Biomedical subjects

K Takada

Publications and source records attributed to K Takada.

At least 469 records · Page 26Linked to original sources

PubMed1993

Amelioration of glycerol-induced acute renal failure in rats by an adenosine A1 receptor antagonist (FR-113453).

A potent adenosine A1 receptor antagonist, FR-113453, was tested for its preventive effect on glycerol-induced acute renal failure in rats. First, the optimum timing of FR-113453 administration was studied. Oral FR-113453 (100 mg/kg) given 1 h before or 5-10 min after glycerol injection produced a significant reduction of the serum creatinine at 24 h (4.3 +/- 0.8 mg/dL [vehicle] vs. 1.4 +/- 0.4 mg/dL [FR-113453], and 4.7 +/- 1.1 mg/dL vs. 1.3 +/- 0.6 mg/dL, respectively, p < 0.001). However, when FR-113453 was given 2 h after glycerol injection, the serum creatinine did not improve. Creatinine clearance at 24 h after the induction of acute renal failure was significantly better in rats given FR-113453 (100 mg/kg) 1 h before glycerol than in rats given vehicle alone (0.08 +/- 0.08 mL/min vs. 0.01 +/- 0.02 mL/min), (p < 0.01). The kidney weight was lower and less severe histologic changes were observed at 24 h in the FR-113453-treated group. Renal blood flow (measured using 85Sr microspheres) did not change at 24 h after glycerol injection (3.0 +/- 0.9 mL/min/g [vehicle] vs. 3.6 +/- 0.9 mL/min/g [FR-113453]), but renal vascular resistance was significantly reduced by FR-113453 (47.9 +/- 37.9 vs. 26.4 +/- 5.2 mm Hg/mL/min/g, p < 0.05). Beta-ATP levels (measured by 31P-magnetic resonance spectroscopy) were reduced in glycerol-induced acute renal failure, with no difference between the vehicle and FR-113453-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

PubMed1993

[Non-Hodgkin's lymphoma with pulmonary involvement and various immunological abnormalities in an elderly patient].

A 85-year-old female was admitted with general fatigue and chest discomfort in July 1991. Her chest X-ray film showed several pulmonary nodules in the bilateral lung fields without hilar lymphadenopathy. Metastatic lung cancer was suspected, but primary cancer was not detected in spite of cancer screening. Hemoglobin was 8.7 g/dl. The patient also had various immunological abnormalities including increased serum cold agglutinin titer, decreased serum complement, positive anti-nuclear antigen and IgM-kappa monoclonal gammopathy detected by immunoelectrophoresis. She was diagnosed as having autoimmune hemolytic anemia with cold agglutinin disease and M-protein. With the administration of corticosteroids, hemolytic anemia improved temporarily, but the patient died of hemorrhagic gastritis. At autopsy, a lung tumor was detected in the left upper lobe, mainly without hilar lymphadenopathy. The autopsy specimens showed Non-Hodgkin's lymphoma (diffuse medium-sized cell type), differentiated from macroglobulinemia by immunohistochemical studies. In elderly patients, with various immunological abnormalities, B-cell lymphoproliferative disorders such as malignant lymphoma should be suspected.

Aged↗

PubMed1993

[Estimated structure of the polysaccharide related eye lesions, and biological actions of 4-O-methylaldobiouronic acid and it's partially acetylated derivative].

From November 1981 to March 1982, an outbreak of scleritis and/or iritis occurred among patients treated with a special series of hemodialyzers. Several works demonstrated that acetylated carbohydrate derivatives derived from hemicellulose played a primary role in the outbreak and that uronic acid residues were present in the carbohydrate derivatives. Based on these previous findings, we tried to clarify the structure of the polysaccharide causing eye lesions. Application of anion-exchange chromatography enabled us to isolate an acidic polysaccharide from the dialyzer extracts. We found that xylose (Xyl) and 4-O-methylglucuronic acid (4-O-Me-GlcA) were contained in the ratio of ca. 7:1 by gas chromatography (GC). The 13C-NMR spectrum of the polysaccharide was similar to 4-O-methylglucuronoxylan. From these experimental results, we estimated that the structure of the acidic polysaccharide was partly equivalent to xylans existing in the wood of gymnosperms. Then we directed our attention to the 4-O-Me-GlcA moiety. In order to evaluate the biological actions of this part structure, we prepared two kinds of related disaccharides; 4-O-methylaldobiouronic acid (4-O-Me-GlcA-Xyl) and partially acetylated 4-O-methylaldobiouronic acid (Ac 4-O-Me-GlcA-Xyl). These disaccharides were examined with rabbits, but no significant biological actions occurred.

Animals↗

PubMed1993

[Gonadotroph adenomas].

Gonadotroph adenomas have previously been considered to be a rare pituitary adenoma, because excessive secretion of gonadotropins does not always associate with its corresponding clinical syndrome. Therefore, these adenomas can be categorized as clinically non-functioning adenomas. However recent studies, including immunohistochemistry, electron microscopy, tissue culture, plaque assay, and in situ hybridization have classified gonadotroph adenomas may be more common than those it has been considered. In addition, many adenomas which previously have been categorized as non-functioning adenomas secrete gonadotropin and/or their subunits. In this paper, the clinicopathological characteristics of gonadotroph adenomas is reviewed.

Adenoma↗

PubMed1993

[Evaluation of activated T cells among isolated colonic mucosal lymphocytes in ulcerative colitis--using three color flow cytometry].

In present study, the subsets of activated (HLA-DR+) lamina propria T cells were evaluated in ulcerative colitis (UC) mucosa using three-color flow cytometry. Activated suppressor-inducer T cells (T(si)), helper T cells (Th) and cytotoxic T cells (Tc) were increased in affected mucosa of UC patients not given steroid hormones (SH) compared with in the normal control mucosa. It was supposed that the increase of activated T(si) was the secondary change of inflammation, because this change was demonstrated in non-IBD colitis too. However, the increase of activated Th and Tc might indicate the immunological abnormalities related to the pathogenesis of UC, because these changes were demonstrated only in UC, not in non-IBD colitis. On the other hand, no increase of these activated T cells were demonstrated in affected mucosa of UC patients given SH, perhaps reflecting the immuno-suppressive effect of SH.

Adolescent↗

PubMed1993

[Usefulness anti-PPD antibody in the medical practice of tuberculosis].

The decline rate of tuberculosis has decreased recently in Japan. One of the problems is the tendency of increasing doctor's delay in the diagnosis of tuberculosis. One of measures against this problem is to develop a new laboratory diagnostic method. We studied anti-PPD (Purified Protein Derivative of tuberculin) antibody in serum, pleural effusion, and bronchoalveolar lavage fluid (BAL), and found its clinical usefulness in the medical practice of tuberculosis. Firstly the methods of enzyme linked immunosorbent assay (ELISA) for the antibody to PPD were examined. The expression of antibody titer in optical density was found to be the most accurate and most simple method, and was applied in this study. IgG, IgM and IgA antibody to PPD were measured in serum, BAL and pleural effusion obtained from 122 patients with pulmonary tuberculosis, 54 patients with tuberculous pleurisy, 39 patients with lung cancer, 39 patients with malignant pleurisy, 37 patients with pneumonia, 26 patients with chronic bronchitis, 51 patients with sarcoidosis, or 49 control subjects. Serum level of IgG, IgM, and IgA antibody to PPD was elevated in tuberculosis compared with those in other diseases or control subjects. The difference was most distinctive in IgG antibody. Serum IgG antibody was higher in chronic case than in acute case and IgM antibody was higher in acute case than in chronic case. IgG, IgM and IgA antibody in pleural effusion was elevated in tuberculous pleurisy compared with those in malignant pleurisy. IgG antibody was higher in chronic tuberculous pleurisy than in acute tuberculous pleurisy and IgM antibody was higher in acute pleurisy than in chronic one.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Bacterial↗

PubMed1993

[Cytologic diagnosis of respiratory diseases].

Diagnostic cytology plays an important role in the management of respiratory diseases, especially in the field of lung cancer diagnosis. This paper deals mainly with the characteristics of various kinds of specimens for cancer cytology, differential cytodiagnostic problems, population screening for detection of early lung cancer, and cytodiagnosis of benign lung lesions.

Carcinoma, Small Cell↗

PubMed1993

[A histiocytosis X without histological findings: a new entity of histiocytosis X].

Histiocytosis X is a disorder of the reticuloendothelial system with manifestations usually present in the form of one of three entities, namely; Letterer-Siwe disease, Hand-Schüller-Christian disease and eosinophilic granuloma of the bone. A 32-year-old female was admitted to our hospital in July 1990 because of a bilateral diffuse granular abnormal shadow in the chest. She had a history of bilateral pneumothorax in July 1987. She had been suffering from diabetes insipidus since October 1987, and amenorrhea since January 1989. Miliary tuberculosis, fungus disease, pneumoconiosis, sarcoidosis and collagen disease of the lung were excluded by laboratory examinations, and by observation of the clinical course. Histiocytosis X often combines pneumothorax, diabetes insipidus, amenorrhea and an abnormal radiograph of the chest. We suspected this case was one of Histiocytosis X. But, in her lung biopsy, neither Langerhans cells nor Birbeck granules were found. Furthermore S100 protein immunoperoxidase stain was negative. Therefore, we posit the existence of a new and different subtype of Histiocytosis X without histological findings.

Adult↗

PubMed1993

[Human parvovirus B19 infection in patients with hematologic disorders on chemotherapy].

We described two cases having erythroid hypoplasia and pancytopenia, respectively, caused by human parvovirus B19 (PVB19) infection on chemotherapy. The first patient was a seven-year-old boy with Non-Hodgkin's lymphoma. He has obtained complete remission with LSA2L2 protocol, but, immediately after this remission, he suddenly developed high fever, erythema on cheeks and severe anemia without reticulocytes. We concluded that the cause of anemia and other symptoms were due to PVB19 infection because PVB19 DNA in his serum was detected by dot blot hybridization and polymerase chain reaction, although specific antibodies to PVB19 remained absent. He received gamma-globulin intravenously (200mg/kg/day for 5 days). The fever and erythema were improved promptly, but viremia and anemia lasted a few weeks and the specific antibodies to PVB19 were negative for about two months thereafter. The second patient was a nine-year-old boy with common ALL in remission. Pancytopenia suddenly occurred under maintenance therapy. Because IgM to PVB19 was detected in his serum, the patient was diagnosed to have temporary pancytopenia due to PVB19 infection. In conclusion, it is important to confirm specific antibodies and PVB19 DNA in serum when anemia or pancytopenia of unknown cause occurs in immunocompromised patients receiving chemotherapy.

Anemia, Aplastic↗

PubMed1993

[Chronic myelogenous leukemia complicated with sarcoidosis].

A 79-year-old man who had been diagnosed as having sarcoidosis when he was 63 year old, was admitted to our hospital because of marked thrombocytosis and leukocytosis in July 1991. The low neutrophil alkaline phosphatase (NAP) score, presence of Philadelphia (Ph1) chromosome in the bone marrow cells, and M-BCR rearrangement by Southern blot hybridization were observed. He was diagnosed as having chronic myelogenous leukemia complicated with sarcoidosis. The coexistence of sarcoidosis and leukemia has rarely been reported. It is difficult to discuss that there is not causal association between of them.

Aged↗

PubMed1993

Hypotensive effects and influence on serum lipids of SQ29,852, a new angiotensin converting enzyme inhibitor, in patients with essential hypertension: a comparison with atenolol.

The effects of SQ29,852 (n = 24), a new angiotensin converting enzyme inhibitor, and atenolol (n = 22), monotherapies were compared in 46 patients with mild to moderate essential hypertension. Both SQ29,852 (mean dose 15.0 +/- 5.1 mg/day) and atenolol (mean dose 37.5 +/- 18.5 mg/day) significantly decreased both systolic and diastolic blood pressures. There were no significant changes in serum lipids, apolipoproteins, lipoproteins or atherosclerotic indices after both SQ29,852 and atenolol. There were also no significant inter-group differences. There were no serious side effects or abnormal laboratory tests in both treatment groups. It is concluded that SQ29,852 is an effective antihypertensive drug without adverse effect on lipid metabolism.

Adult↗

PubMed1993

[Combined use of chest X-rays and body mass index to predict pulmonary hemodynamics in patients with chronic obstructive pulmonary disease].

A study was undertaken to determine whether measurements of radiological indices from chest X-rays and body mass index (BMI) were useful in predicting pulmonary artery hypertension. Measurements of the cardiothoracic ratio (CTR) as well as right descending pulmonary artery diameter (RDPA) and BMI were made in 27 patients with chronic obstructive pulmonary disease (COPD). Mean pulmonary arterial pressure (mPA) correlated with CTR, RDPA and BMI. Multiple regression analysis gave the useful equation: predicted mPA = -3.523 + 0.196xBMI + 0.110xCTR + 0.786xRDPA (r = 0.704, p < 0.002). Fifteen patients were found to have pulmonary hypertension, defined as mPA > or = 20 mmHg. The sensitivity of CTR and BMI were 86.7%. The specificity of BMI was 83.3%. These results suggest that the measurements CTR, RDPA and BMI may be useful in screening for pulmonary hypertension in patients with COPD.

Aged↗

PubMed1992

Tissue factor potentiates the factor VIIa-catalyzed hydrolysis of an ester substrate.

We designed a simple and sensitive method to assay the activity of the factor VIIa-tissue factor complex, using as a substrate N alpha-benzyloxycarbonyl-L-arginine p-nitrobenzyl ester (Z-Arg-ONb) (Zur, M., and Nemerson, Y. (1978) J. Biol. Chem. 253, 2203-2209). The principle was to measure the amount of p-nitrobenzyl alcohol released during ester hydrolysis using reversed-phase high performance liquid chromatography. Z-Arg-ONb had a broad specificity for plasma serine proteases and factor IXa. Using this method, we examined the effect of tissue factor on the esterase activity of factor VIIa under various conditions. We found that tissue factor greatly potentiates the factor VIIa-catalyzed hydrolysis of Z-Arg-ONb. Phospholipids were not required for the factor VIIa-catalyzed hydrolysis of Z-Arg-ONb, even in the presence of tissue factor. The Km value of factor VIIa alone toward the ester substrate was six times higher than that of a VIIa-tissue factor complex (3.2 versus 0.54 mM), whereas the kcat value was 12 times lower than that of the VIIa-tissue factor complex (14.3 versus 173 s-1). Thus, tissue factor apparently affects the catalytic site of factor VIIa and enhances hydrolysis of the ester substrate. This enhancing effect of tissue factor disappeared on removal of the gamma-carboxyglutamic acid domain from factor VIIa, whereas the esterase activity in the absence of tissue factor was not affected by this modification. The gamma-carboxyglutamic acid domain is probably required as a potent determinant for interactions with tissue factor, even in the absence of phospholipids in the reaction mixture.

Amino Acid Sequence↗

PubMed1992

Purification and characterization of furin, a Kex2-like processing endoprotease, produced in Chinese hamster ovary cells.

Furin, a mammalian homolog of the yeast Kex2 protease, is associated with Golgi membranes and is involved in cleavage of precursor proteins at sites marked by the Arg-X-Lys/Arg-Arg (RXK/RR) motif. We have recently shown that a furin mutant lacking the transmembrane domain can be secreted from cDNA-transfected cells with proteolytic activity for the fluorogenic peptide t-butoxycarbonyl-Arg-Val-Arg-Arg-4-methylcoumarin-7- amide. In this study, we purified and characterized the recombinant furin from the conditioned medium of these cells. Furin was purified as a mixture of 83- and 81-kDa forms and a 96-kDa form. The differences in molecular mass were not due to differences in molecular mass were not due to differences in glycosylation. Moreover, all forms had the same NH2-terminal sequence beginning at the residue after the Arg-Ala-Lys-Arg sequence. These data suggest that the three different forms may be produced by differential COOH-terminal processing of a furin molecule and that mature furin may be autocatalytically produced. Both enzyme preparations showed a pH optimum at 7.0, required Ca2+ for the activity, and showed essentially the same inhibitor profile. These properties resembled those of the Kex2 protease. Both preparations efficiently cleaved fluorogenic peptides with an RXK/RR sequence and moderately cleaved a peptide with an RXXR sequence, but did not cleave dibasic peptides. The sequence requirements determined in vitro were compatible with those determined by expression studies in cultured cells. These data unequivocally demonstrate that furin is an endogenous cellular protease responsible for cleavage of precursor proteins mainly at RXK/RR sites.

Amino Acid Sequence↗

PubMed1992

Further mechanistic study on intestinal absorption enhanced by unsaturated fatty acids: reversible effect by sulfhydryl modification.

In order to study the relationship between the sulfhydryl (SH) modification of membrane-associated proteins and the oleic acid-induced permeability enhancement of the colonic mucosa, in vitro and in situ absorption studies were performed using rat colon and carboxyfluorescein as an impermeable dye. The pretreatment of the mucosa with diamide, a bifunctional sulfhydryl modifier, in in vitro experiments with the everted colonic loops reduced the absorption enhancing effect of oleic acid in a concentration-dependent manner, less inhibitory effect, though just a little, was observed as compared to N-ethylmaleimide. The inhibition caused by the addition of diamide was absolutely restored by exposure of the mucosa to dithiothreitol. On the other hand, these SH modifiers showed no pronounced effect on the in vivo permeability of quinine which is well-known to be absorbed by a passive transport system mainly via the membrane lipid bilayer. These results obtained in the present study have identified an important role of the functional SH groups of membrane proteins on modulating the permeability alteration of the mucosal epithelium provoked by oleic acid. Furthermore, the SH proteins have been revealed as being unimportant in the intestinal absorption of lipoid-soluble compounds.

Animals↗

PubMed1992

Discriminative affinity labelling of opioid receptors by enkephalin and morphiceptin analogues containing 3-nitro-2-pyridinesulphenyl-activated thiol residues.

The thiol groups of leucinthiol, cysteamine and cysteine incorporated into opioid peptides enkephalin and morphiceptin were activated by the 3-nitro-2-pyridinesulphenyl (Npys) group to form mixed disulphides highly reactive to a free thiol. Enkephalin analogues containing Npys-leucinthiol or -cysteine at positions 4, 5 and 6 exhibited high affinities for both mu and delta receptors, while morphiceptin analogues containing Npys-cysteine at positions 4 and 5 showed relatively weak affinity only for mu receptors. When these S-activated opioid peptides were incubated with rat brain membrane preparations, it was found, by binding assay using radiolabelled and non-labelled [D-Ala2,MePhe4,Gly-ol5]enkephalin, that they label mu opioid receptors in a dose-dependent manner. The concentrations required to label half of the receptors were 0.2-2 microM for enkephalins and 10-30 microM for morphiceptins. These results suggested that the thiol group labelled by S-activated enkephalins and morphiceptins is present in the ligand binding site of receptor protein, but not in GTPase-binding protein.

Affinity Labels↗

PubMed1992

An exploration of the binding site of aldolase using alkyl glycolamido phosphoric esters and alkyl monoglycolate phosphoric esters.

Alkyl glycolamido phosphoric esters (P-O-CH2-CO-NH-(CH2)n-CH3) and alkyl monoglycolate phosphoric esters (P-O-CH2-CO-O-(CH2)n-CH3), which are analogs of the aldolase substrate fructose-1-phosphate, were synthesized and use for probing the active site of rabbit muscle aldolase. The inhibition constants (Ki) were affected by the length of the alkyl groups of these compounds and a maximum value of Ki was observed between the number of methylene groups 2 and 4, depending on the type of compound. In the previous investigation, N-(omega-hydroxyalkyl)-glycolamido bisphosphoric esters (P-O-CH2-CO-NH-(CH2)n-O-P) and alkanediol monoglyclolate bisphosphoric esters (P-O-CH2-CO-O-(CH2)n-O-P) have a minimum Ki value between the number of methylene groups 1 and 4. The difference spectra of aldolase caused by binding of alkyl glycoamido phosphoric esters or alkyl monophosphates resembled that of their analogous bisphosphoric esters, but the intensity of absorbance was smaller than that of the bisphosphoric ester analogs. These results suggest that rabbit muscle aldolase has two binding sites for the phosphate groups on the entrance end of the active site cavity, the singly wound beta-barrel of the parallel alpha/beta class structure. The distance between the phosphate binding site Lys-107 in the beta-sheet structure (c) and Arg-148 in the beta-sheet structure (d) may possibly be expanded or contracted by the forms of the bending structure of the biphosphate compounds. Also, the change of distance between the beta-sheet structure (c) and (d) containing Trp-147, may have an effect on the environment of the tryptophan and cause a change of the absorbance of aldolase especially at 295-299 nm. On the other hand, the synthetic monophosphate compounds bind at only one of the two phosphate binding sites and have very little effect on the absorbance of Trp-147, in a similar manner as orthophosphate. The alkyl groups of monophosphate may be repelled by the ionic amino acid side chains, Asp-33, Lys-146, Glu-187 and/or Lys-229 in the middle of the active site cavity. However, the end of the long alkyl group of some monophosphates may possibly contact the hydrophobic bottom of the active site cavity without effect on the environment of Trp-147.

Binding Sites↗

PubMed1992

Distribution kinetics of FK-506, a novel immunosuppressant, after intravenous administration to rats in comparison with cyclosporin A.

The distribution kinetics of a novel potent immunosuppressant, FK-506 (FK) has been studied in comparison with cyclosporin A (CyA) both in vivo and in vitro using blood specimens. The infusion studies on FK, 5.0 mg kg-1 through the portal and femoral veins showed that the mean hepatic extraction ratio of FK was 27.9 per cent. The effect of clamping both the hepatic artery and the portal vein on the plasma disappearance profiles of FK, 5.0 mg kg-1, and CyA, 3.5 mg kg-1 was studied. The plasma disposition kinetics of CyA was almost the same as in the normal rats. However, the plasma FK levels were about 10 times higher than those obtained in the control group rats. This difference is attributed to the restricted initial distribution of FK to the liver, because the volume of the initial distribution space, V1, of FK was about 10 times smaller than that obtained in normal rats. In in vitro experiments, drug distribution was studied in blood samples (2.0 ml) spiked with FK or CyA, 1.0 micrograms ml-1. The plasma drug levels measured at 2 min after drug administration were 0.842 +/- 0.012 micrograms ml-1 and 0.769 +/- 0.047 micrograms ml-1 for FK and CyA, respectively. The distribution volume in the blood compartment, VB, was determined by dividing the spiked amount of drugs with these plasma concentrations. The VB was 2.38 +/- 0.04 ml for FK and 2.62 +/- 0.16 ml for CyA. There was no significant difference in VB between FK and CyA. The plasma free fraction, fp of the drugs was measured by the equilibrium dialysis method. For FK, the mean fp values (+/- SE) were 1.31 +/- 0.18 per cent (2.0 micrograms ml-1) and 1.93 +/- 0.18 per cent (5.0 micrograms ml-1). For CyA, the fp values were 4.85 +/- 0.36 per cent (1.0 micrograms ml-1) and 5.75 +/- 0.82 per cent (5.0 micrograms ml-1). The hydrophobicity parameter, logP' determined through the HPLC method was 0.386 for FK and 0.545 for CyA. Although FK was less hydrophobic than CyA, its protein binding was higher than CyA.

Animals↗