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Biomedical subjects

H Kurihara

Publications and source records attributed to H Kurihara.

At least 55 records · Page 3Linked to original sources

FAT is a component of glomerular slit diaphragms.

BACKGROUND: Slit diaphragms are intercellular junctions of podocytes of the renal glomerulus. The molecular composition of slit diaphragms is still elusive. Slit diaphragms are characterized by the presence of a wide intercellular space. The morphological feature is shared by desmosomes and adherens junctions, which contain members of the cadherin superfamily. Thus, we have hypothesized that some components of slit diaphragms belong to the cadherin superfamily. Consequently, we have isolated cDNA encoding FAT from reverse-transcribed (RT) glomerular cDNA by homology polymerase chain reaction (PCR) using primers based on conserved sequences in cadherin molecules. FAT is a novel member of the cadherin superfamily with 34 tandem cadherin-like extracellular repeats, and it closely resembles the Drosophila tumor suppressor fat. METHODS: Expression of FAT was examined in glomeruli of the adult rat kidney by the ribonuclease protection assay and in situ hybridization. To localize the FAT protein in podocytes minutely, we prepared affinity-purified antibody against FAT by immunizing rabbits against an oligopeptide corresponding to the C-terminal 20 amino acids. RESULTS: Expression of FAT mRNA was detected in total RNA from glomeruli. In situ hybridization revealed significant signals in podocytes. Western blot analysis using solubilized glomeruli showed a single band, in which the molecular weight was more than 500 kD. Immunostaining of cultured epithelial cells from rat kidney (NRK52E) revealed FAT accumulation in cell-cell contact sites. In the glomerulus, FAT staining was observed distinctly along glomerular capillary walls. Double-label immunostaining using monoclonal antibody against slit diaphragms (mAb 5-1-6) showed identical localization of anti-FAT antibody and mAb 5-1-6. Furthermore, the double-label immunogold technique with ultrathin cryosections demonstrated that gold particles for FAT cytoplasmic domain were located at the base of slit diaphragms labeled by mAb 5-1-6 and that the cytoplasmic domain of FAT colocalized with ZO-1, a cytoplasmic component associated with slit diaphragms. CONCLUSION: The molecular structure of FAT and its colocalization with 5-1-6 antigen and ZO-1 indicate that FAT is a component of slit diaphragms.

Animals↗

Endothelin-1 protects astrocytes from hypoxic/ischemic injury.

Under pathological conditions such as ischemia (I), subarachnoid hemorrhage, and Alzheimer's disease, astrocytes show a large increase in endothelin (ET) -like immunoreactivity. However, it is not clear whether ET is protective or destructive to these cells during brain injury. Using astrocytes from ET-1-deficient mice, we determined the effect of ET-1 on these cells under normal, hypoxic (H), and hypoxic/ischemic (H/I) conditions. Under normal culture conditions, astrocytes from wild-type and ET-1-deficient mice showed no difference in their morphology and cell proliferation rates. ET-3 and ETA receptor mRNAs were up-regulated whereas ETB receptor mRNA was down-regulated in ET-1-deficient astrocytes, suggesting that ET-1 and ET-3 may complement each other's functions and that the expressions of these endothelins and their receptors are regulated by a complex feedback mechanism. Under H and H/I conditions, ET-1 peptide and mRNA were up-regulated in wild-type astrocytes, and the astrocytes without ET-1 died faster than the wild-type astrocytes, as indicated by greater efflux of lactate dehydrogenase. The present study suggests that astrocytes without ET-1 are more vulnerable to H and H/I injuries and that the up-regulation of astrocytic ET-1 is essential for the survival of astrocytes.

Animals↗

Solitary fibrous tumor of the orbit with extraorbital extension: case report.

OBJECTIVE AND IMPORTANCE: Solitary fibrous tumors (SFTs) are rare tumors of mesenchymal origin that typically arise in the pleura. Only 24 cases of SFTs in the orbit have been reported, all located within the orbit and generally with a benign course. We report the first case of an orbital SFT with extraorbital extension and short-term regrowth. CLINICAL PRESENTATION: A 54-year-old man presented with proptosis and double vision that had persisted for 7 months. The tumor extended from the right extraconal inferolateral orbit to the extradural middle cranial fossa and cavernous sinus, via the superior orbital fissure, on magnetic resonance imaging scans. Positron emission tomography with [(18)F]fluorodeoxyglucose demonstrated faint uptake in the orbital portion. INTERVENTION: Resection of the tumor was performed twice, because of short-term regrowth of the residual tumor in the orbit. The histological diagnosis was a SFT. The MIB-1 labeling index was 7% and the mitotic count was 5 mitotic figures/10 high-power fields at the time of the second operation. These findings indicate the malignant nature of the tumor. CONCLUSION: The natural history of SFTs of the orbit remains unclear, and the importance of careful and continued follow-up monitoring of the tumor should be emphasized.

Brain Neoplasms↗

Evidence for the physiological and pathological roles of adrenomedullin from genetic engineering in mice.

Adrenomedullin (AM) has been implicated as having hypotensive as well as protective effects on organs and vessels against different kinds of injuries. To elucidate the in vivo pathophysiological roles of adrenomedullin, we established transgenic mice (AMTg) overexpressing adrenomedullin driven by preproendothelin-1 promoter and adrenomedullin knockout mice (AMKO). Blood pressure in AMTg was significantly lower than that in wild-type mice, and AMTg was significantly resistant to lipopolysaccharide-induced septic shock and vascular injuries. On the other hand, heterozygotes of AMKO, AM(+/-), were fully viable and hypertensive as compared with wild littermates. Mice homozygous for adrenomedullin null mutation (AM-/-) were embryonic lethal, and no embryos could survive beyond the midterm of gestation. Collectively, our findings indicate the indispensable role of adrenomedullin in circulatory homeostasis and the organ protection as well as the fetal morphogenesis and the maintenance of pregnancy.

Adrenomedullin↗

Association analysis of beta(2)-adrenergic receptor polymorphisms with hypertension in Japanese.

Significant evidence has been provided for the pathophysiological involvement of the beta(2)-adrenergic receptor (ADRB2) in hypertension. Among ADRB2 polymorphisms identified to date, 2 amino acid substitutions, Arg16Gly and Gln27Glu, and a promoter variant, T-47C, are considered functionally important. In particular, Arg16Gly was shown to be associated with hypertension in black and white subjects. To investigate the relevance of ADRB2 polymorphisms to hypertension, we undertook an extensive association study in a Japanese population. An association was tested in 2 ways. First, a case-control study was conducted in 842 hypertensive and 633 normotensive subjects. In addition to the overall comparison between case and control groups, each was stratified by body mass index and compared with an independent panel of 525 diabetic subjects. Second, ANOVA and multivariate analyses were performed to test the significance of an association between ADRB2 genotype and the level of blood pressure within the entire population except for 395 subjects who had been under treatment for hypertension. Although no significant association was observed for Arg16Gly and T-47C, 2 analytical methods indicated a marginal association (P:=0.01 to 0.04) between the Glu27 variant and lower blood pressure levels. Given such a normotensive propensity, the odds ratio for Glu27 versus Gln27 allele frequencies was estimated to be 0.74, with a wide confidence interval (95% CI, 0.55 to 0.99) reflecting the low Glu27-allele frequency (6% to 8%) in Japanese. There were no apparent confounding influences of obesity and diabetes on the postulated association. Our data suggest that 3 ADRB2 polymorphisms tested are unlikely to confer principal genetic susceptibility for hypertension in the Japanese population. However, further investigation is warranted to clarify the relevance of ADRB2 polymorphisms to blood pressure regulation.

Aged↗

Transforming growth factor-beta1 and basic fibroblast growth factor modulate osteocalcin and osteonectin/SPARC syntheses in vitamin-D-activated pulp cells.

Vitamin D deficiency elicits hypocalcified dentin. However, little is known about the action of vitamin D on the syntheses of dentin matrix proteins. In this study, we examined the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on the expressions of osteocalcin and osteonectin/secreted protein, acidic and rich in cysteine (SPARC), by human pulp cells in the presence or absence of transforming growth factor-beta1 (TGF-beta1) or basic fibroblast growth factor (bFGF). 1,25(OH)2D3 markedly increased osteocalcin at protein and mRNA levels. The osteocalcin level induced by 1,25(OH)2D3 was decreased and increased by TGF-beta1 and bFGF, respectively. 1,25(OH)2D3 suppressed SPARC synthesis at protein and mRNA levels. TGF-beta1, but not bFGF, increased SPARC synthesis in the presence of 1,25(OH)2D3. SPARC, but not osteocalcin, increased DNA synthesis in pulp cells. These findings suggest that 1,25(OH)2D3 and growth factors interactively regulate the expression of osteocalcin and SPARC in pulp cells, and that SPARC can stimulate DNA synthesis by pulp cells.

Analysis of Variance↗

Clinical periodontal findings and microflora profiles in children with chronic neutropenia under supervised oral hygiene.

BACKGROUND: This is the first known case report that used a polymerase chain reaction (PCR)-based method to help identify the oral microflora in patients with chronic neutropenia. In this study, we report clinical periodontal findings and microflora profiles of 2 children, 1 with severe congenital neutropenia (SCN, Kostmann type) and 1 with cyclic neutropenia (CN). METHODS: The SCN patient had severe gingivitis, whereas the patient with CN had mild gingivitis in the gingival margins. Monthly oral cleaning instruction and review were performed without subsequent periodontal therapy. Oral hygiene conditions remained satisfactory and visible plaque was scarce, despite the persistence of mild gingivitis. Under supervised oral hygiene, we examined the presence of periodontal pathogens from patient plaque samples. RESULTS: By a PCR-based method, Prevotella nigrescens, Bacteroides forsythus, Campylobacter rectus, and Capnocytophaga gingivalis were detected in the SCN patient and P. intermedia, C. rectus, C. gingivalis, and C. sputigena in the CN patient, suggesting the existence of periodontal pathogens. Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola, and C. ochracea were not found in either patient. CONCLUSIONS: Use of 1% povidone iodine solution and local antibiotic application under supervised oral hygiene were helpful to improve gingival conditions in patients with chronic neutropenia.

Aggregatibacter actinomycetemcomitans↗

Nitric oxide synthase activity in neutrophils from patients with localized aggressive periodontitis.

BACKGROUND: Localized aggressive periodontitis (LAgP) is associated with neutrophil dysfunction including defective chemotaxis and reduced calcium influx factor activity. Nitric oxide (NO) and its enzyme, nitric oxide synthase (NOS), have been suggested to be involved in chemotaxis. Some reports, however, were unable to detect either NO or NOS in human neutrophils. In this study, we focused on NOS activity in LAgP neutrophils and examined the involvement of NOS in chemotaxis of normal neutrophils and NOS activity in neutrophils from normal subjects and patients with LAgP. METHODS: Neutrophils from 10 normal subjects and 10 LAgP patients were isolated from peripheral venous blood. Membrane associated-NOS (MA-NOS) and soluble NOS (S-NOS) were extracted from cells with or without FMLP stimulation. NOS activity was measured using the radiolabeled L-arginine to L-citrulline conversion assay. RESULTS: N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS, significantly inhibited FMLP-induced chemotaxis (P<0.01) and dibutyryl cGMP, an activator of cGMP-dependent protein kinase, significantly attenuated the inhibition by L-NAME (P<0.01). Unstimulated and FMLP-stimulated MA-NOS activity in LAgP neutrophils was statistically significantly higher than that in normal neutrophils (P<0.05). S-NOS activity in LAgP neutrophils was higher than that in normal neutrophils. CONCLUSIONS: This study suggests that NOS is present in human neutrophils and may be involved in FMLP-induced chemotaxis in normal neutrophils. NOS activity is increased in LAgP and is negatively correlated to chemotaxis response.

8,11,14-Eicosatrienoic Acid↗

[Factors related to intraoperative retinal breaks in macular hole surgery].

PURPOSE: To evaluate the factors of intraoperative retinal breaks in macular hole surgery. METHODS: This study included 558 eyes of 506 patients who underwent idiopathic macular hole surgery by one surgeon. Multiple regression was performed using the variables of gender, age, affected eye, lens status, stage, duration of symptoms, hole size, axial length, and lattice degeneration. RESULTS: The rate of retinal breaks was higher in stage 3 (16.0%) than in stage 4 (8.2%) (p = 0.014). In eyes with lattice degeneration intraoperative retinal breaks occurred in about 40% of the cases. Major factors were as follows: lattice degeneration (r = 0.24, p < 0.0001) in all eyes, stage (r = 0.090, p = 0.048) in eyes without lattice degeneration, and gender (r = -0.18, p = 0.035) in eyes of stage 4 without lattice degeneration. CONCLUSIONS: The factors of intraoperative retinal breaks in macular hole surgery were lattice degeneration in all eyes and stage 3 in eyes without lattice degeneration. The high incidence of intraoperative retinal breaks in stage 3 was mainly due to the occurrence of posterior vitreous detachment. Male gender was a significant factor associated with intraoperative retinal breaks.

Adult↗

[Operculum in idiopathic macular holes].

PURPOSE: To detect the factors related to the operculum in idiopathic macular holes and present a pathogenesis of idiopathic macular holes. METHODS: This study included 583 eyes of idiopathic macular hole that underwent macular hole surgery. To detect the factor related to the operculum, the variables of age, duration of symptoms, hole size, preoperative visual acuity, refraction, axial length, refraction axial length ratio were used for the comparison between two groups and multiple regression. The success rate of surgery and postoperative visual acuity were examined whether the operculum was present or not. RESULTS: The variables that were significantly related to the operculum were as follows: refraction axial length ratio (r = 0.18, p = 0.0092) in women of stage 3, duration of symptoms (r = -0.44, p < 0.001), preoperative visual acuity (r = -0.33, p = 0.0025), and refraction axial length ratio (r = -0.22, p = 0.020) in women of stage 4, and age (r = 0.19, p = 0.047) in men of stage 3. There were no significant differences in the success rate of surgery and postoperative visual acuity whether the operculum was present or not. CONCLUSIONS: Generally, operculum tends to occur in aged and round eyes and possibly does not occur in younger and back projected eyes because of retinal fissure. In women of stage 4, the operculum is possibly a torn retina and does not occur in atrophic holes.

Adult↗

Lack of association between the platelet glycoprotein Ia C807T gene polymorphism and myocardial infarction in Japanese. An approach entailing melting curve analysis with specific fluorescent hybridization probes.

The platelet-collagen receptor, glycoprotein Ia/IIa (integrin alpha2beta1) plays a fundamental role in the adhesion of platelets to fibrillar collagen, an event leading to platelet activation and thrombus formation and contributing to the pathogenesis of thrombotic disease. Further, glycoprotein Ia/IIa receptor density and function may be associated with two linked and silent polymorphisms (807C/T and 873G/A) within the glycoprotein Ia gene. We tested the extent to which these polymorphisms serve as genetic markers of myocardial infarction in a Japanese population. A case-control study was carried out using 210 Japanese myocardial infarction patients and 420 age- and sex-matched controls. Genotyping was accomplished using PCR followed by melting curve analysis with specific fluorescent hybridization probes. The 807CC, CT, TT genotypes linked perfectly to the 873GG, GA, AA genotypes, respectively. Allele frequencies of the 807T (873A) variant were similar in the control and patient groups (0.373 vs. 0.352). The 807T and 873A variants of platelet glycoprotein Ia gene are common and in a perfect linkage in the Japanese population, but it appears unlikely that the 807T (873A) variant represents a useful marker of increased risk for myocardial infarction.

Adult↗

Coronary artery bypass grafting in 105 patients with hemodialysis-dependent renal failure.

This study was proposed to define early and long-term results of coronary artery bypass grafting (CABG) in dialysis-dependent renal failure (RF) patients, and preoperative patient characteristics. This study included 105 patients (87 males and 18 females; mean age 60.0 +/- 9.0 years, range 39-79) with RF on maintenance dialysis (hemodialysis 100, peritoneal dialysis 5) who underwent isolated CABG between August 1985 and April 2000. Postoperative follow-up was completed in 100% and averaged 3.1 years. There were 22 emergency and 2 re-CABG cases. Previous myocardial infarction (MI) was found in 55 patients (52%), and unstable angina was noted in 53 patients (50%). Diabetes mellitus was the cause of RF in 50 patients (48%; 24 patients required insulin). There was 1 case of single vessel disease, 31 cases of double vessel disease, 54 cases of triple vessel disease, and 19 cases of left main disease. Preoperative left ventriculography was performed in 92 patients (88%). Left ventricular ejection fraction (LVEF) was 48.3 +/- 15.8% (range 11-74%) and was 40% or less in 25 patients (27%). The mean number of distal anastomoses was 2.5 (range 1-5). Three patients received only vein grafts, but all were cases of emergency CABG. The remaining 102 patients (97%) received at least 1 arterial conduit. Among them, 64 patients received only arterial conduits, and 72 patients received 2 or more distal anastomoses with arterial conduits. Five patients (4.8%) died within 30 days after CABG (2 cardiac deaths and 3 noncardiac deaths), and 8 patients (7.6%) died beyond 30 days after CABG before discharge (all noncardiac deaths). The cause of 2 cardiac deaths was abrupt circulatory collapse during or after hemodialysis in patients with severe left ventricular dysfunction (LVEF; 11% and 28%) in the early postoperative period. The causes of 8 noncardiac deaths included infection in 4 and rupture of aortic aneurysm, stroke, sleep apnea syndrome, and mesenteric infarction. During the follow-up period, there were 29 late deaths (8 cardiac, 13 noncardiac, and 8 sudden death), 6 MIs, 13 percutaneous transluminal coronary angioplasty, and 1 re-CABG. The 5-year actuarial survival rate was 59.8%, the cardiac death-free rate was 83.0%, and the cardiac event-free rate was 62.4%. Although CABG in patients on hemodialysis is associated with high early and long-term mortality in terms of both cardiac and noncardiac deaths in proportion to the severity of the preoperative condition, long-term survival was still better than that of general dialysis patients. Meticulous perioperative management may be the key factor in the improvement of early results.

Adult↗

Incidence of Reopening and Variables That Influence Reopening After Macular Hole Surgery.

Purpose: To evaluate the incidence and variables of reopening of macular holes after macular hole surgery.Methods: Our study included 467 eyes in which macular holes were successfully closed after surgery. Surgical techniques consisted of conventional methods (358 eyes) and scalping methods (109 eyes) with retinal pigment scalping of the macular hole basis added in such cases: reoperation, hole size (more than 0.4 disc diameter), duration of symptoms (more than 2 years). Long term incidence of reopening was predicted by life table method. After we compared reopened cases with non-reopened cases, the variables of gender, stage, biocular occurrence, age, duration of symptoms, hole size, preoperative visual acuity, refraction axial length ratio, and intraoperative retinal tears were used for the multiple regression.Results: Reopening was found in 20 eyes (5.6%) treated by conventional methods and in 10 eyes (9.2%) treated by scalping methods. Survival ratio was 87% for the conventional methods in 6 years and 79% for the scalping methods in 5 years. The variables influencing reopening were as follows: conventional methods: gender (r = 0.065, P =.19), biocular occurrence (r = 0.12, P =.026), and refraction axial length ratio (r = -0.11, P =.045); scalping methods: hole size (r = 0.14, P =.25).Conclusions: Incidence of reopening in scalping methods was high. The variables that influenced reopening after macular hole surgery were biocular occurrence and refraction axial length ratio in conventional methods. The shape of the eye may be related to reopening.

Journal Article↗

[Clinical features of idiopathic macular holes-differences between sexes and stages].

PURPOSE: The purpose of this study was to evaluate the differences in the clinical features of idiopathic macular holes between sexes and stages. METHODS: Five hundred and twenty-six eyes of 480 patients with stage 3 or 4 idiopathic macular hole that had undergone vitrectomy were observed consecutively in this study. The each stage ratio, bilaterality, and affected eye were examined and the differences in age, hole duration, hole size, visual acuity, refractive power, axial length, and corneal refractive power were evaluated. RESULTS: Twenty-six % of the cases were stage 4 in males and 31% in females. There were no significant differences in bilaterality or affected eye between the sexes. Younger age and larger size were found in females of stage 3. Larger size was found in stage 4. More myopic eye and longer axial length were found in males of stage 4. There were no significant differences in hole duration and visual acuity between sexes or stages. CONCLUSIONS: In females the onset of macular hole occurred at a younger age than in males, size of the hole was larger from an earlier stage, and refractive power was less myopic. More myopic eye and longer axial length were found in stage 4, especially in males. This fact might be related to the existence of posterior vitreous detachment. We concluded that there were some differences in the mechanism of the onset and the progression of idiopathic macular hole between males and females.

Adult↗

[Early and mid-term results of elephant trunk method using stent graft during total arch replacement].

Combined therapy of stent graft implantation and open surgery is an alternative method for aortic aneurysm. Seven patients with aortic aneurysm [annulo aortic ectasia (AAE) + Marfan syndrome (4), AAE + arch aneurysm + s/o Behçet disease (1), acute dissected aneurysm (type A) (1), thoracic aortic true aneurysm (1)] were successfully treated by means of elephant trunk method using a stent graft during total arch replacement. There was no complication related to the stent graft during the perioperative period. Postoperative computed tomographic scans were performed 1 and 6 months later. There was no endleak and no migration, and the aortic diameter around the stent graft was not changed in six patients. However, one patient showed thrombus around the stent graft, because of endleak 2 months after the operation. Such patients should therefore have careful long-term follow-up.

Adult↗

[A re-operative case of bentall operation and aortic arch replacement using a stent graft for a Marfan syndrome, post sternum turnover and post mitral valve replacement].

A 36-year-old male with Marfan syndrome succesfully underwent Bentall operation and aortic arch replacement using a stent graft as an elephant trunk. He had received MVR with sternum turn over 14 years previously. Median sternotomy was performed. Under circulatory arrest with rertograde cerebral perfusion we performed Bentall operation and aortic arch replacement using a stent graft. The sternum was cured well. Retractive breathing was not detected. This surgical procedure was effective for cardiovascular disease with Marfan syndrome.

Adult↗