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Biomedical subjects

K Mizuno

Publications and source records attributed to K Mizuno.

At least 145 records · Page 8Linked to original sources

Spectrophotometric assay for serum platelet-activating factor acetylhydrolase activity.

We developed a spectrophotometric assay for serum platelet-activating factor acetylhydrolase (PAF-AH, EC 3.1.1.47.) activity using a platelet-activating factor (PAF) analogue with a 4-nitrophenyl group as substrate. PAF-AH hydrolyzes the sn-2 position of the substrate ¿1-myristoyl-2-(p-nitrophenylsuccinyl)phosphatidylcholine, producing p-nitrophenyl succinate. This liberation was spectrophotometrically monitored and the activity determined from the change in absorption. The assay does not require radioisotopes and is applicable to an automatic analyzer. Utilizing this assay with an automatic analyzer, it is possible to measure the activities of thousands of samples in a few hours with excellent precision (CV 0.5%, n=30) and high correlation (r=0.979, n=100) with the results of a conventional radioisotopic assay. The assay should be particularly useful for clinical diagnostics.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Effects of 15-month aldose reductase inhibition with fidarestat on the experimental diabetic neuropathy in rats.

We examined the effects of long-term treatment with an aldose reductase inhibitor (ARI) fidarestat on functional, morphological and metabolic changes in the peripheral nerve of 15-month diabetic rats induced by streptozotocin (STZ). Slowed F-wave, motor nerve and sensory nerve conduction velocities were corrected dose-dependently in fidarestat-treated diabetic rats. Morphometric analysis of myelinated fibers demonstrated that frequencies of abnormal fibers such as paranodal demyelination and axonal degeneration were reduced to the extent of normal levels by fidarestat-treatment. Axonal atrophy, distorted axon circularity and reduction of myelin sheath thickness were also inhibited. These effects were associated with normalization of increased levels of sorbitol and fructose and decreased level of myo-inositol in the peripheral nerve by fidarestat. Thus, the results demonstrated that long-term treatment with fidarestat substantially inhibited the functional and structural progression of diabetic neuropathy with inhibition of increased polyol pathway flux in diabetic rats.

Aldehyde Reductase↗

A critical role for a Rho-associated kinase, p160ROCK, in determining axon outgrowth in mammalian CNS neurons.

We tested the contribution of the small GTPase Rho and its downstream target p160ROCK during the early stages of axon formation in cultured cerebellar granule neurons. p160ROCK inhibition, presumably by reducing the stability of the cortical actin network, triggered immediate outgrowth of membrane ruffles and filopodia, followed by the generation of initial growth cone-ike membrane domains from which axonal processes arose. Furthermore, a potentiation in both the size and the motility of growth cones was evident, though the overall axon elongation rate remained stable. Conversely, overexpression of dominant active forms of Rho or ROCK was suggested to prevent initiation of axon outgrowth. Taken together, our data indicate a novel role for the Rho/ROCK pathway as a gate critical for the initiation of axon outgrowth and the control of growth cone dynamics.

Actins↗

Effects of carbamazepine on acetylcholine release and metabolism.

To clarify the mechanisms of action of carbamazepine (CBZ), we investigated the effects of CBZ on acetylcholine (ACh) release and metabolism in rat striatum and hippocampus. Acute administration of effective dose of CBZ (25 mg/kg) increased both striatal and hippocampal extracellular levels of ACh, whereas a supraeffective dose of CBZ (50 mg/kg) did not affect the levels and a toxic dose of CBZ (100 mg/kg) decreased the extracellular ACh levels in both brain regions. Both acute and chronic administrations of CBZ (25 and 50 mg/kg, mg/kg per day) increased intracellular ACh levels in striatum and hippocampus. The striatal intracellular ACh levels were decreased by both acute and chronic administrations of CBZ (100 mg/kg, mg/kg per day), whereas the hippocampal intracellular ACh levels were not affected. The effective CBZ concentration did not affect cholinesterase activity, whereas supraeffective CBZ concentration reduced it weakly. Effective dose of CBZ enhanced ACh release and synthesis; however, supraeffective doses of CBZ reduced ACh release and synthesis without enhancement of ACh degradation, indicating that CBZ has biphasic effects on ACh release and synthesis. Thus, the present findings, the slight stimulation of ACh function by effective dose of CBZ, are involved, at least partially, in the antiepileptic and mood stabilizing mechanisms of action of CBZ.

Acetylcholine↗

Inhibitory influences of tranilast on multinucleated giant cell formation from monocytes by supernatant of concanavalin A-stimulated mononuclear cells.

Tranilast is an anti-allergic drug that inhibits the release of chemical mediators from mast cells. There have been cases-reports showing that tranilast is effective for the treatment of granulomatous diseases such as granuloma annulare and cutaneous sarcoidosis. Here we examined the in vitro effects of tranilast on the formation of multinucleated giant cells (MGCs) from human peripheral monocytes. Supernatant of concanavalin A (Con A)-stimulated mononuclear cells induced Langhans-type and foreign body-type MGCs and the addition of 10 or 100 microg/ml tranilast inhibited the formation of total MGCs and foreign body-type MGCs. Tranilast decreased the number of MGCs with 16<nuclei and increased that of MGCs with three to five nuclei. Fluorescence-activated cell sorting analysis showed that tranilast-treated monocytes had lower expressions of intercellular adhesion molecule-1 (ICAM-1). These findings suggest that tranilast is effective for cutaneous lesions in some cases of granulomatous disorders partly through a direct effect on monocyte/macrophage-lineage cells.

Anti-Allergic Agents↗

Cholesterol sulfate, an activator of protein kinase C mediating squamous cell differentiation: a review.

Activity of protein kinase C (PKC) depends on the interaction with polar head-groups of two membrane lipids, i.e., phosphatidylserine and diacylglycerol. We demonstrated that cholesterol metabolism is directly involved in activation of the eta isoform of protein kinase C (PKCeta), which is predominantly expressed in epithelial tissues in close association with epithelial differentiation. We found that PKCeta was activated by cholesterol sulfate (CS), a metabolite of cholesterol formed during squamous cell differentiation. In the presence of CS, phorbol ester only weakly enhanced the activity of PKCeta. CS also activated PKCeta, PKCdelta and PKCepsilon in a dose-dependent manner, when assayed using purified recombinant materials. However, when partially purified materials were used from overexpressing normal human keratinocytes, only PKCeta was activated by CS among the isoforms examined. All the existing lines of evidence, mainly supplied from our laboratory, suggest that CS is involved in a signal transduction of squamous cell differentiation and thereby modifying squamous cell carcinogenesis.

Cell Differentiation↗

Solitary infantile myofibromatosis in the femur.

We report on a case of the solitary type of infantile myofibromatosis of the right femur in an 11-month female. Radiographically, a well-defined osteolytic lesion was seen in the diaphysis of the right femur. Pathological study revealed that the spindle-shaped cells with eosinophilic cytoplasm were arranged in a fascicular and intertwining fashion. The cleft-shaped vascular spaces were observed between tumor nodules. Immunohistochemical staining caused many tumor cells to react for vimentin, alpha-smooth muscle actin and desmin. Ultrastructural study revealed numerous thin and intermediate types of filaments in the cytoplasm of the cells. To our best knowledge, this is the third reported case of solitary infantile myofibromatosis of long bones.

Bone Neoplasms↗

Anaplastic osteosarcoma with abundant eosinophilic cytoplasm and minimal osteoid production.

A case of osteosarcoma with unusual microscopic features, occurring in the right proximal tibial metaphysis of a 12-year-old boy is reported. Radiographically, the tumor was ill-defined and purely osteolytic. On gross examination, the tumor was soft, fragile, spongy and red to brown in color. Microscopically, the tumor consisted of pleomorphic cells possessing abundant eosinophilic cytoplasm, including cells larger than 100 microm in diameter. The cells were arranged in a sheet, with few extracellular collagen fibers. Multiple sectioning of the specimens revealed a small amount of osteoid production. Immunohistochemical study revealed a positive reaction for vimentin and osteocalcin. Electron microscopic study suggested the fibroblastic or osteoblastic origin of the cells.

Antineoplastic Combined Chemotherapy Protocols↗

Dedifferentiated liposarcoma with chondroblastic osteosarcomatous dedifferentiation.

We describe a rare case of dedifferentiated liposarcoma with features resembling chondroblastic osteosarcoma in the dedifferentiated component. The tumor was removed from the left thigh in a 78-year-old male. It consisted of a well-differentiated liposarcoma and an anaplastic component that contained numerous osteoid and cartilaginous tissues surrounded by high-grade spindle cell sarcoma. To our knowledge, only two cases similar to the divergent chondroblastic osteosarcomatous dedifferentiation of this disease have been reported in the literature.

Aged↗

Parosteal fasciitis of the clavicle.

A rare case of parosteal fasciitis arising from the periosteum of the left clavicle in a 27-year-old woman is reported. Magnetic resonance imaging demonstrated the lesion surrounding the periosteum of the clavicle. The lesion was iso-intense with muscle on T(1)-weighted images and hyperintense on T(2)-weighted images. At surgery, the lesion was discovered to be densely adherent with the periosteum, and excised along with the periosteum. Histopathological examination revealed the proliferation of myofibroblasts in a vague storiform or short fascicular pattern. A large amount of extravasated erythrocytes, and a few lymphocytes were present in the matrix. There were some foci of abundant myxoid materials. Immunohistochemical study showed the cells to be positive for vimentin, alpha-smooth muscle actin and HHF35, but negative for desmin. There was no local recurrence at a 6 months postoperative follow up.

Actins↗

Pulmonary tissue volume measured by acetylene rebreathing under artificial ventilation.

OBJECTIVE: In order to evaluate the pulmonary congestive state of patients being mechanically ventilated, an acetylene rebreathing method was employed. Measurement of pulmonary tissue volume by the acetylene (C2H2) rebreathing method was performed in 15 patients under artificial ventilation including four congestive heart failure cases, one renal failure case, and 12 healthy controls. METHODOLOGY: The subjects rebreathed mixed gas containing 0.65% C2H2, 10% argon (Ar), and 60% oxygen (O2) from end-tidal level, and inspiratory and expiratory gas concentrations were measured by a mass spectrometer. Correction for system volume reduction during rebreathing due to gas exchange and C2H2 concentration fluctuation was performed, pulmonary tissue volume was calculated from the C2H2 and Ar concentration difference at the time zero intercept. Time zero was assumed to be the time at which C2H2 and Ar concentration started to differ. RESULTS: Pulmonary tissue volume per functional residual capacity and pulmonary tissue volume per pulmonary capillary blood flow for cases with congestive heart failure and renal failure cases were significantly higher than those for non-pulmonary congestion cases and normal controls. CONCLUSION: The measurement of pulmonary tissue volume by C2H2 rebreathing can be applied to the patients under artificial ventilation in order to quantitatively evaluate pulmonary congestion or edema.

Acetylene↗

Congenital urethrocutaneous fistula.

BACKGROUND: A 3-year-old boy visited our hospital for aberrance of urination. He had a fistula on his ventral penile shaft. Our diagnosis was congenital urethrocutaneous fistula. METHODS/RESULTS: We performed one-stage repair transverse preputial onlay island flap urethroplasty. Postoperatively, the patient was voiding comfortably with no recurrence of fistula. CONCLUSIONS: Congenital urethrocutaneous fistula is rare. Eighteen cases of congenital urethrocutaneous fistula have been reported previously. We consider the etiology of congenital urethrocutaneous fistula as a deficiency of the urethral plate and fusion of urethral folds.

Child, Preschool↗

Involvement of keratinocyte activation phase in cutaneous graft healing: comparison of full-thickness and split-thickness skin grafts.

BACKGROUND: Little is known about keratinocytic activation in the graft take and healing process. OBJECTIVE: To investigate the clinical and molecular differences between pure epidermal sheet graft (PESG), split-thickness skin graft (STSG), and full-thickness skin graft (FTSG). METHODS: Three different thickness skin grafts (PESG, STSG, and FTSG) were performed onto three kinds of porcine wounds: shallow, deep, and full. Graft take, contraction, and Ki-67 and beta1 integrin expression in epidermis were studied. RESULTS: All grafts took well. As expected, full wounds covered by PESG and STSG contracted more than those covered by FTSG, whereas shallow wounds covered by FTSG contracted more than those covered by STSG. No difference in contracture was observed among deep wounds covered by PESG, STSG, and FTSG. Up-regulation of Ki-67 and beta1 integrin expression was greater in PESG and STSG, compared with little expression in FTSG. CONCLUSION: The keratinocytic activation phase may occur both in the STSG and PESG healing process, as well as serum imbibition, inosculatory, and revascularization phases.

Animals↗

Treatment of ununited fracture of the hook of hamate by low-intensity pulsed ultrasound: a case report.

A patient presented 4 months after sustaining a fracture of the hook of hamate. X-rays and computed tomography scanning of the carpal tunnel confirmed the presence of an ununited fracture. Low-intensity ultrasound was applied to the fracture site. After 4.5 months of exposure to ultrasound, union was confirmed by both x-rays and computed tomography scanning of the carpal tunnel. (J Hand Surg 2000; 25A:77-79.

Accidents, Traffic↗

Induction of apoptosis in bovine articular chondrocyte by prostaglandin E(2) through cAMP-dependent pathway.

OBJECTIVE: Regulation of important biological processes such as proliferation and differentiation of articular chondrocytes is known to be mediated by prostaglandin E(2) (PGE(2)) in both normal and pathological states. Articular chondrocytes also undergo apoptosis, a biological phenomenon implicated in many physiological processes. Whether or not PGE(2) induces apoptosis in articular chondrocytes, however, is not known. DESIGN: Bovine articular chondrocytes were cultured with or without PGE(2) for 24 h and amounts of fragmented DNA, which is a distinct characteristic of apoptosis, were measured by enzyme-linked immunosorbent assay. Also effect of cyclic AMP (cAMP), which is one of the intracellular downstream mediator of PGE(2), on chondrocyte apoptosis was investigated. RESULTS: Administration of exogenous PGE(2) on bovine articular cartilage grown as a monolayer culture resulted in the induction of DNA fragmentation. This DNA fragmentation was accompanied with a marked dose-dependent increase in intracellular cAMP. Also cultured cells were treated with cAMP analogue, dibutyryl-cAMP or forskolin, a direct activator of adenylate cyclase, and the incidence of apoptosis in the chondrocytes was determined. As well as PGE(2), dibutyryl-cAMP and forskolin stimulated chondrocyte DNA fragmentation. CONCLUSIONS: It is the first report that PGE(2) can induce articular chondrocyte apoptosis in vitro. It is also suggest that apoptosis of chondrocytes by PGE(2) is linked with cAMP-dependent pathway.

Animals↗