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Biomedical subjects

A Hara

Publications and source records attributed to A Hara.

At least 379 records · Page 21Linked to original sources
PubMed1992

[A case of bucillamine-induced interstitial pneumonia].

Bucillamine [N-(2-mercapto-2-methylpropionyl)-L-cysteine] is an anti-rheumatic drug which was developed in Japan. Interstitial pneumonia induced by bucillamine has been reported in two patients with rheumatoid arthritis. In this report, we describe another patient who developed bucillamine-induced interstitial pneumonia. In August 1990, a 53-year-old man was admitted because of fever, dry cough and dyspnea on exertion (DOE). Five months previously, he had noted polyarthritis, and treatment with bucillamine was started in May 1990. His polyarthritis improved about 2.5 months after starting bucillamine, but he developed fever, dry cough, and DOE in August 1990. Chest X-ray on admission showed diffuse acinar and interstitial shadows predominantly in the bilateral upper lung fields. Pulmonary function tests revealed decreased vital capacity and diffusing capacity. Arterial blood gas (ABG) analysis revealed moderate hypoxemia with PaO2 67 Torr. After stopping bucillamine, the fever, dry cough, and DOE improved gradually, and the abnormal shadows on chest X-ray and ABG analysis showed moderate improvements. Bronchoalveolar lavage studies showed that total cell counts and proportion of lymphocytes were increased, and CD4+/CD8+ ratio of T cell subsets was decreased to 0.56. Transbronchial lung biopsy specimen revealed lymphocytic alveolitis and mild interstitial thickening. Lymphocyte stimulation test to bucillamine was negative, but patch test with bucillamine was positive. From the patient's clinical course, laboratory data, and pathologic findings, we concluded that this is a case of bucillamine-induced interstitial pneumonia. After treatment with corticosteroid, his chest X-ray and pulmonary function test showed marked improvements.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

[Effect of serum factors on the differentiation of a colon cancer cell line Caco-2].

A human colon cancer cell line Caco-2 undergoes spontaneous enterocytic differentiation under the standard culture condition. We examined the changes in the proliferative activity of Caco-2 cells during the differentiation, and the effect of serum factors on this spontaneous differentiation. Caco-2 cells cultured in FCS-containing media exhibited the differentiation phenotypes such as dome formation and increase of ALP activity after the 6th day of culture. Cell cycle analysis showed a marked decrease in S phase cell population during the cell differentiation. When Caco-2 cells were cultured in FCS free media, the cell population of S phase remained unchanged during culture period and the differentiation phenotypes were not induced. The addition of FCS to Caco-2 cell cultured in the absence of FCS resulted in the rapid induction of the differentiation phenotypes. These results suggest that differentiation of Caco-2 cells is closely related to the reduction of cell proliferation and requires some factors in FCS.

Animals↗
PubMed1991

Aldehyde reductase is a major protein associated with 3-deoxyglucosone reductase activity in rat, pig and human livers.

3-Deoxyglucosone reductase activity in the extracts of rat, pig and human livers was potently inhibited by aldehyde reductase inhibitors. The major species of 3-deoxyglucosone reductase purified from human and pig livers were biochemically and immunochemically identical with aldehyde reductase. The two enzymes and rat liver aldehyde reductase exhibited higher catalytic efficiency for 3-deoxyglucosone than for D-glucuronate, a representative substrate of aldehyde reductase.

Alcohol Oxidoreductases↗
PubMed1991

Aldehyde dismutation catalyzed by pulmonary carbonyl reductase: kinetic studies of chloral hydrate metabolism to trichloroacetic acid and trichloroethanol.

The kinetics of the NAD(P)(+)-linked aldehyde dismutation by pulmonary carbonyl reductase of guinea pig were studied using a highly hydrated substrate, chloral hydrate (CH). The enzyme irreversibly converted the substrate into trichloroacetic acid (TCA) and trichloroethanol (TCE) in the presence of the reduced or oxidized cofactors, of which NAD(P)+ gave a higher reaction rate than did NAD(P)H, and the concentration ratios of the two products (TCA plus TCE) to CH utilized were 1:1. In the NAD(P)(+)-linked reaction TCA was the predominant product and its amount was compatible with that of TCE plus NAD(P)H produced, whereas in the NAD(P)H-linked reaction equal amounts of TCA and TCE were formed and the cofactor was little oxidized. These results suggest that the enzyme oxidized the hydrated aldehydes to TCA with NAD(P)+ as the cofactor and reduced the unhydrated aldehyde to TCE with NAD(P)H. The steady-state kinetic measurements in the NADP(+)-linked CH oxidation were consistent with an ordered Bi Bi mechanism which is the same as that for the secondary alcohol oxidation by the enzyme. The dehydrogenase activity was inhibited competitively with respect to CH by a secondary alcohol substrate, propan-2-ol. The CH and propan-2-ol dehydrogenase activities were similarly inactivated by 2,4,6-trinitrobenzene-sulfonate, and NADP(H), several cofactor analogs and a cofactor-competitive inhibitor, Cibacron blue dye, protected against the inactivation, which suggest that lysine residues are essential for catalysis.

Alcohol Oxidoreductases↗
PubMed1991

Distribution and characterization of dihydrodiol dehydrogenases in mammalian ocular tissues.

The immunological relationship of two forms of dihydrodiol dehydrogenase (DD) in pig lens to pig muscle aldose reductase and kidney aldehyde reductase has been studied. Although the minor enzyme form, a monomer of Mr 35,000, was identical with aldose reductase, the major enzyme form, a dimer of Mr 65,000, was distinct from the two reductases. The two enzyme species, although their amounts were low, were distributed in the cornea, iris-ciliary body, retina and choroid of the pig eye. In other mammals, rabbit lens exhibited much higher DD activity than did lens of mice, rats, cats, hamsters, guinea pigs and monkeys, and contained large amounts of the Mr-65,000 enzyme form as well as the minor enzyme form of Mr 35,000. In contrast, only the Mr-35,000 form of the enzyme was found in the lens of other species, except that a small amount of the high-Mr enzyme was detected in mouse lens. The high-Mr enzyme, purified from rabbit lens, was functionally and immunologically similar to dimeric DD of pig lens. The low-Mr enzyme forms, isolated or partially purified from these animal lenses, showed several features in common with aldose reductases from mammalian tissues. The dimeric enzymes of pig and rabbit lenses were NADP(+)-specific, whereas the low-Mr enzymes exhibited dual cofactor specificity and their activities with NAD+ were more than 3-fold higher than those with NADP+.

Alcohol Oxidoreductases↗
PubMed1991

Inhibition of dimeric dihydrodiol dehydrogenases of rabbit and pig lens by ascorbic acid.

The dehydrogenase activity of dimeric dihydrodiol dehydrogenases (DD) purified from pig and rabbit lenses was inhibited by either L-ascorbic acid or its epimer, isoascorbic acid, at pH 7.5. Isoascorbate [IC50 (concn. giving 50% inhibition) = 0.043 mM for the pig enzyme; IC50 = 0.13 mM for the rabbit enzyme] was a more potent inhibitor than ascorbate (IC50 values 0.45 and 0.90 mM respectively), but 1 mM-dehydroascorbate gave less than 30% inhibition. Glucose, glucuronate, gulono-gamma-lactone, glutathione and dithiothreitol did not inhibit the enzyme activity. The inhibition by isoascorbate and ascorbate was instantaneous and reversible, and their inhibitory potency was decreased by addition of ascorbate oxidase. In the reverse reaction, isoascorbate and ascorbate gave low IC50 values of 0.013 and 0.10 mM respectively for the pig enzyme and 0.025 and 0.25 mM for the rabbit enzyme. The inhibition patterns by the two compounds were competitive with respect to dihydrodiols of naphthalene and benzene and uncompetitive with respect to NADP+, but those in the reverse reaction were uncompetitive with respect to both carbonyl substrate and NADPH. The steady-state kinetic measurements in the forward and reverse reactions by the pig enzyme were consistent with an ordered Bi Bi mechanism, in which NADP+ binds to the enzyme first and NADPH leaves last. The results indicate that ascorbate and its epimer directly bind to an enzyme: NADP+ binary complex as dead-end inhibitors. Thus ascorbate may be an important modulator of DD in the lens.

Alcohol Oxidoreductases↗
PubMed1991

Assessment of proliferative potential in gliomatosis cerebri.

The proliferative potential of neoplastic cells in two cases of gliomatosis cerebri was investigated by a combined staining technique, a one-step silver colloid method for nucleolar organizer region-associated protein (AgNOR) and immunohistochemistry for fibrillary acidic protein (GFAP). The neoplastic cells in the two cases had an abnormal shape and showed positive GFAP immunostaining in their cytoplasm. The numbers of AgNORs were counted in central and peripheral lesions of the neoplastic field in each case. The mean AgNOR scores in neoplastic cells were almost the same as those of nonneoplastic astrocytes in both the central and the peripheral lesions. These values were almost equal to the AgNOR score of low-grade gliomas. These findings indicate that gliomatosis cerebri has an invasive character in the central nervous system and often shows a malignant tendency, but its proliferative potential is significantly lower than that of high-grade gliomas.

Adult↗
PubMed1991

Nucleolar organizer region score and Ki-67 labelling index in high-grade gliomas and metastatic brain tumours.

Sixteen cases of malignant brain tumours comprising 6 anaplastic astrocytomas, 3 glioblastoma multiforme, 1 medulloblastoma and 6 metastatic brain tumours were investigated independently by a silver colloid method for nucleolar organizer regions (NORs) and an immunohistochemistry using a monoclonal antibody against a nuclear antigen. Ki-67, in proliferating cells. The correlation between the mean number of NORs and the percentage of Ki-67 labelled cells (Ki-67 labelling index) was examined. In addition, four normal brain tissue samples without neoplastic cells were stained for NOR. The mean number of NORs in these malignant brain tumours was significantly greater than that in normal astrocytes (p less than 0.001). Moreover, both the mean number of NORs and the Ki-67 labelling index in metastatic brain tumours were significantly greater than those in high-grade gliomas (p less than 0.001). The Ki-67 labelling index and the mean number of NORs in malignant brain tumours including metastatic brain tumours were found to be linearly related (r = 0.86). These results suggest that the proliferative potential of malignant brain tumours could be evaluated by NOR score as well as Ki-67 labelling index and that such indices provide clear discrimination between high-grade gliomas and metastatic brain tumours.

Astrocytoma↗
PubMed1991

Rapid detection of proliferating potential in human brain tumors by nucleolar organizer region staining on squash preparations.

Rapid detection of the proliferating potential of 37 human brain tumors was attempted using squash preparations stained by a silver colloid technique for argyrophilic protein associated with nucleolar organizer regions (AgNORs). Less than 1 h was required for staining. The mean number of AgNORs in cell nuclei of malignant or recurrent brain tumors (16 cases) including meningeal sarcoma, recurrent meningioma, recurrent craniopharyngioma, anaplastic astrocytoma, glioblastoma multiforme and metastatic brain tumor was 3.18, and the number for benign brain tumors (21 cases) including meningioma, neurinoma, pituitary adenoma, benign astrocytoma, ependymoma, and adenoma of lachrymal gland was 1.85. The former value was significantly greater than the latter value (P less than 0.001). These results indicate that quantitative analysis of AgNORs in brain neoplastic cells, using squash preparations, is useful to differentiate malignant from benign tumors within 1 h. Thus, this method provides rapid and useful information about the proliferative potential of human brain tumors even during operation.

Adenoma↗
PubMed1991

Correlation between nucleolar organizer region score and bromodeoxyuridine labeling index in C6 glioma cell line.

Correlation between the mean number of nucleolar organizer region-associated argyrophilic proteins (AgNORs) per cell and BrdU labeling index (LI), the percentage of S-phase cells, was investigated in vitro using rat C6 glioma cells under several different conditions such as increased concentration of fetal calf serum (FCS) in a stepwise manner in medium. In addition, the effect of dibutyryladenosine cyclic monophosphate (d-cAMP) on the mean number of AgNORs and the BrdU LI was examined. C6 glioma cells cultured with no FCS showed 5.1% BrdU LI and 3.46 AgNOR score. BrdU LI and AgNOR score of the cells cultured with 1% FCS were 26.5% and 6.25, respectively. Those with 5% FCS were 44.7% and 8.41, with 10% FCS; 49.8% and 10.85, and with 20% FCS; 48.4% and 10.64. Treatment of d-cAMP with 10% FCS induced morphological differentiation and reduced BrdU LI (9.4%) and AgNORs score (4.90), compared with C6 cells cultured in medium containing 10% FCS without d-cAMP. Thus, the BrdU LI and AgNOR score of the C6 cells cultured under several different concentration of FCS were shown to be well linearly related (r = 0.97) and both values were decreased with morphological alteration of C6 glioma cells in the presence of 1 mM d-cAMP.

Animals↗
PubMed1991

Profiles of progesterone- and estradiol-like substances in the hemolymph of female Pandalus kessleri during an annual reproductive cycle.

The changes in GSI and HSI of Pandalus kessleri were monitored during an annual reproductive cycle. GSI reached a peak when ovaries were composed of yolky oocytes and decreased sharply during the spawning season. HSI followed a similar pattern. The changes in the concentrations of progesterone- and estradiol-17 beta-like substances in the hemolymph were also investigated. Progesterone levels increased at the onset of vitellogenesis and decreased during vitellogenesis. In contrast, estradiol concentrations rose during the peak of vitellogenesis and dropped after the release of mature eggs from the gonad.

Animals↗
PubMed1991

Thomsen-Friedenreich (T)-active glycoproteins, blood group N antigen precursor glycoproteins and N antigen precursor glycoproteins with T activity from ascitic fluids of liver cancer patients.

1. Five perchloric acid-soluble fractions (PASFs) obtained from ascitic fluids of three patients with primary hepatocellular carcinoma (HCC), a patient with liver metastatic carcinoma (LUC) from ureteral carcinoma and human normal serum (NS) were subjected to DEAE-cellulose column chromatography to separate seven glycoprotein fractions, respectively. 2. In this chromatography, two HCC-PASFs gave a Thomsen-Friedenreich (T)-active glycoprotein, respectively. 3. Other HCC-PASF gave a T-active glycoprotein, two blood group N antigen precursor glycoproteins and an N antigen precursor glycoprotein with T activity. 4. LUC-PASF gave two T-active glycoproteins and an N antigen precursor glycoprotein with T activity. 5. NS-PASF did not give these serologically active glycoproteins.

Amino Acids↗
PubMed1991

Proliferative assessment of GFAP-positive and GFAP-negative glioma cells by nucleolar organizer region staining.

The proliferative potential of two types of tumor cells that did or did not express glial fibrillary acidic protein (GFAP) in 19 cases of high-grade gliomas, including nine anaplastic astrocytomas (WHO criteria, grade 3) and 10 glioblastoma multiforme (grade 4), was investigated by a combined staining technique, one-step silver colloid method for nucleolar organizer region-associated argyrophilic protein (Ag-NOR) and immunocytochemistry for GFAP. The mean numbers of Ag-NORs in GFAP-positive cells and GFAP-negative cells of high-grade gliomas were 2.68 and 3.74, respectively. The value of GFAP-negative cells was significantly greater than that of GFAP-positive cells (p less than 0.01). Our results show that, by means of the immunocytochemistry for GFAP, tumor cells in human high-grade gliomas can be divided into two groups expressing GFAP or not, and that the mean number of Ag-NORs of GFAP-negative cells is more representative of the degree of histological malignancy than that of positive cells. It is considered that the proliferative assessment of GFAP-negative tumor cells in high-grade gliomas by combined staining of Ag-NOR silver staining and GFAP immunocytochemistry is useful for understanding the histological malignancy of high-grade gliomas.

Astrocytoma↗
PubMed1991

Genotoxicity of pyrene oxide and 1-nitropyrene oxides in hepatocyte primary culture/DNA repair test.

The genotoxicity of a pyrene oxide, 1-nitropyrene (NP) oxides and other related compounds was examined in the hepatocyte primary culture (HPC)/DNA repair test. Pyrene 4,5-oxide and both 1-NP-4,5-oxide and 1-NP-9,10-oxide elicited clearly positive responses of DNA repair. In this assay, 1-NP itself was weakly positive. However, other related chemicals such as pyrene, 1-nitro-3-hydroxypyrene, 1-nitro-6-hydroxypyrene, and 1-nitro-8-hydroxypyrene did not generate positive responses.

Animals↗
PubMed1991

Serum immunoglobulin M (IgM) during early development of masu salmon (Oncorhynchus masou).

1. The development of serum immunoglobulin M (IgM) was studied by measuring IgM concentration in early developmental stages of masu salmon (Oncorhynchus masou) using single radial immunodiffusion. 2. IgM concentration was measurable from 88 days after hatching (46.5 micrograms/ml) and was maintained at a relatively constant level (less than 100 micrograms/ml) until 235 days after hatching. 3. IgM concentration increased significantly to a level of 691 +/- 37 micrograms/ml (mean +/- SE, N = 59) during the period from 251 to 429 days after hatching. The highest level of serum IgM was maintained from 429 days to 489 days after hatching. 4. The increase of IgM concentration was not accompanied by parallel increases in total serum protein concentration.

Animals↗
PubMed1991

Kinetic and stereochemical characterization of hamster liver 3 alpha-hydroxysteroid dehydrogenase and 3 alpha(17 beta)-hydroxysteroid dehydrogenase.

The kinetic mechanism of NADP(+)-dependent 3 alpha-hydroxysteroid dehydrogenase and NAD(+)-dependent 3 alpha(17 beta)-hydroxysteroid dehydrogenase, purified from hamster liver cytosol, was studied in both directions. For 3 alpha-hydroxysteroid dehydrogenase, the initial velocity and product inhibition studies indicated that the enzyme reaction sequence is ordered with NADP+ binding to the free enzyme and NADPH being the last product to be released. Inhibition patterns by Cibacron blue and hexestrol, and binding studies of coenzyme and substrate are also consistent with an ordered bi bi mechanism. For 3 alpha(17 beta)-hydroxysteroid dehydrogenase, the steady-state kinetic measurements and substrate binding studies suggest a random binding pattern of the substrates and an ordered release of product; NADH is released last. However, the two enzymes transferred the pro-R-hydrogen atom of NAD(P)H to the carbonyl substrate.

17-Hydroxysteroid Dehydrogenases↗