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T Usui

Publications and source records attributed to T Usui.

At least 91 records · Page 5Linked to original sources

Expression of the insulin-like growth factor system and cancer progression in hormone-treated prostate cancer patients.

BACKGROUND: The insulin-like growth factor (IGF) system, which is composed of two ligands (IGF-I and IGF-II), two receptors (IGFR-I and IGFR-II) and six binding proteins (IGFBP-1 to -6), plays an important role in cell biology. To identify the main components in the IGF system that contribute to human prostate cancer progression after hormone therapy, mRNA expression of the IGF system in human prostate cancer tissue was systematically examined. METHODS: Expression of the IGF system in 24 carcinomas obtained from total prostatectomies after hormone therapy was examined. Expression levels of mRNA of each component of the IGF system were analyzed by quantitative reverse transcription-polymerase chain reaction procedures and compared with clinicopathologic parameters. RESULTS: Expression of the IGF system, except IGFBP-1, was detected in all prostate cancer tissue samples. The expression of IGF-II and IGFBP-2 significantly correlated with pathologic stage, lymph node metastasis, histologic differentiation and serum prostate-specific antigen (PSA) levels after hormone therapy. However, expression of IGF-I was significantly lower in locally advanced prostate cancer tissue than in tissue from the early stage. Expression of IGFBP-5 was significantly related to only serum PSA levels after hormone therapy. CONCLUSIONS: In the IGF system, IGF-II and IGFBP-2 play a role in human prostate cancer progression and their increased expression is a possible candidate for a prognostic indicator in hormone-treated prostate cancer patients.

Aged↗

Sinus node recovery time assessment by the overdrive suppression test employing an intravenous injection of disopyramide phosphate.

Although sinus node recovery time (SNRT) assessment by the overdrive suppression test (ODST) is important in detecting sick sinus syndrome (SSS), its sensitivity is still inadequate. We have evaluated the effect of intravenous injection (i.v.) of disopyramide phosphate (DP) in ODST. The subjects were 30 SSS patients (64.9 +/- 10.0 years old). If SNRT was <2,000 ms or the corrected SNRT (CSNRT) was < 1,000 ms, ODST was repeated after DP i.v. (2 mg. kg(-1), < or = 100 mg in total). Eleven normal subjects (59.3 +/- 9.0 years old) were also studied. Although SNRT was <2,000 ms or the CSNRT was < 1,000 ms in 13 of the 30 SSS patients (43%), SNRT was prolonged from 1,510 +/- 300ms to 3,400 +/- 1,160 ms (P<0.01), and CSNRT from 510 +/- 190 to 2,470 +/- 1,470 ms (P<0.01) after DP i.v. in these patients. Thus, SNRT was > or = 2,000 ms and the CSNRT was > or = 1,000 ms in 27 of 30 SSS patients (90%) after DP i.v. Using a combination of overdrive suppression and intravenous injection of disopyramide phosphate, the corrected sinus node recovery time was diagnostic (>525 ms) in 29 of the 30 patients (97%). In contrast, SNRT and CSNRT were shortened in the normal subjects during ODST after DP i.v. (P<0.01). The plasma concentration of DP estimated in nine patients was 4.1 +/- 1.0 microg.ml(-1). No serious side effect occurred. ODST employing DP i.v. is safe and seems to be highly effective in diagnosing SSS.

Aged↗

A case of superior oblique myokymia observed by an image-analysis system.

Superior oblique myokymia is a microtremor of the eye that causes monocular torsional oscillopsia. A modified Harada-Ito procedure was used to treat a case of the disease in a 20-year-old woman. The authors used video-image analysis pre- and postoperatively to evaluate the effect of the surgery on abnormal torsional eye movements. This analysis revealed that before surgery, the abnormal torsional movement had a very regular cycle (duration of attack, 8.0 +/- 0.5 s; time interval between attacks, 18.7 +/- 3.2 s; n = 9). After the surgery, amplitude of the abnormal torsional eye movement was reduced, and the oscillopsia had subjectively improved, although the movement cycle remained unchanged. The authors' video-image analysis, which used iris striation, proved to be a useful method for clinical measurement of torsional eye movements.

Adult↗

Expression of estrogen receptor alpha and beta mRNAs in prostate cancers treated with leuprorelin acetate.

OBJECTIVE: The discovery of a novel estrogen receptor (ER), ER-beta, has given rise to new possibilities regarding estrogen's roles in the prostate. Although ER-beta is reported to be expressed preferentially in the rat prostate, its expression in the human prostate and relationship to cancer development has not been investigated. Thus the purpose of the study was to examine mRNA levels of ER-alpha and ER-beta in benign prostatic hyperplasia and prostate carcinoma. METHODS: Samples of 15 prostate cancers obtained at radical prostatectomy were examined. All the patients had been maintained on androgen withdrawal therapy for at least 3 months. ER-alpha and ER-beta mRNAs were measured with a competitive PCR technique. RESULTS: Both ER-alpha and ER-beta mRNAs were detected in all of the prostate cancer tissues examined, as well as in PC3 and LNCap cells, although the levels varied among specimens. Interestingly, both types were significantly decreased in cases with lymph node metastasis. However, there was no correlation between ER mRNA levels and any other clinicopathological parameters. CONCLUSIONS: (1) Both ER-alpha and ER-beta mRNAs are expressed in prostate cancer and (2) expression of ER mRNA may not be related to cancer progression but may be negatively correlated with metastasis.

Aged↗

Ghrelin strongly stimulates growth hormone release in humans.

Ghrelin is a recently identified endogenous ligand for the GH secretagogue receptor and is involved in a novel system for regulating GH release. However, little is known about its GH-releasing activity and other endocrine effects in humans. To address this issue, we studied the GH, ACTH, cortisol, PRL, LH, FSH, and TSH responses to synthetic human ghrelin. In four normal male adults (28-37 yr), iv ghrelin administration released GH in a dose-dependent manner and 0.2, 1.0, and 5.0 microg/kg ghrelin produced 43.3 +/- 6.0, 81.5 +/- 12.7, and 107.0 +/- 10.7 ng/mL of the GH peak values at 30 min, respectively. ACTH, cortisol, and PRL levels were also elevated after ghrelin injection, while the lowest dose (0.2 microg/kg) resulted in only minimum peak values of these hormones (22.8 +/- 3.0 pg/mL, 9.4 +/- 1.9 microg/dL, and 4.6 +/- 0.6 ng/mL, respectively). There were no significant changes in LH, FSH, or TSH levels. This is the first study showing evidence that ghrelin strongly stimulates GH release in humans.

Adrenocorticotropic Hormone↗

Incidence of atrial flutter and atrial fibrillation in patients with implanted physiological pacemakers.

Atrial flutter (AF) is a troublesome arrhythmia for patients with an implanted pacemaker. Although it has recently become possible to eliminate AF by radiofrequency catheter ablation (RF-CA), the incidence of AF before and after pacemaker implantation has not been clarified. The present study was conducted with 123 consecutive patients (69.3+/-11.6 (SD) years old) implanted with pacemakers, excluding patients who had chronic atrial fibrillation (AFib) when the pacemaker was implanted; 69 patients with atrioventricular (AV) block and 54 patients with sick sinus syndrome (including 29 patients with bradycardia-tachycardia syndrome). All patients were implanted with physiological pacemakers. The follow-up period was 4.7+/-1.9 years. In 11 of the 123 patients (8.9%), AF was observed before pacemaker implantation and the incidence was significantly higher in patients with sick sinus syndrome than in those with AV block (16.7 vs 2.9%, p<0.01). Nine of the 29 patients with bradycardia-tachycardia syndrome (31%) had AF. After physiological pacemaker implantation, AF recurred in 9 of the 11 patients, and AF was newly observed in 1 patient. Thus, 10 of the 123 patients (8.1%) had AF after physiological pacemaker implantation. Recurrence of AF was not suppressed by physiological pacing. Thirty of the 123 patients had AFib before implantation of a pacemaker and its occurrence was reduced by physiological pacing (from 24.4% to 12.2%, p<0.05). The incidence of AFib in patients with AF was significantly higher than in those without AF (90.0 vs 5.3%, p<0.001). In conclusion, the recurrence of AF is not prevented by physiological pacing and is closely related to the occurrence of AFib. RF-CA should be considered in patients who have AF before pacemaker implantation.

Aged↗

Efficacy of atrioventricular sequential pacing and diastolic mitral regurgitation in patients with intrinsic atrioventricular conduction.

The efficacy of a short atrioventricular (AV) delay in patients with dilated cardiomyopathy has been reported, but there are deleterious effects of right ventricular pacing. Diastolic mitral regurgitation (MR) is observed in patients with elevated left ventricular end-diastolic pressure and can be induced by prolonging the AV delay in patients with DDD pacemakers. The critical PQ interval that induces diastolic MR may represent the upper limit of the optimal PQ interval. The efficacy of AV sequential pacing and diastolic MR were studied in 11 patients (68.3+/-13.7 (SD) years old) with intrinsic AV conduction and with implanted DDD pacemakers. Cardiac output (CO) and pulmonary capillary wedge pressure (PCWP) were measured by Swan-Ganz catheter and transmitral flow was recorded by pulsed Doppler echocardiography. AV delay was prolonged stepwise by 25 ms starting from 65 ms. Pacing rate was fixed at 70-80 beats/min. In 6 of the 11 patients, diastolic MR was observed under atrial pacing and the critical PQ interval for the appearance of diastolic MR was 0.22+/-0.04 s. CO was increased from 3.8+/-0.8 to 4.3+/-0.9 L/min (p<0.05) and PCWP was decreased from 7.5+/-2.8 to 5.5+/-1.6 mmHg (p<0.05) by shortening the AV delay till the diastolic MR disappeared. On the other hand, in 5 of the 11 patients, diastolic MR was not observed, and CO (4.2+/-0.5 to 4.3+/-0.5L/min, ns) and PCWP (5.8+/-4.6 to 5.4+/-3.9 mmHg, ns) were not improved by AV sequential pacing. In conclusion, cardiac function may be improved by AV sequential pacing and setting the AV delay under the critical PQ interval for the appearance of diastolic MR when the diastolic MR is observed. However, AV sequential pacing may be either ineffective or even deleterious for patients in whom diastolic MR is not observed.

Aged↗

L/M cone ratios in human trichromats assessed by psychophysics, electroretinography, and retinal densitometry.

Estimates of the relative numbers of long-wavelength-sensitive (L) and middle-wavelength-sensitive (M) cones vary considerably among normal trichromats and depend significantly on the nature of the experimental method employed. Here we estimate L/M cone ratios in a population of normal observers, using three psychophysical tasks-detection thresholds for cone-isolating stimuli at different temporal frequencies, heterochromatic flicker photometry, and cone contrast ratios at minimal flicker perception--as well as flicker electroretinography and retinal densitometry. The psychophysical tasks involving high temporal frequencies, specifically designed to tap into the luminance channel, provide average L/M cone ratios that significantly differ from unity with large interindividual variation. In contrast, the psychophysical tasks involving low temporal frequencies, chosen to tap into the red-green chromatic channel, provide L/M cone ratios that are always close to unity. L/M cone ratios determined from electroretinographic recordings or from retinal densitometry correlate with those determined from the high-temporal-frequency tasks. These findings suggest that the sensitivity of the luminance channel is directly related to the relative densities of the L and the M cones and that the red-green chromatic channel introduces a gain adjustment to compensate for differences in L and M cone signal strength.

Color Perception↗

Expression of prostaglandin E receptor EP4 subtype in rat adrenal zona glomerulosa: involvement in aldosterone release.

We examined the role of prostaglandin (PG) E receptors in the secretion of aldosterone. PGE2 is known to exert its various biological functions by binding to PGE receptors. There are four subtypes of PGE receptors, EP1, EP2, EP3, and EP4. Among the PGE receptors EP2 and EP4 subtypes are coupled to Gs protein and stimulate adenylyl cyclase. In this study, PGE2 caused a dose-dependent increase in aldosterone production from the rat adrenal zona glomerulosa cells in vitro accompanied with an increase in intracellular cAMP concentration. A specific agonist for EP2, butaprost, did not increase the cAMP production or the aldosterone release, suggesting the possibility that EP4 mediates the secretion of aldosterone by PGE2. Northern blot hybridization analysis disclosed that EP4 gene was expressed in the rat adrenal gland but that EP2 gene was not. In situ hybridization revealed that EP4 mRNA is present abundantly in the zona glomerulosa of rat adrenal gland. These findings suggest that the PGE2-EP4 system is involved in the regulation of aldosterone secretion from the rat adrenal gland.

Aldosterone↗

Mutation analysis of Gsalpha, adrenocorticotropin receptor and p53 genes in Japanese patients with adrenocortical neoplasms: including a case of Gsalpha mutation.

While the mechanisms of tumorigenesis for adrenocortical neoplasms remain unknown, several genes, such as Gsalpha, ACTH receptor (MC2-R), p53, and p16 tumor suppressor genes, are considered to be candidates for adrenocortical neoplasms. Mutation analysis studies have documented these genes in adrenocortical neoplasms, but these studies focused on the mutation of only one of these genes. In the present study we examined the mutations of three of these genes (Gsalpha, MC2-R, and p53) in adrenocortical neoplasms in Japanese patients. We amplified these genes using polymerase chain reaction and directly sequenced them in 30 functioning adrenocortical neoplasms. As for Gsalpha, we identified a heterogeneous substitution of glutamine to histidine at codon 227 and a gain of an Nru I restriction endonuclease site. The mutation was restricted to adenomatous tissue, and did not occur in the adjacent normal adrenal tissue or leukocytes of the patient. We did not find any mutations in MC2-R and p53. In conclusion, although the contribution of these three genes to adrenocortical tumorigenesis remains to be determined, it is suggested that the mutation of Gsalpha might play a role in functional adrenocortical neoplasms.

Adrenal Cortex Neoplasms↗

Rebound hypersecretion of GH following octreotide withdrawal due to liver dysfunction in an acromegalic patient.

Octreotide usually induces long-acting inhibition of GH secretion without rebound hypersecretion. We report a patient with acromegaly who showed rebound elevation of GH and insulin-like growth factor-1 (IGF-1) after octreotide withdrawal. The patient responded remarkably to octreotide therapy with normalization of GH and IGF-1 and shrinkage of pituitary macroadenoma. Octreotide therapy was stopped when he developed liver dysfunction. GH and IGF-1 were markedly elevated for two weeks after cessation of octreotide.

Acromegaly↗

Functional significance of prop-1 gene expression in pituitary adenomas.

Prophet of Pit-1 (Prop-1), which is a paired-like homeodomain transcription factor, is capable of binding to sites in an early enhancer of the Pit-1 gene and regulating its expression. As human Pit-1 is expressed considerably in pituitary adenomas, we studied human Prop-1 gene expression in pituitary adenomas. We also sequenced the Prop-1 cDNAs in pituitary adenomas. Human Prop-1 transcript was detected in all pituitary adenomas examined by RT-PCR analysis. The expression of human Prop-1 in pituitary adenomas was confirmed by in situ hybridization in one of the GH-producing adenomas. The sequence analysis of human Prop-1 cDNAs in these pituitary adenomas revealed that there were no mutations except 5 silent nucleic acid substitutions, suggesting that mutations of Prop-1 gene do not represent a frequent mechanism of human pituitary tumorigenesis.

Adenoma↗

Elevated risk of tuberculosis by occupation with special reference to health care workers.

We conducted a study to evaluate tuberculosis (TB) risk in Japan by work performed, either paid or unpaid. We collated information on sex, age, employment category, occupation, and family history from 1120 registration cards of new TB cases at two wards in Nagoya City over seven years (1989-1995). We used census data and data from the Survey of Physicians, Dentists and Pharmacists conducted in 1990 to estimate the population at risk by employment category and occupation. Elevated TB incidence rates were observed for female nurses (SIR: 3.81; 95% CI: 1.97-6.65), clinical laboratory technicians (SIR: 25.00; 6.81-63.99), and males without a paid job (SIR: 1.35; 1.20-1.53). A work environment conducive to transmission may have increased the TB risk in female nurses and clinical laboratory technicians. Male jobless people and institutionalized elderly residents may have enhanced the TB risk for males without a paid job.

Adolescent↗

PF1163A and B, new antifungal antibiotics produced by Penicillium sp. II. Physico-chemical properties and structure elucidation.

The structures of new antifungal antibiotics, PF1163A and B, were elucidated by spectroscopic analyses of the degradation products and by X-ray crystallography of the de-2-hydroxyethyl derivative of PF1163B. Both antibiotics consist of a 13-membered macrocyclic structure containing a derivative of N-methyl tyrosine and a hydroxy fatty acid. PF1163A differs from PF 1163B by having an additional hydroxyl group on the side chain.

Antifungal Agents↗

Synthesis of pironetin and related analogs: studies on structure-activity relationships as tubulin assembly inhibitors.

Pironetin (1) and demethylpironetin (2) are potent inhibitors of tubulin assembly. They arrested the mammalian cell cycle in M-phase and showed antitumor activity against a murine tumor cell line, P388 leukemia, transplanted in mice. To investigate the chemical and biological properties of 1, we synthesized several derivatives and investigated the structure-activity relationships. All synthesized derivatives decreased biological activities, such as inhibition of cell cycle progression, and disruption of the microtubule network in situ. The most drastic decrease was observed in 6, 8 and 10. These results suggested that alpha,beta-unsaturated lactone, chirality at the 7-position bearing a hydroxyl group and the terminal portion of the alkyl chain are important for microtubule inhibitory activity of pironetins.

Animals↗

Advanced glycation end products in diabetic corneas.

PURPOSE: Corneal complications are often associated with diabetes mellitus and can be vision threatening. Corneas in diabetic patients are exposed to increased glucose concentration despite cornea's avascular property, and this condition may contribute to the accumulation of advanced glycation end products (AGEs). The focus of this study was to examine the role of AGEs in the pathogenesis of diabetic keratopathy. METHODS: An anti-AGE monoclonal antibody (6D12), which recognizes a N(epsilon)-carboxymethyl lysine (CML)-protein adduct as an epitope, was prepared. Immunohistochemical localization of CML was examined in human age-matched diabetic and nondiabetic corneas (8 of each). In vitro, type I collagen-, type IV collagen-, or laminin-coated 96-well plates were glycated by glucose-phosphate. In some experiments, aminoguanidine was present in the incubation mixture. The amounts of CML-protein adducts in the extracellular matrix (ECM) were determined by enzyme-linked immunosorbent assay using 6D12. SV40-immortalized human corneal epithelial cells were seeded onto modified or unmodified ECM in 96-well plates and allowed to attach for 3 hours. Attached cells were fixed, and the areas of attached cells in each condition were measured. Attached cells without fixation were removed, and cell number was counted. RESULTS: In all of the 8 diabetic corneas, CML immunoreactivity was observed in the epithelial basement membrane, whereas CML immunoreactivity was not found in the corresponding area in 7 of 8 nondiabetic corneas. In vitro, nonenzymatic glycation of laminin on the culture dish attenuated adhesion and spreading of corneal epithelial cells. The presence of amninoguanidine in the incubation mixture during glycation inhibited CML formation and promoted the adhesion and spreading of corneal epithelial cells in a dose-dependent manner. CONCLUSIONS: The accumulation of AGEs on the basement membrane, particularly on laminin, may play a causative role in the corneal epithelial disorders of diabetic patients.

Aged↗

[Multifocal electroretinogram in central serous chorioretinopathy].

PURPOSE: To assess retinal function topographically in the affected eyes with central serous chorioretinopathy (CSC). PARTICIPANTS AND METHOD: We recorded multifocal electroretimogram (mERG) in 5 patients with unilateral CSC, and analyzed the topographical properties in the central visual field (rings #1 + 2). RESULTS: mERG amplitudes in the CSC eyes were significantly reduced compared with the fellow eyes, for P 1-N 1 (58.5 +/- 23.5%, p < 0.05) and for P 1-N 2 (47.5 +/- 15.0%, p < 0.05). mERG latencies in the CSC eyes were significantly increased compared with those in the fellow eyes, for N 1 (by 9.0 +/- 8.1%, p < 0.05) and for P 1 (by 8.4 +/- 7.0%, p < 0.05). mERGs in the CSC eyes gradually recovered in the follow-up period. However, the responses did not recover to normal value during follow-up, even when the subretinal fluid disappeared ophthalmoscopically. CONCLUSIONS: These results show that a topographical analysis of the mERG is useful for clinical observation of CSC.

Adult↗

Waveform changes of the first-order multifocal electroretinogram in patients with glaucoma.

PURPOSE: To investigate the relationship between the components of the first-order multifocal electroretinogram (M-ERG) and glaucomatous visual field loss. METHODS: Twenty-six eyes of 14 patients with primary open-angle glaucoma (POAG) were evaluated with the M-ERG techniques. Twenty-six eyes of 26 normal subjects also were tested as control subjects. To record the M-ERG, a stimulus matrix of 103 scaled hexagonal elements was displayed on a monitor driven at a 75-Hz frame rate according to a binary m-sequence. The M-ERG responses were averaged in each quadrant of the stimulus field and the peak-to-trough amplitudes and peak implicit times of the first trough (N1), the first peak (P1), and the second trough (N2) of the M-ERG were compared with the mean sensitivity values (dB) of the corresponding quadrant of the Humphrey static perimetric field. RESULTS: The changes in the peak latencies of P1 and N2 in the POAG group were small but significant compared with those in the normal group (P < 0.01). However, no significant differences in the amplitudes of (P1-N1) and (P1-N2) between the two groups were found. Significant negative correlations between the peak implicit times of N1, P1, and N2 and the mean sensitivity values (dB) of static perimetry were observed. The correlation coefficients were -0.20 (P < 0.05) for the N1, -0.41 (P < 0.001) for the P1, and -0.59 (P < 0.001) for the N2. No significant correlations were observed between the amplitudes (P1-N1 and P1-N2) and the mean sensitivity values. CONCLUSIONS: The present study findings suggest that the peak implicit times, but not the amplitudes, of the M-ERG increase as the glaucomatous visual field deteriorates. The amplitudes of the M-ERG did not decrease as the glaucomatous optic nerve dysfunction progressed.

Electroretinography↗