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Biomedical subjects

K Ueno

Publications and source records attributed to K Ueno.

At least 37 records · Page 2Linked to original sources

A spontaneously ruptured gastric stromal tumor presenting as generalized peritonitis: report of a case.

Among the diverse clinical presentations of gastrointestinal stromal tumor (GIST), spontaneous rupture with peritonitis is extremely rare. We report herein the unusual case of a 75-year-old man found to have a spontaneously ruptured gastric stromal tumor after presenting with generalized peritonitis. The patient was brought to the emergency department of our hospital by ambulance, with generalized severe abdominal pain. On examination, his abdomen was extensively distended with generalized severe rebound tenderness. Abdominal computed tomography scan showed a giant mass arising from the anterior gastric wall with an irregular internal low-density area and a small amount of ascites. An emergency laparotomy revealed a ruptured gastric tumor with dissemination of its necrotic tissue throughout the peritoneal cavity. The tumor was excised together with normal gastric tissue around its base. The tumor, which was 15 x 11 x 4.4cm in size, had a coarse laceration over its well-capsulated smooth serosal surface with massive necrosis and clotted blood inside. Immunohistochemical examination revealed positive reactivity to C-kit protein, which was consistent with the newly introduced diagnostic criteria of GIST. The patient had an uneventful postoperative course and remains well.

Aged↗

Clinicopathological features of Epstein-Barr virus-associated nasal T/NK cell lymphomas in southern Japan.

OBJECTIVE: Nasal T/natural killer cell lymphomas (NTCL) are highly prevalent among Oriental populations. However the characteristic immunophenotype of NTCL is still controversial and it can be difficult to make a firm histologic diagnosis of malignancy. Therefore, 14 cases of NTCL in patients from southern Japan were evaluated for clinicopathological features and immunophenotypic status. Furthermore, the genetic variations in the latent membrane protein 1 (LMP-1) gene of Epstein-Barr virus (EBV)-related NTCL were evaluated. METHODS: Biopsy specimens were fixed in formalin and embedded in paraffin before examination using in situ hybridization for EBV-encoded RNA-1 (EBER-1) as well as immunohistochemical staining for CD3, CD3epsilon, CD4, CD8, CD43, CD45RA, and CD45RO. To detect genetic variations, single-strand conformation polymorphism (SSCP) analysis and DNA sequencing were applied. RESULTS: Clinically, 14 cases were divided into two groups. The first group consisting of eight patients showed good prognosis. The other group consisting of six patients showed poor prognosis. The vast majority of neoplastic cells in NTCL were EBER-1 positive. These cells did not express CD4, CD8, or CD45RA, but often expressed CD43 and CD45RO. In addition, they were negative for CD3 when stained with a mouse monoclonal antibody but stained for CD3epsilon when a rabbit polyclonal was used. The 3'-terminal of LMP-1 gene of seven cases were amplified and all of them have 30 base pair (bp) deletion. CONCLUSION: NTCL are a heterogeneous mix of cell types although EBV-associated NTCL in patients from southern Japan appear to originate from natural killer cells rather than T cells, and also prognosis is variable and not always poor. The ability to make a firm diagnosis can be enhanced through the combined use of in situ hybridization and immunohistochemistry. High prevalence of the 30-bp deletions of the LMP-1 gene in EBV-related NTCL may also reflect the prevalence of the deletion variant in the normal population in Japan.

Adult↗

Doppler ultrasonographic identification of the critical segmental artery for spinal cord protection.

OBJECTIVE: The purpose of this study is to evaluate the possibility of identifying critical segmental arteries (CSAs) based on Doppler ultrasonographic hemodynamics. METHODS: In 18 mongrel dogs, the descending aorta was scanned directly with a 5-MHz linear probe through left thoracotomies and the flow velocities in segmental arteries were measured by pulsed Doppler. The aorta was cross-clamped between Th13 and L1, and flow velocity changes were recorded. According to flow increases, segmental arteries were divided into three groups: arteries with the largest flow increase (L-arteries), arteries with the smallest increase (S-arteries) and other arteries (O-arteries). Animals were divided into three groups. One aortic segment including an L-artery or an S-artery was perfused via a temporary shunt during 30-min aortic cross-clamping distal to the left subclavian artery (Group L or Group S) and neurological outcomes were compared with those of animals without shunting (Group N) after 24 and 48 h. RESULTS: L-arteries had significantly larger flow increases than S- and O-arteries (74.3+/-33.8, 20.4+/-9.8 and 33.3+/-17.8 cm/s, P<0.01). In Group N, five of the six animals were completely paraplegic (Tarlov Grade 0) and the other was Grade 1. In Group S, four animals were Grade 4 and two were Grade 0 after 24h. However, two animals showed delayed paraplegia. Therefore, four animals were Grade 0 and two were Grade 4 after 48 h. All animals in Group L were neurologically normal (Grade 4) at both after 24h (vs. Group N, P=0.0013) and 48 h (vs. Group N, P=0.0013; vs. Group S, P=0.019). CONCLUSIONS: Flow responses to aortic cross-clamping differed among segmental arteries and selective perfusion of L-arteries completely prevented paraplegia. Therefore, L-arteries were considered to be CSAs. Hemodynamic measurement of segmental arterial flow using Doppler ultrasonography could be clinically useful for spinal cord protection during thoracoabdominal aortic surgery.

Animals↗

Arterial blood gas management in retrograde cerebral perfusion: the importance of carbon dioxide.

OBJECTIVES: Many interventional physiological assessments for retrograde cerebral perfusion (RCP) have been explored. However, the appropriate arterial gas management of carbon dioxide (CO2) remains controversial. The aim of this study is to determine whether alpha-stat or pH-stat could be used for effective brain protection under RCP in terms of cortical cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), and distribution of regional cerebral blood flow. METHODS: Fifteen anesthetized dogs (25.1+/-1.1 kg) on cardiopulmonary bypass (CPB) were cooled to 18 degrees C under alpha-stat management and had RCP for 90 min under: (1), alpha-stat; (2), pH-stat; or (3), deep hypothermic (18 degrees C) antegrade CPB (antegrade). RCP flow was regulated for a sagittal sinus pressure of around 25 mmHg. CBF was monitored by a laser tissue flowmeter. Serial analyses of blood gas were made. The regional cerebral blood flow was measured with colored microspheres before discontinuation of RCP. CBF and CMRO2 were evaluated as the percentage of the baseline level (%CBF, %CMRO2). RESULTS: The oxygen content of arterial inflow and oxygen extraction was not significantly different between the RCP groups. The %CBF and %CMRO2 were significantly higher for pH-stat RCP than for alpha-stat RCP. The regional cerebral blood flow, measured with colored microspheres, tended to be higher for pH-stat RCP than for alpha-stat RCP, at every site in the brain. Irrespective of CO2 management, regional differences were not significant among any site in the brain. CONCLUSIONS: CO2 management is crucial for brain protection under deep hypothermic RCP. This study revealed that pH-stat was considered to be better than alpha-stat in terms of CBF and oxygen metabolism in the brain. The regional blood flow distribution was considered to be unchanged irrespective of CO2 management.

Animals↗

Heteromorphic sex chromosomes of lizardfish (Synodontidae): focus on the ZZ-ZW1W2 system in Trachinocephalus myops.

The karyotype and DNA content of four lizardfish species (family Synodontidae), that is, Saurida elongata, Synodus ulae, Synodus hoshinonis and Trachinocephalus myops, were analyzed. The karyotype of T. myops significantly differed from that of the other three species having diploid chromosome number of 48 with mainly acrocentric chromosomes and the ZZ-ZW sex chromosome system. The chromosome number of male T. myops was 2n = 26, while that of female T. myops was 2n = 27. The karyotype consisted of 11 pairs of metacentrics, one pair of acrocentrics and, in addition, two large metacentrics in the male and a single large metacentric, a distinctly small subtelocentric and a microchromosome in the female. C-banding demonstrated that in the female the subtelocentric chromosome and the microchromosome were heterochromatic. The karyotype of T. myops was thought to be derived from a 48 chromosome type synodontid fish through the involvement of Robertsonian rearrangement; the rearrangement of the sex chromosomes proceeded during karyotype evolution. Among the chromosomes, the large metacentrics were determined to be neo-Z (a fusion of the original Z and an autosome), the microchromosomes the W1 (originally W), and the subtelocentric chromosomes the W2 (derived from an autosome pair). The miniaturization of W1 and W2 chromosomes and their heterochromatinization suggested that sex chromosomes in this species have been already highly differentiated. The findings on DNA content implied that the karyotype of T. myops evolved by centric fusion events without loss in DNA amount.

Animals↗

Bladder reconstruction with autotransplanted ileum in the dog: better functional results than standard enterocystoplasty.

OBJECTIVE: To compare, in a dog model, the properties of a reconstructed bladder (peristalsis, histological changes and absorption) using an autotransplanted ileal segment with standard enterocystoplasty. MATERIALS AND METHODS: Female beagle dogs were divided into two groups. In group 1 (autotransplantation, six dogs), a Heineke-Mikulicz-type pouch was constructed using autotransplanted terminal ileum. The artery and vein of the terminal ileum were anastomosed to the iliac artery and vein, respectively. The pouch was anastomosed to the bladder remnant immediately above the vesical triangle. In group 2 (control, five dogs) the same type of bladder reconstruction using terminal ileum was undertaken but with no vessel anastomosis. Bladder function in these two groups was then compared for peristalsis (by monitoring intravesical pressure), histological changes (by microscopy) and glucose reabsorption (by measuring the amount of glucose remaining in the reconstructed bladder). The mean (range) follow-up was 11 (7-18) months for group 1 and 9.2 (7-12) months for group 2; the recovery time before examination was 4.6 (2-7) months for group 1 and 4.0 (2-6) months for group 2. RESULTS: In group 1, there were no major complications in five dogs after the procedure and they survived for > 7 months; the autotransplant became necrotic in one dog where the arterial diameter was < 1 mm. In the control group, all five dogs survived for > or = 7 months after surgery. Intestinal peristalsis was inhibited in group 1 but not in group 2. The bladder was oval/spherical in group 1 and elongated in group 2, with a thinner epithelium and fewer goblet cells in the latter. Glucose reabsorption was greater in group 2 than in group 1. CONCLUSION: Bladder reconstruction using autotransplanted terminal ileum in dogs is technically feasible. For bowel peristalsis and reabsorption of glucose, autotransplanted ileum may have functional advantages over a standard enterocystoplasty.

Absorption↗

Effect of fluvoxamine on the pharmacokinetics of mexiletine in healthy Japanese men.

BACKGROUND AND OBJECTIVES: Fluvoxamine, a selective serotonin reuptake inhibitor, is known to inhibit several hepatic cytochrome P450 (CYP) isozymes, in particular CYP1A2. Mexiletine is mainly catalyzed by CYP2D6 and partially catalyzed by CYP1A2. Our objective was to study the potential pharmacokinetic interaction between fluvoxamine and mexiletine. METHODS: A randomized crossover design with two phases was used. A 7-day washout period separated the two treatment conditions. In the one phase, 6 healthy Japanese men received an oral dose of 200 mg of mexiletine alone (study 1); in the other phase, the men received fluvoxamine (50 mg twice a day) for 7 days, and on the eighth day they received oral mexiletine (200 mg) and fluvoxamine concomitantly (study 2). The concentrations of mexiletine were measured with HPLC. RESULTS: The area under the concentration-time curve and serum peak concentration of mexiletine in study 2 were significantly increased compared with those in study 1 (10.4 +/- 4.85 versus 6.70 +/- 3.21 microg x h/mL, P =.006 and 0.623 +/- 0.133 versus 0.536 +/- 0.164 microg/mL, P =.008, respectively). CONCLUSION: The effect of fluvoxamine on the mexiletine disposition is comparatively large, and when mexiletine and fluvoxamine are coadministered careful monitoring of mexiletine is needed.

Administration, Oral↗

Successful endovascular repair of juxtarenal and suprarenal aortic aneurysms with a branched stent graft.

This case report describes a new technique for repairing pararenal aortic aneurysms with a transluminally placed triple-branched stent graft with sidearms extending into the superior mesenteric artery and renal arteries. Endovascular repair with the branched stent graft was attempted in two patients with a pararenal aortic Aneurysm. Stent grafting was technically successful in both patients. Although postoperative transient renal function impairment and paralytic ileus occurred in patient 2, these complications were gradually resolved in the perioperative period. A substantial shrinkage of the aneurysm was revealed by means of computed tomographic measurements in patient 1. In both patients, complete exclusion of the aneurysm and patency of the bilateral renal arteries and the superior mesenteric artery were confirmed by means of follow-up computed tomographic images at 2 years. This minimally invasive approach for pararenal aortic aneurysms appears to be a viable therapeutic option for patients who are at high risk for open surgery.

Aged↗

Short-term oral administration of L-arginine improves hemodynamics and exercise capacity in patients with precapillary pulmonary hypertension.

We sought to assess the effects of oral supplementation of L-arginine, the precursor of nitric oxide (NO), on hemodynamics and exercise capacity in patients with pulmonary hypertension. Acute hemodynamic responses to oral L-arginine (0.5 g/10 kg body weight) or placebo were examined in 19 patients with primary or precapillary secondary pulmonary hypertension. Cardiopulmonary exercise tests were performed to measure peak oxygen consumption (peak V O(2)) and the ventilatory response to carbon dioxide production (V E-V CO(2) slope) before and 1 wk after treatment with L-arginine (1.5 g/10 kg body weight/d) or placebo. Oral supplementation of L-arginine significantly increased plasma L-citrulline, which indicated enhancement of NO production. Supplemental L-arginine produced a 9% decrease in mean pulmonary arterial pressure (53 +/- 4 to 48 +/- 4 mm Hg, p < 0.05) and a 16% decrease in pulmonary vascular resistance (14.8 +/- 1.5 to 12.4 +/- 1.4 Wood units, p < 0.05). L-arginine modestly decreased mean systemic arterial pressure (92 +/- 4 to 87 +/- 3 mm Hg, p < 0.05). A 1-wk supplementation of L-arginine resulted in a slight increase in peak V O(2) (831 +/- 88 to 896 +/- 92 ml/min, p < 0.05) and a significant decrease in the V E- V CO(2) slope (43 +/- 4 to 37 +/- 3, p < 0.05) without significant systemic hypotension. Hemodynamics and exercise capacity remained unchanged during placebo administration. These results suggest that oral supplementation of L-arginine may have beneficial effects on hemodynamics and exercise capacity in patients with precapillary pulmonary hypertension.

Administration, Oral↗

The stereoselective effects of bucolome on the pharmacokinetics and pharmacodynamics of racemic warfarin.

The objective of this study was to investigate the stereoselective influence of bucolome on the pharmacokinetics and pharmacodynamics of warfarin in Japanese inpatients with heart disease. Thirty patients were administered a fixed-maintenance dose of warfarin alone once a day for at least 7 days. The other 25 patients were concomitantly administered warfarin and a 300 mg dose of bucolome once a day, and blood samples were collected on days 1, 4, 7, 14, or 21 after administration of bucolome. Serum concentration of warfarin enantiomers was measured by a chiral reversed-phase HPLC-ultraviolet detection method. The PT-INR was used as a measure of the pharmacodynamic effect of warfarin. Coadministration of bucolome and warfarin had no effect on serum (R)-warfarin concentration and significantly increased serum (S)-warfarin concentration compared with warfarin alone. The PT-INR of warfarin alone was significantly lower with bucolome cotreatment. These results indicate that the augmented anticoagulant effect of warfarin by bucolome is due to inhibition of (S)-warfarin metabolism in vivo. When bucolome is added to a stabilized regimen of warfarin therapy, the dose of warfarin should be reduced by about 30% to 60%, and caution should be exercised during the first 7 days after coadministration of bucolome.

Administration, Oral↗

Inactivation of rat cytochrome P450 2D enzyme by a further metabolite of 4-hydroxypropranolol, the major and active metabolite of propranolol.

Repetitive administration of propranolol (PL) in rats decreases the activities of cytochrome P450 (CYP) 2D enzyme(s) in hepatic microsomes. We examined the properties of 4-hydroxypropranolol (4-OH-PL) as an inactivator of rat liver microsomal CYP2D enzyme(s) using bunitrolol (BTL) 4-hydroxylation and PL 5- and 7-hydroxylations as indices of CYP2D enzyme activity. Rat microsomal BTL 4-hydroxylase activity was inhibited by the addition of 4-OH-PL to the incubation medium. The inhibition was greater after preincubation of microsomes with 4-OH-PL in the presence of NADPH than in its absence. The type of inhibition kinetics of BTL 4-hydroxylase by 4-OH-PL was changed from a competitive type to a noncompetitive type by the preincubation. The inhibition of rat liver microsomal PL 5- and 7-hydroxylases by 4-OH-PL was blocked efficiently by co-incubation with quinine, a typical inhibitor of rat CYP2D enzyme(s), or to a lesser extent by BTL. However, quinidine, a diastereomer of quinine, did not significantly protect against the enzyme inactivation. The protective capacities of the substrate and inhibitors reflected their affinities for rat CYP2D enzyme(s). BTL hydroxylase was not affected by either 1,4-naphthoquinone or 1,4-dihydroxynaphthalene which are possible metabolites of 4-OH-PL. These results provide further evidence to support the notion that PL is biotransformed by rat CYP2D enzyme(s) to 4-OH-PL, which is further oxidized to a chemically reactive metabolite in the active site. The inactivation of CYP is likely the result of covalent binding of the reactive species to an amino acid residue of the active site.

Adrenergic beta-Antagonists↗

[Fukuronori (Gloiopeltis furcata) extract: 90-day dietary toxicity study in F344 rats].

Fukuronori extract (FE), which is mainly composed of polysaccharides, and is an extract of the seaweed Gloiopeltis furcata, is permitted for use as a food thickening agent by the Ministry of Health and Welfare, Japan. In order to study the subchronic toxicity of FE, F344 rats of both genders were administered FE at concentrations of 0% (basal diet, control group), 0.5%, 1.5% and 5.0% in basal powder diet for 90 days, and observation of general condition, recording of body weight and food consumption, examination of hematology and blood chemistry, measurement of organ weight, and pathological examination were performed. Food consumption tended to increase in both sexes given FE at 1.5% and 5.0% throughout most of the experimental period. This was, however, considered not to be a toxic effect because the differences in body weight were small. Total cholesterol and triglycerides in serum decreased significantly (p < 0.05) and not significantly, respectively, in males of the 5.0% group. These changes were considered to be related to the intake of FE, but the differences were slight and within physiological ranges. Hematological and pathological examination revealed neither any particular adverse effect nor any significant difference from the control. Hence, dietary intake of 5.0% of FE, 3,362 mg/kg/day for males and 3,594 mg/kg/day for females as mean daily intake, for 90 days was considered to be a no observable adverse effect level in rats.

Algorithms↗

[Changes in otoacoustic emission during the glycerol test in the ears of patients with Meniere's disease].

Monitoring of cochlear function is one proposed clinical application of otoacoustic emission (OAE). To determine the clinical utility of OAE in monitoring, we studied changes in OAE during the glycerol test used to diagnose endolymphatic hydrops. Transiently evoked OAE (TEOAE) and distortion product OAE (DPOAE) were measured before and 3 hours after oral administration of glycerol in 22 ears of patients with Meniere's disease. The positive result in the glycerol test was observed in 11 of 22 ears. TEOAE was recorded using a nonlinear click stimulus, and total echo power (TEP) of the whole response and filtered echo power (FEP) of its mid-frequency (1000-2000 Hz) component were used as TEOAE parameters. The growth functions of DPOAE were recorded at 3 F2 frequencies--1000, 1500, and 2000 Hz. Changes in the growth function were determined based on changes in 2 parameters--maximum level and detection threshold of DPOAE. When changes in these 4 parameters exceeded 2 standard deviations above mean test-retest variability determined from OAE data for 17 normal ears, they were considered significant. Significant changes indicating improved cochlear function in 4 OAE parameters or the appearance of OAE during the glycerol test were judged positive for OAE. Regardless of glycerol test results, positive findings were observed in both OAEs whenever a pure-tone threshold at 1000 or 2000 Hz improved. However, even in ears for which pure-tone thresholds at these frequencies did not improve, both OAEs frequently exhibited positive findings. In all ears with a positive result in the glycerol test, positive findings were observed in DPOAE, but not in TEOAE. Of the 2 parameters of TEOAE, FEP always exhibited a positive finding in ears with a positive TEP finding and FEP positivity was higher than that of TEP. In DPOAE, no cases showed a positive finding only at F2 = 2000 Hz, and DPOAE at F2 = 1000 Hz could not be detected in 4 ears due to high noise floor. Overall, positive findings were obtained in 14 ears (63.9%) for TEOAE and 20 ears (90.9%) for DPOAE. In only 1 ear were no positive findings observed in either OAE. The sensitivity of OAE measurement as a diagnostic test for endolymphatic hydrops was higher than that of pure-tone audiometry. Of the 2 OAEs, test sensitivity was much higher for DPOAE than for TEOAE. These results show that OAE measurement detects changes in cochlear function during the glycerol test more sensitively than pure-tone audiometry. They also suggest that FEP is a better indicator than TEP as a parameter of TEOAE, and that DPOAE measurement at F2 = 1000 and 1500 Hz is sufficient for practical clinical use. However, of the 2 OAEs, DPOAE was considered more appropriate than TEOAE for monitoring during the glycerol test because of its high sensitivity in detection of changes in cochlear function. In conclusion, clinical use of OAE, especially DPOAE, as a test complementary to pure-tone audiometry during the glycerol test is very useful and will improve the diagnosis of endolymphatic hydrops.

Adult↗

Evidence for involvement of central 5-HT(4) receptors in cholinergic function associated with cognitive processes: behavioral, electrophysiological, and neurochemical studies.

The possible involvement of 5-HT(4) receptors in cognitive function was investigated with a view toward modulating the cholinergic neuronal system. For this purpose, behavioral, electrophysiological, and neurochemical studies were performed in rats. The behavioral study, using a passive avoidance test, demonstrated that the 5-HT(4) receptor agonist SC 53116 (10 microg/rat i.c.v.) had an ameliorative effect on the muscarinic receptor antagonist scopolamine-induced (1 mg/kg i.p.) impairment of learning. The electrophysiological study showed that SC 53116 (1 and 10 microg/rat i.c.v.) enhanced the population spike amplitude in the hippocampal CA1 field evoked by Schaffer collateral stimulation. SC 53116 (10 microg/rat i.c.v.) also augmented the tetanus-induced long-term potentiation (LTP). This augmented LTP was blocked not only by the selective 5-HT(4) receptor antagonist GR 113808 (20 microg/rat i.c.v.) but also by scopolamine (1 mg/kg i.p.). These findings suggest that the functional interaction between the serotonergic system mediated via 5-HT(4) receptors and the cholinergic system associated with cognitive processes exists in vivo. This possibility was further strengthened by neurochemical study using in vivo microdialysis; local administration of SC 53116 (10 and 100 microM) concentration-dependently enhanced the extracellular levels of acetylcholine (ACh) in the hippocampus. SC 53116-induced (10 microM) facilitation of ACh release was prevented by coperfusion of GR 113808 (10 microM). Taken together, the present findings obtained by these different approaches indicate the possibility that the 5-HT(4) receptors are involved in cognitive impairment induced by the cholinergic neuronal system.

Acetylcholine↗

Evolution of heteromorphic sex chromosomes in the order Aulopiformes.

The fish order Aulopiformes contains both synchronously hermaphroditic and gonochoristic species. From the cytogenetic viewpoint, few reports show that gonochoristic Aulopiformes have heteromorphic sex chromosomes. Because fish in this order give us a unique opportunity to elucidate the evolution of sex chromosomes, it is important to examine a phylogenetic relationship in Aulopiformes by both molecular evolutionary and cytogenetic methods. Thus, we conducted molecular phylogenetic and cytogenetic studies of six Aulopiform species. Our results suggested that hermaphroditic species were evolutionarily derived from gonochoristic species. It follows that the hermaphroditic species might have lost the heteromorphic sex chromosomes during evolution. Here, we suggest a possibility that heteromorphic sex chromosomes can disappear from the genome, even if they have appeared once in evolution. Taking into account Ohno's hypothesis that heteromorphic sex chromosomes might have emerged from autosomes, we propose the hypothesis that heteromorphic sex chromosomes may have undergone repeated events of appearance and disappearance during the course of fish evolution.

Animals↗