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Biomedical subjects

H Mizutani

Publications and source records attributed to H Mizutani.

At least 91 records · Page 5Linked to original sources
PubMed1997

Role of increased production of monocytes TNF-alpha, IL-1beta and IL-6 in psoriasis: relation to focal infection, disease activity and responses to treatments.

To evaluate the immunological function of peripheral blood monocytes (PBMC) in psoriasis, we measured spontaneous production of the inflammatory cytokines, TNF-alpha, IL-1beta and IL-6 from the PBMC of psoriasis patients, by enzyme linked immunosorbent assay (ELISA). The production of all three inflammatory cytokines by psoriatic PBMC was significantly higher than that by normal control PBMC. PBMC sampled from active psoriasis produced three cytokines significantly higher than samples from inactive psoriasis. In addition, IL-1beta and TNF-alpha production showed a positive relation to clinical severity, but IL-6 did not. TNF-alpha production increased much more than did the others. Therefore, the TNF-alpha to IL-1beta ratio was significantly higher, even in inactive psoriasis, than that of the normal control. In relation to focal infection, psoriatic PBMC sampled 3 h after a tonsillar provocation test increased cytokine production, compared with the level before provocation. The cases which responded to tonsillectomy or systemic methotrexate therapy, but not the non-responding cases, showed a significant decrease in PBMC cytokine productivity. These results strongly suggest that inflammatory cytokines, especially TNF-alpha, from monocytes are involved in the pathogenesis of psoriasis, and activated monocytes may work as an effective mediator of focal infection in skin lesions.

Adolescent↗
PubMed1997

Structural and mechanistic studies on D-amino acid oxidase x substrate complex: implications of the crystal structure of enzyme x substrate analog complex.

As an extension of our recent X-ray crystallographic determination of the tertiary structure of D-amino acid oxidase (DAO) [Mizutani, H. et al. (1996) J. Biochem. 120, 14-17], we solved the crystal structure of the complex of DAO with a substrate analog, o-aminobenzoate (OAB). The alignment between flavin and OAB in the crystal structure of the complex is consistent with charge-transfer interaction through the overlap between the highest occupied molecular orbital of OAB and the lowest unoccupied molecular orbital of flavin. Starting with the atomic coordinates of this complex as the initial model, we carried out molecular mechanics simulation for the DAO-D-leucine complex and thus obtained a model for the enzyme-substrate complex. According to the enzyme-substrate complex model, the alpha-proton is pointed toward N(5) of flavin while the lone-pair of the substrate amino group can approach C(4a) of flavin within an interacting distance. This model as well as DAO-OAB complex enables the evaluation of the substrate-flavin interaction prior to electron transfer from the substrate to flavin and provides two possible mechanisms for the reductive-half reaction of DAO, i.e., the electron-proton-electron transfer mechanism and the ionic mechanism.

Amino Acid Oxidoreductases↗
PubMed1997

Scleroderma renal crisis complicated by hemolytic uremic syndrome in a case of elderly onset systemic sclerosis.

We report a case of renal crisis in a patient with elderly onset systemic scleroderma (SSc). A sixty-one-year-old woman was diagnosed as having SSc with rapidly advancing generalized skin sclerosis. After experiencing an upper respiratory infection, she suddenly developed renal failure, hemolytic anemia and malignant hypertension. Laboratory examination revealed uremia with a significantly high plasma renin level. Ophthalmologic study revealed Keith-Wagner's retinopathy Grade IV. Combination therapy including captopril, systemic corticosteroid and prostaglandin E1 venous infusion for the hemolytic uremic syndrome was effective and saved her from the renal crisis. However, her renal function deteriorated and she needs permanent hemodialysis. Rapidly progressive skin sclerosis in SSc, especially in elderly onset cases, suggests a high risk for renal crisis and indicates the need for careful consideration of hypertension and renal function.

Acute Disease↗
PubMed1997

A case of multicentric reticulohistiocytosis, systemic sclerosis and Sjögren syndrome.

We report the case of a 42-year-old Japanese woman who developed multicentric reticulohistiocytosis (MR) complicated by systemic sclerosis (SSc) and Sjögren syndrome (SS). The patient complained of tender nodules on the left hand, polyarthralgia in the finger joints and knees, and xerostomia. The skin nodules were distributed mainly on her hands and fingers with skin sclerosis. The serum anti-nuclear test revealed anti-centromere antibody and the discrete speckled pattern of anti-nuclear antibody. The biopsy specimens from the finger nodule and the sclerotic finger skin showed a perivascular infiltration of multinucleated giant cells with ground-glass cytoplasm and dermal thick collagen proliferation, respectively. The lip biopsy and sialography specimens showed periductal lymphocyte infiltration and apple tree-like changes. Systemic corticosteroid treatment improved the polyarthritis, xerostomia, and skin sclerosis rapidly but suppressed the nodular lesions only gradually. This is the first report of a combined case of MR, SSc and SS. This multiple autoimmune complication suggests the involvement of an immunological disturbance in the pathogenesis of MR.

Adrenal Cortex Hormones↗
PubMed1997

Hepatic carnitine palmitoyltransferase activity in cattle.

A fluorometric assay for the determination of hepatic carnitine palmitoyltransferase (CPT) activity was slightly modified for use with cattle samples. With this assay, the Km value was 0.56 +/- 0.10 mM with respect to L-carnitine (mean +/- SD, n = 4) and was 9.6 +/- 2.2 microM (n = 3) with respect to palmitoyl-CoA. The average hepatic CPT activity was 33.6 +/- 2.0 mumol CoASH/min/g protein in 38 healthy cattle and was similar in both sexes and among breeds. Hepatic CPT activity showed no correlation with serum phospholipid, free fatty acid, triglyceride or total cholesterol concentrations.

Animals↗
PubMed1997

Association of type VI collagen with D-periodic collagen fibrils in developing tail tendons of mice.

The process of the arrangement of D-periodic collagen fibrils and their growth in maturing tail tendon of mice were studied with the association of type VI collagen, from fetal day 10 to 10 weeks after birth. In tail tendons, the amount of collagen fibers gradually increased along with the diameters of D-periodic collagen fibrils during maturation. Type VI collagens first appeared on fetal day 10, when D-periodic collagen fibrils were not recognizable. Type VI collagens were observed around the fibroblastic cells in early stages of development, but were among thick collagen fibrils in the adult tendon. While the periodic distances of type VI collagen fibrils were over 100 nm at fetal days, they were packed to 80-90 nm after birth. The periodic bands were stained well with ruthenium red in adult but not in young tendons, indicating the close association of proteoglycans or glycosaminoglycans (PGs/GAGs) with maturing type VI collagens. Since type VI collagen in native form is known to associate with D-periodic collagen fibrils via PGs/ GAGs, ruthenium red-stainability on the surface of D-periodic collagen fibrils was also examined; results showed that ruthenium red-stainable elements were D-periodically associated. When the surface morphology of D-periodic collagen fibrils in adult animals was examined by atomic force microscopy, a large depth of the groove between elevated and depressed surfaces became prominent when the fibril surface was digested with hyaluronidase. Thus, it is possible to observe topologically the association of PGs/GAGs and probably that of type VI collagens with D-periodic collagen fibrils.

Animals↗
PubMed1997

[A case of recurrent gastric cancer with liver metastasis responding to combination chemotherapy with cisplatin and carmofur].

The patient was a 65-year-old male with recurrent gastric cancer accompanied by metastasis to the liver and distant lymph nodes. He was treated by combination chemotherapy consisting of cisplatin 20 mg/body (day 8-14) and Carmofur 400 mg/body (on consecutive days), in three four-week courses of therapy. After 1 course of administration, the target lesion was reduced in size and the performance status was improved. Generally, a partial response was confirmed by computed tomography (CT). The patient has survived for 8 months in a state of PR. Adverse effects were mild and transient. Though treatment of recurrent gastric cancer with liver metastasis is often ineffective, this case suggests that a combination therapy of cisplatin and carmofur might be effective.

Aged↗
PubMed1997

Loss of cutaneous delayed hypersensitivity reactions in nevus anemicus. Evidence for close concordance of cutaneous delayed hypersensitivity and endothelial E-selectin expression.

BACKGROUND: The relationship of adhesion molecules in the dermis to immunologically mediated cutaneous inflammation can be understood by focusing on a serendipitous phenomenon: a lack of dermatitis within the margins of a nevus anemicus (NA) in generalized contact dermatitis. The expression and induction of endothelial and epithelial adhesion molecules with intradermally injected cytokines were investigated. OBSERVATIONS: Nevus anemicus without dermatitis lacked histopathological changes consistent with inflammatory cellular infiltration. The surrounding skin of the dermatitic lesion expressed HLA-DR, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1, and E-selectin on endothelial cells, and HLA-DR and ICAM-1 in the epidermis. However, the skin of the NA lacked endothelial E-selectin and epidermal HLA-DR and ICAM-1 expression. Interferon gamma, injected intradermally, induced endothelial and epidermal HLA-DR and ICAM-1 expression in the NA and surrounding normal skin. While interferon gamma strongly induced E-selectin expression on endothelial cells in normal skin, it failed to induce endothelial E-selectin expression in the NA. CONCLUSIONS: This study suggests that vessels in the NA do not respond normally to proinflammatory cytokines, at least at the level of E-selectin expression. The absence of keratinocyte ICAM-1 and HLA-DR expression in the NA lesion in contact dermatitis is likely caused by the absence of infiltrating lymphocytes, rather than by the intrinsic unresponsiveness of keratinocytes to interferon gamma. Among the endothelial cell adhesion molecules in delayed hypersensitivity, E-selectin appears to be indispensable in recruiting circulating T lymphocytes to the skin.

Antigens, CD↗
PubMed1997

Epidermal apoptotic cell death in erythema multiforme and Stevens-Johnson syndrome. Contribution of perforin-positive cell infiltration.

OBJECTIVE: To clarify the mechanism of epidermal cell death in erythema multiforme. DESIGN: Retrospective study. SETTING: Academic referral center. PARTICIPANTS: Nine patients with Stevens-Johnson syndrome (SJS), 9 patients with Hebra disease (EMH), and 5 healthy volunteers. INTERVENTIONS: Biopsy specimens were obtained from the border of the fresh lesions before treatment. Control specimens were obtained from normal skin. MAIN OUTCOME MEASURES: Histopathological epidermal apoptosis detected with nuclear DNA fragmentation and counts of dermal immunoreactive perforin-positive infiltrates were compared between SJS and EMH. RESULTS: Eight patients (89%) with SJS showed clear apoptosis with keratinocyte DNA fragmentation. All SJS samples had intensive perforin-positive dermal infiltrates. Only 3 patients (33%) with EMH showed apoptotic change, and it was to a far less extent with far less dermal perforin-positive infiltrates. Control specimens showed no apoptotic cells in the epidermis or expression of perforin in the dermis. CONCLUSIONS: Perforin mediates apoptosis in the pathogenesis of the epidermal cell changes in SJS but not in EMH. In addition to the differences in clinical severity and histopathological conditions, our findings indicate a pathogenic difference between SJS and EMH.

Antibodies, Monoclonal↗
PubMed1997

All-cast-titanium removable partial denture for a patient with a severely reduced interarch distance: a case report.

A patient had a maxillary posterior edentulous area and severely reduced interarch distance that precluded the use of a conventional removable partial denture. An all-cast-titanium denture base and occlusal surface was designed to fabricate a removable denture to restore the edentulous area. Titanium was cast in a centrifugal casting machine with electric are melting design. The desirable characteristics of titanium, such as favorable mechanical properties, low density, and comparatively low cost, make this metal particularly effective and suitable for construction of an all-cast-metal denture base with a metal occlusal surface.

Adult↗
PubMed1996

Evaluation of endometriosis in uterosacral ligaments by transrectal ultrasonography.

Uterosacral ligaments are one of the common targets of pelvic endometriosis, which is usually clinically rather than surgically diagnosed. This study was performed to determine if uterosacral ligaments infiltrated by endometriosis could be detected by transrectal ultrasonography. Uterosacral ligaments in non-endometriosis subjects (n = 64) were observed as low echoic homogeneous arcs in both sides of the uterine cervix. Patients who had endometriosis (n = 29) on the ligaments showed thick and irregularly-shaped uterosacral ligaments by the transrectal ultrasound examination. The results also suggested that the thickness of uterosacral ligaments was associated with the clinical symptoms. Transrectal ultrasonography may provide quantitative information to manage patients with infiltrating endometriosis.

Adult↗
PubMed1996

Crystallization of expressed porcine kidney D-amino acid oxidase and preliminary X-ray crystallographic characterization.

The cDNA for porcine kidney D-amino acid oxidase (DAO) was cloned by means of the reverse transcription-polymerase chain reaction system from porcine kidney RNA and over-expressed in Escherichia coli which had been transformed with a vector containing the DAO cDNA. The expressed DAO was purified to homogeneity by a three-step procedure, i.e., heat-treatment, DEAE Sepharose column chromatography, and hydroxyapatite column chromatography. The purified DAO preparation, rDAO (recombinant DAO), showed an identical UV-visible absorption spectrum and catalytic activity with those of the wild-type enzyme purified from porcine kidney. Crystallization of rDAO was performed by the hanging-drop method and crystals of suitable quality for X-ray crystallography were obtained. The crystals so obtained diffracted to 2.5 A with a conventional X-ray source, and to 2.0 A with synchrotron radiation. The crystals belong to the orthorhombic space group P2(1)2(1)2(1) with unit cell dimensions of a = 110.3, b = 92.9, c = 71.6 A. A Vm value of 2.35 A3/Da indicates that there are two subunits related by a twofold non-crystallographic axis in the asymmetric unit. Two heavy atom derivatives have been identified.

Animals↗
PubMed1996

Three-dimensional structure of porcine kidney D-amino acid oxidase at 3.0 A resolution.

The X-ray crystallographic structure of porcine kidney D-amino acid oxidase, which had been expressed in Escherichia coli transformed with a vector containing DAO cDNA, was determined by the isomorphous replacement method for the complex form with benzoate. The known amino acid sequence, FAD and benzoate were fitted to an electron density map of 3.0 A resolution with an R-factor of 21.0%. The overall dimeric structure exhibits an elongated ellipsoidal framework. The prosthetic group, FAD, was found to be in an extended conformation, the isoalloxazine ring being buried in the protein core. The ADP moiety of FAD was located in the typical beta alpha beta dinucleotide binding motif, with the alpha-helix dipole stabilizing the pyrophosphate negative charge. The substrate analog, benzoate, is located on the re-face of the isoalloxazine ring, while the si-face is blocked by hydrophobic residues. The carboxylate group of benzoate is ion-paired with the Arg283 side chain and is within interacting distance with the hydroxy moiety of Tyr228. The phenol ring of Tyr224 is located just above the benzene ring of benzoate, implying the importance of this residue for catalysis. There is no positive charge or alpha-helix dipole near N(1) of flavin. Hydrogen bonds were observed at C(2) = O, N(3)-H, C(4) = O, and N(5) of the flavin ring.

Animals↗
PubMed1996

Epidemiological analysis of prognosis of 496 Japanese patients with progressive systemic sclerosis (SSc). Scleroderma Research Committee Japan.

For the first time, we performed an epidemiological study of SSc in Japan to study the factors influencing prognosis, survival rate and cause of death of Japanese SSc patients and to compare our data with those from foreign countries. Prognosis of 496 Japanese patients with progressive systemic sclerosis (SSc) was analyzed based on clinical data described in case cards provided by the members of the Scleroderma Research Committee of the Japanese Ministry of Health and Welfare. The essential observation period was from 5 to 20 years, at ending in 1994. Ninety patients died (males 11, females 79). The age of onset of the deceased patients was significantly higher than that of surviving patients (deceased, 45.6 yrs, surviving 41.3 yrs). Statistically significant factors for a poor prognosis were as follows: Barnett type III > type II > type I, positive for anti-Scl-70 antibody, negative for anti-centromere antibody. The survival rate at 5 years after the onset of the disease was 0.937, followed by 0.82 at 10 years, 0.567 at 20 years and 0.40 at 30 years after the onset. Sex was not a predictor for prognosis, although male patients died at an earlier stage of the disease. The most common causes of death were heart failure, pulmonary insufficiency, lung fibrosis, and renal failure. Twenty-four patients had cancer of which 13 were lung cancers. The current status of the survival rate and prognostic factors of 496 Japanese SSc patients is summarized. In future, more well-controlled studies using the same criteria should be performed for the better understanding and management of SSc.

Adult↗
PubMed1996

Progressive systemic sclerosis sine scleroderma which developed after exposure to epoxy resin polymerization.

Progressive systemic sclerosis (PSS) sine scleroderma is well known as a special form of scleroderma. Because of its rarity, its pathogenesis has not yet been elucidated. We experienced a 33-year-old man who developed PSS sine scleroderma while working with epoxy resin polymerization. He had short white frenulum linguae, diffuse hyperpigmentation and facial telangiectasia, positive antinuclear antibody, and pulmonary dysfunction, but not acrosclerosis or sclerodactylia. Modest dermal collagen proliferation in the forearm skin confirmed PSS sine scleroderma. Epoxy resin polymerizer appears to be a potent causative agent for PSS sine scleroderma as well as for generalized morphea-like PSS.

Adult↗
PubMed1996

Influence of experimental occlusal discrepancy on masticatory muscle activity during clenching.

The influence of the experimental occlusal discrepancy on masticatory muscle activity was investigated on 12 subjects. Specially designed occlusal interferences were fabricated and various occlusal states were simulated with their aid. Subjects were asked to carry out eccentric clenching efforts and electromyographic activity of the masseter plus the anterior and posterior temporal muscles was measured. When compared with clenching on the unaltered natural dentition, clenching on the experimental interferences resulted in distinct patterns in the jaw elevator muscles, and the most characteristic change was observed when clenching effort was exerted on the experimental non-working side interference. Electromyographic activity in the anterior and posterior temporal muscles was decreased on the working side and increased on the non-working side and originally unilateral activity pattern with clear dominance on the working side was altered to a bilateral pattern, while that of the masseter muscles remained uninfluenced. Resultant bilateral activity in the anterior and posterior temporal muscles is thought to cause a superior movement of the working side condyle and an inferior movement of the non-working side condyle.

Adult↗
PubMed1996

Tissue factor and thrombomodulin expression on keratinocytes as coagulation/anti-coagulation cofactor and differentiation marker.

Immunohistochemistry was used to investigate the expression of tissue factor (TF) as a coagulation factor and thrombomodulin (TM) as an anticoagulation cofactor in the epidermis. TM was expressed on Malpighian layer keratinocytes while TF was located on the supra-Malpighian layer. Epidermal shave extracts were biologically active for both factors. Keratinocytes cultured in high calcium, but not low calcium media, expressed both TF and TM. In pemphigus vulgaris pemphigus foliaceus and bullous pemphigoid, TF expression was increased on keratinocytes shielding the blister compared to the down-regulated TM expression by keratinocytes around the blister.

Biomarkers↗