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Biomedical subjects

T Okada

Publications and source records attributed to T Okada.

At least 325 records · Page 18Linked to original sources

Clinical characteristics of children with hypoparathyroidism due to 22q11.2 microdeletion.

UNLABELLED: The phenotypes of chromosomal 22q11.2 microdeletion are quite variable among individuals and hypoparathyroidism (HP) constitutes a definite portion of the clinical spectrum. For the correct diagnosis and pertinent follow up of the HP children due to del22q11.2, we tried to delineate the clinical characteristics of such patients. By employing fluorescence in situ hybridization (FISH) to all the patients diagnosed as HP in our clinic, ten possessed the 22q11.2 microdeletion. Among them, the incidence of cardiac defect (5/10), recurrent infection (1/10) and cleft palate (1/10) was modest. Additionally, seven of them had been diagnosed as HP during the infantile period, when their facial abnormality and intellectual problem had not become evident. Notably, two patients were complicated by Graves disease, while the association of idiopathic thrombocytopenic purpura was also observed in two girls. CONCLUSION: HP due to del22q11.2 may be misdiagnosed as idiopathic, especially in an infant who lacks apparent complications like cardiac anomaly. They should be closely followed up for auto-immune complications.

Child↗

Idiopathic benign biliary stricture.

A rare case of idiopathic benign biliary stricture is reported. A 50-year-old man with liver dysfunction underwent ultrasonography, which revealed dilation of the intrahepatic bile ducts, and endoscopic retrograde cholangiopancreatography, which revealed a short, ring-like stenosis at the junction of the left and right hepatic ducts. Although a benign stricture was suspected, radiologic tests alone were insufficient to make a firm diagnosis. Therefore, a cholecystectomy and resection of the extrahepatic biliary tract were performed. Microscopic examination of the resected specimen demonstrated no evidence of malignancy. The final diagnosis was mild, localized, chronic cholangitis. The patient had not had previous biliary tract surgery, choledocholithiasis, nor did he have a congenital abnormality of the biliary tract, bile duct carcinoma, or pancreatic disease. Since there was no evidence of primary sclerosing cholangitis, the stricture was considered to be idiopathic.

Anastomosis, Surgical↗

Interstitial laser coagulation for management of benign prostatic hyperplasia: a Japanese experience.

PURPOSE: The principle of interstitial laser coagulation is to shrink the prostate by generating intraprostatic necrosis without damaging the urethra or causing tissue sloughing. The clinical efficacy and durability of interstitial laser coagulation in the treatment of benign prostatic hyperplasia (BPH) were evaluated. MATERIALS AND METHODS: From December 1993 to June 1996, 76 patients with symptomatic BPH were treated with interstitial laser coagulation. A neodymium:YAG laser was used in combination with a specially designed interstitial thermotherapy light guide. The tip of the light guide was inserted into each lobe of the prostate transurethrally under direct vision. All evaluations were made at baseline and then 1, 3, 6 and 12 months after therapy. Treatment outcome was evaluated by International Prostate Symptom Score (I-PSS), flow rate and post-void residual urine volume. Disease specific quality of life was assessed via a quality of life assessment score and a BPH impact index. Independent of symptom assessment, a self-reporting questionnaire was prepared at 3 months postoperatively regarding satisfaction with treatment and sexual function. RESULTS: Among 44 patients followed to 12 months the mean I-PSS significantly decreased from 20.4 at baseline to 7.4, representing 64% improvement (p <0.001). Peak flow rate increased by 50% from a preoperative average of 7.4 to 11.1 ml. per second at 12 months in 42 patients (p <0.001). The post-void residual volume decreased by 57% from 102 to 44 ml. at 12 months in 40 cases (p <0.001). Steady and progressive improvement was observed on quality of life assessment and BPH impact index scores at 3, 6 and 12 months. No patients reported new onset of erectile dysfunction. No serious side effects were observed, except for loss of ejaculation in 3 cases and seminal vesicle abscess in 1. Only 6 patients (8%) required re-treatment for persisting obstructive symptoms during 12 months of followup. A recent change in methods towards more aggressive treatment plausibly influenced the outcomes to require less repeat treatment. CONCLUSIONS: After the interstitial laser coagulation procedure satisfactory results were obtained and improvement lasted through 12 months. Although the optimal number of fiber placements for each prostate is not known, more aggressive treatment appears to provide better outcomes.

Aged↗

Regulation of inducible NO synthase expression by endothelin in primary cultured glial cells.

Nitric oxide (NO), initially identified as an endothelium-derived relaxing factor, is a molecular mediator that has been implicated in many physiological and pathological processes. In primary cultured rat glial cells, a combination of inflammatory cytokines (tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta)) and bacterial lipopolysaccharide (LPS) stimulates production of nitrite via expression of the inducible form of nitric oxide synthase (iNOS). In these cells, simultaneous addition of endothelin (ET) markedly inhibited TNF-alpha/IL-1beta-induced and LPS-induced nitrite production and iNOS expression, although ET by itself had no effect. The inhibitory effect of ETs appears to be mediated by ET(B) receptors. Forskolin also inhibited the iNOS expression. By contrast, pretreatment with ET for 24 hours enhanced LPS-induced nitrite production and iNOS expression. This stimulatory effect of ETs was suppressed by calphostin C, a protein kinase C inhibitor, and pretreatment with phorbol ester enhanced LPS-induced iNOS expression. Our findings present the possibility that ET has dual effects on iNOS expression in glial cells.

Animals↗

Activation of PI 3-kinase by G protein betagamma subunits.

We have reported that fMLP-induced activation of pertussis toxin-sensitive GTP-binding proteins in THP-1 cells potentiates the insulin-induced accumulation of PtdIns(3,4,5)P3, a product of phosphoinositide 3-kinase (T. Okada et al., Biochem. J. 317, 475-480, 1996). The synergism in PtdIns(3,4,5)P3 accumulation was observed in Chinese hamster ovary cells expressing both insulin and fMLP receptors. In rat adipocytes, which represent the physiological target cells of insulin, receptor-mediated activation of GTP-binding protein by adenosine and prostaglandin E2 potentiated the insulin-induced PtdIns(3,4,5)P3 accumulation. In cell-free systems, the activity of the p85/p110beta subtype of phosphoinositide 3-kinase was, while that of p85/p110alpha was not, stimulated by the betagamma subunits of the GTP-binding proteins. We propose here a hypothesis that the p85/p110beta subtype is under the control of both the insulin receptors and the GTP-binding protein-coupled receptors in intact cell systems.

Animals↗

Tetrahydropapaveroline and its derivatives inhibit dopamine uptake through dopamine transporter expressed in HEK293 cells.

Tetrahydropapaveroline (THP), an isoquinoline alkaloid, has been detected in brain and urine of Parkinsonian patients on L-dopa medication, and in the urine and brain of rats after L-dopa or acute ethanol administration. Since THP is considered to be synthesized from dopamine, it may affect dopaminergic neurons through the reuptake system, i.e. dopamine transporter (DAT). To determine whether THP has affinity for DAT, we generated a cell line which stably expresses DAT and examined whether THP and its derivatives could inhibit [3H]DA uptake in these cells. Ki of THP and three derivatives (1-benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ), 1-(3',4'-dibydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline (3',4' DHBnTIQ) and 6,7-dihydroxy-1-benzyl-1,2,3,4-tetrahydroisoquinoline (6,7 DHBnTIQ)) for inhibition of [3H]DA uptake were about 41, 35, 23 and 93 microM, respectively, which were similar to the Ki of 1-methyl-4-phenylpyridinium ion (MPP+) (28 microM). These results suggest that THP and its derivatives might be uptaken through DAT and be involved in Parkinson's disease and/or alcohol addiction.

Animals↗

Vertical gaze palsy induced by midbrain lesions and its structural imaging.

We experienced four cases of vertical gaze palsy induced by midbrain lesions. Lesions commonly covered the rostral midbrain, including the rostral interstitial nucleus, dorsomedial to the red nucleus. Two of the four cases resulted from vascular insult, in which a single, unpaired perforator is supposed to innervate the rostral midbrain and medial thalamus bilaterally. One case showed vertical gaze palsy accompanied by bilateral ptosis. The findings agree with recent experimental evidence that a neural substrate in eyelid control lies in the supraoculomotor area immediately dorsal to the oculomotor nucleus. The remaining two cases, a brain hemorrhage and an inflammatory tumor, showed unilateral lesions of the rostral midbrain. In these cases, vertical gazes were not abolished, but were limited in an incomplete way. This may be explained by partial damages of the descending fibers, some of which decussate through the posterior commissure before it reaches the oculomotor nucleus. Thus, clinical signs and symptoms were clarified based on anatomical and physiological points of view.

Adult↗

Body-cavity-based lymphoma in an elderly AIDS-unrelated male.

Body-cavity-based lymphoma (BCBL) is a recently described subtype of human non-Hodgkin's lymphoma characterized by the localization of neoplastic cells exclusively in the body cavities. BCBL is found most commonly in AIDS patients, and is known to be highly associated with Kaposi's sarcoma-associated herpes virus (KSHV). We describe here a case of BCBL that occurred in a 101-year-old man. He was successively treated with etoposide, but died 8 months after the diagnosis of BCBL. No lymphoma masses were noted at pre- and postmortem examinations. KSHV was demonstrated in large numbers in the neoplastic cells using semiquantitative PCR analysis. Although there have been four brief reports of HIV negative BCBL, the present case is the first for which the detailed clinical course and response to chemotherapy have been recorded.

Aged↗

Assessment of affinities of beta-CIT, beta-CIT-FE, and beta-CIT-FP for monoamine transporters permanently expressed in cell lines.

We investigated the effects of three cocaine analogs, beta-CIT (2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane), beta-CIT-FE (2-beta-carbomethoxy-3-beta-(4-iodophenyl)-N-(2.fluoroethyl)-nortropa ne), and beta-CIT-FP (2-beta-carbomethoxy-3-beta-(4-iodophenyl)-N-(3-fluoropropyl)-n ortropane), on the uptake of [3H]dopamine(DA), serotonin(5-HT), and 1-norepinephrine (NE) using cell lines permanently expressing DA, 5-HT, and NE transporters, respectively, to determine their affinities for these three transporters. We generated cell lines stably expressing DA, 5-HT, and NE transporters, respectively, by the Chen-Okayama method, and then tested the abilities of (-)cocaine, beta-CIT, beta-CIT-FE, beta-CIT-FP, and clomipramine to inhibit the uptake of [3H]DA, 5-HT, and 2-NE. Ki values of beta-CIT, beta-CIT-FE, and beta-CIT-FP for [3H]DA, 5-HT, 1-NE uptake were 6, 29, and 33 nM, 91, 133, and 130 nM, and 28, 113 and 70 nM, respectively, whereas those of cocaine and clomipramine were 316, 581, and 176 nM and > 10,000, 437, and 851 nM, respectively. Beta-CIT, beta-CIT-FE, and beta-CIT-FP were shown to be potent DA, 5-HT, and NE uptake inhibitors. Beta-CIT and beta-CIT-FP were highly potent and selective dopamine uptake inhibitors, and therefore might be useful for imaging of DA transporter with single photon emission computed tomography (SPECT) or positron emission tomography (PET).

Animals↗

Enhancement of type IV collagenases by highly metastatic variants of HT1080 fibrosarcoma cells established by a transendothelial invasion system in vitro.

A novel in vitro invasion assay system was established in this laboratory, in which the invasion of tumor cells after interaction with endothelial cells could be examined. Two variant cell lines (FP-10, FP-21) were established from parental HT1080 cells using this assay system. FP-10 and FP-21 cells had higher invasive and metastatic potential than the parental cells both in vitro and in vivo. The activity of anchorage-independent proliferation and the adhesion to the HUVEC monolayer of FP-10 and FP-21 was greater than the parental cells. The secretion of type IV collagenase (both MMP-2 and MMP-9) was also increased more significantly by the variant cells than by the parental cells, and the expression of uPA mRNA was higher in FP-10 and FP-21. Treatment of variant cells with human TIMP-2 remarkably suppressed the increment of the in vitro invasion to the same level as parental cells. These results suggest that this in vitro transendothelial invasion system accelerates multiple mechanisms of the metastasis by HT1080, especially the production of type IV collagenases. It can thus provide a useful model of tumor metastasis.

Animals↗

Case report: facial asymmetry and early condylar fracture.

This report describes the surgical-orthodontic treatment of two adult females who exhibited dentofacial asymmetry. Their medical histories included early condylar fractures. Growth was disturbed on the fractured side, resulting in mandibular deviation and maxillary canting. Following the completion of growth, the asymmetries were corrected by combined orthodontic-surgical treatment. The treatment planning procedures and the results are presented.

Adult↗

A phenytoin-sensitive cationic current participates in generating the afterdepolarization and burst afterdischarge in rat neocortical pyramidal cells.

We report here on the ionic mechanisms underlying the depolarizing afterpotential (DAP) in neocortical pyramidal cells, with special interest in those underlying the burst afterdischarge. Injections of short depolarizing current pulses under whole-cell current clamp with a CsCl-based internal medium generated, in most pyramidal cells, a single action potential with a plateau phase (plateau-AP), followed by a slowly decaying DAP both in the absence and presence of TTX. Under voltage-clamp, the same cells displayed a slow tail current (tail-I) at the offset of depolarization. When intracellular free Ca2+ was chelated with 10 mM BAPTA or when extracellular Ca2+ was replaced with equimolar Ba2+, neither the slow DAP nor the slow tail-I was observed. Extracellular application of Co2+ or Cd2+ reduced Ca2+ currents and the slow tail-I. Cation substitution experiments revealed that the channel generating the slow tail-I was permeable to K+ and Cs+ more than to Na+ (PK is approximately equal to PCs > PNa > PNMDG is approximately equal to PTEA). The cationic slow tail-I was not reduced by applying antagonists of the metabotropic glutamate receptor (MCPG, 1 mM) and the muscarinic receptor (atropine, 1-10 microM). Thus, the slow DAP was produced by activation of the cationic channel whose gating is solely dependent on [Ca2+]i. An increase in [K+]o from 3 to 6 or 9 mM enhanced the slow DAP, and resulted in a generation of burst afterdischarges. An anticonvulsant, phenytoin (PT; 1-10 microM) suppressed the slow DAP while enhancing the plateau-AP in the presence of TTX, most likely by blocking the cationic channel.

Animals↗

Relationship of apolipoprotein E phenotypes to serum lipid and lipoprotein levels in Japanese schoolchildren.

The distribution of apolipoprotein (apo) E phenotypes was investigated in Japanese schoolchildren and an attempt was made to determine whether the apoE phenotypes influence the serum levels of lipid and lipoprotein. The subjects were 289 children from a junior high school (145 M, 144 F, aged 12-13 y). The E3/3 phenotype was demonstrated in 69.9%, E4/3 in 18.7%, E2/3 in 9.0%, E4/2 in 1.4%, E4/4 in 0.7% and E5/4 in 0.3%. E2/2 was not detected. Serum levels of total cholesterol and low-density lipoprotein-cholesterol were progressively lower in the phenotypes E4/3, E3/3 and E2/3. The serum level of high-density lipoprotein-cholesterol showed a progressive increase in the same order. In conclusion, Japanese schoolchildren with E4/3 already had an atherogenic serum lipid profile.

Adolescent↗

Ketamine inhibits monoamine transporters expressed in human embryonic kidney 293 cells.

BACKGROUND: Ketamine has been characterized as having psychotomimetic and sympathomimetic effects. These symptoms have raised the possibility that ketamine affects monoaminergic neurotransmission. To elucidate the relation between ketamine and monoamine transporters, the authors constructed three cell lines that stably express the norepinephrine, dopamine, and serotonin transporters and investigated the effects of ketamine on these transporters. METHODS: Human embryonic kidney cells were transfected using the Chen-Okayama method with the human norepinephrine, rat dopamine, and rat serotonin transporter cDNA subcloned into the eukaryotic expression vector. Using cells stably expressing these transporters, the authors investigated the effects of ketamine on the uptake of these compounds and compared them with those of pentobarbital. RESULTS: Inhibition analysis showed that ketamine significantly inhibited the uptake of all three monoamine transporters in a dose-dependent manner. The Ki (inhibition constant) values of ketamine on the norepinephrine, dopamine, and serotonin transporters were 66.8 microM, 62.9 microM, and 162 microM, respectively. Pentobarbital, a typical general anesthetic agent with no psychotic symptoms, did not affect the uptake of monoamines, however. Further, neither the glycine transporter 1 nor the glutamate/aspartate transporter was affected by ketamine, indicating that ketamine preferentially inhibits monoamine transporters. CONCLUSIONS: Ketamine inhibited monoamine transporters expressed in human embryonic kidney cells in a dose-dependent manner. This result suggests that the ketamine-induced inhibition of monoamine transporters might contribute to its psychotomimetic and sympathomimetic effects through potentiating monoaminergic neurotransmission.

ATP-Binding Cassette Transporters↗

Structural studies on endothelin receptor subtype B specific agonist IRL 1620 [suc-[Glu9, Ala11,15]ET-1(8-21)] and its analogs with dipalmitoyl phosphatidylcholine vesicles by NMR spectroscopy.

IRL 1620 ¿suc-[Glu9,Ala11,15]ET-1(8-21)¿ is a potent and specific agonist for the ET(B) receptor. Five analogs of IRL 1620 were synthesized in this study. These were all C-terminal linear peptides of endothelin 1 (ET-1) comprising 14 amino acid residues and exhibiting highly potent ET(B) receptor binding affinities. The peptides consisted of three pairs and each component of the pairs differed from its partner in only the 18th residue, i.e. Asp was replaced by Gly. The replacements resulted in more than a 10-fold increase in affinity to the ET(A) receptor. The structures of these peptides were investigated in the presence of phospholipid vesicles (dipalmitoyl phosphatidylcholine) by NMR spectroscopy. By the replacement of Asp by a less bulky Gly, the C-terminal tripeptide region folded back toward the helical region, making it shorter than the Asp-substituted peptide helical region. Such a folded conformational feature may explain the increased binding affinity to ET(A) receptor.

1,2-Dipalmitoylphosphatidylcholine↗