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Biomedical subjects

H Kurihara

Publications and source records attributed to H Kurihara.

At least 109 records · Page 6Linked to original sources

[Factors related to initial success in macular hole surgery].

PURPOSE: To evaluate the factors of initial success in macular hole surgery. METHODS: This study included 526 eyes of 480 patients who underwent idiopathic macular hole surgery by one and the same surgeon. Surgical methods included conventional method (392 eyes), retinal pigment epithelium (RPE) scalping (61 eyes), internal limiting membrane (ILM) removal (62 eyes), and RPE scalping combined with ILM removal (11 eyes). To evaluate the factors of initial success multiple regression was performed using the variables of (gender, age, stage, duration of symptoms, hole size, axial length, and preoperative visual acuity). RESULTS: The rate of initial success was 81.4% in all eyes, 80.9% in the conventional method, 78.7% in RPE scalping, 83.9% in ILM removal, and 100% in RPE scalping combined with ILM removal. Significant factors of initial success were as follows: gender (r = -0.091, p = 0.053), age (r = -0.14, p = 0.0062), duration of symptoms (r = -0.23, p < 0.0001), hole size (r = -0.23, p < 0.0001), and axial length (r = -0.21, p < 0.0001) in the conventional method, hole size (r = -0.56, p = 0.0006) in ILM removal and stage (r = -0.43, p = 0.0011) and preoperative visual acuity (r = 0.30, p = 0.018) in RPE scalping. CONCLUSIONS: Significant factors of initial success were being male being young, shorter duration of symptoms, smaller hole size, and shorter axial length in the conventional method, smaller hole size in ILM removal and stage 4 and better preoperative visual acuity in RPE scalping method.

Adult↗

[Clinical features of idiopathic macular holes].

PURPOSE: The purpose of this study was to evaluate the clinical features of idiopathic macular holes. MATERIALS AND METHODS: The clinical features were examined in consequentive 526 eyes of 480 patients with idiopathic macular hole who underwent vitrectomy. RESULTS: Sixty-seven% of the patients were female. The mean onset age was 64.4 years of age and 60% of the cases were in their 60's at the time of onset. The mean refractive value was -0.66 dioptor and 40% of the cases were emmetropia with a refractive value between -1.0 dioptor and +1.0 dioptor. The onset age was positively correlated with refractive value. The visual acuity was negatively correlated with onset age, duration after onset, and the size of the macular hole. The duration was positively correlated with onset age. The size of the macular hole was positively correlated with age and duration. The factors for good visual acuity were determined by bilaterality, youth, or small size. Also we found the factors for large size of macular holes to be female gender, long duration of the hole, being in stage 4, and low visual acuity. CONCLUSIONS: The incidence of idiopathic macular hole is seen more in eyes of patients in their 60's and in emmetropic eyes. Patients with myopic eyes tend to have younger onset. The size of the macular hole in females tends to be larger than in males.

Adult↗

Molecular cloning and characterization of rat trp homologues from brain.

Identification of trp (transient receptor potential) gene from Drosophila photoreceptor and subsequent molecular cloning of the human cDNA homologues suggest its participation in capacitative calcium entry (CCE) or so called store-operated Ca2+ channel (SOC). We identified five different trp-related amplifications of reverse-transcription-polymerase chain reaction (RT-PCR) from rat brain; these corresponded to mouse trp homologues, mtrp1,3,4,5,6 and were distributed in various tissues with multiple expression levels. Two cDNAs, homologous to Drosophila trp from rat brain, designated rtrp3 and rtrp6, were isolated and characterized. By RT-PCR analysis, mRNAs of rtrp3 and rtrp6 were found to be expressed differently in brain and other tissues. In situ hybridization analysis revealed that rtrp6 mRNA was preferentially expressed in hippocampal dentate gyrus and cortical layers II and III. Expression of rat TRP3 and TRP6 in COS cells revealed an increase in CCE, as compared to that in the mock-transfected COS cells of the control. Isolation of cDNAs of rat trp gene family provides a useful model for studying mechanism of CCE.

Animals↗

Enzyme immunoassay for the measurement of 17alpha-estradiol 17-N-acetylglucosaminide in rabbit urine.

17alpha-estradiol 17-N-acetylglucosaminide (17alphaE2 17NAG) is an estrogen metabolite hitherto obtained only in rabbits. To gain insight into this unique conjugate, an enzyme immunoassay (EIA) was established by using antiserum elicited against 3-[3-(1-carboxypropyl)] ether of 17alphaE2 17NAG-bovine serum albumin conjugate; horseradish peroxidase, as a label; and 3,3',5,5'-tetramethylbenzidine, as a chromogen. The method proved to be specific, and the detection range of the assay was 0.20-10.00 ng/ml. A proposed double conjugate, 3-glucuronide of 17alphaE2 17NAG, was synthesized to validate the EIA. The EIA was applied to the determination of the urinary level of 17alphaE2 17NAG in male and female (pregnant and non-pregnant) rabbits with and without beta-glucuronidase-sulfatase preparation from Helix pomatia. The results showed that 17alphaE2 17NAG was mainly excreted as a double conjugate (17alphaE2 17NAG 3-glucuronide and/or 3-sulfate) and that its level varies during pregnancy.

Acetylglucosamine↗

Preparation of specific antisera to 15alpha-hydroxyestrogens.

The synthesis of haptens of 15alpha-hydroxyestrone, 15alpha-hydroxyestradiol, and 15alpha-hydroxyestriol (estetrol) was undertaken, to obtain specific antisera required for enzyme immunoassay. 3-(1-Carboxypropyl) ethers of these 15alpha-hydroxyestrogens were prepared and conjugated with bovine serum albumin and horseradish peroxidase. The specificity of antisera elicited against bovine serum albumin conjugates was checked by the enzyme immunoassay by using horseradish peroxidase-labeled antigen, and proved to be satisfactory in terms of cross-reactivities to related compounds.

Animals↗

Two new bromophenols from the red alga odonthalia corymbifera

Two novel bromophenols (1 and 2) were isolated from an extract of a red alga, Odonthalia corymbifera, together with a known bromophenol (3). The novel bromophenols were determined as 4-bromo-2, 3-dihydroxy-6-hydroxymethylphenyl 2, 5-dibromo-6-hydroxy-3-hydroxymethylphenyl ether (1) and bis(2, 3-dibromo-4,5-dihydroxybenzyl) ether (2), from spectroscopic evidence. Compounds 1-3 were found to be inactivators of alpha-glucosidase.

Journal Article↗

A novel target recognition revealed by calmodulin in complex with Ca2+-calmodulin-dependent kinase kinase.

The structure of calcium-bound calmodulin (Ca2+/CaM) complexed with a 26-residue peptide, corresponding to the CaM-binding domain of rat Ca2+/CaM-dependent protein kinase kinase (CaMKK), has been determined by NMR spectroscopy. In this complex, the CaMKK peptide forms a fold comprising an alpha-helix and a hairpin-like loop whose C-terminus folds back on itself. The binding orientation of this CaMKK peptide by the two CaM domains is opposite to that observed in all other CaM-target complexes determined so far. The N- and C-terminal hydrophobic pockets of Ca2+/CaM anchor Trp 444 and Phe 459 of the CaMKK peptide, respectively. This 14-residue separation between two key hydrophobic groups is also unique among previously determined CaM complexes. The present structure represents a new and distinct class of Ca2+/CaM target recognition that may be shared by other Ca2+/CaM-stimulated proteins.

Amino Acid Sequence↗

Endothelin in the central control of cardiovascular and respiratory functions.

1. Exogenously administered endothelin (ET) modulates the activity of cardiovascular and respiratory neurons in the central nervous system (CNS) and, thus, affects arterial blood pressure (ABP) and ventilation. However, a physiological role(s) for endogenous ET in the CNS has not been elucidated. To address this question, we examined ABP and ventilation in mutant mice deficient in ET-1, ETA and ETB receptors and endothelin-converting enzyme-1, which were made by gene targeting. 2. Respiratory frequency and volume was measured in mice by whole body plethysmography when animals breathed normal room air and hypoxic and hypercapnic gas mixtures. A few days after respiratory measurements, a catheter was implanted into the femoral artery under halothane anaesthesia. On the following day, the ABP of awake mice was measured through the indwelling catheter and heart rate was calculated from the ABP signal. After 2 h ABP measurement, arterial blood was collected through the catheter and pH and the partial pressures of O2 and CO2 were measured by a blood gas analyser. 3. Compared with corresponding controls, the mean (+/- SEM) ABP in ET-1+/- and ETB-deficient mice was significantly higher (118 +/- 2 vs 106 +/- 3 mmHg for ET-1+/- (n = 22) and ET-1+/+ (n = 17) mice, respectively; 127 +/- 3 vs 109 +/- 4 mmHg for ETB-/s (n = 9) and ETB+/s (n = 9) mice, respectively; P < 0.05 for both). In ET-1+/- mice, PCO2 tended to be higher and PO2 was significantly lower than corresponding values in ET-1+/+ mice. Under resting conditions, there was no significant difference in respiratory parameters between mutants and their corresponding controls. However, reflex increases of ventilation to hypoxia and hypercapnia were significantly attenuated in ET-1+/-, ET-1-/- and ETA-/- mice. 4. In another series of experiments in ET-1+/- mice, we found that sympathetic nerve activity (SNA) was augmented and reflex excitation of phrenic nerve activity (PNA) in response to hypoxia and hypercapnia was blunted. Attenuation of the reflex PNA response to hypercapnia was also observed in the medulla-spinal cord preparation from ET-1-/- mice. 5. Elevation of ABP in ETB-deficient mice was most likely due to a peripheral mechanism, because SNA and respiratory reflexes were not different from those in control animals. 6. We conclude that endogenous ET-1 plays an important role in the central neural control of circulation and respiration and that ETA receptors mediate this mechanism.

Animals↗

Angiotensinogen gene and essential hypertension in the Japanese: extensive association study and meta-analysis on six reported studies.

BACKGROUND: Accumulating evidence has supported the pathophysiological role of angiotensinogen in essential hypertension. However, some studies of molecular genetics have implicated that there may be an ethnic variation concerning the disease susceptibility of the AGT gene. OBJECTIVES AND METHODS: To evaluate the importance of this candidate gene for hypertension, we undertook an extensive association study in the Japanese. This case-control study was conducted in a total of 1232 individuals consecutively enrolled in a single institution, divided into two subgroups: one subgroup comprised 254 hypertensive and 224 normotensive subjects and the other comprised 463 hypertensive and 291 normotensive subjects. A meta-analysis was subsequently performed on six Japanese studies including the present study. RESULTS: No significant association was observed between a molecular variant of AGT, Thr235, and hypertension status in our case-control study. Moreover, this finding was extendible to another AGT polymorphism, G-6A, one of the potential functional polymorphisms in the promoter region, because these two polymorphisms proved to be in complete linkage disequilibrium in the studied population. The meta-analysis revealed that the pooled estimate of the odds ratio across the studies was 1.22 (95% CI 1.05-1.42), and that there was significant evidence against homogeneity of the odds ratios among the studies included (phi2 = 19.8, df = 5, P = 0.0014). In particular, a large range of variation (60-83%) was found for the allele frequency of Thr235 among control subjects of the six Japanese case-control studies. CONCLUSIONS: Although the meta-analysis appears in favour of association between the AGT variant and essential hypertension in the Japanese, there is considerable heterogeneity among the studies and the evidence is also rather borderline. Further comprehensive approaches are needed to resolve this debatable issue.

Adult↗

Chemotactic response of periodontal ligament cells decreases with donor age: association with reduced expression of c-fos.

OBJECTIVE: To understand the effects of aging on cellular motility of human periodontal ligament (PDL) cells, and to determine the possible link between cell proliferation and migration in relation to cellular aging. MATERIALS AND METHODS: The chemotactic response of PDL cells from three juvenile and four older donors were compared. Then, migrated or unmigrated cells were examined for their cell cycle by morphological and immunocytochemical procedures. Finally, migrated or unmigrated cells were examined for the expression of c-fos and c-myc by in situhybridization. RESULTS: PDL cells from older donors showed lower chemotaxis compared with the cells from juvenile donors (P < 0.05). Cells undergoing migration were found not to be in the S- or M-phase of the cell cycle. However, all migrated cells were found to express c-fos, while many of the cells which did not migrate were found not to express c-fos. CONCLUSIONS: Cellular motility of PDL cells decreases with donor age as well as cell proliferation. Since the cells reaching senescence fail to express c-fos, the mechanisms linked to cellular senescence may be a possible underlying mechanism for low migration seen in the older cells.

Adolescent↗

[Preventive effect of postoperative disinfection of endoscope on bacterial adhesion to endoscope].

We took culture of throat swab from 77 subjects who were negative for infection of HBV, HCV, HIV and syphilis infection before and after endoscopy. Moreover, the existence of bacterium including Helicobacter pylori at overcoat of endoscopic instrument was investigated right after examination and after disinfection of endoscope. Povidoneiodine, 70% alcohol and 1% benzalkonium chloride was used as a disinfectant for endoscope, and it took less than 10 minutes to wash by hand to disinfection. alpha-haemolytic streptococci, Staphylococcus epidermids, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Enterococcus faecalis, Candida, Pseudomonas aeruginosa and MRSA were cultured in throat swab. The rate of adhesion of bacterium especially such as Candida, K. pneumoniae and S. epidermids to endoscope was considerably high. 23 of 77 subjects had H. pylori infection, and the adhesion of H. pylori to endoscope was found to be 65.2% of the subjects. On the contrast, no bacterium was detected from the endoscopic instrument after careful disinfection. These findings stress the importance of postoperative disinfection of the endoscope to prevent the chance to acquire bacterial infection.

2-Propanol↗

Disruption of ET-1 gene enhances pulmonary responses to methacholine via functional mechanism in knockout mice.

Endothelin (ET)-1 has been shown to have various pathophysiological roles in the lung. Recently, it has been reported that ET-1 and a gene encoding ET-1 (Edn1) might be involved in airway hyperresponsiveness, which is a major feature of bronchial asthma. Meanwhile, it remains unclear whether ET-1 might be involved in airway remodeling in vivo. In the present study, we hypothesized whether ET-1 might play a role in airway remodeling, leading to altered responsiveness. To test this hypothesis, we investigated airway function in vivo and airway wall structure in Edn1(+/-) heterozygous knockout mice, which genetically produce lower levels of ET-1, and Edn1(+/+) wild-type mice. In the physiological study, enhanced responses in lung elastance and resistance to methacholine administration were observed in Edn1(+/-) mice, whereas there was no difference in serotonin responsiveness. In the morphometric study, there were no differences in either lamina propria or airway smooth muscle thickness between Edn1(+/-) mice and Edn1(+/+) mice. These findings suggest that ET-1 gene disruption is involved in methacholine pulmonary hyperresponsiveness via functional mechanism, but not airway remodeling, in mice. The ET-1 knockout mice may provide appropriate models to study diseases related to ET-1 metabolism.

Airway Resistance↗

An in vitro coculture model of transmigrant monocytes and foam cell formation.

To analyze in vitro the migration of monocytes to the subendothelial space, their differentiation into macrophages, and the subsequent formation of foam cells in vitro, we have developed a 2-coculture system with rabbit aortic endothelial cells (AECs), aortic smooth muscle cells (SMCs), and a mixture of matrix proteins on polyethylene filters in chemotaxis chambers. AECs were seeded on a mixture of type I and IV collagen with or without various types of serum lipoproteins (method 1) or on matrix proteins secreted by SMCs (method 2). In these coculture systems, rabbit AECs can maintain a well-preserved monolayer for up to 2 weeks. When human CD14-positive monocytes were added to the upper medium of the system, with monocyte chemotactic protein-1 treatment approximately 60% of the monocytes transmigrated within 24 hours and were retained for up to 7 days, whereas without MCP-1 treatment, <30% of monocytes transmigrated. On day 1, transmigrant monocytes were negative for immunostaining of type I and II macrophage scavenger receptors but by day 3, became positive for scavenger receptors as well as other macrophage markers. When oxidized low density lipoprotein was added to the matrix layer of the method I coculture, on day 4 transmigrant cells exhibited lipid deposit droplets, and by day 7, they had the appearance of typical foam cells. Some of the transmigrant cells recovered in the lower medium on day 7 also appeared to be foam cells, indicating foam cell motility and escape from the coculture layer through the filter. In summary, this coculture system is a useful in vitro tool to dissect the cellular and molecular events that make up the process of foam cell formation.

Animals↗

Polymorphism of the methionine synthase gene : association with homocysteine metabolism and late-onset vascular diseases in the Japanese population.

Methionine synthase and 5,10-methylenetetrahydrofolate reductase (MTHFR) sequentially catalyze the remethylation of homocysteine to methionine. A point mutation in the encoding region of the methionine synthase gene, which results in substitution of an aspartic acid for a glycine residue (D919G), has been identified in patients of the cblG genetic complementation group; these patients exhibit significantly decreased methionine synthase activity. Nevertheless, the D919G mutation has also been reported to be common in the general population. In this study, we analyzed the distribution of methionine synthase D/G polymorphism in the Japanese population and examined the extent to which it is associated with altered homocysteine metabolism and late-onset vascular diseases. We studied 215 patients with coronary artery disease, 251 patients with histories of ischemic stroke, and 257 control subjects. The methionine synthase genotype was analyzed by polymerase chain reaction followed by HaeIII digestion; allele frequencies for the D919G variant of the enzyme proved to be similar in all 3 subject groups (control subjects, 0.17; coronary artery disease patients, 0. 17; and ischemic stroke patients, 0.19). Furthermore, in patients with ischemic stroke, plasma levels of homocyst(e)ine and folate were similar, irrespective of methionine synthase genotype. Thus, the methionine synthase D919G mutation was found to be common in the Japanese general population, and it appears unlikely that this polymorphism has a major effect on homocysteine metabolism and/or the onset of vascular diseases.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Lack of evidence for association between the endothelial nitric oxide synthase gene and hypertension.

Significant association between a Glu298Asp polymorphism of the endothelial nitric oxide synthase (eNOS) gene and essential hypertension was recently reported in Japanese populations, with the 298Asp variant showing a higher prevalence in hypertensive patients (10.3% to 12.0%) than in normotensive subjects (5.0% to 5.8%). In contrast, another study demonstrated that the 298Glu variant was significantly associated with hypertension in a Caucasian population. We therefore undertook an extensive association study in Japanese to resolve these contradictory claims. A total of 1165 individuals were selected from clinic outpatients and hospital staff in a single institution. The relevance of the Glu298Asp polymorphism to hypertension in this population was tested in 2 ways. First, a case-control study was conducted in 549 hypertensive and 513 normotensive subjects within the study population, with the chi2 statistic used to test the significance of an association between eNOS genotype and the presence of hypertension. Second, an ANOVA was used to test the significance of an association between eNOS genotype and the level of blood pressure within the entire population except for 167 hypertensive subjects who had been under treatment for hypertension. No significant association was observed in either of the statistics tested. Allele frequencies of 298Asp were concordant across the panels: 8.4% in hypertensive subjects, 8. 2% in normotensive subjects, and 7.9% and 9.5% in 2 additional sample populations used as reference panels. Taken together, our results do not support the previous observation that the molecular variant of the eNOS gene may confer principal susceptibility for essential hypertension but rather suggest the existence of sampling variation.

Adult↗

Angiotensin II type 2 receptor overexpression activates the vascular kinin system and causes vasodilation.

Angiotensin II (Ang II) is a potent vasopressor peptide that interacts with 2 major receptor isoforms - AT1 and AT2. Although blood pressure is increased in AT2 knockout mice, the underlying mechanisms remain undefined because of the low levels of expression of AT2 in the vasculature. Here we overexpressed AT2 in vascular smooth muscle (VSM) cells in transgenic (TG) mice. Aortic AT1 was not affected by overexpression of AT2. Chronic infusion of Ang II into AT2-TG mice completely abolished the AT1-mediated pressor effect, which was blocked by inhibitors of bradykinin type 2 receptor (icatibant) and nitric oxide (NO) synthase (L-NAME). Aortic explants from TG mice showed greatly increased cGMP production and diminished Ang II-induced vascular constriction. Removal of endothelium or treatment with icatibant and L-NAME abolished these AT2-mediated effects. AT2 blocked the amiloride-sensitive Na(+)/H(+) exchanger, promoting intracellular acidosis in VSM cells and activating kininogenases. The resulting enhancement of aortic kinin formation in TG mice was not affected by removal of endothelium. Our results suggest that AT2 in aortic VSM cells stimulates the production of bradykinin, which stimulates the NO/cGMP system in a paracrine manner to promote vasodilation. Selective stimulation of AT2 in the presence of AT1 antagonists is predicted to have a beneficial clinical effect in controlling blood pressure.

Actins↗

Management of Helicobacter pylori infection: gastroenterological and surgical perspectives.

Diagnosis and treatment of Helicobacter pylori is a crucial point in the management of the different gastroduodenal disorders. Management involves the general practitioner and different specialists such as internists, gastroenterologists and surgeons. Among the most frequent H. pylori-related gastroduodenal disorders of medical interest are some diseases such as dyspepsia and gastroesophageal reflux, where the role of the bacterium is not well defined and therefore the importance H. pylori eradication is still controversial. On the contrary, the relationship of H. pylori and gastric and duodenal peptic ulcer is widely and definitively proven, and there are no doubts regarding the importance of curing the bacterium in these disorders. However, the surgical aspect of peptic ulcer, in particular the relevance and management of its complications, has not been widely investigated so far. In fact, the prevalence of H. pylori in perforated, bleeding and stenotic peptic ulcers seem to be lower that in non-complicated peptic ulcer, and whenever H. pylori eradication virtually prevents the re-bleeding of peptic ulcer in all cases, the effect of curing the bacterium in perforated and stenotic ulcers is still largely unknown. The management of H. pylori infection after gastric surgery is also still controversial. Most studies suggest that H. pylori can persist after gastric surgery whenever its incidence is much lower than that before operation. However it seems most unlikely that the infection plays a major role in the development of ulcer recurrence after gastric surgery or in the induction of gastric carcinoma. In any case, there are no convincing data that its cure may prevent the occurrence of gastric carcinoma following gastrectomy procedures.

Digestive System Surgical Procedures↗

Peptide based interleukin-1 beta converting enzyme (ICE) inhibitors: synthesis, structure activity relationships and crystallographic study of the ICE-inhibitor complex.

Based on the X-ray structure of the complex of Ac-Tyr-Val-Ala-Asp-H (L-709049) and interleukin-1 beta converting enzyme (ICE), we synthesized compounds which were derived from 2-NapCO-Val-Pro-Asp-CH2OPh (1) to obtain a potent inhibitor in the cell assay. Among these compounds, (3S)-N-methanesulfonyl-3-[[1-[N-(2-naphthoyl)-L-valyl]-L-prolyl]amino]- 4-oxobutanamide (27c) showed high potency not only in the enzyme assay but also cell assay with IC50 values of 38 nM and 0.23 microM, respectively. Compound 27c, with a c log P value of 1.76, had a more hydrophilic character compared with 1. Compound 27c also dose dependently inhibited LPS-primed ATP-induced IL-1 beta release in mice. The crystal structure of the complex of compound 27c and ICE revealed that compound 27c had further interactions with ICE in the naphthoyl group at the P4 position and in the methyl group of the methanesulfonamidecarbonyl group at the P1 position, compared with L-709049. To our knowledge, compound 27c is the first example that shows a strong inhibitory activity without the carboxyl group at the P1 position.

Animals↗