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Biomedical subjects

K Mizuno

Publications and source records attributed to K Mizuno.

At least 181 records · Page 10Linked to original sources
PubMed2000

Dexa-measured bone density changes over time after intertrochanteric hip fractures.

The local bone density after an intertrochanteric hip fracture changes over time. In this study, bone density was measured in proximal femur and third lumbar vertebrae in patients treated for an intertrochanteric hip fracture at various periods. There were 60 patients (mean age 71.4 years) and 50 control patients (mean age 62.4 years). Bone density measurements were performed with Dual energy X-ray absorptiometry (DEXA). Bilateral measurements of the greater trochanter, lesser trochanter and femoral diaphysis as well as the third lumbar vertebrae were performed. Each area showed different course of change. The bone density of the greater trochanter and the lesser trochanter in the injured side increased after three months as compared with the control. After three years, the bone density of the greater trochanter decreased. The bone density of the femoral diaphysis and the third vertebrae gradually decreased over time. The authors suggest that bone density changes under the influence of callus formation, bone remodeling, decrease in daily activity, and use of ambulatory aids, etc.

Absorptiometry, Photon↗
PubMed2000

The role of cyclooxygenase-2 and inflammatory cytokines in pain induction of herniated lumbar intervertebral disc.

Lumbar disc herniation (LDH) is the disease which is the major cause of radiculopathy. In terms of the pathogenesis of disease, it is reported that prostaglandinE2 (PGE2) plays an important role to induce radiculopathy. Arachidonate cascade, which is the process of PGE2 synthesis, is mainly regulated by two kinds of enzymes, phospholipaseA2 (PLA2) and cyclooxy genase (COX). Previously, PLA2 was recognized as the rate-limiting enzyme of this cascade, and some authors reported the clinical significance of PLA2 at the site of LDH concerning the radicular pain. Recently, COX was elucidated to consist of 2 types of isoform, a constitutive form of COX-1 and an inducible form of COX-2. COX-2 has been focused as a key enzyme to regulate PGE2 synthesis and plays an important role in inflammation, because COX-2 was induced in many types of cells by the stimulation of inflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha). However, it is not fully discussed whether or not, COX-2 is induced in lumbar disc tissue and if it plays a significant role in the pathogenesis of LDH. To clarify the role of COX-2 in the pathomechanism of radiculopathy of LDH, we have investigated the expression of COX-2, IL-1 beta and TNF alpha in herniated lumbar disc tissue. Immunohistologically, they were detected in the cytosol of chondrocytes constituting the disc tissue. RT-PCR showed that herniated lumbar disc-derived cells expressed mRNA of COX-2, IL-1 beta and TNF alpha in the presence of inflammatory cytokines in vitro. The disc-derived cells also produced much PGE2 by stimulating of inflammatory cytokines at the same time and this PGE2 production was distinctly suppressed by a selective inhibitor of COX-2, 6-methoxy-2-naphtyl acetic acids (6MNA). These results suggest that COX-2 and inflammatory cytokines might play a causative role in the radiculopathy of LDH through upregulating PGE2 synthesis.

Adolescent↗
PubMed2000

Chondromyxoid fibroma of the finger.

We report a case of chondromyxoid fibroma arising from the middle phalanx of the index finger. The radiographic and pathologic findings are described.

Adult↗
PubMed2000

Radiographic and computed tomographic analysis of the position of the tibial tubercle in recurrent dislocation and subluxation of the patella.

Among the factors that influence the patellofemoral alignment and stability, the position of the tibial tubercle was evaluated using plain radiographs and computed tomography (CT). Radiographs of the Q-angle with the knee in full extension and quadriceps muscle relaxed showed that mean Q-angles in the dislocation or subluxation group and control group were 13.8 degrees and 14.3 degrees, respectively. The major reason for this deceptive measurement was a patella positioned laterally in the dislocation or subluxation group. Better estimation was made with the modified Q-angle measurement by using the most concave point of the intercondylar notch as a reference point instead of the center of the patella. By overshadowing CT images of the levels of the patellofemoral joint and the tibial tubercle, it was possible to evaluate the location of the tibial tubercle in relation to the femoral trochlea. Both the angular measurement (lateral deviation angle [LDA]) and the distance measurement (lateral deviation index [LDI]) showed that the tibial tubercle in the dislocation or subluxation group was rotated externally and shifted laterally (LDA, 36.3+/-7.0 degrees and LDI, 30.1+/-5.6) compared with the control group (LDA, 20.2+/-7.1 degrees and LDI, 15.1+/-5.6). Further study is warranted to elucidate the exact mechanism of recurrent patellar dislocation and subluxation.

Adult↗
PubMed2000

Effect of prostaglandin E2 on nitric oxide synthesis in articular chondrocytes.

Both nitric oxide (NO) and prostaglandin E2 (PGE2) are known to play an important role in cartilage metabolism. The present study investigated the novel intercellular mechanism of inducible NO synthase (iNOS) induction mediated by PGE2 in articular chondrocytes. Bovine articular chondrocytes were stimulated by cyclic adenosine monophosphate (cAMP) elevating agents like PGE2 in the presence of interleukin-1 alpha (IL-1 alpha). NO generation was measured by using the Griess reaction. Inducible NOS mRNA was semi-quantitated by reverse transcription-polymerase chain reaction (RT-PCR). While little NO was released from articular chondrocytes in the presence of PGE2 or direct adenylate cyclase activator such as forskolin, synergistic augmentation of NO generation was observed when chondrocytes were stimulated by PGE2 or forskolin in combination with IL-1 alpha. Further expression of iNOS mRNA by stimulation of PGE2 in the presence of IL-1 alpha simultaneously was also detected by RT-PCR in comparison with the mRNA induction by IL-1 alpha stimulation alone. These results indicated that PGE2 might modulate the articular cartilage metabolism by augmentation of chondrocyte NO synthesis in inflammatory process through cAMP-protein kinase A system.

Adenylyl Cyclases↗
PubMed2000

The effect of MS-818, newly synthesized pyrimidine compound, on fracture repair.

Both periosteal cell proliferation and endochondral ossification accompanied are characteristic of the fracture healing process. This process is regulated by various kinds of soluble factors including prostanoids, cytokines and growth factors. In particularly, basic fibroblast growth factor (bFGF) stimulates the mesenchymal cell proliferation and differentiation in the periosteum and leads to the fracture healing. Recently, newly synthesized pyrimidine compound, 2-piperadino-6-methyl-5-oxo-5,6-dihydro (7H) pyrrolo [3,4-d] pyrimidine maleate (MS-818) has been reported to augment the biological effect of bFGF in vitro. Therefore, we have studied the effect of MS-818 on fracture healing process in which bFGF has been reported to play an important role. In the rat fracture model, 5 mg/kg MS-818 which had been administered intraperitoneally for fourteen consecutive days enhanced the cartilage matrix formation. In the bone defect model, in which we can find only membranous ossification without chondrogenesis, cartilage matrix formation was observed in seven days after 1 microgram of human bFGF containing polymer pellet was embedded in the defect site. Chondrogenesis induced by bFGF was enhanced significantly after 5 micrograms MS-818 containing pellet was implanted with bFGF pellet. These results suggest that MS-818 might promote the fracture healing process through enhancement of the effect of bFGF on endochondral ossification.

Animals↗
PubMed2000

Intervertebral disc cell apoptosis by nitric oxide: biological understanding of intervertebral disc degeneration.

While the unphysiological mechanical load is a central etiologic factor of disc degeneration, biologic factors including nitric oxide (NO) seems to play an important role in this condition. It is, therefore, investigated whether NO is related to the degeneration of intervertebral disc by way of inducing the disc cell apoptosis. Twelve herniated lumbar disc and eight control specimens were obtained from the patients underwent surgery. Apoptotic cells were identified by TUNEL procedure and the percent apoptotic cell index (ACI%) of each sample was calculated. Detection of iNOS expression was performed by immunohistochemical analysis. Disc cell monolayer culture was prepared from the surgical specimen of the patients with lumbar disc herniation. NO generation of the disc cells was measured by Griess reaction. Cell proliferation was detected by measuring the incorporation of 3H-Thymidine. The extent of fragmented DNA induced by NO donor, NOC-18, was also measured by an enzyme-linked immunosorbent assay. The incidence of apoptotic cell death (ACI%) was greater in the herniated group (61.3 +/- 24.5%) than that of control group (5.6 +/- 6.8%; P < 0.001). iNOS positive disc cells were detected in all the samples. NO production of disc cells was enhanced by the stimulation of IL-1 alpha. Suppression of 3H-Thymidine incorporation and DNA fragmentation in the disc cells were promoted by treatment of 100 microM NOC-18. These results suggest that disc cells are able to release NO and NO may play an important role in the pathogenesis of disc degeneration through the induction of apoptosis of disc cells in situ.

Adolescent↗
PubMed2000

[Diagnostic value of arthrography and MRI in rotator cuff tears].

OBJECTIVE: To prospectively compare arthrography with MRI to determine the sensitivity and specificity in detecting rotator cuff tear. METHODS: 53 shoulders were studied. All patients underwent both arthrography and MRI. The results were compared with the findings of arthroscopy or open surgery. RESULTS: The sensitivity in demonstrating partial-thickness tears was 70% for arthrography and 80% for MRI; the specificity was 75% for arthrography or MRI. The sensitivity in detecting full-thickness tears was 87% for arthrography and 90% for MRI, and the specificity was 100% for arthrography and 75% for MRI. CONCLUSION: The sensitivity of arthrography and MRI in detecting rotator cuff tears was identical. The specificity of arthrography in detecting full-thickness tears was higher that of MRI.

Adult↗
PubMed1999

Phosphorylation of extracellular signal-regulated kinases 1 and 2 in 3T3-L1 adipocytes by stimulation of beta(3)-adrenoceptor.

Recent studies have revealed that activated extracellular signal-regulated kinases (ERKs) 1 and 2 by the stimulation of beta(3)-adrenoceptors played a critical role in cell survival in brown adipocytes. On the other hand, phosphorylation of ERK1/2 via beta(3)-adrenoceptors and its physiological and pathological significance in white adipocyte has remained uncertain despite the increasing significance of functioning white adipocytes. Accordingly, we here studied phosphorylation of ERK1/2 caused by the stimulation of beta(3)-adrenoceptors in 3T3-L1 adipocytes, and the roles of phosphorylated ERK1/2 in lipolysis. Phosphorylation of ERK1/2 was induced by a selective beta(3)-adrenoceptor agonist, DL-4-[2'-¿2-hydroxy-2-(3-chlorophenyl)ethylamino¿propyl] phenoxyacetic acid sodium salt sesquihydrate (BRL37344), in 3T3-L1 adipocytes in a time- and dose-dependent manner. The phosphorylation of ERK1/2 by BRL37344 was sensitive to the cyclic AMP (cAMP)-dependent protein kinase inhibitor, N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide (H89). To elucidate the roles of phosphorylated ERK1/2 in lipolysis, the effect of a selective inhibitor of ERK1/2 phosphorylation, 2'-amino-3'-methoxyflavone (PD98059), was examined. This inhibitor did not alter the lipolytic action caused by BRL37344, even at concentrations sufficient to block phosphorylation of ERK1/2, suggesting that ERK1/2 play no role in the lipolysis caused by BRL37344 in 3T3-L1 adipocytes.

3T3 Cells↗
PubMed1999

Semaphorin 3A growth cone collapse requires a sequence homologous to tarantula hanatoxin.

Axonal guidance is key to the formation of neuronal circuitry. Semaphorin 3A (Sema 3A; previously known as semaphorin III, semaphorin D, and collapsin-1), a secreted subtype of the semaphorin family, is an important axonal guidance molecule in vitro and in vivo. The molecular mechanisms of the repellent activity of semaphorins are, however, poorly understood. We have now found that the secreted semaphorins contain a short sequence of high homology to hanatoxin, a tarantula K(+) and Ca(2+) ion channel blocker. Point mutations in the hanatoxin-like sequence of Sema 3A reduce its capacity to repel embryonic dorsal root ganglion axons. Sema 3A growth cone collapse activity is inhibited by hanatoxin, general Ca(2+) channel blockers, a reduction in extracellular or intracellular Ca(2+), and a calmodulin inhibitor, but not by K(+) channel blockers. Our data support an important role for Ca(2+) in mediating the Sema 3A response and suggest that Sema 3A may produce its effects by causing the opening of Ca(2+) channels.

Amino Acid Sequence↗
PubMed1999

The N-terminal LIM domain negatively regulates the kinase activity of LIM-kinase 1.

LIM-kinase 1 (LIMK1, where LIM is an acronym of the three gene products Lin-11, Isl-1 and Mec-3) is a serine/threonine kinase that phosphorylates cofilin and regulates actin cytoskeletal reorganization. LIMK1 contains two LIM domains and a PDZ (an acronym of the three proteins PSD-95, Dlg and ZO-1) domain in the N-terminal half and a kinase domain in the C-terminal half. In this study we examined the role of the extra-catalytic region in the regulation of kinase activity of LIMK1. Limited proteolysis of LIMK1 resulted in the production of the 35-40-kDa kinase core fragments with 3.5-5. 5-fold increased kinase activity. The LIMK1 mutants with deleted LIM domains (DeltaLIM) or conserved cysteines in the two LIM domains replaced with glycines (dmLIMK1) had 3-7-fold higher kinase activities in vitro, compared with the wild-type LIMK1. The C-terminal kinase fragment of LIMK1 bound to the LIM domain but not to the PDZ domain. Furthermore, the LIM fragment dose-dependently inhibited the kinase catalytic activity of the kinase core fragment of LIMK1. Taken together, these results suggest that the N-terminal LIM domain negatively regulates the kinase activity of LIMK1 by direct interaction with the C-terminal kinase domain. In addition, expression of the DeltaLIM mutant in cultured cells induced punctate accumulation of actin filaments, an event distinct from the pattern of actin organization induced by expression of the wild-type LIMK1, suggesting that the LIM domain plays a role in the function of LIMK1 in vivo.

Actins↗
PubMed1999

Effects of humid heat exposure on human sleep stages and body temperature.

The objective of this study was to confirm the effect of humid heat exposure on sleep stages and body temperature. Seven healthy male volunteers with a mean age of 22.7+/-1.63, served as the subjects. The experiments were carried out under four different conditions of room temperature and relative humidity: 29 degrees C RH 50% (29/50), 29 degrees C RH 75% (29/75), 35 degrees C RH 50% (35/50), and 35 degrees C RH 75% (35/75). The subjects wearing only shorts slept from 23:00 to 7:00 on a bed, which was covered with a 100% cotton sheet. EEG, EOG, and mental EMG were recorded through the night. Rectal temperature (Tr) and skin temperature were measured continuously. The 35/75 condition caused more wake and a lower sleep efficiency index (SEI) and stage S3+S4 than 29/50 and 29/75. Stage REM and stage 3 were significantly decreased at 35/75 than at 29/50 and 35/50. Tr was maintained at a higher level at 35/75 than under the other conditions. Mean skin temperature was higher at 35/50 and 35/75 than at 29/50 and 29/75. These results suggest that humid heat exposure during night sleep increases the thermal load to supress the sleep-evoked Tr decrease, stage 3, SWS, and REM, and increase wakefulness.

Adult↗
PubMed1999

Characterization of polyol pathway in Schwann cells isolated from adult rat sciatic nerves.

To elucidate the molecular mechanisms underlying the development of diabetic neuropathy, we isolated the Schwann cells from the sciatic nerves of adult rats and characterized the polyol pathway activity. Despite the presence of aldose reductase (AR) activity, no accumulation of sorbitol was observed in the cells cultured under 30 mM glucose conditions. Increased levels of sorbitol were detected in the medium conditioned by these cells. SNK-860 (fidarestat), an inhibitor of AR, decreased the sorbitol levels at 10(-6)M, while addition of SDI-158, an inhibitor of sorbitol dehydrogenase, did not affect the level in the cells grown in high glucose. These observations suggested that sorbitol produced by AR in the isolated Schwann cells may be predominantly excreted. In contrast, a significant increase in sorbitol level was observed in cells cultured under hyperosmotic conditions with 30 mM glucose. A significant correlation was observed between sorbitol level and AR activity (r = 0.998). The increase was suppressed by addition of SNK-860, while SDI-158 augmented sorbitol accumulation in a dose-dependent manner. These results suggested that the isolated Schwann cells may not accumulate sorbitol unless the activity of AR is augmented by some as yet undetermined mechanism under high glucose conditions, such as the hyperosmotic stress induced in this study.

Animals↗
PubMed1999

Signaling from Rho to the actin cytoskeleton through protein kinases ROCK and LIM-kinase.

The actin cytoskeleton undergoes extensive remodeling during cell morphogenesis and motility. The small guanosine triphosphatase Rho regulates such remodeling, but the underlying mechanisms of this regulation remain unclear. Cofilin exhibits actin-depolymerizing activity that is inhibited as a result of its phosphorylation by LIM-kinase. Cofilin was phosphorylated in N1E-115 neuroblastoma cells during lysophosphatidic acid-induced, Rho-mediated neurite retraction. This phosphorylation was sensitive to Y-27632, a specific inhibitor of the Rho-associated kinase ROCK. ROCK, which is a downstream effector of Rho, did not phosphorylate cofilin directly but phosphorylated LIM-kinase, which in turn was activated to phosphorylate cofilin. Overexpression of LIM-kinase in HeLa cells induced the formation of actin stress fibers in a Y-27632-sensitive manner. These results indicate that phosphorylation of LIM-kinase by ROCK and consequently increased phosphorylation of cofilin by LIM-kinase contribute to Rho-induced reorganization of the actin cytoskeleton.

Actin Cytoskeleton↗
PubMed1999

CD45 negatively regulates lyn activity by dephosphorylating both positive and negative regulatory tyrosine residues in immature B cells.

Using CD45-deficient clones from the immature B cell line, WEHI-231, we previously demonstrated that CD45 selectively dephosphorylates the Src-family protein tyrosine kinase Lyn and inhibits its kinase activity. To further define the mechanisms of CD45 action on Lyn, we metabolically labeled Lyn from CD45-positive and -negative WEHI-231 cells and analyzed cyanogen bromide fragments by SDS-PAGE analysis. Phosphoamino acid analysis confirmed that Lyn is tyrosine phosphorylated with little serine or threonine phosphorylation. In CD45-negative cells, two bands at 8.2 and 4.1 kDa were phosphorylated in the absence of B cell Ag receptor (BCR) ligation. The 8.2-kDa band corresponded to a fragment containing the positive regulatory site (Tyr397), as assessed by its size and its phosphorylation in an in vitro kinase assay. The 4.1-kDa band was phosphorylated by COOH-terminal Src kinase, suggesting that it contains the COOH-terminal negative regulatory site (Tyr508). CD45 was also shown to dephosphorylate autophosphorylated Lyn in vitro. Thus, CD45 dephosphorylates not only the negative but also the positive regulatory tyrosine residues of Lyn. Furthermore, coimmunoprecipitations using anti-Igalpha Ab demonstrated that Lyn associated with the resting BCR was constitutively phosphorylated and activated in CD45-negative cells. In the parental cells, both regulatory sites were phosphorylated on BCR ligation. Taken collectively, these results suggest that CD45 keeps both BCR-associated and total cytoplasmic pools of Lyn in an inactive state, and a mechanism by which Lyn is activated by relative reduction of CD45 effect may be operative on BCR ligation.

Animals↗
PubMed1999

Polyunsaturated fatty acid anilides as inhibitors of acyl-coA: cholesterol acyltransferase (ACAT).

A series of polyunsaturated fatty acid anilides were synthesized and evaluated as ACAT inhibitors. Compound 24 had potent inhibitory activity against microsomal ACAT derived from U937, HepG2 and Caco-2 cell lines. Therefore, it might be expected to act as an antiarteriosclerotic and hypocholesterolemic agent. Interestingly, the ACAT inhibitory potency of 24 varied significantly depending on the source of the enzyme.

Adrenal Glands↗