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Biomedical subjects

Akira Kimura

Publications and source records attributed to Akira Kimura.

At least 19 recordsLinked to original sources
PubMed2006

[Cerebral hemorrhage following ovariectomy in a woman undergoing a gamma knife treatment for intracranial arteriovenous malformation].

We report a case of cerebral hemorrhage following ovariectomy in a 39-year-old woman undergoing a gamma knife treatment for intracranial arteriovenous malformation (AVM). She underwent bilateral ovariectomy with combined spinal-epidural anesthesia. Tracheal intubation was not performed so that severe changes in blood pressure, partial carbon dioxide pressure, and partial pressure of oxygen could be avoided. There were no complications during surgical anesthesia, but the AVM ruptured soon after her being discharged. AVM is errors in the development of the vasculature that, together with the effects of blood flow, may lead to a focal arteriovenous shunt. In some cases, aneurysms may coexist with AVM. It is said that radiosurgery significantly decreases the risk of hemorrhage in patients with AVM, even before there is angiographic evidence of obliteration. But it should be kept in mind that anesthetic management must be performed carefully.

Adult↗
PubMed2005

Autoimmunity against neurofilament protein and its possible association with HLA-DRB1*1502 allele in glaucoma.

Glaucoma is understood as a neurodegenerative disease and intraocular pressure has been regarded as the major risk factors for the optic nerve damages. However, recent studies suggested that several risk factors including autoimmunity are also shown to play important roles in glaucoma. To identify the retinal antigen in glaucoma, we used the serological analysis of recombinant cDNA expression libraries (SEREX) approach and quantified IgG antibodies directed against the identified antigens in an ELISA. We identified neurofilament protein and the prevalence of anti-bovine neurofilament light subunit (NF-L) autoantibodies in glaucomatous patients was significantly higher than in healthy controls and patients with other uveitic and optic nerve diseases (P<0.05). In addition, our immunogenetic analysis showed a possible association between HLA-DRB1*1502 allele and the patients positive for anti-NF-L autoantibodies. It suggests that the HLA class II-linked gene may be involved in development of autoimmunity in patients with glaucoma.

Adult↗
PubMed2005

A case of Chandler's syndrome revealed by ultrastructural studies of the trabecular meshwork.

PURPOSE: To investigate ultrastructural changes in the aqueous outflow route and discuss the mechanisms associated with intraocular pressure (IOP) elevation in a patient with presumably early stage Chandler's syndrome. METHODS: A 47-year-old man underwent trabeculectomy because of elevated IOP. A specimen obtained during surgery was studied by transmission electron microscopy. RESULTS: Electron microscopy showed the presence of a monolayer composed of corneal endothelium-like cells and thick basement membrane-like material. Neovascularization was also observed in the corneoscleral trabeculum. CONCLUSIONS: Our results indicate that several mechanisms, including the formation of basement membrane-like tissue, infiltration of inflammatory cells and neovascularization, might contribute to the elevation of IOP in Chandler's syndrome. These may occur even when there is no history of conspicuous inflammatory reaction in the anterior ocular segments.

Aqueous Humor↗
PubMed2005

[A case of malignant mesothelioma showing rapid progression during one month].

A 57-year-old man with massive right pleural effusion was admitted to our hospital. Thoracoscopy revealed, fine granulations and small nodules scattered on the parietal pleura. Biopsy specimens suggested malignant mesothelioma. We performed thoracoscopy again one month later under general anesthesia to make a definitive diagnosis. At that time, the parietal pleura was covered with a large tumor and malignant mesothelioma was diagnosed by biopsy. We could find early pleural lesions of malignant mesothelioma in thoracoscopy. While we managed to make a definitive diagnosis, the tumor progressed rapidly during one month. If malignant pleural mesothelioma is suspected, it is necessary to make all efforts, including surgical biopsy, to diagnose during the early stage of disease.

Biopsy↗
PubMed2004

Intrahepatic flow disturbance by clomipramine in the isolated perfused rat liver.

Intrahepatic flow disturbance may have important pharmacological and toxicological significance. However, apart from pathological conditions, flow disturbance by drugs has received little attention. In the isolated perfused rat liver (IPRL), we found that infusion of tricyclic antidepressants increased portal perfusion pressure (PP) with a coincidental decrease in oxygen uptake at concentrations of 3-30 microM; the order of potency was clomipramine > amitriptyline > imipramine approximately nortriptyline >> desipramine. The characteristics of clomipramine action were as follows: (1) The extrahepatic portal vein was much less sensitive to clomipramine than the IPRL. (2) Changes in PP and oxygen uptake required Ca(2+) in the perfusate and were inhibited by papaverine, staurosporine, sodium nitroprusside and indomethacin. (3) Compared with endothelin-1, clomipramine produced a greater decrease in the ratio of oxygen uptake/PP together with a greater overflow of loaded indocyanine green for an increase in PP by about 2 cm H(2)O. (4) Vital staining with trypan blue and rhodamine 6G and histological examinations revealed that 3-10 microM clomipramine produced marked flow redistribution due to the constriction of portal vein branches. Portal flow was short-circuited to the hepatic vein at a deeper and hilar portion of the liver, with minimal perfusion of the periphery. These results demonstrate an example of drug-induced intrahepatic flow disturbance in vitro. Its contribution to the development of toxicity in vivo remains to be studied.

Animals↗
PubMed2004

Crystal structure of gamma-glutamylcysteine synthetase: insights into the mechanism of catalysis by a key enzyme for glutathione homeostasis.

Gamma-glutamylcysteine synthetase (gammaGCS), a rate-limiting enzyme in glutathione biosynthesis, plays a central role in glutathione homeostasis and is a target for development of potential therapeutic agents against parasites and cancer. We have determined the crystal structures of Escherichia coli gammaGCS unliganded and complexed with a sulfoximine-based transition-state analog inhibitor at resolutions of 2.5 and 2.1 A, respectively. In the crystal structure of the complex, the bound inhibitor is phosphorylated at the sulfoximido nitrogen and is coordinated to three Mg2+ ions. The cysteine-binding site was identified; it is formed inductively at the transition state. In the unliganded structure, an open space exists around the representative cysteine-binding site and is probably responsible for the competitive binding of glutathione. Upon inhibitor binding, the side chains of Tyr-241 and Tyr-300 turn, forming a hydrogen-bonding triad with the carboxyl group of the inhibitor's cysteine moiety, allowing this moiety to fit tightly into the cysteine-binding site with concomitant accommodation of its side chain into a shallow pocket. This movement is caused by a conformational change of a switch loop (residues 240-249). Based on this crystal structure, the cysteine-binding sites of mammalian and parasitic gammaGCSs were predicted by multiple sequence alignment, although no significant sequence identity exists between the E. coli gammaGCS and its eukaryotic homologues. The identification of this cysteine-binding site provides important information for the rational design of novel gammaGCS inhibitors.

Amino Acid Sequence↗
PubMed2004

Higher viscosity participates in the regulation of coronary flow via nitric oxide and indomethacin-sensitive contracting factor.

Few studies have reported on the association of viscosity with coronary circulation. We evaluated the change in coronary flow after dextran was added to a perfusion solution to increase viscosity in isolated rat hearts. We also measured NOx- production induced by the change in shear stress in the coronary effluent, as a marker of NO synthesis. The baseline coronary flow was not influenced by the presence of either the cyclooxygenase inhibitor indomethacin, the thromboxane A2 (TXA2)-prostaglandin H2 (PGH2) receptor antagonist ONO-3708, or the TXA2 synthase inhibitor OKY-046. After exposure to solution containing 0.5% dextran, the coronary flow first decreased and then gradually increased until 10 min. The initial decrease in coronary flow was inhibited by indomethacin, ONO-3708, and OKY-046 individually. The gradual increase was completely inhibited by the NO inhibitor L-NAME, but not by indomethacin or ONO-3708. OKY-046 partially inhibited the increase. NOx- levels in the effluent were higher after the dextran solution was administered, and the increased NOx- levels were inhibited by L-NAME. The increased NOx- levels were not inhibited by inhibitors of the cyclooxygenase pathway. It appears that a higher viscosity of perfusion solution induced a gradual increase in NO production and was associated with increased production of indomethacin-sensitive contracting factor.

Animals↗
PubMed2004

[Thymic carcinoma. A clinicopathological study of seven patients].

The treatment of seven cases of thymic carcinoma is reported. According to the Masaoka classification of the disease, there were five cases of stage III and two of stage IVb. Five were identified histopathologically as squamous cell carcinoma, one as undifferentiated carcinoma, and one as small cell neuroendocrine carcinoma. Surgery was performed during the course of chemotherapy and radiotherapy in 5 cases, and in 2, the organs infiltrated by neoplastic cells were partially excised together. Radiotherapy was performed as adjuvant therapy in one case of partial excision. In another case, after six years of chemotherapy and radiotherapy that yielded a partial response (PR), cancerous infiltration of the chest wall occurred, and partial removal of the chest wall became necessary. After the remaining case showed a PR to chemotherapy, complete macroscopic excision of the tumor was undertaken, but mediastinal lymph gland metastasis was present, and so radiotherapy was also initiated. In two cases, surgery was not performed. One of these was treated with chemotherapy alone, the other, only with radiotherapy. The mean survival period of the five patients who died as a result of their tumors was 44.8 months. One of the two who survived for over four years had squamous cell carcinoma, the other, undifferentiated carcinoma. The case of small cell neuroendocrine carcinoma was assessed as having a PR, and so complete extraction of the thymic neoplasm was carried out, and followed with radiotherapy. This patient is still alive.

Adult↗
PubMed2003

Lens epithelium-derived growth factor: neuroprotection on rat retinal damage induced by N-methyl-D-aspartate.

The purpose of this study is to investigate possible neuroprotective effects of lens epithelium-derived growth factor (LEDGF) against cell death induced by N-methyl-D-aspartate (NMDA) in the rat retina. LEDGF and/or NMDA were intravitreally injected into rat eyes. NMDA-induced retinal death and protective effects of LEDGF were evaluated by morphometric analysis, cell numbers in the ganglion cell layer (GCL) and the thickness of the inner plexiform layer (IPL). Retrograde labeling with a fluorescent tracer (Fluoro-Gold) was applied for counting retinal ganglion cells (RGCs) that survived after NMDA injection. Terminal deoxyribonucleotidyl transferase (TdT)-mediated fluroscein-16-dUTP nick end-labeling (TUNEL) staining was used to evaluate of retinal cell death. Morphometric analysis and retrograde labeling analysis showed that retinal damage induced by NMDA was protected significantly by LEDGF. TUNEL assay revealed that pretreatment with LEDGF prevents NMDA-induced apoptosis. Retinal damage (ganglion and amacrine cells) induced by NMDA was protected by an intravitreal injection of LEDGF.

Animals↗
PubMed2003

Secondary glaucoma in patients with familial amyloidotic polyneuropathy.

OBJECTIVE: To elucidate the clinical features and surgical outcomes of the treatment of secondary glaucoma associated with transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP). DESIGN: Retrospective case study. PARTICIPANTS: Forty-nine Japanese patients with FAP. METHODS: For all patients, measurement of best-corrected visual acuity, intraocular pressure, and visual fields as well as slitlamp and ocular fundus examinations were conducted and compared. In addition, the exact mutation of the amyloidogenic TTR variants was analyzed for all 49 patients with FAP. The TTR mutations included amyloidogenic TTR (ATTR) Val30Met in 41 patients, ATTR Tyr114Cys in 6, ATTR Ser50Ile in 1, and a compound heterozygous mutation of ATTR Val30Met + Arg104His in 1. RESULTS: The onset of secondary glaucoma was defined as elevation of intraocular pressure and glaucomatous changes in visual field defects. Secondary glaucoma was detected in 12 (24%) of the 49 patients. The incidence of secondary glaucoma in patients with the Val30Met mutation (17%) was lower than for the other FAP genotypes (P =.02 using the chi(2) test). Of 20 glaucomatous eyes, amyloid deposition on the pupil and anterior surface of the lens was found in 18 eyes. Amyloid deposition was found prior to glaucoma in 11 eyes and at the first visit to our clinic in another 7 eyes. In the 11 eyes in which the onset of glaucoma occurred following amyloid deposition along the pupil, the mean +/- SD period between the onsets of pupillary amyloid deposition and glaucoma was 2.55 +/- 1.43 years (range, 0.2-4.0 years). Further statistical analyses revealed significant relationships between the onset of secondary glaucoma and both amyloid deposition (P<.001) and vitreous opacity (P<.001). Surgical treatment was required in 15 (75%) of the 20 glaucomatous eyes. In 9 (81%) of the 11 eyes that underwent trabeculectomy, the intraocular pressure was well controlled at or lower than 20 mm Hg during the follow-up period. In the eyes that underwent combined trabeculotomy and sinusotomy (2 eyes), nonpenetrating trabeculectomy (1 eye), or a cyclodestructive procedure (1 eye), the intraocular pressure was poorly controlled. CONCLUSIONS: Glaucoma is not a rare condition in patients with FAP, especially because liver transplantation now enables patients with FAP to live longer. Careful observation of amyloid deposition along the pupil allows the prediction of glaucoma onset.

Adult↗
PubMed2003

Vitreous opacities and outcome of vitreous surgery in patients with familial amyloidotic polyneuropathy.

PURPOSE: To report the prevalence of vitreous opacities and the outcome of vitreous surgery in patients with familial amyloidotic polyneuropathy (FAP). DESIGN: Observational case series. METHODS: In 37 patients with FAP and the ATTR Val30 Met mutation, vitreous opacities were present in 14 eyes of 9 patients and vitrectomy combined with phacoemulsification and intraocular lens implantation was performed in five eyes of three patients. In six patients with the ATTR Tyr114Cys mutation, vitreous opacities were present in both eyes of all six patients and vitrectomy combined with phacoemulsification and intraocular lens implantation was performed in nine eyes of six patients. The mean follow-up period after vitreous surgery was 20.9 +/- 16.8 months (range, 3 to 52 months). RESULTS: The prevalence of vitreous opacities is much higher in patients with ATTR Tyr114Cys (100%) than in those with ATTR Val30 Met (24%). The mean age at the onset of vitreous opacities was significantly lower in the patients with ATTR Tyr114Cys (37.0 +/- 5.3 years) than in the nine patients with ATTR Val30 Met (52.8 +/- 9.1 years; P <.005). Visual acuity improved in all 14 eyes after vitreous surgery; however, final visual acuity decreased in one eye owing to the occurrence of a central retinal vein occlusion. Vitreous opacities mildly increased in two eyes. CONCLUSIONS: Our data suggest that the ATTR Val30 Met and ATTR Tyr114Cys mutations induce different clinical features of vitreous opacities. Vitreous surgery combined with phacoemulsification and implantation of an intraocular lens is a safe and useful treatment. Careful long-term follow-up should be performed.

Adult↗
PubMed2003

A case of primary B-cell type non-Hodgkin lymphoma originating in the iris.

PURPOSE: To report a case of primary malignant B-cell type non-Hodgkin lymphoma originating in the iris. DESIGN: Interventional case report. METHODS: An 83-year-old woman presented with anterior uveitis resulting from primary malignant lymphoma in the iris. Ultrasound biomicroscopy and indocyanine green angiography using a scanning laser ophthalmoscope showed abnormalities in the iris. Diagnostic biopsy of the iris revealed B-cell type non-Hodgkin lymphoma. RESULT: The patient was treated with radiotherapy, and the tumorous lesion resolved. CONCLUSION: Primary lymphoma localized in the iris only is rare. In this case, diagnostic biopsy and radiotherapy of the iris lymphoma provided good results.

Aged↗
PubMed2002

Biphasic effects of oxethazaine, a topical anesthetic, on the intracellular Ca(2+) concentration of PC12 cells.

There have been few reports on the mechanism(s) of action of oxethazaine (OXZ) despite its potent local anesthetic action. Generally, local anesthetics (LAs) not only inhibit Na(+) channels but also affect various membrane functions. In the present study, using PC12 cells as a nerve cell model, the effects of OXZ on intracellular Ca(2+) concentration ([Ca(2+)](i)) were examined in relation to cytotoxicity and dopamine release. [Ca(2+)](i) was determined by the quin2 method. In resting cells, (6-10)x10(-5)M OXZ produced lactate dehydrogenase leakage, which was Ca(2+)-dependent, inhibited by metal Ca(2+) channel blockers, and preceded by a marked increase in [Ca(2+)](i). Some other LAs showed no cytotoxicity at these concentrations. In K(+)-depolarized cells, however, lower concentrations of OXZ (10(-6)-10(-7)M), that had no effect on resting [Ca(2+)](i), inhibited both the dopamine release and the increase of [Ca(2+)](i) in parallel. The inhibitory potency against the [Ca(2+)](i) increase was in the order of nifedipine>OXZ approximately verapamil>diltiazem, and OXZ acted additively on the Ca(2+) channel blockers. OXZ showed the least effect on K(+)-depolarization as determined by bisoxonol uptake. OXZ also inhibited the increase in [Ca(2+)](i) induced by S(-)-BAY K 8644, a Ca(2+) channel agonist. These observations suggested that low concentrations of OXZ interact with L-type Ca(2+) channels. The biphasic effects of OXZ on Ca(2+) movement may be due to a unique chemical structure, and may participate in and complicate the understanding of the potent pharmacological and toxicological actions of OXZ.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2002

The repolarizing effects of volatile anesthetics on porcine tracheal and bronchial smooth muscle cells.

UNLABELLED: This study was conducted to determine the effects of volatile anesthetics (potent bronchodilators) on membrane potentials in porcine tracheal and bronchial smooth muscle cells. We used a current-clamp technique to examine the effects of the volatile anesthetics isoflurane (1.5 minimum alveolar anesthetic concentration [MAC]) and sevoflurane (1.5 MAC) on membrane potentials of porcine tracheal and bronchial (third- to fifth-generation) smooth muscle cells depolarized by a muscarinic agonist, carbachol (1 microM). The effects of volatile anesthetics on muscarinic receptor binding affinity were also investigated by using a radiolabeled receptor assay technique. The volatile anesthetics isoflurane and sevoflurane induced significant repolarization of the depolarized cell membranes in the trachea (from -19.8 to -23.6 mV and to -24.8 mV, respectively) and bronchus (from -24.7 to -29.3 mV and -30.4 mV, respectively) without affecting carbachol binding affinity to the muscarinic receptor. The repolarizing effect was abolished by a Ca(2+)-activated Cl(-) channel blocker, niflumic acid. These results indicate that volatile anesthetic-induced repolarization of airway smooth muscle cell membranes might be caused by a change in Ca(2+)-activated Cl(-) channel activity and that the different repolarized effects of the volatile anesthetics could in part contribute to the different effects of volatile anesthetics on tracheal and bronchial smooth muscle contractions. IMPLICATIONS: By use of a current-clamp technique, the volatile anesthetics isoflurane and sevoflurane repolarized porcine airway smooth muscle cell membranes depolarized by a muscarinic agonist. This effect might be caused mainly by change in Ca(2+)-activated Cl(-) channel activity, not in K(+) channel activity.

Anesthetics, Inhalation↗
PubMed2002

Proteoglycans in the eye.

PURPOSE: Various proteoglycans are expressed in ocular tissues. We investigated and reviewed the distribution and the potential roles of proteoglycans in cornea, trabecular meshwork, and retinal tissues. METHODS: Immunohistochemical studies were performed in rat ocular tissues. The concentration of transforming growth factor (TGF)-beta2, which regulates the expression of proteoglycans in aqueous humor from human glaucomatous eyes, was evaluated by enzyme-linked immunosorbent assay (ELISA). In retinal tissues, we examined the localization of 2 soluble nervous tissue-specific chondroitin sulfate proteoglycans, neurocan and phosphacan, by immunohistochemical analysis, then investigated the effect on the neurite outgrowth of cultivated retinal ganglion cells. RESULTS: The expression of chondroitin sulfate in stroma was upregulated at early postnatal stages and reduced during development in rat eyes. In trabecular meshwork tissues, immunohistochemical studies showed the intense expression of decorin. Moreover, elevated levels of TGF-beta2 in the aqueous humor from glaucomatous patients were observed. In retinal tissues, neurocan and phosphacan were expressed mainly in nerve fiber-rich layers during rat postnatal stages. In vitro, the neurite extension from retinal ganglion cells was inhibited by neurocan and phosphacan. CONCLUSIONS: Soluble extracellular proteoglycans in corneal and trabecular meshwork tissues contribute to the stromal transparency in the corneal tissues and the resistance of the aqueous humor outflow in trabecular meshwork tissues. In retinal tissues, chondroitin sulfate and heparan sulfate proteoglycans are not only secreted into the extracellular space of retinal tissues but also expressed in the membrane of the retinal cells, contributing to the neural network formation and the maintenance of the interphotoreceptor matrix.

Animals↗