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Biomedical subjects

T Onitsuka

Publications and source records attributed to T Onitsuka.

At least 73 records · Page 4Linked to original sources

Roles of intestinal trefoil factor (ITF) in human colorectal cancer: ITF suppresses the growth of colorectal carcinoma cells.

Intestinal trefoil factor (ITF) is a member of trefoil peptide family and is expressed almost exclusively in the goblet cells of small intestine and colon. Its expression is up-regulated by inflammatory and ulcerative conditions in the intestinal mucosa, and ITF has a role to maintain the mucosal integrity and repair the damaged mucosa. On the other hand, human colorectal carcinoma cells also express ITF peptide. In this review, we discussed the current views on the biological functions of ITF in the intestinal mucosa, and its suppressive effect on the growth of colorectal carcinoma cells.

Cell Differentiation↗

Prostaglandin I2 analog enhances the expression of urokinase-type plasminogen activator and wound healing in cultured human fibroblast.

This study examines the effects of prostaglandin I2 (PGI2) on urokinase-type plasminogen activator (uPA) production and wound healing by human fibroblasts. Employing fibrin autography, it was found that beraprost sodium, a stable PGI2 analog, enhanced the fibrinolytic activity in media conditioned by human fibroblasts, TIG-3-20 cells. Fibrin zymography, ELISA, and Northern blot analysis confirmed that the enhanced activity was caused by an increase in uPA synthesis and secretion and a decrease in type-1 plasminogen activator inhibitor. While cycloheximide and 2',5'-dideoxyadenosine, an adenylate cyclase inhibitor, suppressed the effect of PGI2, dibutyryl cyclic AMP increased the fibrinolytic activity and uPA mRNA. These findings indicate that PGI2 promotes uPA production in TIG-3-20 cells via direct stimulation of the cyclic AMP intracellular pathway. A similar effect was observed in two other fibroblast cell lines, TIG-7-20 and TIG-7-30. Although PGI2 itself did not affect cellular proliferation, it promoted in vitro repopulation of the denuded area in a wounded monolayer. These observations suggest that PGI2 can stimulate wound healing through the enhanced production of uPA.

Cell Movement↗

Adaptation of visually guided behavior during reversed vision in schizophrenia: a preliminary study.

This preliminary study evaluated the adaptation of visually guided behavior to reversed vision in schizophrenia. The study included 54 patients who met DSM-III-R criteria for schizophrenia. Visuomotor reaction times (VRTs) during reversed vision were measured in six blocks of 35 consecutive trials. The VRTs of schizophrenics were compared with those of normal subjects. A good fit (R2 = 0.9981) for the adaptation process of VRTs during reversed vision was found with the equation y = 1030 + 1499/x, where x is the order of the block and y is the group mean VRT for each block. The VRTs in schizophrenics were significantly slower than those in normal subjects. However, the adaptation process to reversed vision essentially did not differ from normal. The adaptation of visually guided behavior during reversed vision may involve procedural learning; this task may thus be useful in evaluating such learning. The VRTs during reversed vision may be related to some aspects of symptoms in the patient with schizophrenia and may also be useful in predicting clinical outcome.

Adult↗

P300 in response to the subject's own face.

The P300 event-related potentials in response to self-relevant stimuli has been reported to be different from those to non-target stimuli under a passive attention condition. In the present study the P300 in response to the subject's own face was examined. Twelve right-handed volunteers served as subjects. In two separate conditions, deviant (subject's own face and red square; 30%), non-target (two unfamiliar faces; 30% each), and target (famous face; 10%) stimuli were randomly presented on a computer screen. P300 amplitudes in response to the red square were larger than those to the unfamiliar faces, but were significantly lower than those to the subject's own face. The subject's own face in normal population may have an intense relevance to the subjects which has an additional effect over the simple orienting response.

Adult↗

In vitro performance of a centrifugal, a mixed flow, and an axial flow blood pump.

We specially devised 3 types of turbo pumps, a centrifugal pump (CFP), a mixed flow pump (MFP), and an axial flow pump (AFP), and analyzed their in vitro performance. The common structural design elements were an impeller diameter of 20 mm and sealless magnet couple driving. In vitro tests were carried out using heparinized fresh bovine blood. The hemolysis was comprehensively evaluated at 7-16 points by changing the flow rate and pressure head (mapping of hemolytic property). The maximum efficiency (motor output to pump output) was 44.9% at 7,000 rpm, 3.17 L/min, 191 mm Hg in the CFP; 66.3% at 7,000 rpm, 6.9 L/min, 136 mm Hg in the MFP; and 20.6% at 9,000 rpm, 5.54 L/min, 74 mm Hg in the AFP, respectively. The minimum normalized index of hemolysis (NIH) (g/100 L) was 0.038 at 5,000 rpm, 4.60 L/min, 38 mm Hg in the CFP; 0.010 at 7,000 rpm, 8.22 L/min, 100 mm Hg in the MFP; and 0.033 at 7,000 rpm, 2.84 L/min, 48 mm Hg in the AFP, respectively. The best efficiency and NIH were achieved in the MFP.

Animals↗

Site-directed mutagenesis and steady-state kinetic analysis of mutant enzymes of human adenylate kinase.

Site-directed mutagenesis of human adenylate kinase (AK) was carried out on residues His36, Lys55, and the C-terminal segment (Val182, V186, and Leu193). Five mutants [(H36T, K55G, V182G, V186S, and L193Stop (deletion of residues 193-194)] were generated and analyzed by steady-state kinetics. H36T, K55G, and L193Stop mutants showed an increase of K(m) values (19.8-, 19.7-, and 11.3-fold) for AMP2- compared to that for the wild-type enzyme, and these residues appeared to interact with AMP2-. V182G showed an increased K(m) value (7.4-fold) for MgATP2-. Therefore, V182 may be essential for interaction with MgATP2-. V186S increased the K(m) value (7.0- and 7.5-fold) for MgATP2- and AMP2-. V186 may thus interact with both substrates. The C-terminal domain of AK appears to be essential for MgATP2- and AMP2- binding.

Adenylate Kinase↗

[Surgical treatment of differentiated thyroid cancer with tracheal invasion].

Thirty patients with tracheal invasion of differentiated thyroid cancer underwent partial resection of the tracheal wall between 1978 and 1996 at National Cancer Center Hospital. In most cases, the defect in the tracheal wall was reconstructed secondarily using a local flap. This method was easy in comparison with end-to-end anastomosis of the trachea following circumferential resection of the wall. Partial resection of the tracheal wall proved to be a effective treatment for thyroid cancer invasion of the tracheal, because of low incidence of local recurrence. When the defect of the tracheal wall was too large to be reconstructed using a local flap, hydroxylapatite was employed and good results were obtained.

Adult↗

Power Doppler sonography of cervical lymph nodes in patients with head and neck cancer.

PURPOSE: The purpose of this preliminary study was to evaluate the usefulness of power Doppler sonography in differentiating metastatic from nonmetastatic cervical lymph nodes in patients with cancer. METHODS: Histologically proved metastatic (n = 71) and nonmetastatic (n = 220) lymph nodes were examined with power Doppler sonography in 77 patients with head and neck cancer. Power Doppler sonography was assessed for its ability to differentiate metastatic from nonmetastatic lymph nodes. RESULTS: Power Doppler sonography showed characteristic features of parenchymal blood flow signal in 59 (83%) of the 71 metastatic lymph nodes. By contrast, only four (2%) of the 220 nonmetastatic nodes showed these power Doppler signals. In addition, power Doppler sonography showed high levels of sensitivity (83%) and specificity (98%) in depicting metastatic lymph nodes, which were superior to the values (66% sensitivity and 92% specificity) obtained by applying size criteria (transverse to longitudinal ratio). However, a combination of the two criteria (parenchymal color signal and transverse to longitudinal ratio) improved diagnostic accuracy to 92% sensitivity and 100% specificity. CONCLUSION: Our preliminary findings suggest that the power Doppler criteria of no hilar flow, peripheral parenchymal nodal flow, and a transverse to longitudinal ratio of more than 0.65 together constitute a powerful tool for depicting metastatic lymph nodes in patients with cancer.

Adult↗

Influence of age on extended thymectomy as a treatment for myasthenia gravis.

This retrospective study examines the influence of age on extended thymectomy as a treatment for myasthenia gravis. From 1979 to 1997, 58 patients with myasthenia gravis underwent extended thymectomy at Miyazaki Medical College Hospital. We used the onset age of the disease to divide these patients into two groups: Group A included 14 patients >/= 50 years of age; Group B, 44 patients < 50. Using Osserman's classification and the duration of the disease prior to hospitalization, we observed no significant differences between the two groups although thymoma were more prevalent in Group A. All 58 patients underwent extended thymectomy, with no surgical mortalities. The mean duration of tracheal intubation after thymectomy for Group A was 6.25 days; for Group B, 4.66 days without statistically significant differences between both groups. Using Masaoka's criteria, we evaluated the clinical course of myasthenia gravis following extended thymectomy for each of the 58 patients. The remission rates in Groups A and B were 28.6% and 29.5%, respectively; the improvement rates, 71.4% and 79.5%, respectively with no significant differences among groups. These findings suggest that the clinical course of myasthenia gravis following extended thymectomy is not age-dependent and that extended thymectomy is a clinically safe and effective treatment option for myasthenia gravis patients >/= 50 years of age.

Adolescent↗

[Surgical correction of complete rupture of the anterior papillary muscle complicating acute myocardial infarction].

A 71-year-old female patient with complete post infarction rupture of the anterior papillary muscle and severe congestive heart failure is presented. The diagnosis was determined by echocardiography and cardiac catheterization. Two days after the acute episode, the patient underwent emergency mitral valve replacement with an ATS 27 M prosthetic valve. The mitral annulus was edematous and friable. Postoperatively, the patient improved dramatically. In this case, two factors were important-repairing the nonfunctioning mitral valve as soon as possible and handling the friable mitral annulus with great care.

Aged↗

Effect of prolonged hypothermic ischemia and reperfusion on oxygen consumption and total mechanical energy in rat myocardium: participation of mitochondrial oxidative phosphorylation.

BACKGROUND: To reduce ischemia-reperfusion injury of hearts in open heart surgery and transplantation, it is important to know the critical period of ischemia in which donor hearts can sustain their function satisfactorily. Cardiac function has been deduced from oxygen consumption (VO2) and mechanical parameters such as pressure-volume area (PVA). Inhibited mitochondrial oxidative phosphorylation during ischemia indicates that ATP production is uncoupled from VO2. Therefore, both mitochondrial oxidative phosphorylation and total mechanical energy should be examined to evaluate cardiac function after ischemia and reperfusion. METHODS: Isolated rat hearts were stored in Euro-Collins solution at 4 degrees C for 8, 12, and 24 hr and reperfused in a working mode with a modified Krebs-Henseleit bicarbonate solution. PVA and VO2 were examined in isovolumic contraction, and ventricular contractility and total mechanical energy were assessed, respectively, by the end-systolic elastance (Ees) and PVA. Mitochondrial oxidative phosphorylation in the presence of succinate and mitochondrial lipid peroxide levels were estimated in similarly treated rat hearts. RESULTS: Ees was decreased by ischemia without significant difference. The VO2 to PVA ratio remained linear, although VO2 at null PVA and the VO2 to PVA ratio significantly increased after 12 hr of ischemia. Mitochondrial oxidative phosphorylation was decreased significantly by reperfusion after 12 hr of ischemia. Mitochondrial lipid peroxide levels were increased significantly after 12 hr of ischemia. CONCLUSIONS: In isolated rat hearts, decreased efficiency for energy conversion from consumed oxygen to cardiac performance occurs between 8 and 12 hr of hypothermic ischemia, which was coincident with disturbed mitochondrial oxidative phosphorylation, to which lipid peroxidation may contribute.

Animals↗

Essential lysine residues in the N-terminal and the C-terminal domain of human adenylate kinase interact with adenine nucleotides as found by site-directed random mutagenesis.

To elucidate the minimum requirement of amino acid residues for the active center in human adenylate kinase (hAK1), we carried out random site-directed mutagenesis of key lysine residues (K9, K21, K27, K31, K63, K131, and K194), which were conserved in mammalian AK1 species, with the pMEX8-hAK1 plasmid [Ayabe, T., et al. (1996) Biochem. Mol. Biol. Int. 38, 373-381]. Twenty different mutants were obtained and analyzed by steady-state kinetics, and all mutants showed activity loss by Km and/or k(cat) effects on MgATP2-, AMP2-, or both. The results have led to the following conclusions. (1) Lys9 would appear to interact with both MgATP2- and AMP2- but to a larger extent than with AMP2-. (2) Lys21 is likely to play a role in substrate binding of both MgATP2- and AMP2- but more strongly affects MgATP2-. (3) Lys27 and Lys131 would appear to play a functional role in catalysis by interacting strongly with MgATP2-. (4) Lys31 would appear to interact with MgATP2- and AMP2- at the MgATP2- site. (5) Lys63 would be more likely to interact with MgATP2- than with AMP2-. (6) Lys194 in the flanking C-terminal domain would appear to interact not only with MgATP2- but also with AMP2- at the MgATP2- site by stabilizing substrate binding. The loss of the positively charged epsilon-amino group of lysine affects both the affinity for the substrate and the catalytic efficiency. Hence, hydrophilic lysine residues in hAK1 would appear to be essential for substrate-enzyme interaction with the coordination of some arginine residues, reported previously [Kim, H. J., et al. (1990) Biochemistry 29, 1107-1111].

Adenine Nucleotides↗

Growth of tracheal autografts in puppies.

The growth of tracheal autografts and the patency of anastomotic regions were studied in 11 mongrel puppies (2.5-4 months of age, 1.9-4.3 kg in weight). Thoracic tracheal autotransplantation of 7 cartilage rings was performed. The tracheal autografts and anastomotic regions were covered with an omental pedicle flap to facilitate revascularization. Seven of the 11 dogs were evaluated for 12 months. The cross-sectional area of the lumen at the center of the tracheal autograft, as measured by thoracic computed tomography (CT), showed a significant increase from 0.37 +/- 0.11 cm2 to 1.13 +/- 0.44 cm2 after 12 months (P < 0.05). At 12 months postoperatively, all of the experimental dogs were killed, their entire tracheas were resected, and the cross-sectional areas of the anastomosis on the proximal and distal sides were measured. The cross-sectional areas at sites 5 mm apart from both anastomoses in the ungrafted trachea were measured as controls. The percent cross-sectional area (%CSA) showed good values of 67.2% +/- 19.6% on the proximal side and 85.1% +/- 12.6% on the distal side. The tracheal autografts appeared both visually and histologically viable 12 months postoperatively. This study was able to demonstrate the growth potential of the tracheal autograft in a growing puppy model.

Age Factors↗

Possible overlapping potentials of the auditory P50 in humans: factor analysis of middle latency auditory evoked potentials.

The auditory P50 in humans may consist of overlapping potentials. To test this hypothesis, we manipulated the conditions of stimulus discrimination and motor response difficulty and evaluated the data by factor analysis. Twenty right-handed males (mean age 27 years) performed the following 4 tasks: (1) a counting task, (2) an easy Go, No-Go task, (3) a difficult Go, No-Go task, and (4) a choice reaction task. Middle latency auditory evoked potentials were obtained with 100 times summation triggered by the onset of the auditory stimulus. Four factors were extracted by factor analysis for a 0-100 ms time period. Factor 1, the maximum factor loading at 91 ms, corresponded to N1, and factor 4, the maximum factor loading at 23 ms, appeared to correspond to P30. The latency of the maximum factor loading in factor 2 was adjacent to that in factor 3, the latency of factor 2 being 12 ms earlier than that of factor 3. Factor 2 and factor 3 latencies were approximately 55 ms which corresponded to the P50. Factor 3 started rising at the point that factor 2 reached the maximum factor loading, and the factor score demonstrated a significant group difference only when analyzed by motor response criteria. These results suggest that the P50 in humans consists of overlapping potentials and that a part of the potential might relate to a motor response process.

Adult↗

Substrate-binding and catalytic roles of Lys194 in the C-terminus in human adenylate kinase by site-directed random mutagenesis.

Site-directed random mutagenesis of Lys194 residue in the C-terminus of human adenylate kinase (AK) was performed, and six mutants were analyzed by steady-state kinetics. K194-mutants variously affected the apparent Michaelis constants (K(m) values) for ATP and AMP, although the kcat values strikingly decreased. The Lys194 residue appears to interact not only with MgATP2- but also with the AMP2- substrates by salt bridge formation with a nucleotide and to play a functional role in stabilizing the phosphate-transfer during catalysis. Lys194 could be essential for substrate-holdings and in catalysis and not replaceable to the other amino acids.

Adenylate Kinase↗

Influence of reference electrodes, stimulation characteristics and task paradigms on auditory P50.

To clarify the nature of auditory P50, middle latency auditory evoked potentials were recorded by using different conditions of reference electrodes (linked earlobes, LE; balanced non-cephalic, BN), stimulation characteristics (tone burst, human voice) and tasks (counting, simple reaction) in 10 right-handed males (aged 21-36 years). EEG was recorded from Fz, Cz, Pz, C3, C4, T3 and T4 according to the 10-20 system. Two groups of electrode sites were made for the statistical analysis: a midline group, Fz, Cz and Pz, and a lateral group, T3, C3, Cz, C4 and T4. The results were that the P50 amplitudes with BN electrodes were significantly higher than those with LE in both groups (midline, P < 0.01; lateral, P < 0.01); the P50 amplitudes by voice stimulation were significantly higher than those by tone stimulation in the lateral group (P < 0.05), and the P50 latencies under a simple reaction paradigm were significantly shorter than those under a counting task in both groups (midline, P < 0.05; lateral, P < 0.05). These results suggest that various factors including motor response affect the P50 amplitudes and latencies.

Acoustic Stimulation↗

Negative correlation of reaction times and the auditory P50 in a Go, No-Go paradigm.

We investigated the relationship between reaction times in a Go, No-Go paradigm and various components of the auditory event-related potentials. The P50 latencies in the Go trials were significantly earlier than those in the No-Go trials. The N200 and P300 were positively associated with the reaction times. However, the P50 latencies showed negative correlation with the reaction times, and the negative correlation at F3 was the largest. Referring to source studies on P50, it is suggested that the activation of either the ascending activating system or the left premotor area through that system might affect the speed of reaction.

Adult↗

A study of verbal and spatial information processing using event-related potentials and positron emission tomography.

The activated cerebral regions and the timing of information processing in the hemispheres was investigated using event-related potentials (ERP) and regional cerebral blood flow (rCBF) as the neurophysiological indicators. Seven men and one woman (age 19-27 years) were asked to categorize two-syllable Japanese nouns (verbal condition) and to judge the difference between pairs of rectangles (spatial condition), both tests presented on a monochrome display. In the electroencephalogram (EEG) session, EEG were recorded from 16 electrode sites, with linked earlobe electrodes as reference. In the positron emission tomography (PET) session, rCBF were measured by the 15O-labeled H2O bolus injection method. Regions of interest were the frontal, temporal, parietal, occipital and central lobes, and the entire cerebral hemispheres. When the subtracted voltages of the ERP in homologous scalp sites were compared for the verbal and spatial conditions, the significant differences were at F7.F8 and T5.T6 (the 10-20 system). The latencies of the differences at T5.T6 were around 200, 250 and 320 ms. A significant difference in rCBF between the verbal and spatial conditions was found only in the temporal region. It was concluded that early processing of information, that is, registration and simple recognition, may be performed mainly in the left temporal lobe for verbal information and in the right for spatial information.

Adult↗