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Biomedical subjects

K Ueno

Publications and source records attributed to K Ueno.

At least 127 records · Page 7Linked to original sources

Population pharmacokinetic analysis of mexiletine in adult arrhythmic patients in Japanese population.

We analyzed mexiletine in Japanese patients using population pharmacokinetics. 139 serum concentration data, which were collected for therapeutic drug monitoring from 121 patients, were used for this analysis. We also investigated influence of age and gender on pharmacokinetics, and age was found to be an influential factor on clearance. The final pharmacokinetic parameters are, CL/F=0.580-0.00369 x AGE (l/h/kg) and Vd/F=6.63 (l/kg). These results should be useful for adjusting the dosage to a patient's age for the prevention of an adverse reaction caused by overexposure.

Adult↗

Lack of pharmacokinetic interaction between mexiletine and omeprazole.

OBJECTIVE: To investigate the effect of omeprazole on the pharmacokinetics of mexiletine. METHODS: Nine healthy male Japanese volunteers participated in a crossover study. On day 1, the subjects received mexiletine 200 mg. On days 2-7, they received omeprazole 40 mg, and on day 8 they received mexiletine 200 mg and omeprazole 40 mg concomitantly. Serum concentrations of mexiletine were determined just before drug administration and at 1, 2, 3, 4, 6, 8, 12, and 24 hours on day 1 and day 8. RESULTS: No differences in mexiletine concentrations were observed between the two phases of the study. The mean AUCs after administration of mexiletine alone and in combination with omeprazole 40 mg/d were 6.26 and 6.20 ng.h/L, respectively. CONCLUSIONS: These findings suggest that omeprazole does not affect mexiletine metabolism.

Administration, Oral↗

Myocardial rest iodine-123-beta-methyl-iodophenyl-pentadecanoic acid scintigraphy compared with dipyridamole stress thallium-201 scintigraphy in unstable angina.

Twelve patients with stable angina and 12 patients with unstable angina underwent rest iodine-123-beta-methyl-iodophenyl-pentadecanoic acid (BMIPP), dipyridamole stress thallium scintigraphy and delayed thallium scintigraphy. In stable angina, sensitivity for detecting ischemic segments was higher in dipyridamole thallium (74%) than rest BMIPP (48%) images (p<0.05), but there was no significant difference between the 2 images in unstable angina. In unstable angina, the incidence of segments with higher defect scores on BMIPP images than on delayed thallium images and the opposite pattern was 27 and 5 (p<0.01). In stable angina, there was no difference. The mean defect score on BMIPP (6.3 +/- 5.6) was higher than that on delayed thallium scintigraphy (2.9 +/- 2.7) and it was almost the same as on the initial dipyridamole stress test (6.5 +/- 5.2). In conclusion, BMIPP scintigraphy is safer and may be as useful in detecting myocardial ischemia in patients with unstable angina as thallium scintigraphy.

Angina Pectoris↗

Recanalization after coil embolotherapy of pulmonary arteriovenous malformations: study of long-term outcome and mechanism for recanalization.

OBJECTIVE: We investigated the efficacy of steel coils for embolotherapy of pulmonary arteriovenous malformations (PAVMs) by reimaging the embolized PAVMs. CONCLUSION: We found a high incidence (57%; 8/14) of recanalization in PAVMs embolized with steel coils. Contrast-enhanced CT is useful for detection of recanalized PAVMs. Half of the recanalized PAVMs were fed by bronchial artery branches. Thus, coil embolization should be performed as close as possible to the PAVM to avoid future development of bronchial artery-to-pulmonary artery anastomoses that may cause recanalization.

Adolescent↗

[Open heart surgery in patients with a tracheostoma].

From April 1992 to May 1997 six patients underwent open heart surgery, who had tracheostoma at the time of operation. The sternum was divided completely in three patients whose tracheostoma lay highly on the neck, and it was cut transversely on the manubrium at the level of the first intercostal space, below which it was split longitudinally in two patients (partial median sternotomy). In one patient right anterolateral thoracotomy was used. There were no operative death and no complication related to infection. A left internal thoracic artery (LITA) was used successfully for a bypass conduit in two patients who underwent partial median sternotomy. Dissection of the proximal portion of the LITA through the second intercostal space prior to the sternotomy made the graft procurement feasible in this particular situation. In conclusion, full-length sternotomy is performable safely when the tracheostoma lies highly on the neck, and the partial sternotomy up to the midmanubrium is applicable, including LITA harvesting, even if it is just at the sternal angle.

Adolescent↗

[Fleroxacin treatment for acute uncomplicated cystitis in women: comparison of 3-day and 7-day therapy].

The clinical efficacy of fleroxacin (FLRX), a new fluoroquinolone, for acute uncomplicated cystitis (AUC) in women was assessed. Two regimens, 3-day and 7-day courses of FLRX, 200 mg once a day, were compared. Clinical and bacteriological efficacy were evaluated after the therapy, and recurrence rate was evaluated 1 week and 4 weeks after termination of the therapy. Of 136 registered subjects, 35 in the 3-day group and 47 in the 7-day group were evaluated. According to the criteria of Japanese UTI Committee (3rd edition), the rate of excellent results was significantly higher in the 7-day group (78.9%) than in the 3-day group (48.6%), but the overall clinical efficacy rate was similar being 100% and 97.9%, respectively. Although no recurrence was seen 1 week after the therapy in either group, recurrence was seen in 14.3% and 7.4% of the cases in the 3-day and 7-day groups, respectively, 4 weeks after the therapy. Adverse reactions were observed in 2 and 3 cases in the 3-day and 7-day groups, respectively. Both 3-day and 7-day regimens of FLRX treatment showed good efficacy. Although the 7-day treatment was superior to the 3-day treatment as to high rate of excellent results and low rate of recurrence, the 3-day treatment was concluded to be sufficient for AUC.

Adult↗

Sound lateralization and speech discrimination in patients with sensorineural hearing loss.

Sound lateralization and speech discrimination abilities are both closely related to central auditory system function. In this study, we investigated the relationship between sound lateralization and speech discrimination in patients with sensorineural hearing loss (SNHL) of unknown aetiology or presbycusis. Interaural intensity difference (IID) and interaural time difference (ITD) discriminations were measured using a self-recording apparatus for dichotic sound presentation, and the means of bilateral maximum scores in speech discrimination tests were calculated. Subjects with normal sound lateralization had good speech discrimination scores above 70%, while those with abnormal sound lateralization had poor scores below 70%. Some patients, however, had good speech discrimination but abnormal sound lateralization. These findings were obtained in both IID and ITD discrimination tests. Furthermore, some subjects could not discriminate ITD, although all could discriminate IID. These findings suggest that sound lateralization ability may be affected more than speech discrimination in SNHL of unknown aetiology or in presbycusis.

Adult↗

Patterns of change in growth function of distortion product otoacoustic emissions in Menière's disease.

The patterns of change in the growth function of distortion product otoacoustic emissions (DPOAEs) associated with hearing improvement in six patients with Menière's disease were investigated. The growth functions of 2F1-F2 DPOAEs at F2 frequencies of 1001, 2002 and 4004 Hz (DP-1, DP-2 and DP-4, respectively) were measured with F2 intensities ranging from 70 to 37 dBSPL in 3-dB steps. The F1 intensity was maintained 10 dB higher than the F2 intensity. The growth function was paired with the hearing threshold at the corresponding F2 frequency, and the relationships between changes in DP-1, DP-2 and DP-4 and those in hearing thresholds at 1, 2 and 4 kHz, respectively, were also investigated. The patterns of change in the growth function associated with hearing improvement could be classified into five types. In the first type, the DPOAE growth function became detectable, while the remaining four types were distinguished by combinations of changes in DPOAE amplitudes for lower and higher primary intensities. Multiple parameters, such as maximum amplitude and detection threshold of the growth function, appeared to be required for simple detection and discrimination of these patterns of change. It was also found that the DPOAE growth functions clearly changed in some cases even though the hearing thresholds did not change significantly at the corresponding F2 frequencies. This finding suggests that DPOAE growth function measurement can detect small changes in cochlear function which do not lead to changes in hearing threshold, and has higher sensitivity than pure tone audiometry in monitoring of cochlear function. In conclusion, our findings suggest that measurement of the DPOAE growth function is useful for monitoring cochlear function, and that information on its patterns of change is clinically important and useful.

Adult↗

Changes in distortion product otoacoustic emissions from ears with Menière's disease.

To investigate changes in distortion product otoacoustic emissions (DPOAEs) associated with hearing improvement in ears with Menière's disease, four parameters were studied. These were: DPOAE amplitudes for a moderate (L1/L2 = 65/55 dBSPL) and a high (L1/L2 = 74/64 dBSPL) primary level (65/55-DP and 74/64-DP amplitudes, respectively); maximum level of DPOAE amplitudes in the growth function (maximum DP level); and DPOAE detection threshold (DP threshold) of the growth function. Significant correlations were found between all four parameters and hearing threshold, except for the 65/55-DP amplitude at 1 kHz, and each parameter appeared to reflect the hearing threshold to some extent. However, the changes in the four parameters associated with hearing improvement were somewhat complicated. Changes could not be evaluated due to lack of detection of responses when the hearing thresholds exceeded 50 dBHL. Findings that parameters became detectable, the DP amplitude or the maximum DP level increased significantly, or the DP threshold lowered significantly were classified as "improved" findings. The number of ears with "improved" findings was larger for the maximum DP level or the DP threshold than for the 65/55-DP and 74/64-DP amplitudes in ears with a 10 dB or greater improvement in hearing threshold at the corresponding F2 frequency. Furthermore, a significant decrease in amplitude was found in some ears, although the hearing threshold was not elevated when the 65/55- or 74/64-DP amplitude was used as a parameter. On the other hand, "improved" findings for the maximum DP level or the DP threshold were observed for a relatively large number of ears without a significant change in hearing threshold, and it was thought that small changes in cochlear function which did not lead to changes in hearing threshold were detected by changes in DPOAEs. These findings suggest that parameters determined from the growth function, such as maximum DP level and DP threshold are better indicators for monitoring cochlear function than is DPOAE amplitude for a single primary level, and demonstrate the usefulness of the growth function measurement for monitoring purposes. Furthermore, evaluation by changes in the overall growth function using combined parameters appeared to increase sensitivity in detection of subtle changes in cochlear function. In conclusion, DPOAE measurement can be a useful examination for clinical monitoring of cochlear function in Menière's disease when the growth function is measured.

Adolescent↗

Conversion of Bcl-2 to a Bax-like death effector by caspases.

Caspases are a family of cysteine proteases implicated in the biochemical and morphological changes that occur during apoptosis (programmed cell death). The loop domain of Bcl-2 is cleaved at Asp34 by caspase-3 (CPP32) in vitro, in cells overexpressing caspase-3, and after induction of apoptosis by Fas ligation and interleukin-3 withdrawal. The carboxyl-terminal Bcl-2 cleavage product triggered cell death and accelerated Sindbis virus-induced apoptosis, which was dependent on the BH3 homology and transmembrane domains of Bcl-2. Inhibitor studies indicated that cleavage of Bcl-2 may further activate downstream caspases and contribute to amplification of the caspase cascade. Cleavage-resistant mutants of Bcl-2 had increased protection from interleukin-3 withdrawal and Sindbis virus-induced apoptosis. Thus, cleavage of Bcl-2 by caspases may ensure the inevitability of cell death.

Animals↗

Cloning and functional analysis of new members of STAT induced STAT inhibitor (SSI) family: SSI-2 and SSI-3.

Upon the corresponding ligand's stimulation, the cytokine receptors activate several signal pathways: JAK-STAT pathway, Ras-MAP kinase pathway and so on. Recently, we demonstrated that one of the STAT3 (signal transducer and activator of transcription-3) target genes could suppress the function of STAT3 and designated as SSI-1(STAT induced STAT inhibitor-1). SSI-1 is thought to play a critical role in negative feedback control of JAK-STAT signaling pathway. In the present study, we identified two novel human genes which products have homologous region in their SH2 domain and its COOH-terminal region to mouse SSI-1. Northern blotting analysis and functional studies demonstrated that SSI-2 and SSI-3 mRNA were also induced by cytokine stimulation and their forced expression in mouse myeloid leukemia cell, M1, suppressed the apoptotic effect of LIF, like SSI-1. We also demonstrated the structure of human SSI-1.

Amino Acid Sequence↗

Molecular epidemiology of Epstein-Barr virus (EBV) in EBV-related malignancies.

The prevalent strain of Epstein-Barr virus (EBV) in EBV-related malignancies and in healthy adults in Southern Japan was examined by means of polymerase chain reaction (PCR) and/or restriction fragment length polymorphism (RFLP) analysis. In EBV-related gastric cancers, 51/73 cases were subtype A, 4 were subtype B and the EBNA-2 region was not amplified in 18 cases. Sixty-three were wild-type F, and only one was variant "f". Sixty-one cases had type C and 2 type D. EBNA-2 subtype A was found in 10/12 EBV-related T/NK-cell lymphomas, and 11 samples harbored the wild-type F. Neither subtype B nor the "f" variant was detected. Type C EBV was found in 8 cases and type D in 3 specimens. Two Japanese nasopharyngeal carcinomas (NPC) harbored subtype A with wild-type F and type C. Throat washings from healthy adults harbored wild-type F virus in 60/153 cases, and 25 of these samples were EBNA-2 subtype A. Type C viruses were detected in 92% of cases and type D in 7.4%. Therefore, the prevalent strain in EBV-related malignancies in Southern Japan was the same as in the healthy population in this geographical region.

Adult↗

Involvement of the Bombyx Scr gene in development of the embryonic silk gland.

Homeotic selector genes determine the identity of each segment and induce the differentiation of segment-specific organs. To analyze how the silk glands of the lepidopteran, Bombyx mori, develop, we cloned and identified two genes that encode the homeodomain and its flanking regions identical to the corresponding regions of Deformed and Sex combs reduced. Using in situ hybridization and immunohistochemistry, we analyzed the expression patterns of these genes during Bombyx embryogenesis. Bombyx Deformed is expressed in the mandibular and maxillary segments, whereas expression of Bombyx Sex combs reduced is first limited to the labial segment and at later stages extended to the anterior part of the prothoracic segment. The expression of Bombyx Sex combs reduced then disappears from the invaginating placodes of silk glands where expression of Bombyx fork head/SGF-1 follows. In the Nc/Nc mutant embryos, which lack the 3' end region of Bombyx Antennapedia, in addition to the expression in the labial segment, the Bombyx Sex combs reduced is expressed ectopically in the thoracic and abdominal regions, and Bombyx fork head/SGF-1 is also ectopically expressed in the T1, T2, and T3 segments, resulting the ectopic induction of the silk gland invaginations. These results suggest that Bombyx homeobox genes such as the Bombyx Deformed and Sex combs reduced are associated with determination of the segment identities and Bombyx Sex combs reduced is involved in the induction of silk gland development.

Amino Acid Sequence↗

p260/270 expressed in embryonic abdominal leg cells of Bombyx mori can transfer palmitate to peptides.

During the study on the mechanisms of abdominal leg development in the silkworm Bombyx mori, we found that a high molecular mass protein (p260/270) was expressed specifically in abdominal leg cells during early embryonic stages and disappeared by a late embryonic stage. p260/270 consists of two polypeptides with molecular masses of 260 and 270 kDa. We have established a purification procedure for p260/270 and have raised an antibody against p260/270. Immunoblot analysis of the ECa/ECa (additional crescent) and EN/EN (new additional crescent) mutants, which lack the Bombyx abdominal-A gene and therefore do not express abdominal legs, demonstrated that the two mutants lacked p260/270. Therefore, we speculate that the expression of p260/270 may be regulated by the Bombyx abdominal-A gene. cDNA cloning and sequencing demonstrated that p260 and p270 have structures similar to that of rat fatty-acid synthase, which synthesizes palmitate. Most of the enzymatic domains for palmitate synthesis were well conserved in the amino acid sequences of p260 and p270, while the thioesterase domains of p260 and p270 were less homologous to that of rat fatty-acid synthase. Purified p260/270 can transfer palmitate to cysteine residues of synthetic peptides in vitro. We propose that p260/270 may be involved in protein palmitoylation and may function in abdominal leg development.

Abdomen↗

Nasal and pharyngeal abnormalities caused by the mouse goosecoid gene mutation.

The Goosecoid (gsc) gene is a homeobox-containing gene expressed first in the gastrula, and later during organogenesis in development. The gsc gene transcript is found in the first and second branchial arches, frontonasal mass in its late phase of expression. We have previously shown that targeted mutation of the mouse gsc gene leads to neonatal death and craniofacial defects. In this study, we performed histological studies on craniofacial phenotypes in order to elucidate the processes underlying the neonatal death of gsc mutant mice. We found that gsc mutant mice have aplastic nasal cavities and lack the Sinus Paranasalis. We also showed that secretory olfactory glands in the basal layers are aplastic. This is suggested to be essential defects for olfaction. gsc mutant mice also show several pharyngeal phenotypes, including defects in the pharyngeal muscles and the pharyngeal mucosa. It is therefore suggested that mutant mice develop lethal gastro-intestinal phenotypes caused by defects in breathing and sucking of milk as a consequence of these craniofacial disorders. These results should help elucidating the molecular genetic programs essential to the neonatal development of mammals.

Animals↗

Clinical significance of asymptomatic sinus abnormalities on magnetic resonance imaging.

OBJECTIVE: To investigate the prevalence of abnormalities of the paranasal sinus detected by magnetic resonance imaging (MRI) in asymptomatic subjects. DESIGN: Prospective study. SETTING: Outpatient clinic. PATIENTS: A total of 325 patients who underwent MRI for suspected intracranial disease. Of those, 257 patients lacked nasal or sinus symptoms. RESULTS: Sinus abnormalities were seen on MRI in 153 (47.1%) of 325 patients, including 107 (41.6%) of the 257 asymptomatic patients. Subjects older than 50 years had a significantly higher frequency of sinus abnormalities on MRI (49.8%) vs those younger than 50 years (39.5%) (P < .05). The maxillary sinus abnormality was observed in 99 patients (38.5%) and the ethmoid sinus abnormality was observed in 52 (20.2%) (P < .01). The most common abnormality was mucosal thickening in the maxillary and ethmoid sinuses. CONCLUSION: A high prevalence of sinus abnormalities was detected in asymptomatic subjects on MRI.

Ethmoid Sinus↗

Total resection of the head of the pancreas preserving the duodenum, bile duct, and papilla with end-to-end anastomosis of the pancreatic duct.

Many surgeons have recently attempted operative procedures for limited resection of the head of the pancreas. This site-specific approach has emerged as a result of precise diagnostic radiologic studies that have become available. The author performed a new operative procedure in 2 patients with mucin-producing pancreatic cysts that included total resection of the head of the pancreas with careful regard to its vasculature. The procedure provided a way of resecting the head of the pancreas while preserving the duodenum, bile duct, and papilla. The pancreatic duct was cut 5 mm before the point of confluence with the bile duct, and an end-to-end anastomosis was performed on the pancreatic duct. Both patients were discharged within 1 to 1.5 months after surgery, without complication. The operative procedure requires no processing of the jejunum, only a simple anastomosis of the pancreatic duct.

Anastomosis, Surgical↗