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Biomedical subjects

S Imamura

Publications and source records attributed to S Imamura.

At least 397 records · Page 22Linked to original sources

Ultrastructural lupus band test in the skin of MRL mice.

The ultrastructural localization of immunoglobulin deposits in the dermoepidermal junction of MRL/l mice was examined using immunoperoxidase staining. All specimens that showed positive findings at the basement membrane zone of the skin on light microscopy had reaction products at the sub-basal laminar area when observed by electron microscopy. In the skin that had no distinct eruptions or which was distant from the lesions, the reaction products were distributed mostly just beneath the basal lamina in fine to course granular deposits. In the lesional skin, they formed a rather uniformly granular pattern among the irregularly arranged collagen fibrils and increased fine fibrillar amorphous material under the highly infolded basal lamina. Some of the reaction products were located just on the collagen fibrils and some appeared to be related to the free basal lamina. From the perspective of immunoelectron microscopy, the skin eruptions of MRL/l mice may serve as a good dermatological model of human systemic lupus erythematosus.

Animals↗

Regulation of the activity of histamine-N-methyltransferase from guinea pig skin by biogenic amines.

Histamine-N-methyltransferase, a major histamine-degrading enzyme in the skin, was purified from guinea pig skin about 150-fold. The enzymological characteristics including pH optimum, Km values for substrates, and molecular weight were almost consistent with those reported in the brain. Regulatory mechanism of the enzyme activity by biogenic amines was investigated using the purified specimen. Serotonin, tryptamine, and 5-methoxytryptamine intensely inhibited the activity while tryptophan, melatonin, N-acetylserotonin, tryptophol, and 5-hydroxyindole acetic acid had no significant effects. Dopamine, tyramine, 3-methyltyramine, and phenylethylamine also inhibited the activity while no particular effects were obtained by adrenaline, noradrenaline, tyrosine, and DOPA. Spermidine and cadaverine caused significant but weaker inhibition. These amines acted competitively with respect to histamine, although varying manners were observed with respect to S-adenosyl-L-methionine. From these results, it was concluded that the enzyme activity was inhibited by such compounds in which a certain chemical structure, CH2-CH2-NH2 group neighboring the hydrophobic group, was contained. A possible mechanism of inhibition by the amines is postulated, and possible roles of such compounds in the inflammation by impairing the histamine metabolism is discussed.

Animals↗

Histamine metabolism in the Arthus reaction.

Histamine metabolism, i.e., concentration of histamine and activities of histamine-degrading enzymes, histamine-N-methyltransferase (HMT), and diamine oxidase (DAO), were examined in the Arthus reaction induced in guinea pig skin. The specific activity of HMT was 44.12 +/- 3.80 pmole/min/mg protein and was about 15 times greater than that of DAO in control specimens. However, HMT activity decreased time dependently to 35% of the control at 3 hr and to 10% 48 hr after the initiation of the reaction. DAO activity increased to 150% till 1 hr followed by a linear decrease to 35% at 6 hr and to 10% at 48 hr. Histamine concentration showed a prominent linear decrease to 15% of the control at 2 hr followed by an increase to about 85% at 6 hr. This biphasic change seemed to be well explained by the dynamic changes in the activities of histamine-degrading enzymes. Such decrease in enzyme activities were not observed in other experimentally induced inflammations including dinitrochlorobenzene allergic and croton oil dermatitis. The addition of tissue extract from the Arthus reaction sites resulted in about 30% inhibition in both of two enzyme activities, suggesting the presence of some inhibitory factor(s) in the reaction sites.

Amine Oxidase (Copper-Containing)↗

Immunoelectron microscopic observations in a case of linear IgA bullous dermatosis of childhood.

A 16-month-old boy exhibited vesicobullous skin lesions on the lower part of his abdomen, in his genital region, and on the buttocks and extremities. The eruptions presented small, tense bullae with or without erythematous changes of the surrounding skin, some of which clustered around the resolving lesions. Histologic examination of the eruptions showed subepidermal, ultrastructurally suprabasal laminar blister formation with infiltration of the polymorphonuclear cells and large mononuclear cells in the blister cavity. Immunoelectron microscopy revealed IgA deposits at the basilar surface of the basal keratinocytes of the lesional skin, as well as the presence of circulating IgA-class antibodies reacting to the basilar surface of the hemidesmosomes. The eruptions responded well to a combination therapy of small doses of a corticosteroid agent and a sulfonamide. There were neither clinical nor laboratory findings suggesting dermatitis herpetiformis. This case, diagnosed as linear IgA bullous dermatosis of childhood by immunofluorescence microscopy, ultrastructurally had a pathogenic site close to that observed in bullous pemphigoid.

Autoantibodies↗

Mechanisms of contact photosensitivity in mice. VI. Oxygen intermediates are involved in contact photosensitization but not in ordinary contact sensitization.

To investigate the possible participation of oxygen intermediates (OIs) in the contact photosensitization process, mice were treated with long-acting liposomal-superoxide dismutase (L-SOD) before photosensitization. Photosensitization to 3,3',4',5-tetrachlorosalicylanilide (TCSA) was significantly suppressed by the pretreatment of mice with L-SOD. This suppression was not mediated by suppressor cells or due to an unresponsive state produced by the use of L-SOD. Rather, the suppression appeared to be due to the failure of production of photoallergen. L-SOD treatment induced the suppression of contact photosensitivity to TCSA but not ordinary contact sensitivity to TCSA or dinitrofluorobenzene, suggesting that the production of photoallergen is more critically dependent on the presence of OIs than that of ordinary contact allergen. The results provide evidence that OIs are produced by light absorption in the presence of oxygen and react with the biologic substrate to form photoallergens.

Animals↗

Biochemical demonstration and immunohistochemical localization of calpain in human skin.

The biochemical properties and immunohistochemical localization of calpain, a Ca++-dependent, intracellular, nonlysosomal cysteine proteinase was examined in human skin. Human epidermal calpain I was fractionated on a DEAE-cellulose column and was found to be half-maximally activated at 3.5 microM free Ca++ and fully activated at 10 microM Ca++ as measured by casein hydrolysis. Immunoelectrophoretic blotting of calpain revealed only a single band of Mr 83,000, when the blot was made with affinity-purified anti-calpain I heavy subunit IgG. Immunohistochemical staining of normal human epidermis showed that calpain I was localized in the cytoplasm of keratinocytes in the mid to upper epidermis but not in the basal cells. In untreated psoriatic epidermis, the deposition of this proteinase was visualized weakly just beneath the stratum corneum. However, remarkable staining was observed after photochemotherapy of topical psoralen plus long-wave UV irradiation. Whether the photochemotherapy induced a quantitative increase in the amount of calpain or merely made calpain more stainable by altering the membrane remains unknown.

Antibody Specificity↗

Effect of antibiotics on the generation of reactive oxygen species.

The relative antioxidant efficacy, in vitro, of several antibiotics was examined by studying their effects on the generation of reactive oxygen species (ROS) using zymosan-stimulated polymorphonuclear leukocytes (PMNL) and the cell-free, xanthine-xanthine oxidase system. The species investigated are superoxide radical anion (O2-.), hydrogen peroxide (H2O2), and hydroxyl radical (OH.). Three tetracyclines (tetracycline HCl, oxytetracycline HCl, and minocycline HCl), erythromycin, cephalexin, penicillin G, chloramphenicol, and streptomycin were used as test drugs. At concentrations comparable to therapeutic blood levels, tetracycline HCl, oxytetracycline HCl, minocycline HCl, and erythromycin inhibited some of the ROS production by PMNL. In the xanthine-xanthine oxidase system, only minocycline HCl suppressed the H2O2 level. Cephalexin, penicillin G, chloramphenicol, and streptomycin did not affect any of the ROS examined at the concentrations tested. The capacity of some of these agents to inhibit ROS generation by PMNL may account, in part, for their efficacy in inflammatory skin diseases such as acne vulgaris. The antioxidant effect of these antibiotics does not stem from their capability to scavenge ROS, but originates rather from their effect on PMNL cell function directly with resultant anti-inflammatory effects on the inflammatory processes.

Antioxidants↗

UVB/PUVA-induced suppression of human natural killer activity is reduced by superoxide dismutase and/or interleukin 2 in vitro.

We have evaluated the effects of ultraviolet irradiation or PUVA treatment [8-methoxypsoralen (8-MOP) plus long-wave ultraviolet (UVA) irradiation] on natural killer (NK) activity of human peripheral blood mononuclear cells (PBMC). In vitro exposure of PBMC to UVB (280-320 nm, 1-30 mJ/cm2) or PUVA [8-MOP, 0.1 microgram/ml; UVA (320-400 nm), 0.5-5 J/cm2] resulted in a dose-dependent suppression of NK activity, whereas UVA (0.5-5 J/cm2) or 8-MOP (0.1 microgram/ml) treatment alone did not have the inhibitory effects. This suppressive effect of UVB/PUVA irradiation was successfully reduced in the presence of superoxide dismutase (SOD) (100 or 1000 U/ml) during the irradiation. The addition of interleukin 2 (IL-2) (100 U/ml) markedly enhanced the NK activity of both irradiated and nonirradiated PBMC. Combination treatment with both SOD and IL-2 to UVB/PUVA-irradiated PBMC resulted in a more remarkable improvement of NK suppression than with either SOD or IL-2 treatment alone.

Adult↗

A monoclonal antibody specifically reactive to human Langerhans cells.

We prepared a mouse monoclonal antibody that reacts specifically to human Langerhans cells (LC). The protein recognized by this antibody was mainly in the membranes of Birbeck granules and related structures. Using this antibody, we could identify LC in various tissues; these cells were in the skin, stratified squamous mucosal epithelia, lymph nodes, and the thymus. The antibody did not react with monocytes, tissue macrophages, lymphoid dendritic cells, follicular dendritic cells, or interdigitating cells. The antigen purified with this antibody was a heterogeneously glycosylated protein of Mr approximately 40,000 without interchain disulfide bonds. This antibody may be useful for identifying LC in various human tissues with or without abnormalities, and for studying the origin and fate of Birbeck granules of LC.

Antibodies, Monoclonal↗

Discrepancy between the localization of in vivo bound immunoglobulins in the skin and in vitro binding sites of circulating anti-BMZ antibodies in bullous pemphigoid: immunoelectron microscopic studies.

The immunoelectron microscopic reaction products showing in vivo bound immunoglobulins or complement in the basement membrane zone (BMZ) of the lesional skin of 12 patients with bullous pemphigoid (BP) were homogeneously distributed in the lamina lucida in 3 cases, just beneath the basilar surface of the basal cells in 5 cases, and were associated with the basal lamina in 4 cases. No reaction products could be found beneath the melanocytes in any of the first 2 groups; however, positive reaction products were found on the basal lamina beneath some melanocytes, and were associated with the detached basal lamina in the dermis in the latter 4 cases. In vitro binding sites of circulating anti-BMZ antibodies in the sera from 7 patients with BP indicated that the antibodies reacted with the basilar surface of the hemidesmosomes, with a weak reaction on the basal lamina in 5 cases and with no reaction in 2 cases. No positive findings were obtained beneath the melanocytes or on the basal lamina under the melanocytes. The discrepancy between the antigenic sites and the localization of immune deposits in BP is assumed to be due to the renewal of the hemidesmosomes and constant clearance of immune deposits in vivo. The in vivo bound immunoglobulins and complement seen in the BP skin are the result of their accumulation in the lamina lucida or in association with the basal lamina.

Autoantibodies↗

Mechanisms of contact photosensitivity in mice. VII. Diminished elicitation by reserpine and defective expression in mast cell-deficient mice.

The involvement of mast cells in the elicitation of contact photosensitivity (CPS) was examined in mice treated with pharmacologic agents and in genetically mast cell-deficient W/Wv mice. Contact photosensitivity responses were diminished by pretreatment with reserpine, which may have been due to depletion of vasoactive amines in mast cells. This inhibition was almost reversed by the monoamine oxidase inhibitor, pargyline-HCl, which prevented reserpine-induced depletion of vasoactive amines such as serotonin. Defective CPS was also found in W/Wv mice, but not in their congenic littermates (+/+). Abnormal CPS in mast cell-deficient mice was due to a defect in the elicitation of CPS rather than a defect in the induction of effector T cells, since the ability to elicit CPS could be transferred to normal +/+ mice by photosensitized cells from mast cell-deficient mice. These findings favor the view that mast cells are involved in the elicitation of CPS.

Animals↗

Anti-oxidant action of metronidazole: a possible mechanism of action in rosacea.

To elucidate the mechanism of action of metronidazole in the treatment of rosacea, the effect of metronidazole on the generation of reactive oxygen species was examined both in neutrophil and xanthine-xanthine oxidase systems. Metronidazole had anti-oxidant action which was not exerted by the scavenging of reactive oxygen species, but by having an effect on neutrophil cell functions. Beneficial effects of metronidazole in the treatment of papulopustular rosacea can in part be attributable to this anti-inflammatory effect.

Cells, Cultured↗

Langerhans cells in the dermal infiltrate of hyperkeratosis lenticularis perstans.

Typical papules obtained from a patient with hyperkeratosis lenticularis perstans (HLP) were examined by light and electron microscopy. Dense cellular infiltrate, which consisted mainly of mononuclear cells, was observed in the dermis underlying the lesion. Electron microscopic studies revealed that these cells were mostly lymphocytic cells. In addition, several Langerhans cells were found in the infiltrate, some of which were apposed to the lymphocytic cells. These findings suggested that immunologic reactions via Langerhans cells might occur in HLP and further raises a possibility that Langerhans cells might be involved in the pathogenesis of HLP.

Aged↗

A case of xeroderma pigmentosum with clinical appearance of dyschromatosis symmetrica hereditaria.

A 9-year-old boy complained of increased freckling on the extremities since very early infancy. Examination showed mottled pigmentation with areas of depigmentation on the backs of the hands and tops of the feet, and less strikingly on the arms and legs. Scattered, small, pigmented freckles on the face were also noticed. The condition was clinically diagnosed as dyschromatosis symmetrica hereditaria (DSH) at first. Unscheduled DNA synthesis was reduced to 66% of the normal value, however, and an ultraviolet sensitivity test by colony formation on fibroblasts revealed moderate sensitivity. Therefore this case was finally diagnosed as xeroderma pigmentosum. It is necessary to study cellular repair capacity to make a precise diagnosis when the distinction is so difficult.

Child↗