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Biomedical subjects

M Sone

Publications and source records attributed to M Sone.

At least 19 recordsLinked to original sources

Blood flow to the promontory in cochlear otosclerosis.

OBJECTIVE: To investigate Schwartze sign with measurements of blood flow to the promontory in patients with cochlear otosclerosis. DESIGN: Prospective clinical study. SETTING: Tertiary referral centre. PARTICIPANTS: Five patients with cochlear otosclerosis and five control subjects. Significant decalcification around the cochlea was observed by computed tomography (CT) in patients with cochlear otosclerosis. However, no recognizable lesion was observed at the oval window in two patients. One patient had mixed hearing loss and four patients had sensorineural hearing loss without an air-bone gap. MAIN OUTCOME MEASURES: The relationship between CT findings and the presence or absence of Schwartze sign was investigated. Blood flow to the promontory was measured through the tympanic membrane using laser speckle flowgraphy and laser Doppler flowmetry. RESULTS: The Schwartze sign correlated significantly with otosclerotic lesions invading the promontory. Patients with otosclerosis exhibited elevated and pulsating blood flow to the promontory with the Schwartze sign. CONCLUSIONS: Computed tomography demonstrated that cochlear otosclerosis can exist without the oval window lesion. Schwartze sign can be used as a sign of the otosclerotic invasion to the promontory. The reddening of the Schwartze sign is likely due to increased blood flow.

Adult↗

Accelerated reendothelialization with suppressed thrombogenic property and neointimal hyperplasia of rabbit jugular vein grafts by adenovirus-mediated gene transfer of C-type natriuretic peptide.

BACKGROUND: Vein graft disease limits the late results of coronary revascularization. C-type natriuretic peptide (CNP) inhibits the growth of vascular smooth muscle cells. Given the effects of CNP on cGMP cascade, we hypothesized that transfected CNP genes modulate endothelial repair and thrombogenicity in the vein graft. METHODS AND RESULTS: Autologous rabbit jugular vein grafts were incubated ex vivo in a solution of adenovirus vectors containing CNP gene (Ad.CNP) or Escherichia coli lac Z gene (Ad.LacZ) and then interposed in the carotid artery. Reendothelialization, mural thrombi formation, and intima/media ratio were evaluated on the 14th and 28th postoperative days. More reendothelialization was seen in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts both at 14 days (0.81+/-0.05 versus 0.30+/-0.14, P<0.01) and at 28 days (0.96+/-0.01 versus 0.45+/-0.08, P<0.001). The mural thrombus area was smaller in Ad.CNP-infected grafts than in Ad.LacZ-infected grafts. Neointimal thickening was significantly suppressed in the Ad.CNP group. The in vitro wound assay with human coronary artery endothelial cells revealed significant potentiation of the wound repair process by CNP and atrial natriuretic peptide administration. CONCLUSIONS: Infected Ad.CNP accelerated reendothelialization and suppressed thrombosis and neointimal hyperplasia. The method may potentially prevent vein graft disease in patients undergoing coronary artery revascularization.

Adenoviridae↗

Role of urotensin II in patients on dialysis.

Urotensin II is a potent vasoconstrictor, which also has some vasodilatory properties. We investigated its expression in various tissues and in the plasma of patients with renal dysfunction. Plasma concentrations of urotensin II-like immunoreactivity were 2-fold higher in patients not on dialysis and 3-fold higher in those on haemodialysis thanin healthy individuals. Messenger RNA encoding theurotensin II precursor and the urotensin II receptor precursor were expressed in various human tissues. The peptidemight act as an important regulator in the cardiovascularand renal systems. Urotensin II antagonists could, therefore, be useful in the treatment of diseases affecting theseorgans.

Adult↗

cGMP-dependent protein kinase phosphorylates and inactivates RhoA.

Small GTPase Rho and cGMP/cGMP-dependent protein kinase (cGK) pathways exert opposing effects in specific systems such as vascular contraction and growth. However, the direct interaction between these pathways has remained elusive. We demonstrate that cGK phosphorylates RhoA in vitro at Ser188, the same residue phosphorylated by cAMP-dependent protein kinase. In HeLa cells transfected with constitutively active cGK (C-cGK), stress fiber formation induced by lysophosphatidic acid or V14RhoA was blocked. By contrast, C-cGK failed to inhibit stress fiber formation in cells transfected with mutant RhoA with substitution of Ser188 to Ala. C-cGK did not affect actin reorganization induced by Rac1 or Rho-associated kinase, one of the effectors for RhoA. Furthermore, C-cGK expression inhibited the membrane translocation of RhoA. Collectively, our findings suggest that cGK phosphorylates RhoA at Ser188 and inactivates RhoA signaling. The physiological relevance of the direct interaction between RhoA and cGK awaits further investigation.

Actins↗

Younger patients have a higher rate of recovery of taste function after middle ear surgery.

BACKGROUND: Although the chorda tympani nerve (CTN) is frequently damaged during tympanoplasty, little attention has been given to the patients' symptoms and taste function. OBJECTIVE: To investigate patients' symptoms and the functional recovery of taste after surgery using electrogustometry (EGM). DESIGN: Prospective study. PATIENTS: Analysis of 163 ears of 156 patients who underwent middle ear surgery from April 1997 through December 1999. There were 18 ears with noninflammatory diseases, 80 with chronic otitis media, and 65 with cholesteatoma. The patients' taste functions were examined 2 days before surgery and 2 weeks and 6 months after surgery. MAIN OUTCOME MEASURES: The taste disturbance before and after middle ear surgery and the relationship between age and the recovery rate of CTN function. RESULTS: Two weeks after surgery, the mean EGM threshold was elevated in all groups regardless of preservation or section of the CTN. Numbness in the tongue and taste disturbance were more frequently found in patients with preservation of CTN than in those with section of the CTN (P =.008 and P =.001, respectively). In patients with preservation of the CTN, 6 months after surgery, the recovery rate of EGM threshold was 83% in those aged 20 years or younger (P =.008 compared with the 2 older groups), 53% in the those aged 21 to 40 years, and 44% in those aged 41 to 60 years. CONCLUSION: Age is an important factor for recovery of taste function after middle ear surgery, which is useful information when explaining complications to patients.

Adolescent↗

Amino acids protect epithelial cells from local toxicity by absorption enhancer, sodium laurate.

To develop the safe absorption-enhancing formulation attenuating the local toxicity caused by an absorption enhancer, sodium laurate (C12), the effects of amino acids on the local toxicity by C12 were examined in rats. The absorption of phenol red, an unabsorbable marker drug, was significantly enhanced by 10 mM C12 in an in situ colon loop study and the addition of L-glutamine (L-Gln), L-arginine, or L-methionine at 10 mM did not change the promoting effect of C12. However, C12 significantly increased the elution of phospholipids, total protein, and lactate dehydrogenase, which are markers for local toxicity, from colon, but these amino acids attenuated the local toxicity caused by C12 significantly. Transport study using an Ussing-type chamber showed that the permeability of colonic membrane to phenol red was significantly enhanced by C12 and that L-Gln did not decrease the permeability enhanced by C12. Transmucosal electrical resistance was extensively decreased by C12, indicating that C12 could enhance the drug absorption at least partly by expanding the paracellular route. L-Gln significantly, but not completely, recovered resistance lowered by C12. Electrical potential difference was markedly reduced by C12, suggesting that C12 lowered the viability of mucosal cells, but 10 mM L-Gln significantly recovered potential difference almost to the control level. These results suggested the possibility that absorption-enhancing formulation with low local toxicity, which is low enough to be used practically, could be developed by using an amino acid like L-Gln as an ingredient attenuating the local toxicity caused by C12.

Amino Acids↗

Expression and localization of leptin receptor in the normal rat pituitary gland.

Leptin receptor (leptin-R) is a polypeptide consisting of a single transmembrane-spanning component. Recent studies performed by reverse transcriptase polymerase chain reaction (RT-PCR) have shown the production of leptin-R in various tissues including the pituitary, hypothalamus and reproductive organs. The localization of leptin-R protein in the pituitary gland, however, has not been extensively studied. This study deals with the expression of leptin-R in the normal rat pituitary gland, which was disclosed primarily in the plasma membrane fraction by immunoblotting and immunohistochemical staining methods. Double immunohistochemical staining revealed that the colocalization of leptin-R and anterior pituitary hormone expression was seen mainly in growth hormone (GH)-secreting cells (97.4 +/- 1.3%; GH-positive cells/leptin-R-positive cells), but in less than 1% of prolactin (PRL)-, adrenocorticotropic hormone (ACTH)-, thyroid-stimulating hormone-beta (TSH beta)- and follicle-stimulating hormone-beta (FSH beta)/luteinizing hormone-beta (LH beta)-positive cells. In contrast, leptin was localized most frequently in FSH beta/LH beta- and less frequently in TSH beta-positive cells. The above findings suggest that, in the rat anterior pituitary gland, there are paracrine relationships between leptin-producing cells and cells with leptin-R, which may regulate the function of GH cells.

Adrenocorticotropic Hormone↗

Immunoreactive orexin-A in human plasma.

Orexin-A and orexin-B are newly discovered neuropeptides which are implicated in feeding behavior and arousal state. We studied immunoreactive(IR)-orexin-A concentrations in human plasma by radioimmunoassay. IR-orexin-A concentrations in plasma obtained from 17 healthy subjects in the morning were 1.94 +/- 0.24 pmol/liter (mean +/- SEM). IR-orexin-A levels in the plasma obtained at night were not significantly different from those obtained in the morning in 9 female subjects. The HPLC analysis of the plasma extract showed two immunoreactive peaks; one peak eluting in an identical position to synthetic orexin-A, and one eluting earlier. This study has shown for the first time the presence of orexin-A in human plasma.

Adult↗

Adrenomedullin and its receptor complexes in remnant kidneys of rats with renal mass ablation: decreased expression of calcitonin receptor-like receptor and receptor-activity modifying protein-3.

Adrenomedullin (AM) has vasodilator and diuretic actions, similarly to natriuretic peptides. AM receptor complexes are composed of calcitonin receptor-like receptor (CRLR) and receptor-activity modifying protein-2 (RAMP2), or CRLR and RAMP3. We aimed to know whether gene expression of AM and AM receptor complexes are regulated in kidneys under pathophysiological conditions. Expression of AM, RAMP2, RAMP3 and CRLR mRNA was studied in the remnant kidney of rats with renal mass ablation using competitive quantitative RT-PCR techniques. Partial cloning was performed to determine the rat RAMP3 nucleotide sequence. In normal rat kidneys, expression levels of RAMP2, RAMP3, CRLR and AM mRNAs were 26.5 +/- 1.9 mmol/mole of GAPDH, 7.7 +/- 0.9 mmol/mole of GAPDH, 3.6 +/- 0.2 mmol/mole of GAPDH and 0.57 +/- 0.03 mmol/mole of GAPDH (mean +/- SE, n = 6), respectively. RAMP3 mRNA levels decreased significantly to about 50% and about 70% of control (sham-operated rats) 4 days and 14 days after 5/6 nephrectomy, respectively. CRLR mRNA levels also decreased significantly to about 30% and about 43% of control. Sodium intake restriction had no significant effects on the RAMP3 and CRLR gene expression. On the other hand, RAMP2 mRNA expression in the kidney was suppressed by sodium intake restriction regardless of nephrectomy, while RAMP2 levels in the remnant kidney were not significantly changed by 5/6 nephrectomy. Neither 5/6 nephrectomy or sodium intake restriction had any significant effects on the AM gene expression in the kidney. The present study showed that expression of mRNAs encoding AM, RAMP2, RAMP3 and CRLR were differentially regulated in remnant kidneys of rats with renal mass ablation.

Adrenomedullin↗

Effect of the reducing agent on the oxygen-inhibited layer of the cross-linked reline material.

The purpose of this study was to clarify the effect of the reducing agent on the oxygen-inhibited layer of the cross-linked reline material. A commercial autopolymerizing reline resin containing 1,6-hexanediol dimethacrylate as cross-linking agent and 1 wt.% sodium sulphite solution as a reducing agent was prepared. The inhibited layer was observed using an optical transmission microscope under the conditions of the application of sodium sulphite for 0, 1, 5 and 15 min after curing for 10 min in air. As a control, the reline material was cured on sealing from air. Moreover, the three-point flexural strength test was performed under the same conditions. The fracture was then observed using scanning electron microscopy (SEM). Although hardness of the inhibited layer was enhanced after the application of the reducing agent, the layer was still observed. The flexural strength of the control and the groups after application of the reducing agent was significantly higher than the group without reducing agent. SEM examination revealed many polymer beads on the group without reducing agent, whereas polymer beads could not be observed on the groups applying the reducing agent. These results indicated that the application of sodium sulphite was effective in hardening the surface unpolymerized zone.

Analysis of Variance↗

Oxidized LDL regulates vascular endothelial growth factor expression in human macrophages and endothelial cells through activation of peroxisome proliferator-activated receptor-gamma.

Vascular endothelial growth factor (VEGF) has been recognized as an angiogenic factor that induces endothelial proliferation and vascular permeability. Recent studies have also suggested that VEGF can promote macrophage migration, which is critical for atherosclerosis. We have reported that VEGF is remarkably expressed in activated macrophages, endothelial cells, and smooth muscle cells within human coronary atherosclerotic lesions, and we have proposed the significance of VEGF in the progression of atherosclerosis. To clarify the mechanism of VEGF expression in atherosclerotic lesions, we examined the regulation of VEGF expression by oxidized low density lipoprotein (Ox-LDL), which is abundant in atherosclerotic arterial walls. A recent report has revealed that peroxisome proliferator-activated receptor-gamma (PPARgamma) is expressed not only in adipocytes but also in monocytes/macrophages and has suggested that PPARgamma may have a role in the differentiation of monocytes/macrophages. Furthermore, 9- and 13-hydroxy-(S)-10,12-octadecadienoic acid (9- and 13-HODE, respectively), the components of Ox-LDL, may be PPARgamma ligands. Therefore, we investigated the involvement of PPARgamma in the regulation of VEGF by Ox-LDL. PPARgamma expression was detected in human monocyte/macrophage cell lines, human acute monocytic leukemia (THP-1) cells, and human coronary artery endothelial cells (HCAECs). Ox-LDL (10 to 50 microg/mL) upregulated VEGF secretion from THP-1 dose-dependently. VEGF mRNA expression in HCAECs was also upregulated by Ox-LDL. The mRNA expression of VEGF in THP-1 cells and HCAECs was also augmented by PPARgamma activators, troglitazone (TRO), and 15-deoxy-(12,14)-prostaglandin J(2) (PGJ2). In contrast, VEGF expression in another monocyte/macrophage cell line, human histiocytic lymphoma cells (U937), which lacks PPARgamma expression, was not augmented by TRO or PGJ2. We established the U937 cell line, which permanently expresses PPARgamma (U937T). TRO and Ox-LDL augmented VEGF expression in U937T. In addition, VEGF production by THP-1 cells was significantly increased by exposure to 9-HODE and 13-HODE. In conclusion, Ox-LDL upregulates VEGF expression in macrophages and endothelial cells, at least in part, through the activation of PPARgamma.

Arteriosclerosis↗

C-type natriuretic peptide induces redifferentiation of vascular smooth muscle cells with accelerated reendothelialization.

We recently reported that C-type natriuretic peptide (CNP) occurs in vascular endothelial cells and acts as a vascular-type natriuretic peptide. In the present study, we stimulated the cGMP cascade in proliferating smooth muscle cells (SMCs), in which particulate guanylate cyclase-B, the specific receptor for CNP, is predominantly expressed, by use of an adenovirus encoding rat CNP cDNA (Ad.CNP). In the Ad.CNP-treated cultured SMCs, CNP caused the growth inhibition of SMCs at G(1) phase with an early increase of p21(CIP1/WAF1) expression and subsequent upregulation of p16(INK4a). The expression of smooth muscle myosin heavy chain-2, which is the molecular marker of highly differentiated SMCs, was reinduced in the Ad.CNP-treated SMCs. The Ad.CNP-treated SMCs also reexpressed particulate guanylate cyclase-A, which shows high affinity to atrial and brain natriuretic peptide and is exclusively expressed in well-differentiated SMCs. CNP, which was overexpressed in rabbit femoral arteries in vivo at the time of balloon injury, significantly suppressed neointimal formation. Furthermore, an enhancement of the expression of smooth muscle myosin heavy chain-2 occurred in the residual neointima. In addition, early regeneration of endothelial cells was observed in the Ad.CNP-infected group. Thus, stimulation of cGMP cascade in proliferating dedifferentiated SMCs can induce growth inhibition and redifferentiation of SMCs with accelerated reendothelialization.

Adenoviridae↗

Expression of melanin-concentrating hormone receptor messenger ribonucleic acid in tumor tissues of pheochromocytoma, ganglioneuroblastoma, and neuroblastoma.

Expression of melanin-concentrating hormone (MCH) receptor messenger ribonucleic acid (mRNA) was studied by RT-PCR and Northern blot analysis in human brain; pituitary; adrenal glands; tumor tissues of adrenal tumors, ganglioneuroblastomas, and neuroblastomas; and various cultured tumor cell lines. RT-PCR analysis showed that MCH receptor mRNA was widely expressed in brain tissues, pituitary, normal portions of adrenal glands (cortex and medulla), tumor tissues of adrenocortical tumors (12 of 13 cases), pheochromocytoma (all 7 cases), ganglioneuroblastoma (1 case), neuroblastoma (all 5 cases), and various cultured tumor cell lines (6 of 7 cell lines), including 2 neuroblastoma cell lines. Northern blot analysis showed the expression of MCH receptor mRNA ( approximately 2.4 kb) only in the tumor tissues of 5 pheochromocytomas, 1 ganglioneuroblastoma, and 4 neuroblastomas, indicating that the expression levels of MCH receptor mRNA are much higher in these tumors than in the other tissues. These findings raised the possibility that MCH or MCH-like peptides may be related to the pathophysiology of these neural crest-derived tumors.

Adrenal Gland Neoplasms↗

Dynamic computer tomography is useful in the differential diagnosis of juxtaglomerular cell tumor and renal cell carcinoma.

We compared dynamic computer tomographic CT images of 3 cases of juxtaglomerular (JG) cell tumor with those of 8 cases of renal cell carcinoma (RCC). The JG cell tumor was visualized as a low- to high-density area in case 1, a low-density area in case 2, and a low- to iso-density area in case 3 before contrast enhancement. None of the JG cell tumors were stained during the early phase (1 min), but all were stained moderately during the late phase (5 min) after contrast enhancement. Although all cases of RCC were visualized as a low- to iso-density area before contrast enhancement, they were intensely stained during the early phase with significant washout during the late phase. The present results suggest that the dynamic CT scan is useful in the differential diagnosis of the JG cell tumor and RCC.

Adenocarcinoma↗

[Audiological and equilibrium study of perilymphatic fistulas].

We clinically analyzed 15 cases of perilymphatic fistulas--11 caused by barotraumas and 4 idiopathic--identified by surgery between March 1995 and March 1999 at the Hyogo College of Medicine and affiliated hospitals. Subjects were 11 men and 4 women (aged 14 to 79 years (mean: 46.7 years)). All showed hearing loss in audiography and 12 cases reported tinnitus--stream-like in 5 and poping in 4. Dysequilibrium was seen in 9 cases. Perilymph leakage was detected intraoperatively from the oval window in 9, from the round window in 4, and from both windows in 1, while another had leakage from the fissura ante fenestram. After surgery, hearing level improved by over 10 dB in 9 of the 11 cases operated on within 14 days after onset. Hearing did not improve in 3 of 4 operated on later. Vertigo disappeared after surgery. Dizziness tended to persist in those having canal paresis or paralytic nystagmus before surgery. We suggest that patients with progressive hearing loss should be operated on as soon as possible and that patients with dysequilibrium or without response to conservative treatment undergo surgery within 14 days of onset.

Adolescent↗

[A case of recurrent aseptic meningitis caused by high-dose intravenous gammaglobulin therapy for chronic inflammatory demyelinating polyneuropathy].

We experienced a patient of CIDP who was twice complicated with aseptic meningitis following high-dose intravenous gammaglobulin therapy. The patient was a 29-year-old woman who first developed gait disturbance in September 1998. Neurological examination revealed muscle weakness and sensory disturbance in the distal parts of four extremities and decrease of deep tendon reflexes. Cerebrospinal fluid analysis revealed an elevated protein content and a normal cell count. Steroid therapy was effective in early stage, however, this effectiveness had been reduced gradually. She received high-dose intravenous gammaglobulin administrations in September 1999. On the fourth day after start of this therapy, she developed severe headache, nausea and nuchal rigidity without fever. Cerebrospinal fluid analysis revealed an increased cell count of mononuclear predominance and an elevated protein content. As bacterial culture remained negative and viral titers were not elevated, aseptic meningitis was diagnosed. The therapy was stopped, and thereafter her headache continued for 7 days. The muscle weakness and sensory disturbance were remarkably improved, but 9 months later, her symptoms became worse again. She received high-dose gammaglobulin administrations for 2 days in June 2000 and developed aseptic meningitis again. Over again, 9 months later, she received the same medication for only 1 day in March 2001 and she developed mild headache but not meningitis. Aseptic meningitis with CIDP following high-dose gammaglobulin therapy was rare, however, we should pay attention to this therapy in patients with CIDP and may prevent the occurrence of aseptic meningitis by reducing the total dose and shortening the administration periods of gammaglobulin.

Adult↗

GAL4/UAS-WGA system as a powerful tool for tracing Drosophila transsynaptic neural pathways.

Visualization of specific transsynaptic neural pathways is an indispensable technique for understanding the relationship between structure and function in the nervous system. Here, we demonstrate the application of the wheat germ agglutinin (WGA) transgene technique for tracing transsynaptic neural pathways in Drosophila. The intracellular localization of WGA was examined by immunoelectron microscopy. WGA signals were detected in granule-like structures in both the outer photoreceptor cells expressing WGA and the second-order laminar neurons. Misexpression of tetanus toxin (TNT), which inactivates N-synaptobrevin, in the outer photoreceptor cells resulted in the elimination of on/off transients in electroretinogram (ERG) recordings and in a great reduction in WGA transfer into laminar neurons, suggesting that anterograde WGA transsynaptic transfer is dependent mainly on synaptic transmission. Retrograde WGA transfer was also detected upon its forced expression in muscle cells. WGA primarily expressed in muscle cells was taken up by motoneuron axons and transported to their cell bodies in the ventral nerve cord, suggesting that WGA can trace motoneuronal pathways in combination with the muscle-specific GAL4 driver. Thus, the GAL4/UAS-WGA system should facilitate the dissection of the Drosophila neural circuit formation and/or synaptic activity in various regions and at various developmental stages.

Animals↗