Search PubMed⌕ Search

Biomedical subjects

A Hara

Publications and source records attributed to A Hara.

At least 415 records · Page 23Linked to original sources
PubMed1990

Demonstration of 3 alpha(17 beta)-hydroxysteroid dehydrogenase distinct from 3 alpha-hydroxysteroid dehydrogenase in hamster liver.

NAD(+)-linked and NADP(+)-linked 3 alpha-hydroxysteroid dehydrogenases were purified to homogeneity from hamster liver cytosol. The two monomeric enzymes, although having similar molecular masses of 38,000, differed from each other in pI values, activation energy and heat stability. The two proteins also gave different fragmentation patterns by gel electrophoresis after digestion with protease. The NADP(+)-linked enzyme catalysed the oxidoreduction of various 3 alpha-hydroxysteroids, whereas the NAD(+)-linked enzyme oxidized the 3 alpha-hydroxy group of pregnanes and some bile acids, and the 17 beta-hydroxy group of testosterone and androstanes. The thermal stabilities of the 3 alpha- and 17 beta-hydroxysteroid dehydrogenase activities of the NAD(+)-linked enzyme were identical, and the two enzyme activities were inhibited by mixing 17 beta- and 3 alpha-hydroxysteroid substrates, respectively. Medroxyprogesterone acetate, hexoestrol and 3 beta-hydroxysteroids competitively inhibited 3 alpha- and 17 beta-hydroxysteroid dehydrogenase activities of the enzyme. These results show that hamster liver contains a 3 alpha(17 beta)-hydroxysteroid dehydrogenase structurally and functionally distinct from 3 alpha-hydroxysteroid dehydrogenase.

17-Hydroxysteroid Dehydrogenases↗
PubMed1990

Beneficial effect of magnesium on the isolated perfused rat heart during reperfusion after ischaemia: comparison between pre-ischaemic and post-ischaemic administration of magnesium.

The effect of high concentration of magnesium on both mechanical dysfunction and metabolic damage after ischaemia-reperfusion was studied in isolated rat hearts. The heart was perfused by the Langendorff's technique at a constant flow (10 ml/min) with modified Krebs-Henseleit solution and driven at 300 beats/min. The heart was made ischaemic by reducing the flow to 0 ml/min for 25 min, and then reperfused at the constant flow for 15 min. MgSO4 was added to the perfusate for 5 min before the onset of ischaemia, or after the end of ischaemia (after the onset of reperfusion). Ischaemia-reperfusion produced both mechanical dysfunction (as evidenced by an increase in the left ventricular end diastolic pressure and a decrease in the left ventricular developed pressure) and metabolic damage [as evidenced by a decrease in the myocardial adenosine triphosphate (ATP)]. When 15 mmol/l MgSO4 was given before ischaemia, there was no appreciable recovery of mechanical function, whereas when given after ischaemia (during reperfusion), there was a marked recovery of mechanical function. Lower concentrations (10 or 5 mmol/l) of MgSO4 given after ischaemia recovered the mechanical function concentration-dependently. The beneficial effect of 15 mmol/l MgSO4 was minimized by the coexistence of 4.5 mmol/l CaCl2 in the reperfusion solution. The decrease in the myocardial level of ATP induced by ischaemia-reperfusion was attenuated by 15 mmol/l MgSO4 given in the reperfusion solution. These results suggest that high Mg2+ is effective in attenuating both functional and metabolic damage of the post-ischaemic heart, provided it is given after ischaemia.

Adenosine Triphosphate↗
PubMed1990

Immunohistochemical expression of glutathione S-transferase placental type (GST-pi), a detoxifying enzyme, in normal arachnoid villi and meningiomas.

Human normal dura mater containing arachnoid villi were examined for their expression of glutathione S-transferase placental type (GST-pi), a detoxifying enzyme, using an immunohistochemical method. All of the arachnoid villi and arachnoid cells in five normal cases were found to have expression of GST-pi, although no positive reaction for the enzyme was present in other tissues of the dura mater. The results show a possible role for arachnoid tissues in protecting human brain from hazardous xenobiotics in the cerebrospinal fluid. Twenty-six meningiomas were also examined for expression of the enzyme. Tissues of meningotheliomatous meningiomas were always positive for expression of the enzyme. Transitional meningiomas also showed the expression in their meningotheliomatous components. No staining reaction of GST-pi was recognized in fibroblastic meningiomas except for two cases with a tendency to meningotheliomatous differentiation. The findings suggest a functional similarity between the arachnoid tissues and meningotheliomatous components of meningiomas.

Arachnoid↗
PubMed1990

Effect of diltiazem on the oxymyoglobin level of myocardial cells in the isolated, perfused rat heart during hypoxia.

The effect of diltiazem on the oxymyoglobin level was studied in the isolated rat heart during hypoxia. The heart was perfused with Krebs-Henseleit solution equilibrated with a gas mixture containing 95% O2 + 5% CO2 (normoxic perfusion solution) at a constant flow rate (9 ml/min) according to Langendorff's method. All the hearts were paced at 300 beats/min. The myocardial oxymyoglobin level (i.e., intracellular oxygen level) of the left ventricular surface was continuously measured by means of an optical technique. Diltiazem (infused into the aortic cannula for 10 minutes at concentrations of 0.72, 2.41, or 4.82 microM, expressed as the final concentration in the solution) decreased the left ventricular pressure (LVP) and perfusion pressure (PP) dose dependently, and did not change the oxymyoglobin (MbO2) level during normoxic perfusion. Hypoxic perfusion (using a gas mixture containing 30% O2 + 5% CO2 + 65% N2) decreased the MbO2, LVP, and PP. Diltiazem (infused 5 minutes after the hypoxic perfusion) at a concentration of 2.41 or 4.82 microM increased the MbO2 level and further decreased the LVP, without affecting the PP. The low concentration of 2.41 or 4.82 microM increased the MbO2 level and further decreased the LVP, without affecting the PP. The low concentration (0.72 microM) of diltiazem, however, had practically no effect on these parameters. In summary, diltiazem in high concentrations decreased the LVP and increased the intracellular oxygen level of the myocardial cells during hypoxia, but not during normoxia.

Animals↗
PubMed1990

Correlation between nucleolar organizer region staining and Ki-67 immunostaining in human gliomas.

Fourteen cases of various grades of gliomas were investigated by an immunohistochemical method using a monoclonal antibody, Ki-67, which reacted with a nuclear antigen in proliferating cells, and the correlation between Ki-67 labeling index and the number of nucleolar organizer regions stained by an argyrophilic method. Four normal brain tissue samples without neoplastic cells, which were obtained at surgery, were also examined for nucleolar organizer region staining. Both the mean number of nucleolar organizer regions and the percentage of Ki-67 positive cells well reflected the histological grade of gliomas (astrocytoma grade 2: Ki-67, 0.5% and nucleolar organizer regions, 1.6; astrocytoma grade 3: Ki-67, 3% and nucleolar organizer regions, 2.5; astrocytoma grade 4: Ki-67, 5.2% and nucleolar organizer regions, 2.8). Also, the percentage of Ki-67 positive cells and the mean number of nucleolar organizer regions were found to be linearly related (r = 0.91). Both values of high-grade astrocytomas were significantly greater than those of low-grade astrocytomas (p less than 0.01 and p less than 0.001). Thus, the mean number of nucleolar organizer regions as well as Ki-67 labeling index reflect the proliferating potential of gliomas.

Antigens, Neoplasm↗
PubMed1990

Genotoxicity of heterocyclic amines in the hepatocyte/DNA repair assay using hepatocytes of rats or mice pretreated with 3-methylcholanthrene.

The genotoxicity of 4 heterocyclic amines, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2) was examined in the hepatocyte primary culture (HPC)/DNA-repair assay using hepatocytes of rats and mice pretreated with 3-methylcholanthrene (MC), and the results were compared with those obtained in a previous assay with hepatocytes of normal rodents. All of these heterocyclic amines clearly elicited positive responses of DNA repair in the assay with hepatocytes of the rodents given MC, although in the regular HPC/DNA-repair test without MC pretreatment Tyr-P-2 and Glu-P-2 were negative in rat hepatocytes, and Try-P-2 was also negative in mouse hepatocytes. The level of unscheduled DNA synthesis induced by these positive compounds in the assay with hepatocytes of MC-treated rodents was much higher than that in the assay with hepatocytes of normal rodents. These results are basically in agreement with the reports that this class of compounds is highly activated metabolically by the cytochrome P-450 system from liver microsomes.

Amines↗
PubMed1990

A guanine nucleotide-binding protein in human astrocytoma.

We compared, by immunoblotting and immunohistochemical staining, the distribution of the alpha subunit of Go in human normal brain tissue with that in human brain tumours of neuroectodermal origin. The ten tumour samples included seven high-grade astrocytomas (grades III and IV) and three low-grade astrocytomas (grade II). Immunoreactivity of high-grade astrocytomas with the alpha subunit of Go (Go alpha) antibody was lower than that of low-grade astrocytomas and normal white matter. In the immunohistochemical study, neoplastic cells in the astrocytomas were found to contain little or no significant Go alpha, although nonlesional white matter was strongly stained with Go alpha antibody. This study suggests that Go alpha antibody may assist in defining the boundary of an astrocytoma, and the difference in Go content may affect the alteration in the physical properties of the membrane, which exhibit, in part, the character of the transformation.

Astrocytoma↗
PubMed1990

Carcinogenicity of naturally occurring 1-hydroxyanthraquinone in rats: induction of large bowel, liver and stomach neoplasms.

The carcinogenic potential of 1-hydroxyanthraquinone (HA), a naturally occurring compound, was examined. A total of 60 male ACI/N rats, 1.5 months old at the commencement were divided into two groups. Group 1 (30 rats) were fed the diet containing HA at a concentration of 1% throughout the experiment (480 days). Group 2 (30 rats) served as the control given a basal diet alone. Twenty-five of 29 effective animals in group 1 developed adenomas or adenocarcinomas in the cecum or upper portion of the colon, the mean number of large bowel tumors/tumor bearing rat being 2.3. In addition to these intestinal tumors, liver neoplasms (neoplastic nodules and hepatocellular carcinomas) were observed in 12 rats and benign stomach tumors were obtained in five animals; no rats of group 2 demonstrating development of any of these tumor types. The incidences of the large bowel, liver and stomach neoplasms in group 1 were all significant as compared with group 2 (P less than 2 x 10(-13), P less than 5 x 10(-5) and P less than 3 x 10(-2) respectively) clearly indicating that HA is carcinogenic in rats.

Animals↗
PubMed1990

Inhibitory effect of sinigrin and indole-3-carbinol on diethylnitrosamine-induced hepatocarcinogenesis in male ACI/N rats.

The modifying effects of sinigrin (Sin) and indole-3-carbinol (I3C) on the hepatocarcinogenesis induced by diethylnitrosamine (DEN) were investigated in male ACI/N rats. Rats were divided into six groups: group 1 was given DEN (40 p.p.m.) in the drinking water for 5 weeks, starting at 7 weeks of age; group 2 was treated with DEN and diet containing 1200 p.p.m. Sin; group 3 received DEN and diet containing 1000 p.p.m. I3C; group 4 was given Sin diet alone; group 5 was given I3C diet alone; and group 6 served as controls. The diet containing Sin or I3C was fed to the rats starting at 6 weeks of age until 1 week after the carcinogen exposure. At termination of the experiment (week 29), the incidences of iron-excluding altered foci (11.22 +/- 3.22/cm2) and liver cell tumors (6/12, 50%) and the tumor multiplicity (0.9/rat) in rats of group 2 were significantly smaller than those of group 1 (foci incidence, 48.33 +/- 6.34/cm2, tumor incidence, 10/10, 100%; multiplicity, 9.5/rat) (P less than 0.02). Similarly, the incidence of iron-excluding hepatocellular foci (17.65 +/- 4.67/cm2) and tumor multiplicity (2.4/rat) with a slight reduction of tumor incidence (9/12, 75%) in rats of group 3 were significantly lower than those of group 1 (P less than 0.001). There were no liver cell neoplasms in rats of groups 4, 5 and 6. Thus, Sin and I3C inhibited the hepatocarcinogenesis induced by DEN when they were administered concurrently with the carcinogen.

Animals↗
PubMed1990

New approach for characterization of lysosulfatide by TLC, fast atom bombardment mass spectrometry and NMR spectroscopy.

Thin layer chromatography of lysosulfatide showed anomalous Rf-values in contrast with such lysosphingolipids as glucopsychosine and galactopsychosine with neutral, acidic, and alkaline developing solvents. This was thought to be due to the presence of oppositely charged sulfate and amino groups in the lysosulfatide. In the negative mode of fast atom bombardment mass spectrometry, the lysosulfatide showed the pseudo molecular ion (M-H)- peak at m/z 540 and sulfate ion peak at m/z 97, whereas in the positive mode, it showed not only the pseudo molecular ion (M+H)+ peak at m/z 542, but also the major peaks of protonated psychosine at m/z 462 and fragment ions of dehydrated sphingosine at m/z 282 and 264, 13C-NMR signals of all carbons of lysosulfatide were determined by using distortionless enhancement by polarization transfer. The difference in chemical shifts of ring carbons of galactose residue between lysosulfatide and galactopsychosine was largest at C-3 (downfield shift), thereby indicating the location of the sulfate group to be at C-3 of galactose. This conclusion is supported by the 1H-NMR spectra of the lysosulfatide and galactopsychosine. Thus, the chemical structure of lysosulfatide was confirmed by fast atom bombardment mass spectrometry and 13C- and 1H-NMR spectroscopy. Furthermore, 13C-NMR signals of C-1 to C-5 of the sphingosine moiety showed significantly different chemical shifts between the lysosulfatide and galactopsychosine. These differences suggested that C-1 to C-5 of sphingosine might be influenced by intramolecular or intermolecular interaction between the sulfate group of the galactose residue and the amino group of sphingosine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Purification and properties of multiple forms of dihydrodiol dehydrogenase from human liver.

Two acidic and three basic forms of monomeric dihydrodiol dehydrogenase with molecular weights in the range of 36,000-39,000 were purified from human liver. One acidic enzyme (pI 5.2), which was specific for NADP- and dihydrodiols of benzene and naphthalene, was immunologically identified as aldehyde reductase. The other four enzymes oxidized alicyclic alcohols as well as the dihydrodiols using both NADP+ and NAD+ as cofactors, but showed differences in specificity for hydroxysteroids and inhibitor sensitivity. Two of the basic enzymes (pI 9.7 and 9.1) exhibited a 20 alpha-hydroxysteroid dehydrogenase activity and sensitivity to 1,10-phenanthroline, whereas the third basic enzyme (pI 7.6) oxidized some 3 alpha-hydroxysteroids at low rates and was inhibited by cyclopentane-1,1-diacetic acid. Another acidic enzyme, which accounted for the largest amount of enzyme activity in the tissue and appeared in two heterogenous forms with pI values of 5.9 and 5.4, showed a high 3 alpha-hydroxysteroid dehydrogenase activity and was the most sensitive to inhibition by medroxyprogesterone acetate. The Km values of the enzymes, except the pI 5.2 enzyme, for hydroxysteroids (10(-6) to 10(-7) M) were lower than those for xenobiotic alcohols.

Alcohol Oxidoreductases↗
PubMed1990

Effect of an inhibitor of glucosylceramide synthesis on cultured rabbit skin fibroblasts.

1-Phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), an effective inhibitor of UDP-glucose:ceramide glucosyltransferase, caused growth inhibition of cultured rabbit skin fibroblasts in a dose-dependent manner. At 50 microM both threo and erythro isomers of PDMP completely suppressed the cell growth. Major gangliosides of the fibroblasts, GM3 and GD3, were greatly reduced in amounts in the presence of threo-PDMP and accumulation of ceramides was observed. Surface labeling with galactose oxidase and [3H]NaBH4 demonstrated that neural glycosphingolipids with four or more sugars present on the surface of control cells were not detectable when the fibroblasts were grown in medium containing threo-PDMP. Metabolic labeling of cellular glycosphingolipids with [14C]-galactose showed reduced incorporation of radioactivity into gangliosides and neutral glycosphingolipids when threo-PDMP was present in the medium. In contrast, the erythro isomer of PDMP did not affect the biosynthesis of glycosphingolipids, a result suggesting that the inhibitory effect of erythro-PDMP on cell growth was due to a mechanism other than the inhibition of glucosyltransferase.

Animals↗
PubMed1990

In vitro anticolon antibody production by mucosal or peripheral blood lymphocytes from patients with ulcerative colitis.

Serum anticolon antibody and in vitro anti-colon antibody production by peripheral blood and mucosal lymphocytes was investigated in patients with ulcerative colitis. The frequency of serum anticolon antibody was 71% in 41 patients with ulcerative colitis, estimated by enzyme linked immunosorbent assay (ELISA) using isolated rat colon epithelial cells. This finding confirms our previous report on the frequency of serum anticolon antibody detected by flow cytometry analysis. The estimated frequencies of IgG anticolon antibody secreting cells were 1.5-12.5/10(6) cells in the colonic mucosa and 0.1-0.5/10(6) cells in peripheral blood, from patients with ulcerative colitis when Epstein-Barr virus (EBV) was used as a B cell polyclonal activator. Poisson analysis of limiting dilution culture showed that about one per 140 IgG cells in the colonic mucosa synthesised anticolon antibody. Two monoclonal IgG antibodies were obtained from EBV transformed anticolon antibody secreting cells by limiting dilution method. One reacted with goblet cells in the intestine, and the other reacted mainly with colonic epithelial cells. These results suggest that heterogeneous anticolon antibodies are present in patients with ulcerative colitis and that colonic mucosa may be the main source of anticolon antibody. Local autoimmune reaction might have an important role in causing the inflammation of colonic mucosa in this disease.

Antibody-Producing Cells↗
PubMed1990

Localization of pulmonary carbonyl reductase in guinea pig and mouse: enzyme histochemical and immunohistochemical studies.

We studied the localization of carbonyl reductase (E.C. 1.1.1.184) in guinea pig and mouse lung by enzyme histochemistry and immunohistochemistry, using antibodies against the guinea pig lung enzyme which crossreacted with the lung enzymes of both animals. Carbonyl reductase activity was detectable in the bronchiolar epithelial cells of small airways and in alveolar cells. In the immunohistochemical staining for carbonyl reductase, the reaction was strongest in the non-ciliated bronchiolar cells (Clara cells) and was weak in the ciliated cells and type II alveolar pneumocytes. Injection of a single dose of naphthalene led to significant impairment of carbonyl reductase activity and of microsomal mixed-function oxidase activities in mouse lung, with a marked decrease in both activity and immunoreactive staining in the bronchiolar epithelial cells. The results indicate that carbonyl reductase is localized primarily in the Clara cells, which are known to be sites of pulmonary drug metabolism.

Alcohol Dehydrogenase↗
PubMed1990

[The COP-BLAM therapy for non-Hodgkin's lymphoma in elderly patients].

COP-BLAM therapy, which has recently been reported to be useful in the treatment of malignant lymphoma, was performed on aged patients with non-Hodgkin's lymphoma, and the results and adverse effects of the treatment were evaluated. The subjects of the present study included 13 patients with non-Hodgkin's lymphoma, aged 60 years or older, treated during the period from October, 1987 to June, 1989. They included four recurrent cases after CHOP therapy. According to the Ann-Arbor classification of pathological stage there were two patients in stage I, one in stage II, two stage III and eight in stage IV. COP-BLAM therapy was conducted using the following procedure, irrespective of the patient's age, intravenous drip infusion of cyclophosphamide (CPM) at a dose of 400 mg/m2 and intravenous infusion of 1 mg/m2 vincristine (VCR), and 30 mg/m2 adriamycin (ADM), on day 1; oral administration of 40 mg/m2 prednisone (PSL), and 100 mg/m2 procarbazine (PCZ), from day 1 through day 10, followed by intravenous infusion of bleomycin (BLM), 10 mg/body on day 14. BLM was withdrawn or decreased to less than 70% of the initial dose in patients who exhibited disturbed pulmonary function. Treatment resulted in complete remission (CR) in 11 and partial remission (PR) in 2 out of the 13 patients. Analyzing results according to pathological stage. CR was obtained in all of those in staged I and II, and eight out of the 10 in staged III and IV. The four patients with recurrent disease after CHOP therapy exhibited a CR rate of 50%, indicating that therapy is highly effective in recurrent cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

[The COP-BLAM therapy for malignant lymphoma].

COP-BLAM therapy, which has recently been reported to be useful in the treatment of malignant lymphoma, was performed on 36 patients, and the results and adverse effects of treatment were evaluated. Complete remission (CR) and partial remission (PR), was obtained in 32 (88.9%) and in 4 (11.1%) out of the 36 patients, respectively. So the effective ratio was 100%. Analyzing results according to staging classification, CR was obtained in all of those in stages I and II, and in 84% of those in stages III and IV. The four patients with recurrent disease after CHOP therapy exhibited a CR ratio of 50% indicating that therapy is effective in recurrent cases. Adverse effects observed among the patients included leukocytopenia under 1,000/microliters (5.6%), thrombocytopenia under 5 x 10(4)/microliters (2.8%), gastrointestinal symptoms (25%), peripheral neuropathy (8.3%) and alopecia (27.3%). The efficacy of COP-BLAM therapy appears to be satisfactory with malignant lymphoma, and all adverse effects were of mild degree. In addition, it may be effective in the treatment of recurrent cases which remitted after CHOP and other therapies.

Adult↗
PubMed1990

[Massive bilateral non-Hodgkin's lymphoma of the adrenal glands].

The patient was a 47-year-old male who attended our hospital complaining of back pain. Masses in the bilateral adrenal glands were noted on abdominal ultrasonography and the patient was admitted to the hospital on August 9, 1988. Upon test laparotomy, non-Hodgkin's lymphoma (diffuse small-cell type, B-cell type) was diagnosed, and endocrinological examination revealed hypofunction of the adrenal gland. The results of various tests showed absence of distance metastasis except for that to the bilateral adrenal glands. Since complete remission was attained after 2 courses of COP-BLAM III therapy, and adrenal function also became normal, the patient was discharged on January 9, 1989. Malignant lymphoma originating from the adrenal gland seems to be a rare condition, and only 16 cases have been reported to this date.

Adrenal Gland Neoplasms↗