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Biomedical subjects

S Imamura

Publications and source records attributed to S Imamura.

At least 361 records · Page 20Linked to original sources

Pathogenesis of lupus dermatoses in autoimmune mice. X. Evaluation of histamine-N-methyltransferase activity in the skin of autoimmune.

We measured histamine concentration and its metabolizing enzymes in the skin of MRL/Mp-lpr/lpr (MRL/l) and BXSB mice to clarify the contribution of histamine metabolism to the mechanisms of the development of lupus dermatoses. The concentration of histamine seemed to differ with the mouse strain. The activity of histamine-N-methyltransferase (HMT), one of two major metabolizing enzymes, was significantly lower in the tail and back skin of MRL/l mice at the age of 5 months than in the control MRL/Mp-+/+(MRL/n) mice, although there were no characteristic differences among several mouse strains of 1 mo of age. In the back skin of MRL/l mice, an age-dependent decrease of HMT activity was observed along with a corresponding decrease in histamine concentration, whereas an age-dependent increase of both HMT activity and histamine concentration was demonstrated in BXSB mice and other control mouse strains. Autoimmune-prone male BXSB mice and non-autoimmune female BXSB mice at 5 mo of age showed similar HMT activity. Corticosteroid treatment restored HMT activity in the skin of MRL/l mice but not in MRL/n mice. In addition, the change in HMT activity in MRL/l mice treated with corticosteroid appeared earlier than changes in clinicopathological examinations including skin eruptions, dermatopathology and proteinuria. Diamine oxidase (DAO) activity, another major metabolizing enzyme, was not detected in the skin of any autoimmune or control mouse strains. These findings suggest that the low activity of HMT in the skin of MRL/l mice plays a significant pathological role in the development of spontaneous lupus-like eruption. In other mouse strains, it is assumed that HMT activity is regulated by genetic factors.

Abdomen↗

Immunoscintigraphy and pharmacokinetics of indium-111-labeled ZME-018 monoclonal antibody in patients with malignant melanoma.

Immunoscintigraphic and pharmacokinetic characteristics of 111In-labeled ZME-018 monoclonal antibody were examined in 8 patients with malignant melanoma. Each patient received a single intravenous infusion of 20 mg of ZME-018, coupled to 3 mCi of 111In without any acute toxicity. Scintigrams were taken 1, 3, and 6 days after the administration, and blood and urine samples were also taken frequently. Rapid clearance of some radioactivity was seen in early urine samples in the form of 111In DTPA, but after 1 day, urinary excretion of radioactivity was slow and steady, with an average of 2.5% of the injected dose excreted per day. The scans demonstrated that there was blood retention of radioactivity in the heart and great vessels 1 day after infusion and considerable clearance from the blood pool occurred by 3 days. However, 111In was deposited in the liver, spleen and bone for up to 6 days. The optimal time for imaging appeared to be at 3 days. Nineteen out of 26 known lesions or 6 out of 8 patients were positive. There were 21 lesions detected that were not suspected during the work-up the patient. Five patients developed human anti-mouse antibody in the serum by 3 weeks. These results suggest that immunoscintigraphy with 111In-labeled ZME-018 antibody is safe and useful for the detection of metastatic lesions in a selected group of patients with malignant melanoma.

Adult↗

A case of a lymphoproliferative disorder: usefulness of DNA analysis in diagnosis.

We describe a patient in whom a suppressor/cytotoxic T cell lymphoma was suspected on the basis of histology and immunohistochemistry. DNA analysis of specimens from three different lesions, using restriction enzymes Eco RI and Bam HI, showed the same rearrangement of the T cell receptor beta-chain genes. We consider this technique to be of value in the early diagnosis of malignant lymphoma when differential diagnosis from other lymphoproliferative disorders is difficult with conventional methods.

Aged↗

Increased serum levels of squamous cell carcinoma-related antigen in pemphigus.

Serum levels of squamous cell carcinoma-related antigen (SCC-RAG) were measured in five cases of pemphigus, five cases of bullous pemphigoid and 18 cases of benign and malignant dermatoses other than SCC. The SCC-RAG titres were significantly raised in four of five patients with pemphigus, while they remained within the normal range in the other dermatoses except in one case. In three pemphigus cases in whom serial measurements were made, SCC-RAG levels seemed to be related to disease activity. The SCC-RAG levels in blister fluids were much higher than those in serum, suggesting that the skin is a major source of serum SCC-RAG. These results show that SCC-RAG is increased not only in SCC, but also in some cases of pemphigus, and suggest that pemphigus antibodies may cause the production or release of SCC-RAG.

Antigens, Neoplasm↗

Contact dermatitis from a compound mixture of sugar and povidone-iodine.

2 patients with leg ulcers got worse after the application of a compound mixture of sugar and povidone-iodine (sugar/PI compound). Because they had been suffering from stasis dermatitis, symptoms of contact dermatitis were ambiguous. Patch tests showed positive reactions to 10% povidone-iodine in water and 5% potassium iodide in water, with no response to sugar. They were also tested with sugar/PI compound, containing 3% povidone-iodine, resulting in another positive reaction. They improved after the application of sugar/PI compound was discontinued. Contact dermatitis from topical agents should be considered as more probable than angry back syndrome in cases of leg ulcer.

Aged↗

Peripheral neuropathy in four cases of group A xeroderma pigmentosum.

We describe the clinical features and findings of biopsied sural nerves of 4 cases of xeroderma pigmentosum. Nine genetic forms of xeroderma pigmentosum have been reported by complementation studies. These four cases were diagnosed as Group A xeroderma pigmentosum by complementation studies using cultured skin fibroblasts. All cases had delayed mental and motor development in areas such as head control over 4 months of age and walking without support over 18 months of age. Three cases had the gradual onset of a gait disturbance between 6 and 9 years of age. Motor conduction velocity and sensory conduction velocity of the ulnar nerve were slightly delayed. The sural nerve of the slightly impaired patient showed a normal density of myelinated fibers, but a selective reduction of the large myelinated fibers with zebra-body-like structures in Schwann cell cytoplasm. The population density of all nerve fibers was severely diminished in the severely impaired cases. Ultrastructural observation disclosed many denervated Schwann cells and pockets of collagen isolated by loops of denervated Schwann cell cytoplasm. These findings suggest that the degenerative process in peripheral nerves of xeroderma pigmentosum is axonal. Peripheral neuropathy in Group A xeroderma pigmentosum resembles that of patients with ataxia telangiectasia who are known to have a defect in the repair mechanisms of their DNA in cultured skin fibroblasts.

Adolescent↗

Adenylate and guanylate cyclase activities in isolated guinea pig epidermal cells at various stages of differentiation.

The enzymatic properties of adenylate and guanylate cyclases were examined in sonicates of trypsinized guinea pig epidermal cells as enzyme source. Adenylate cyclase was found to be membrane-bound, while guanylate cyclase activity was detected in both membrane and cytosolic fractions. The maximal activities of the enzymes were obtained in the presence of Mn++ in the pH range 7.8-8.8. The apparent Km values of adenylate cyclase for Mn++- and Mg++-ATP were 20.5 and 38.6 microM, respectively, while the value of guanylate cyclase for Mn++-GTP was 500 microM. Examinations of cells separated by velocity sedimentation at unit gravity revealed that the basal activity of adenylate and guanylate cyclases was maximal in the germinative cells, falling gradually to the low level as cells differentiated. We assume that in the epidermis, the control and coordination of proliferation require higher concentrations of adenylate and guanylate cyclases as compared with events occurring during terminal differentiation.

Adenylyl Cyclases↗

Epidermolytic hereditary palmoplantar keratoderma. Histologic, ultrastructural, protein-chemical, and DNA analyses in two patients.

Two cases of epidermolytic hereditary palmoplantar keratoderma were studied by histologic, ultrastructural, protein-chemical, and genetic methods. Histologically, epidermolytic hyperkeratosis was seen at the spinous and granular layers. Electron microscopy showed the aggregation of tonofibrils and an early appearance of keratohyaline granules as well as vacuolar formation in the epidermal cells. Some of these morphologic abnormalities were detected even in the basal cells. The decrease of 67-kilodalton (kd) keratin and the appearance of 48-kd keratin were noted by using sodium dodecyl sulfate polyacrylamide gel electrophoresis. Genetic analysis of the keratin gene family using 67-kd keratin complementary DNA by Southern blot analysis revealed the conserved gene organization of the 67-kd keratin gene. These findings suggest that undetermined regulatory abnormalities of keratinization, but not the gene structure itself, may be causative factors of this rare disease.

Adult↗

Immunological status of nude mice engrafted with allogeneic or syngeneic thymuses.

Restoration of T-cell functions and changes in autoantibody production were studied in BALB/c nu/nu (nude) mice engrafted with syngeneic (BALB/c) or allogeneic (C57BL/6J) thymuses across major histocompatability barriers. T-cell functions, including mitogen responses and antibody production to sheep red blood cells (SRBC), were restored in nude mice engrafted with either allogeneic or syngeneic thymuses. Alloreactivity was evaluated by analysis of the pattern of skin allograft rejection, generation of alloreactive cytotoxic T-lymphocytes (CTLs), or quantitation of mixed-lymphocyte reaction (MLR). BABL/c nude mice engrafted with thymuses from newborn C57BL/6J mice accepted the skin from either thymus donor-type mice or from host-type mice. By contrast, such thymic chimeras rejected skin grafts from a third-party donor. CTLs from nude mice engrafted with C57BL/6J thymuses were cytotoxic to target cells of the third party but not to target cells of the host-type or of the thymus-type. In the MLR assay, spleen cells of nude mice engrafted with C57BL/6J thymuses responded vigorously to third party cells and only slightly to cells of the thymus-type. Low levels of serum IgG and high titers of IgM antibodies to nuclear antigens (but not dsDNA) or skin basal cells were also found in nude mice. Antibodies to both nuclear antigens and skin basal cells disappeared after transplantation of syngeneic thymuses, but not after transplantation of allogeneic thymuses. By contrast, serum IgG levels were restored to normal in nude mice engrafted with either syngeneic or allogeneic thymuses. These results suggest that either HLA-matched or HLA-mismatched thymus grafts may become a viable treatment for certain patients with T cell deficiencies associated with deficient development or maintenance of thymic structure and/or function.

Animals↗

Platelet factor XIII is activated by calpain.

The action of calpain (EC 3.4.22.17; Ca2+-dependent cysteine proteinase) on platelet factor XIII has been studied. Calpain I activated platelet factor XIII up to 76% of the maximum level observed with thrombin. Activation was accompanied by the limited proteolysis of the a subunit of platelet factor XIII to produce a 76 kDa fragment which was comparable to the proteolytic product by thrombin. Activation of platelet factor XIII by calpain was inhibited by EDTA, leupeptin, and endogenous calpain-specific inhibitor calpastatin. These findings suggest that calpain is responsible for the intracellular activation of platelet factor XIII.

Blood Platelets↗

Detection of desialylated forms of human chorionic gonadotropin.

Urinary forms of human chorionic gonadotropin (hCG) with oligosaccharides deficient in sialic acid content (ashCG) have been reported to be excreted by patients with choriocarcinoma in greater amounts than by healthy, pregnant women. Although ashCG potentially could be a useful marker for the diagnosis and management of gestational trophoblastic neoplasia, the methods previously used for its detection were not suitable for routine clinical application. Therefore, we have devised a simpler method which can provide specific and sensitive measurements of ashCG in urine. This method, which is designated as a lectin-immunoradiometric assay (LIRMA), employs an agarose-coupled lectin to selectively extract the ashCG, which is then quantified directly with a purified and radiolabelled rabbit antibody. The LIRMA has been applied to demonstrate that there is an increased excretion of ashCG by choriocarcinoma patients. It is also applicable, in principle, for the study of any glycoprotein which has a reduced content of sialic acid in its carbohydrate side chains.

Chorionic Gonadotropin↗

Comparison of the epinephrine-induced arrhythmogenic effect of sevoflurane with isoflurane and halothane.

The effect of sevoflurane on cardiac arrhythmias induced by the infusion of epinephrine into dogs was compared with those of isoflurane and halothane. The arrhythmogenic doses of epinephrine determined in this comparative study were expressed by both infusion rates of epinephrine and the corresponding plasma levels obtained by a series of three-minute epinephrine infusions during sevolurane, isoflurane, and halothane anesthesia at 1.25 MAC. The mean values of the arrythmogenic infusion rates of epinephrine and the corresponding plasma levels were 17.3 microg/kg/min and 275.7 ng/ml for sevoflurane, 6.7 microg/kg/min and 149.2 ng/ml for isoflurane and 1.9 microg/kg/min and 39.1 ng/ml for halothane, respectively. These results indicate that the arrythmogenic doses of epinephrine during sevoflurane and isoflurane anesthesia were significantly higher than those during halothane anesthesia.

Journal Article↗

Effects of ultraviolet light irradiation on the skin of MRL/l mice.

MRL/Mp-lpr/lpr (MRL/l) and MRL/Mp-+/+ mice were irradiated with middle-wavelength ultraviolet light (UVB), and the development of skin lesions, skin lupus band test (LBT), anti-DNA antibodies in sera, and the extent of glomerulonephritis of the kidney were examined. Long-term exposure to low doses of UVB irradiation accelerated the development of skin lesions and enhanced the intensity of the positive skin lupus band in MRL/l mice. The contents of anti-DNA antibodies in sera, the incidence of positive findings in LBT, and the extent of glomerulonephritis were not influenced by the UVB irradiation. The promotion of the development of the skin lesions in MRL/l mice by the UVB exposure was not considered to be associated with acceleration of systemic autoimmune phenomena.

Animals↗

The effect of the supernatants obtained from Sporothrix schenkii and Candida albicans culture on the generation of reactive oxygen species by polymorphonuclear leukocytes.

The effect of the supernatants obtained from the liquid culture medium of Sporothrix schenkii and Candida albicans on the generation of superoxide anion (O2- and hydroxyl radicals OH., the elements of reactive oxygen species (ROS), and chemoluminescence (CL), a measure of several ROS, by polymorphonuclear leukocytes (PMNs) was examined. In our study, it was shown that the supernatant of S. schenkii increased all types of ROS generation examined and CL, while that of C. albicans increased OH. generation and CL. The effect of the supernatants of S. schenkii on OH. generation and CL and that of C. albicans on CL were most remarkable when the supernatant obtained 8 weeks after the inoculation was used. The supernatant of S. schenkii was shown to be a much more potent stimulant than the supernatant of C. albicans. This ROS-stimulating effect of the supernatant of S. schenkii was heat stable but not dialyzable. These findings suggest the possible role of ROS produced by infiltrated PMNs in the inflammatory skin lesions induced by S. schenkii.

Candida albicans↗