With acridine orange, in the control livers, all the dye infused was taken up and the periportal zones were uniformly stained over all the liver sections, whereas in the OXZ-treated livers, about 30% of the dye drained out, and extensive staining was observed in the central portion of the liver mass, but the peripheral portions of the liver were much less stained. The staining was often localized around large portal vein branches and spread toward the hepatic veins. These changes were recoverable in the absence of OXZ. Distributions of 1-microm and 15-microm FMSs were likewise altered by OXZ. Thus, uneven perfusion may be the primary cause of decreased tissue spaces and also of the metabolic effects produced by OXZ. Endothelin 1 also produced OXZ-like changes, while U-46619 had lesser effects. The methodology used in this study may help delineate the hepatic perfusion disturbance caused by various vasoconstrictors.

Acridine Orange↗
PubMed1997

[Normal predicted values of CT indices reflect emphysematous alterations in the lung].

In order to obtain normal values and 95% confidence limits of various CT indices, healthy adult subjects with no history of smoking (n = 36) underwent CT scanning under a variety of conditions. By then applying the normal limits thus obtained to CT images of COPD patients (n = 45), we examined the sensitivity for detecting abnormal emphysematous changes in the lung fields. To measure emphysematous alterations, we used the average value of lung CT densities (ROI), the maximally appearing value in a CT histogram (Hist. Peak), the relative area with low CT densities below -910 HU (%LDA) and the total cross-sectional area (Area) in each lung section. Regardless of the section thickness (10 mm or 1 mm), the lung volume level at which the breath was held or the site from which CT images were taken (upper, middle or lower lung field), no significant correlation was observed between the CT indices associated with emphysematous changes and the subjects' age. This allowed us to define, independently of the subjects' age, normal values and 95% confidence limits for the CT indices. Among the CT indices surveyed, %LDA was found to be the most sensitive indicator for detecting emphysematous abnormalities. In so far as the extent of emphysema may be determined by lung CT density, classical CT images of 10-mm section thickness appear to have a sufficiently high sensitivity for the detection of emphysematous abnormalities, such that high-resolution CT may be unnecessary.

Adult↗
PubMed1996

A phase I clinical and pharmacokinetic study of the angiogenesis inhibitor, tecogalan sodium.

BACKGROUND: Tecogalan sodium is an angiogenesis inhibitor isolated from a sulfated polysaccharide produced by the bacterium Arthrobacter. The antiangiogenic effect of tecogalan sodium is thought to be mediated by the inhibition of binding of basic fibroblast growth factor to cellular receptors. PATIENTS AND METHODS: A phase I study was conducted in thirty-three patients with refractory malignancies, including AIDS-associated Kaposi's sarcoma. Patients received a single i.v. infusion every three weeks with the infusion duration ranging from one to twenty-four hours. Seven different dosage levels were studied (125, 185, 240, 300, 390, 445, and 500 mg/m2). RESULTS: The primary dose-limiting toxicity was prolongation of the activated partial thromboplastin time with peak times being between 1.0-4.0 times the upper limit of normal. This toxicity was ameliorated at a given dose level by prolonging the infusion time. Other common toxicities included fever (40%) and rigors (31%) which were well controlled with acetominophen and meperidine. The serum half-life of tecogalan sodium was between 1-1.5 hours and < 25% of unchanged drug was excreted in the urine. CONCLUSIONS: The recommended phase II dose of tecogalan sodium on this schedule is 390 mg/m2 over 24 hours. Other schedules including continuous administration should be investigated to maximize the efficacy of this novel angiogenesis inhibitor.

Antineoplastic Agents↗
PubMed1996

[Roles of inflammatory cells in the pathogenesis of acute lung injury in guinea pigs exposed to heat-killed bacteria].

To study the contribution of polymorphonuclear (PMN) and mononuclear (MN) phagocytes to the development of acute lung injury, we studied lung injury after intratracheal instillation of lipopolysaccharide (0.02 mg/kg) in guinea pigs previously exposed to heat-killed Corynebacterium parvum. In on group, cyclophosphamide was given to deplete peripheral PMNs. In another group, gadolinium chloride (GdCl3) was injected to suppress the function of MNs. Four hours after instillation of lippoly soccharide, the animals were killed, bronchoalveolar lavage was done, and the lungs were examined histopathologically. 125I-labeled albumin was injected to estimate the endothelial damage, and 131I-labeled albumin was injected to correct for blood contamination in the samples. In the group given cyclophosphamide, lung injury was no less than in the control group. In contrast, lung injury was less sever in the group given GdCl3 than in the control group. These findings suggest that MN are important in the pathogenesis of lung injury, especially in individuals who are immunologically primed by infection.

Acute Disease↗
PubMed1996

[Indices allowing early detection of chronic pulmonary emphysema].

To establish criteria allowing early detection of pathologically significant alterations in pulmonary emphysema caused by smoking, pulmonary-function tests and high-resolution computed tomography were done in 104 subjects categorized into three groups: nonsmoking healthy adults, smokers with a normal FEV1%, and smokers with a low FEV1% (cross-sectional analysis). Fifty-six of the 104 patients underwent pulmonary-function testing and high-resdution computed fomography once per year for 3 years (longitudinal analysis). Cross-sectional and longitudinal analyses showed that abnormalities in functional residual capacity, in single-breath diffusing capacity for carbon monoxide, and in the average tomographic density of sections in the lower lung fields obtained after a deep inspiration could be used to predict whether the disease would reach an advanced stage, even if the patients had no significant symptoms at the time of testing. Relative areas of low-attenuation regions, which were alleged to directly reflect the size of emphysematous areas, appear not to be useful for early detection of pathological emphysema.

Chronic Disease↗
PubMed1995

Inhibition of dextran and mutan synthesis by cycloisomaltooligosaccharides.

Novel cyclic isomaltooligosaccharides, cyclodextran, strongly inhibited the dextransucrase reaction. The inhibition was dependent on the cyclodextran concentration and greatly enhanced by the first incubation at 30 degrees for 30 min. Cyclodextran-heptaose and -octaose were competitive inhibitors for sucrose yielding Ki's of 0.25 and 0.64 mM, respectively. Both reducing sugar and dextran producing activities of dextransucrase were almost equally inhibited by the cyclodextrans. Although gamma-cyclodextrin, palatinose, sucrose-monocaprate, and maltitol gave 5-35% inhibition, cyclodextran-heptaose gave 95% inhibition. Moreover, water-insoluble glucan (mutan) synthesis by the glucosyltransferase from Streptococcus mutans was significantly repressed by the addition of cyclodextran.

Cyclodextrins↗
PubMed1995

[Identical male twins showing progression from hypertrophic cardiomyopathy to dilated cardiomyopathy-like features].

Twenty-three-year-old identical male twins with hypertrophic cardiomyopathy which progressed into the dilated phase are reported. The younger brothers first presented at age 16 with an abnormal electrocardiogram. Hypertrophic nonobstructive cardiomyopathy with an asymmetric septal hypertrophy was diagnosed. He was treated with beta-blocker, but he stopped taking the drug as he had no symptoms at that time. He presented again at age 21 years with symptoms of apparent congestive heart failure. Echocardiography showed marked dilatation of the left ventricle with thin wall which was compatible with dilated cardiomyopathy. The elder brother presented with an initial echocardiogram showing systolic anterior movement of the mitral valve without asymmetric septal hypertrophy. He presented again with his brother aged 21 years when his echocardiogram showed slight dilatation of the left ventricle, although he did not complain of cardiac symptoms. These identical twins are the first reported cases of hypertrophic cardiomyopathy progressing to the deteriorated dilated phase.

Adult↗
PubMed1995

Enhancement of tobramycin binding to rat renal brush border membrane by vancomycin.

Effects of vancomycin (VCM) on tobramycin (TOB) binding to rat renal brush border membrane were examined by using isolated brush border membrane vesicles. The binding of TOB to the membrane vesicle was enhanced by the preincubation of the vesicle with VCM. The Scatchard analysis showed that this enhancement was due mainly to the increase in the number of binding sites. D-Glucose uptake was not affected by VCM, which suggests that the vesicles were not damaged by VCM. The binding of spermine, a typical polycationic compound, to the membrane vesicles also was increased by VCM treatment, and this also was because of the increase in the number of binding sites. These results suggested that the enhanced binding of these cationic compounds by VCM was due to the change in the negative charge on the membrane surface. Considering that the binding of aminoglycosides to brush border membranes is the initial step for the renal accumulation followed by the aminoglycosides-induced nephrotoxicity, this enhancement of TOB binding to the membrane by VCM may be one of the reasons for the enhanced TOB nephrotoxicity by VCM, which has often been reported in experimental animals and patients.

Animals↗
PubMed1994

Purification and properties of a novel enzyme from Bacillus spp. T-3040, which catalyzes the conversion of dextran to cyclic isomaltooligosaccharides.

A novel enzyme, cycloisomaltooligosaccharide glucanotransferase (CITase), catalyzes the conversion of dextran to cyclic isomaltooligosaccharides by intramolecular transglucosylation (cyclization reaction). CITase was purified to homogeneity from the culture filtrate of Bacillus sp. T-3040 isolated from soil. The Mr of the enzyme was estimated to be 98,000 by SDS-PAGE. The enzyme catalyzed the cyclization reaction and gave three cyclic isomaltooligosaccharides (cycloisomalto-heptaose, -octase, and -nonaose) at a total yield of about 20%. Coupling and disproportionation reactions were also observed. These results showed that this enzyme is a multi-functional enzyme which catalyzes intramolecular and intermolecular transglucosylation.

Bacillus↗
PubMed1993

Syntheses of subtractively modified 2-chloro-4-nitrophenyl beta-maltopentaosides and their application to the differential assay of human alpha-amylases.

Three novel maltopentaosides, 2-chloro-4-nitrophenyl O-(6-deoxy-alpha-D-xylo-hex-5-enopyranosyl)-(1-->4)-tris[O-alpha-D - glucopyranosyl-(1-->4)]-beta-D-glucopyranoside (3), 2-chloro-4-nitrophenyl O-(6-deoxy-alpha-D-glucopyranosyl)-(1-->4)-tris[O- alpha-D-glucopyranosyl-(1-->4)]-beta-D-glucopyranoside (10), and 2-chloro-4-nitrophenyl O-(3,6-anhydro-alpha-D-glucopyranosyl)-(1-->4)-tris[O-alpha-D-glucopyran osyl- (1-->4)]-beta-D-glucopyranoside (26) were synthesized by chemical and enzymatic reactions. Two human alpha-amylases, salivary alpha-amylase (HSA) and pancreatic alpha-amylase (HPA), hydrolyzed 3 and 10 with the same specificity, almost entirely at a single D-glucosidic linkage, but had no hydrolytic activity for 26. Compound 3 was hydrolyzed by each of these amylases at an approximately equal rate, while 10 was hydrolyzed by HSA 4-fold faster than by HPA. Taking advantage of the difference in the hydrolytic rate of 10, we developed a new method for the differential assay of these two human alpha-amylases.

Carbohydrate Sequence↗
PubMed1993

Comparative hepatic transport of desglycylated and cyclic metabolites of rilmazafone in rats: analysis by multiple indicator dilution method.

Rilmazafone (RZ) is an orally active sleep inducer which can be activated to its cyclic form (M1) via the labile desglycylated metabolite (DG). In this scheme, RZ is exclusively metabolized to DG and M1 by aminopeptidases in the small intestine. The concentration of M1 in the systemic plasma after oral administration of RZ has been reported to be higher than that observed after administration of M1, due to the lower hepatic extraction of DG than M1 (Koike et al., Drug Metab. Dispos., 16, 609 (1988)). In the present study, the disposition of DG and M1 in rat liver was investigated, using the multiple indicator dilution method. The hepatic availabilities (F) of DG and M1, assessed from the recovery into the hepatic vein, were 0.16 and 0.07, respectively, which was consistent with the previous in vivo finding that the first-pass elimination of M1 was greater than that of DG. The kinetic analysis based on the distributed model showed that the influx (k'1) and efflux (k'2) rate constants for M1 were larger than those for DG, whereas no significant difference in the sequestration rate constant (k'3) was observed between the two ligands. Based on the concept proposed by Miyauchi et al. (J. Pharmacokinet. Biopharm., 15, 25 (1987)), it was suggested that the determinant factor of the hepatic intrinsic clearance was the influx clearance for both ligands, because the values of k'2 for each ligand were much smaller than the respective k'3 values. It was concluded that the higher plasma concentration of M1 after oral administration of RZ than that observed after administration of M1 is due to the fact that the hepatic uptake of DG is lower than that of M1.

Administration, Oral↗
PubMed1993

Effects of protein binding on the isomerization of ceftibuten.

Isomerization of ceftibuten to trans-ceftibuten, a less active isomer of ceftibuten, was observed in human serum in vitro. Investigation of the isomerization mechanism in the serum clarified that albumin accelerated the isomerization. The isomerization rate constant correlated significantly with the percent of binding to albumin, suggesting the binding of ceftibuten to albumin might be the driving force for the isomerization under in vitro conditions. This isomerization was also observed in clinical studies in humans. Results of physiological model analysis indicate that the isomerization catalyzed by albumin contributes significantly to the overall isomerization in the human body following oral administration.

Ceftibuten↗