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Biomedical subjects

K Mizuno

Publications and source records attributed to K Mizuno.

At least 91 records · Page 5Linked to original sources

Involvement of nitric oxide in the ocular hypotensive action of nipradilol.

PURPOSE: To evaluate the role of nitric oxide (NO) in the mechanism of the ocular hypotensive action of nipradilol, a beta-blocker with alpha( 1)-blocking activity. METHODS: Change in intraocular pressure (IOP) of albino rabbits was measured after a single application of carboxy-PTIO (c-PTIO), an NO trapping agent. Next, IOP change was measured every hour for 5 hours after the instillation of 0.25% nipradilol into one of the eyes with and without c-PTIO pretreatment of both eyes. IOP change induced by desnitro-nipradilol was also examined. The outflow facility and uveoscleral outflow were determined by two-level constant pressure and anterior chamber perfusion methods before and at 3 hours after the application of nipradilol with and without c-PTIO pretreatment. RESULTS: Topical administration of c-PTIO showed no significant effect on IOP. Unilateral instillation of nipradilol reduced IOP significantly compared with control eyes with a maximum reduction of 3.6 mmHg and effect duration of 3 hours. Pretreatment with c-PTIO partially inhibited the reduction during an earlier period (1 approximately 2 hours) and completely at 3 hours. IOP change by desnitro-nipradilol was similar to that by nipradilol with c-PTIO pretreatment. Nipradilol increased both outflow facility and uveoscleral outflow at 3 hours, whereas pretreatment with c-PTIO inhibited both of these outflows. CONCLUSIONS: Results indicate that ocular hypotensive action by nipradilol during the relatively late period may be mainly due to enhancement of aqueous humor outflow by NO at least in the rabbits.

Administration, Topical↗

Development of sucking behavior in infants with Down's syndrome.

UNLABELLED: The aim of this study was to gain a better understanding of the development of sucking behavior in infants with Down's syndrome. The sucking behavior of 14 infants with Down's syndrome was consecutively studied at 1, 4, 8 and 12 mo of age. They were free from complications that may cause sucking difficulty. The sucking pressure, expression pressure, frequency and duration were measured. In addition, an ultrasound study during sucking was performed in sagittal planes. Although levels of the sucking pressure and duration were in the normal range, significant development occurred with time. Ultrasonographic images showed deficiency in the smooth peristaltic tongue movement. CONCLUSION: The sucking deficiency in Down's syndrome may result from not only hypotonicity of the perioral muscles, lips and masticatory muscles, but also deficiency in the smooth tongue movement. This approach using the sucking pressure waveform and ultrasonography can help in the examination of the development of sucking behavior, intraoral movement and therapeutic effects.

Down Syndrome↗

Cofilin phosphorylation by protein kinase testicular protein kinase 1 and its role in integrin-mediated actin reorganization and focal adhesion formation.

Testicular protein kinase 1 (TESK1) is a serine/threonine kinase with a structure composed of a kinase domain related to those of LIM-kinases and a unique C-terminal proline-rich domain. Like LIM-kinases, TESK1 phosphorylated cofilin specifically at Ser-3, both in vitro and in vivo. When expressed in HeLa cells, TESK1 stimulated the formation of actin stress fibers and focal adhesions. In contrast to LIM-kinases, the kinase activity of TESK1 was not enhanced by Rho-associated kinase (ROCK) or p21-activated kinase, indicating that TESK1 is not their downstream effector. Both the kinase activity of TESK1 and the level of cofilin phosphorylation increased by plating cells on fibronectin. Y-27632, a specific inhibitor of ROCK, inhibited LIM-kinase-induced cofilin phosphorylation but did not affect fibronectin-induced or TESK1-induced cofilin phosphorylation in HeLa cells. Expression of a kinase-negative TESK1 suppressed cofilin phosphorylation and formation of stress fibers and focal adhesions induced in cells plated on fibronectin. These results suggest that TESK1 functions downstream of integrins and plays a key role in integrin-mediated actin reorganization, presumably through phosphorylating and inactivating cofilin. We propose that TESK1 and LIM-kinases commonly phosphorylate cofilin but are regulated in different ways and play distinct roles in actin reorganization in living cells.

Actin Depolymerizing Factors↗

Counteracting regulation of chromatin remodeling at a fission yeast cAMP response element-related recombination hotspot by stress-activated protein kinase, cAMP-dependent kinase and meiosis regulators.

In fission yeast, an ATF/CREB-family transcription factor Atf1-Pcr1 plays important roles in the activation of early meiotic processes via the stress-activated protein kinase (SAPK) and the cAMP-dependent protein kinase (PKA) pathways. In addition, Atf1-Pcr1 binds to a cAMP responsive element (CRE)-like sequence at the site of the ade6-M26 mutation, which results in local enhancement of meiotic recombination and chromatin remodeling. Here we studied the roles of meiosis-inducing signal transduction pathways in M26 chromatin remodeling. Chromatin analysis revealed that persistent activation of PKA in meiosis inhibited M26 chromatin remodeling, suggesting that the PKA pathway represses M26 chromatin remodeling. The SAPK pathway activated M26 chromatin remodeling, since mutants lacking a component of this pathway, the Wis1 or Spc1/Sty1 kinases, had no M26 chromatin remodeling. M26 chromatin remodeling also required the meiosis regulators Mei2 and Mei3 but not the subsequently acting regulators Sme2 and Mei4, suggesting that induction of M26 chromatin remodeling needs meiosis-inducing signals before premeiotic DNA replication. Similar meiotic chromatin remodeling occurred meiotically around natural M26 heptamer sequences. These results demonstrate the coordinated action of genetic and physiological factors required to remodel chromatin in preparation for high levels of meiotic recombination and eukaryotic cellular differentiation.

Cell Differentiation↗

Characterization of an isoform of rice starch branching enzyme, RBE4, in developing seeds.

cDNA clones encoding an isoform of starch branching enzyme, RBE4, have been identified from a developing rice seed cDNA library, using a synthetic oligonucleotide probe corresponding to the N-terminal amino acid sequence of RBE4. The cDNA-derived amino acid sequence indicated that RBE4 is initially produced as a precursor protein of 841 amino acids, including a 53-residue transit peptide at the N-terminus. The mature form of RBE4 shared a high degree of sequence identity (80%) with mature RBE3, and possessed an N-terminal extra sequence, as found in RBE3. Northern blot analysis demonstrated that the RBE4 gene is expressed in both leaves and developing seeds. The RBE4 gene was distinguished from the RBE1 and RBE3 genes by expression at the earlier stages of seed development. To examine enzymatic functions of RBE4, recombinant proteins were produced in Escherichia coli cells, and purified by two chromatographic separations. The branched alpha-glucans produced by the recombinant enzymes from potato amylose revealed the different patterns of oligosaccharide chain transfer. The peak of major branches of the products by RBE3 or RBE4 was 6 glucose units, whereas the peaks of major branches of the products by RBE1 were 6 and 11 glucose units. The similar property between RBE3 and RBE4 is supported by high similarity of the amino acid sequences between them.

1,4-alpha-Glucan Branching Enzyme↗

Oblique wedge osteotomy for femoral diaphyseal deformity in fibrous dysplasia: a case report.

A patient with fibrous dysplasia who had a three-dimensional diaphyseal deformity in the left femur was treated using an oblique wedge osteotomy. The patient was 26-year-old man with a history of two pathologic fractures in the midshaft of the femur. A 22 degrees angular deformity in the coronal plane and 15 degrees anterior bowing were corrected. The results at a followup 2 years after surgery were satisfactory in functional and radiologic terms. The technique and advantages of the oblique wedge osteotomy are discussed.

Adult↗

Parosteal lipoma of the distal phalanx: a case report and review of the literature.

A rare case of parosteal lipoma of the distal phalanx in a small finger of a 68-year-old woman is reported. Radiographs revealed an osseous projection and cortical irregularity in the distal phalanx of the right small finger. Magnetic resonance imaging showed a hyperintense soft tissue mass adjacent to the phalanx on T1-weighted and T2-weighted images. Histologically, the lesion consisted of mature fat cells. Marginal excision of the lesion was curative.

Aged↗

Pancreaticobiliary arteriovenous malformation with common bile duct dilation in a patient with hemobilia.

Arteriovenous malformation of the pancreas is a very rare entity. We describe a case involving the head of the pancreas associated with progressive hemobilia bleeding from the lower part of the common bile duct. The patient was a 50-year-old man with acute epigastralgia. Endoscopic retrograde cholangiopancreatography revealed hemobilia and cystic dilation of the common bile duct. Angiography demonstrated increased blood volume in the head of the pancreas and early filling of the superior mesenteric and portal veins. Abdominal pain and progressive anemia caused by hemobilia required surgical treatment. Histologic examination of the resected specimen revealed marked proliferation of the blood vessels in the pericholedochal area and the exact point of bleeding from the pancreaticobiliary arteriovenous malformation.

Angiography↗

Ulnar bursa distention following volar subluxation of the distal radioulnar joint after distal radial fracture: a rare cause of carpal tunnel syndrome.

This report describes an eighty-four-year-old woman with persistent carpal tunnel syndrome attributable to an ulnar bursa distention associated with the subluxation of the distal radioulnar joint after distal radial fracture. During surgery, when the forearm was placed in supination, the ulna head with a sharp osteophyte was found to be displaced into the carpal tunnel through a defect of the ruptured capsule of the wrist joint. This volar subluxation of the ulnar head had caused distention of the ulnar bursa, causing compression of the median nerve, which resulted in carpal tunnel syndrome. In addition to reduce displaced fractured segment to obtain anatomic articular surface, original radial length and tilt, the anatomic restoration of the distal radioulnar joint is essential to maintain better long-term function after fracture of the distal radius.

Accidental Falls↗

Tissue-specific autoregulation of the stat3 gene and its role in interleukin-6-induced survival signals in T cells.

Signal transducer and activator of transcription 3 (STAT3) mediates signals of various growth factors and cytokines, including interleukin-6 (IL-6). In certain IL-6-responsive cell lines, the stat3 gene is autoregulated by STAT3 through a composite IL-6 response element in its promoter that contains a STAT3-binding element (SBE) and a cyclic AMP-responsive element. To reveal the nature and roles of the stat3 autoregulation in vivo, we generated mice that harbor a mutation in the SBE (stat3(mSBE)). The intact SBE was crucial for IL-6-induced stat3 gene activation in the spleen, especially in the red pulp region, the kidney, and both mature and immature T lymphocytes. The SBE was not required, however, for IL-6-induced stat3 gene activation in hepatocytes. T lymphocytes from the stat3(mSBE/mSBE) mice were more susceptible to apoptosis despite the presence of IL-6 than those from wild-type mice. Consistent with this, IL-6-dependent activation of the Pim-1 and junB genes, direct target genes for STAT3, was attenuated in T lymphocytes of the stat3(mSBE/mSBE) mice. Thus, the tissue-specific autoregulation of the stat3 gene operates in vivo and plays a role in IL-6-induced antiapoptotic signaling in T cells.

Animals↗

Pharmacological properties of fidarestat, a potent aldose reductase inhibitor, clarified by using sorbitol in human and rat erythrocytes.

We examined the effect of fidarestat on the increase in sorbitol content in erythrocytes from healthy volunteers in vitro. Fidarestat inhibited the increase with an IC50 value of 18 nmol/l. A subsequent experiment showed that fidarestat had a similar inhibitory effect on the increase in sorbitol content in erythrocytes from diabetic patients. On the other hand, epalrestat, the only aldose reductase inhibitor used clinically, inhibited increase in sorbitol content at a concentration over 500-fold higher than fidarestat. Although the IC50 value of fidarestat was not affected by fasting plasma glucose, HbA1C, age, aldose reductase content or gender, there was a significant positive relationship between the IC50 value of epalrestat and fasting plasma glucose. In addition, in fidarestat (0.25-2 mg/kg)-treated diabetic rats, the inhibitory rate for erythrocyte sorbitol accumulation was well correlated with that for nerve sorbitol accumulation, which indicates that erythrocyte sorbitol is available for assessing the state of sorbitol pathway flux in target tissue after fidarestat administration. These results suggest that fidarestat potently inhibits the increase in sorbitol pathway flux in diabetic patients independent of various factors and that erythrocyte sorbitol is useful for its estimation.

Age Factors↗

Fibroma of a tendon-sheath presenting as toe deformity.

We describe a rare manifestation fibroma in a tendon-sheath in an 83-year-old man. The patient complained initially of a slowly progressive spreading, apart of the right second and third toes. A mass was found in the plantar aspect of the foot. It was completely excised at surgery. Histological examination revealed sparse spindle or stellate cells with slit-like vessels in the dense collagenous matrix. There had been no recurrence at follow-up 17 months after surgery.

Aged↗

Low-intensity pulsed ultrasound initiates bone healing in rat nonunion fracture model.

Low-intensity pulsed ultrasound exposure has been shown clinically to shorten the fracture repair process and to induce healing of nonunions in humans, but its mechanism of action remains unclear. In this study we investigated the effect and mechanism of low-intensity pulsed ultrasound on nonunion fracture healing in rat tibias. A consistently reproducible nonunion was produced in rat tibias by muscle interposition without osteotomy. This model was produced by creating a closed tibial fracture with only the distal end of the tibialis anterior muscle interposed into the fracture site. One limb was noninvasively exposed to low-intensity pulsed ultrasound (a 200-millisecond burst of sine waves of 1.5 MHz, repeating at 1.0 kHz) for 20 minutes daily. The incident intensity was approximately 30 mW/cm2. Rats were killed at intervals between 2 and 6 weeks. The events were assessed by radiographs, microfocus X-ray computed tomograms, and histologic examination. After 6 weeks of exposure, 7 of 14 nonunion fractures showed healing on radiologic assessment. The results of three-dimensional microfocus X-ray computed tomographic reconstruction and histologic examination also supported this finding. On the other hand, all control tibias remained in a state of nonunion during the same period. These results indicate that low-intensity pulsed ultrasound promotes healing in the rat nonunion fracture model.

Animals↗

Neuroprotective effect and intraocular penetration of nipradilol, a beta-blocker with nitric oxide donative action.

PURPOSE: To investigate the effect of nipradilol, an alpha(1),beta-blocker with a nitric oxide donative action, on N:-methyl-D-aspartate (NMDA)-induced retinal damage in rats and to determine whether topically instilled nipradilol penetrates the ipsilateral posterior retina-choroid at pharmacologically active concentrations in rabbits. METHODS: To determine effects on NMDA-induced damage, drugs were injected alone or with NMDA into the vitreous of one eye, and cell loss in the ganglion cell layer (GCL) and thinning of the retinal neural cell layers were histologically evaluated. To evaluate posterior penetration, first, [(14)C]-nipradilol was instilled, and its tissue concentration was measured. Second, nipradilol or timolol was instilled, and their effects on intravitreal injection of endothelin-1-induced retinal artery contraction were compared, to evaluate whether a pharmacologically active level of nipradilol penetrates the inner limiting layer by topical application. RESULTS: Intravitreous injection of NMDA reduced cell numbers in the GCL and the thickness of the inner plexiform layer (IPL) to 50.4% +/- 2.6% and 47.8% +/- 4.9% (n = 8) of control, respectively. Nipradilol alone had no effect. Coadministration of nipradilol with NMDA reduced cell numbers in the GCL and IPL thickness to 67.8% +/- 2.2% and 74.4% +/- 5.2% of control, respectively (P: < 0.05-0.01). Sodium nitroprusside, but not timolol or bunazosin, also significantly prevented the NMDA-induced reduction of cell numbers in the GCL and IPL thickness. Radioactivity of nipradilol was found in the ipsilateral posterior retina-choroid at 318.6 +/- 42.9 ng/g (n = 4), which was significantly higher than in the contralateral control (107.4 +/- 21.8 ng/g). Topical application of nipradilol, but not timolol, significantly suppressed the endothelin-1-induced contraction of the retinal artery (83.95% +/- 8.15% and 35.24% +/- 5.62% of baseline vessel diameter for nipradilol and timolol, respectively). CONCLUSIONS: Nipradilol suppressed the NMDA-induced retinal damage in rats for which nitric oxide released from nipradilol may be responsible. Posterior penetration studies suggested that an effective concentration of nipradilol reached the posterior retina after topical application.

Adrenergic alpha-Antagonists↗

Elastofibroma in shoulder osteoarthritis: a theoretical concept of the etiology.

A case of unilateral, subscapular elastofibroma dorsi secondary to degenerative osteoarthritis in the ipsilateral glenohumeral joint is presented. A 69-year-old woman had experienced symptoms of osteoarthritis in the right shoulder since contracting septic arthritis when she was 7 years old. The patient noticed a soft tissue mass in the right subscapular region when she was 65 years old. The range of motion of the glenohumeral joint was severely restricted. Histopathologic examination of the excised mass revealed elastofibroma. The authors think the excessive scapulothoracic motion was important in formation of the lesion. This case indicates that elastofibroma is not a true neoplasm but a reactive lesion formed by repetitive minor trauma.

Aged↗