Biomedical subjects
Publications and source records attributed to M Ohashi.
Tryptic digests of purified recombinant apoaequorin were analyzed, before and after reduction with DTT, by fast atom bombardment mass spectrometry. The results showed that apoaequorin contains a disulfide bond between Cys145 and Cys152 and that the reduction of this bond is involved in the regeneration of aequorin.
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E6 (or E7) genes of some genital and cutaneous human papillomaviruses (HPVs) were compared for their ability to transform cells of a rat fibroblastic line (3Y1) by using recombinant retroviruses. The E6 gene of genital cancer-associated HPV 16 or 18 was found to induce a characteristic morphological change, i.e., densely packed arrays of elongated cells forming swirl patterns. This change is the same as that induced by the E6 gene of cutaneous cancer-associated HPV 5, 8, or 47, which we described previously. The E6 gene of HPV 1 or 11, associated with benign tumor of cutaneous or genital tissue, respectively, induced no such change. The E6 genes of all these cutaneous and genital HPVs enhanced anchorage-independent growth of the target cells induced by E7 gene of HPV 16 or 18, and this enhancing activity of HPVs 16, 18, and 47 was stronger than that of HPVs 1 and 11. A distinct type of morphological transformation of 3Y1 cells, i.e., rounded miniaturized cells that were densely packed without forming any distinctive arrays, was found to be induced strongly by E7 genes of HPVs 16 and 18, weakly by E7 of HPVs 1 and 11, and not at all by E7 of HPV 47. The results suggest that the intensity of the morphological change induced by E6 genes, rather than E7 genes, is correlated to the risk of malignant conversion of the lesion with which the corresponding HPVs are associated.
Serum IgE levels of 22 patients with juvenile dermatomyositis (JDMS), 44 normal children, and 43 patients with adult dermatomyositis were compared. The geometric mean of serum IgE levels was significantly higher in the juvenile patients when compared with normal children (p < 0.01) and adult patients (p < 0.01). Of the 22 patients with JDMS, 11 (50%) had elevated serum IgE levels accompanied by atopic disease. Dermatomyositis was accompanied by atopic dermatitis (AD) in 9 (41%) of these 22 patients, a high prevalence when compared with reports among the general population. Following the appearance of muscular symptoms in JDMS patients with AD, the ratio of OKT4 to OKT8 cells rose due to a reduction in the percentage of OKT8-positive cells, along with further elevations in serum IgE levels and intractable cutaneous manifestations of dermatomyositis. All this may be a result of an interaction between the immuno-mechanism of this disease and that of AD. We suspect that, in general, children with impaired cell-mediated immunity, presenting with such symptoms as AD, may have a higher tendency for developing JDMS.
BACKGROUND: Expression of HLA-DP and HLA-DQ antigens on the microvasculature in normal skin is uncertain. OBJECTIVE AND METHODS: We investigated expression of HLA-DR, HLA-DP, and HLA-DQ antigens on the microvasculature in normal skin by light and electron microscopic immunohistochemistry. RESULTS: HLA-DP and HLA-DQ antigens were expressed on the microvasculature, but the intensity of positiveness was variable. By immunoelectron microscopy, HLA-DR, HLA-DP, and HLA-DQ antigens were expressed on the endothelial cells of the microvasculature, but not on the pericytes and the smooth muscle cells. The luminal surface of endothelial cells had a stronger expression of these antigens than the abluminal surface. CONCLUSION: HLA-DR, HLA-DP, and HLA-DQ antigens are expressed on endothelial cells of the microvasculature in normal skin.
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Dermatomyositis, recognized as an autoimmune disorder, occurs not only in adults but also in children. In this study, we evaluated lymphocyte subpopulations in the peripheral blood of 24 adult dermatomyositis and 14 juvenile dermatomyositis patients and in 17 healthy adults and 9 healthy children by flow cytometry using monoclonal antibodies. When compared with healthy adults and adult patients with inactive dermatomyositis, the adult patients with active disease had significantly lower percentages of CD3+ and CD8+ cells and a significantly higher percentage of CD20+ cells. In contrast, juvenile dermatomyositis patients had lymphocyte subpopulations not significantly different from those of healthy children; the activity/inactivity of disease did not make any difference. These results support our hypothesis that adult and juvenile dermatomyositis may be diseases of entirely different scope.
Hypoxic effects on glutamate uptake and ATP content in glial cells were investigated by using cultured C6 glioma cells. Mild regressive changes were found depending on the duration of the hypoxic insult, but necrosis or detachment of the cells from the substratum was rarely observed. Glutamate uptake was relatively well preserved after a short hypoxic insult, while a marked decrease in glutamate uptake was observed after hypoxia of long duration. The uptake of sucrose was reduced in a similar pattern to glutamate uptake. Hypoxic insult resulted in a significant reduction of the ATP content in glial cells. Therefore, the decrease in glutamate uptake by glial cells under hypoxia is likely to be due to ATP dependency, and not to the failure of a specific glutamate uptake system, but the failure of a general uptake of the glial cells owing to the energy-dependent membrane dysfunction by ATP depletion. These findings suggest that there are phased changes of astrocytic functions in a hypoxic condition, a preservative phase in the initial stages and then a dysfunctional phase in the later stages of hypoxia.
3,7-Dimethyl-2,4,6,8,10-dodecapentaenal was synthesized for reconstitution of the retinochrome analog. Its opsin shift was 1000 cm-1 smaller than that of native retinochrome, whose chromophore contains the same number of double bonds. The conformational change from 6-s-trans to 6-s-cis, as figured in a retinal molecule, plays an important role in the formation of the retinochrome analog, based on the estimation of opsin shifts for retinal analogs locked in the 6-s conformation. Thus the conformation of the 6-7 single bond in the native retinochrome was suggested to be 6-s-cis. Analysis of the circular dichroic spectra of retinochrome analogs revealed that the 6-s conformation is independent of the appearance of the beta-band. The stereoselectivity in the photoisomerization of the retinal analogs by a retinochrome template depends on the hydrophobic binding in the region of the beta-ionone ring.
In vitro and in vivo antifungal activities of D0870 were evaluated in comparison with those of fluconazole. D0870, which is the R-enantiomer of ICI195,739, was found to be the mycologically active enantiomer by comparing the activities of D0870 with those of M16355 (S-enantiomer of ICI195,739). D0870 showed a broad spectrum of antifungal activity and MICs and minimum antibiotic concentrations 4- to 2,000-fold lower in synthetic amino acid medium (fungal) agar than those of fluconazole for various fungi. Although MICs of D0870 were affected by variation of the test conditions, such as type of medium, inoculum size of fungi, supplementation with fetal bovine serum, and pH of medium, they were consistently much lower than those of fluconazole under any condition. In vivo activities of D0870 in the systemic infection models with Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus in normal mice and in the mice immunosuppressed with cyclophosphamide or cortisone acetate were 2- to 7-fold and 3- to 89-fold greater than those of fluconazole, respectively. In these infection models in immunosuppressed mice, the therapeutic efficacy of D0870 was almost equivalent to that in normal mice, whereas the efficacy of fluconazole was 2- to 50-fold lower than that in normal mice.
The effect of ibudilast on anaphylactic bronchoconstriction was studied in guinea pigs sensitized actively with ovalbumin (OA). Animals were treated with indomethacin, tripelennamine and propranolol prior to the antigen challenge. Anaphylactic bronchoconstriction was prevented by ibudilast (1-4 mg/kg i.v. and 5-20 mg/kg p.o.) dose-dependently. FPL55712 and phenidone were also effective. Even when administered at the maximum development of bronchoconstriction, ibudilast (0.5 and 2 mg/kg i.v.) and FPL 55712 caused significant reduction of the increased airway tone, while phenidone did not. Ibudilast (1-4 mg/kg i.v.) and FPL55712 inhibited leukotriene D4-induced airway responses in nonsensitized guinea pigs pretreated with indomethacin and propranolol. Ibudilast (1.6 and 4 mg/kg i.v.) inhibited platelet-activating-factor (PAF)-induced airway responses in nonsensitized guinea pigs pretreated with indomethacin and propranolol, however, FPL 55712 inhibited PAF-induced airway responses only at a high dose such as 10 mg/kg i.v. Ibudilast (4 mg/kg i.v.) did not inhibit acetylcholine-induced airway response. Ibudilast showed inhibition of the release of slow-reacting substance of anaphylaxis (SRS-A) from guinea pig chopped lung sensitized with OA, which was significantly diminished by indomethacin. The drug little affected the activity of phospholipase A2 and 5-lipoxygenase in guinea pig polymorphonuclear leukocytes. These results indicate that ibudilast inhibits anaphylactic bronchoconstriction which is considered to be largely mediated by endogenously released SRS-A. The inhibitory effect of ibudilast on anaphylactic bronchoconstriction in the presence of indomethacin is considered to be exerted through its antagonism to SRS-A.
We report a 31-year-old woman in her 4th month of pregnancy who presented with a sudden decrease in her right visual acuity. The right ocular fundus showed marked retinal edema and a cherry-red spot. A cranial computerized tomographic scan showed cerebral infarction. Cerebral angiography disclosed moyamoya disease. Ischemia of the ophthalmic artery due to constriction of the origin of the internal carotid artery and hypercoagulability due to pregnancy have presumably caused visual impairment in this patient.
Following oral dosing of [14C]clentiazem to rats the metabolites in urine and bile were separated and their chemical structures were investigated by HPLC and GC-MS analyses. Fifteen basic, 6 acidic, 2 neutral and 4 conjugated metabolites were found in urine and/or bile. Eight basic metabolites (MB1-8) were identified as the synthetic compounds; deacetyl clentiazem (MB1), N-monodemethyl clentiazem (MB2), deacetyl-N-monodemethyl clentiazem (MB3), deacetyl-O-demethyl clentiazem (MB4), N-monodemethyl-O-demethyl clentiazem (MB5), deacetyl-N-monodemethyl-O-demethyl clentiazem (MB6), O-demethyl clentiazem (MB7) and N-didemethyl clentiazem (MB8). The chemical structures of seven basic metabolites (MB9-15) were assigned as follows, deacetyl-N-didemethyl clentiazem (MB9), O-demethyl-N-didemethyl clentiazem (MB10), deacetyl-O-demethyl-N-didemethyl clentiazem (MB11), N-monodemethyl-2-hydroxy-methoxyphenyl clentiazem (MB12), deacetyl-2-hydroxy-methoxyphenyl clentiazem (MB13), deacetyl-N-monodemethyl-2-hydroxy-methoxyphenyl clentiazem (MB14) and deacetyl-N-didemethyl-2-hydroxy-methoxyphenyl clentiazem (MB15). Four acidic metabolites were identified as the synthetic compounds: (+)-(2S,3S)-3-(acetyloxy)-8-chloro-3,4-dihydro-2-(4-methoxyphenyl) -4-oxo-1, 5-benzothiazepin-5(2H)-acetic acid (MA1), deacetyl-MA1 (MA2), O-demethyl-MA1 (MA3) and deacetyl-O-demethyl-MA1 (MA4); and the two remaining acidic metabolites, MA5 and MA6, were presumed to be hydroxylated MA3 and MA4, respectively. Two neutral metabolites were identified as the synthetic compounds; (+)-(2S,3S)-3-(acetyloxy)-8-chloro-3,4-dihydro-2-(4-methoxyphenyl) -4-oxo-1, 5-benzothiazepin-5(2H)-acetonitrile (MN1) and deacetyl MN1 (MN2). Other two metabolites conjugated with glucuronic acid were found in bile and the structures were presumed to be 8-chloro-2,3-dihydro-3-hydroxy-5-(2-hydroxyethyl)-2-(4-hydroxyphenyl)-1, 5-benzothiazepin-4(5H)-one (MN3) and 2-methoxyphenyl MN3 (MN4). The glucuronide or sulfate of MA4 was also detected. These metabolites were formed by a number of pathways including deacetylation, deamination, N-demethylation, O-demethylation, aromatic hydroxylation and conjugation.
The plasma concentrations and time courses of radioactivity and unchanged drug, the excretion of radioactivity into urine and feces, and the proportion of metabolites in plasma and urine were studied after oral administration of [14C]clentiazem to male and female rats and dogs. Apparent sex-related differences were found in the disposition and metabolism of clentiazem in rats. The plasma levels of radioactivity and acidic metabolites were higher in males than in females. The plasma levels of unchanged drug, on the other hand, were about the same in both sexes. Higher conversion of clentiazem to its acidic metabolites in the liver of male rats and higher excretion of the acidic metabolites in the urine of female rats, presumably due to sex-related differences in cytochrome P-450 and renal clearance, respectively, seem to explain these differences in the disposition of clentiazem in male and female rats. No suggestion of a similar sex difference was found in dogs. The plasma concentrations and time courses of radioactivity and unchanged drug in male dogs were similar to those in female dogs, and the excretion of radioactivity in both sexes was also similar. The main plasma metabolite in male and female dogs was O-demethyl clentiazem (MB7). A species difference between rat and dog was suggested, since the major metabolic pathways were different and no sex difference was found in dogs.
The current availability of 3 dimensional (3-D) imaging from Computed Tomography (CT) has yielded new anatomical information and pre-and postoperative evaluations. However, little discussion as to the 3-D structural image of the temporal bone has been reported because conventional CT does provide sufficient data to produce such images. The Helical scanning CT gathers continuous and multiple slice image data since it consists of an X-ray tube that continuously rotates around the patient while the patient moves continuously into the CT scanner. Thus, application of the Helical scanning CT has made it possible to reconstruct 3-D images of the minute and complicated structure of the temporal bone. We evaluated 3-D images from 9 typical cases, examined from February to October 1992. As a result, we found that the 3-D images reconstructed with this system are useful for evaluation of the postoperative state of tympanoplasty, the diagnosis of anomalies of the bony labyrinth, and examining the extent of bone destruction induced by trauma, cholesteatoma, etc.
Plasma myeloperoxidase levels in patients with cirrhosis were compared with those in patients with chronic hepatitis and healthy controls by means of a specific radioimmunoassay for myeloperoxidase. The mean concentration of plasma myeloperoxidase in cirrhotic patients (309.1 +/- 17.2 ng/ml, n = 41) was markedly higher than that in chronic hepatitis patients (222.6 +/- 17.2 ng/ml, n = 21) (p < 0.01) and normal controls (219.5 +/- 5.7 ng/ml, n = 50) (p < 0.01). Plasma myeloperoxidase showed good negative correlations with neutrocyte count (r = -0.32, p < 0.01), thrombocyte count (r = -0.40, p < 0.01), red blood cell count (r = -0.32, p < 0.01), serum albumin (r = -0.35, p < 0.01), and cholinesterase (r = -0.32, p < 0.02) and positive correlations with serum alkaline phosphatase (r = 0.49; p < 0.01) and lactate dehydrogenase (r = 0.31, p < 0.01) in patients with cirrhosis or chronic hepatitis. Among lactate dehydrogenase isozymes, a good positive correlation was seen between plasma myeloperoxidase and lactate dehydrogenase-2 (r = 0.40, p < 0.01) and lactate dehydrogenase-1 (r = 0.03, p < 0.02). Plasma myeloperoxidase was significantly higher in the cirrhotic and chronic hepatitis patients with splenomegaly (341.1 +/- 19.4 ng/ml, n = 31) than in those without splenomegaly (217.4 +/- 12.2 ng/ml, n = 29) (p < 0.01). We also examined the difference between plasma levels of myeloperoxidase in the portal and peripheral blood.(ABSTRACT TRUNCATED AT 250 WORDS)
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