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Biomedical subjects

T Ohta

Publications and source records attributed to T Ohta.

At least 325 records · Page 18Linked to original sources

Tryptophan-niacin metabolism in liver cirrhosis rat caused by carbon tetrachloride.

We investigated the change of tryptophan-niacin metabolism induced by carbon tetrachloride (CCl4) in rats with liver cirrhosis. The rats were injected with CCl4 (0.5 or 1 mL of 50% olive oil solution/kg body weight) twice a week for 1 or 2 mo and given phenobarbital water simultaneously. The urinary excretions of nicotinamide (Nam) and its metabolites were assayed. As the result, the urinary excretion of Nam, N1-methyl-4-pyridone-3-carboxamide (4-Py), Nam + N1-methylnicotinamide (MNA) + N1-methyl-2-pyridone-5-carboxamide (2-Py) + 4-Py was lower in the CCl4-treated groups than in the non-treated group (control) regardless of the experimental period (1 mo and 2 mo) or dosing amount of CCl4 (0.5 and 1 mL). Moreover, we investigated which pathway of tryptophan-niacin metabolism was affected in CCl4-treated rat. As the result, the possibility that the MNA-->4-Py reaction is inhibited by CCl4 treatment was suggested in this experiment.

Alanine Transaminase↗

Activated lansoprazole inhibits cancer cell adhesion to extracellular matrix components.

Integrins play an important role in tumor dissemination. The purpose of this study was to examine whether a SH-reactive reagent inhibits the adhesion of the human pancreatic cancer cell line AsPC-1 to extracellular matrix components. Activated lansoprazole (AG-2000) was used as the SH-reactive reagent because this compound is known to react with SH groups but does not permeate the cell membrane. The effect of AG-2000 on the adhesion of AsPC-1 cells to matrix was examined, using both an in vitro adhesion assay and an in vivo nude mouse xenograft model of peritoneal implantation. In the in vitro adhesion assay, a 60-min exposure of AsPC-1 cells to AG-2000 resulted in a dose-dependent inhibition of AsPC-1 cell adhesion to laminin, fibronectin and type IV collagen, although AG-2000 did not affect the viability of AsPC-1 cells by MTT assay. In the in vivo assessment of AsPC-1 cell implantation, the AsPC-1 cells were initially preincubated with AG-2000 for 60 min to ensure adequate exposure of the AsPC-1 cells to AG-2000 before intraperitoneal injection. AG-2000 significantly inhibited the peritoneal implantation of the AsPC-1 cells in nude mice. These findings suggest that a short exposure of cancer cells to AG-2000 can inhibit cancer cell adhesion to extracellular matrix components.

Animals↗

Medical students' perception of inpatients' anxiety, self-esteem, purpose-in-life and health locus of control as compared with nursing practitioners'.

Medical students (fourth-year: n = 67; fifth-year: n = 63) estimated inpatients' feelings of anxiety, self-esteem, purpose-in-life, and multidimensional health locus of control. Their ratings were compared both with the ratings given by the 121 inpatients themselves and with those given by nursing practitioners (nurses and nursing students). Findings showed that the medical students overestimated inpatients' anxiety, while they underestimated the inpatients' purpose-in-life and internal health locus of control. Hence they underestimated, as did the nursing practitioners, the inpatients' positive emotional states and their positive attitude toward their own lives. Fifth-year medical students, with clinical experience, rated the inpatients' score of chance health locus of control higher than did the fourth-year medical students, who had no clinical experience. These findings indicate that medical students, like nursing practitioners, are inclined to pay more attention to inpatients' weaknesses than to their strengths.

Analysis of Variance↗

Combination therapy for advanced breast cancer: cyclophosphamide, doxorubicin, UFT, and tamoxifen.

We evaluated combination therapy for advanced and recurrent breast cancer with cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), UFT (uracil and tegafur), and tamoxifen (Nolvadex) (CAUT), designed as chemoendocrine therapy with a high antitumor effect and less severe adverse reactions. In this therapy, one 3-week cycle consisted of doxorubicin 30 mg/m2 intravenously on day 1, cyclophosphamide 65 mg/m2 orally (po) and UFT 300 mg/m2 po on days 1 to 14, and tamoxifen at 20 mg/day po on days 1 to 21. Twenty patients were registered and 19 were eligible, including seven with advanced breast cancer and 12 with recurrent disease. Six patients had received previous treatment. The comprehensive evaluation for objective response revealed one patient with a complete response and 10 patients with partial responses, producing an overall response rate of 58% (95% confidence interval, 29% to 87%). Three patients experienced no change, and five patients had progressive disease. Adverse events > or = grade 3 were leukopenia in six patients, erythropenia in one patient, alopecia in four, and severe generalized malaise in one. One patient who developed grade 4 leukopenia and one of five patients who developed grade 3 leukopenia recovered after receiving granulocyte colony-stimulating factor. CAUT therapy produced high response rates and relatively mild adverse reactions and is considered useful for the treatment of advanced and recurrent breast cancer.

Adult↗

[Simulation study on parent artery occlusion therapy for basilar head giant aneurysms: hemodynamic efficacy of additional bypass on enhancing aneurysmal thrombosis].

Parent artery occlusion therapy has been used as an alternative for directly untreatable basilar head giant aneurysms. However, some aneurysms still require additional technique to further induce intraaneurysmal stagnation and thrombosis. Using a hydraulic model, half-life of the dye in the model aneurysm was measured as an index of the intraaneurysmal stagnation. The ratio of diameters (D1, D2) of the two posterior communicating arteries (PCom) is defined as diameter ratio (DR) (D1/D2, D1 < D2). Occlusion therapy was simulated in 4 different sites. The most distal site was at the distal BA (Type A) and the most proximal site at the bilateral VA (Type D). The additional technique investigated was bypass placement to the P2 segment of the posterior cerebral artery (PCA) on the smaller PCom side. The half-life was 2.5 +/- 0.2 (mean +/- 2SD) sec before occlusion. Occlusion therapy significantly increased the half-life depending on the occlusion site and DR values with the maximum values of infinite in Type A and 25 sec in Type D. Placement of the bypass decreased the tangential flow volume to the aneurysmal neck, and increased the time markedly in Types A and B, considerably in Type C and slightly in Type D. Parent artery occlusion therapy has been considered less beneficial for patients with a diameter ratio of less than 0.70 since aneurysmal stagnation depends on the diameter ratio. Bypass placement additional to the occlusion therapy is very useful in enhancing the aneurysmal stagnation, which would make those patients indicated for the therapy.

Basilar Artery↗

[Microsurgical results of paraclinoid aneurysms of the internal carotid artery: microsurgery versus intravascular surgery].

Since paraclinoid aneurysms exhibit considerable variations in the surrounding skull base structures, some skill and experience are considered essential for their microsurgical treatment. On the other hand, intravascular coil embolization would be free from these extravascular factors. Fifty-two aneurysms in 48 patients were treated microsurgically. They were divided into an early series treated before 1995 and a late series treated after 1996. Three aneurysms in 3 patients were treated by intravascular surgery. Preoperative neuroimages, topographic anatomy and surgical results were compared retrospectively. The results in the microsurgical late series were better than those in the early series. While 89% of the patients exhibited excellent results with two patients left with partial visual field defect (7%) and one death (3%) in the early series, the rates in the late series were 95%, 5% and 0%, respectively. Complications and failure in neck clipping were considered to be due to such topography as, 1) C3 aneurysms extending into the anterior clinoid process, 2) multiple aneurysms, 3) ophthalmic artery originating near the dome, 4) atheroma or calcification at the neck, 5) marked medical shift of C2 segment, and 6) tight adhesion of the dural ring to the dome. Coil embolization was successful in two aneurysms, while it was given up in one. We currently propose that intravascular surgery is indicated for cases 1), 4), 5) and 6), and microsurgery would be more advantageous for cases where the neck is broad and where the topography concerning aneurysmal multiplicity or the branching site of the ophthalmic artery is not fully understood by preoperative imaging.

Aneurysm↗

[Peak oxygen uptake, ventilatory threshold and leg extension power in apparently healthy Japanese].

Peak oxygen uptake, ventilatory threshold (VT) and leg extension power were measured in 832 apparently healthy subjects (421 males, 411 females) aged 30-60 decades who performed medical examination at 4 health check up facilities. 1) Peak oxygen uptake was greater in male than female, and decreased with age in both sexes. Single regression formula on age were Y (ml/kg/min) = 46.6 - 0.36 x AGE, (r = 0.447, p < 0.001) in male and Y (ml/kg/min) = 35.3 - 0.23 x AGE, (r = 0.407, p < 0.001) in female. 2) VT was greater in male than female, and less decreased with age compared to maximal aerobic power. Single regression formula on age were Y (ml/kg/min) = 22.6 - 0.13 x AGE, (r = 0.371, p < 0.001) in male, Y (ml/kg/min) = 20.0 - 0.10 x AGE, (r = 0.301, p < 0.001) in female. 3) Leg extension power was greater in male than female, and decreased with age in both sexes. Single regression formula on age were Y (W/kg) = 31.9 - 0.27 x AGE, (r = 0.539, p < 0.001) in male and Y (W/kg) = 20.9 - 0.18 x AGE, (r = 0.510, p < 0.001) in female. Subjects in the present study showed height, weight and walk steps per day similar to those in National Nutrition Survey. Comparison of Peak oxygen uptake, ventilatory threshold and leg extensor power to previous studies revealed that these parameters were quite similar to the counterparts in the previous studies with less selection bias. It was suggested that subjects in this study were quite similar to normal Japanese population, and that Peak oxygen uptake, VT and leg extension power in the present study were of value for the evaluation of health related fitness in community and workplace.

Adult↗

[Trigeminal neuralgia with the offending artery transfixing the trigeminal nerve: a case report].

We report a rare case of a patient manifesting trigeminal neuralgia with the offending artery transfixing the trigeminal nerve. A 67-year-old woman was admitted with typical episodes of trigeminal neuralgia on the right side. Magnetic resonance angiograms revealed the right superior cerebellar artery (SCA) compressing the nerve. Through a retromastoid suboccipital craniotomy on the right side, the right SCA was found to compress the root entry zone (REZ) and then penetrate the portio major of the trigeminal nerve. The nerve was dissected parallel to the axis, 7 mm distally from the transfixing point to facilitate transposition of the SCA. In addition to anchoring the distal portion of the SCA to the tentrium, a prosthesis was interposed between the proximal portion and the pons to secure the decompression. The pain was completely relieved immediately after operation with no neurological deficit. Procedures, such as the longitudinal rhizotomy employed in this case, must be carried out for microcompression, in response to individual anatomical variations in neurovascular structures.

Aged↗

[A case of advanced gastric cancer with abdominal para-aortic lymph node metastasis successfully treated with FLP therapy].

A 73-year-old woman was admitted to our hospital in June 1998, suffering from upper abdominal pain. The upper G-I series and endoscopic examination revealed stenosis of the pylorus and antrum by a type 2 cancer, and a poorly differentiated adenocarcinoma and a signet-ring cell carcinoma were confirmed on endoscopic biopsy. A CT scan showed the enlargement of many regional and abdominal para-aortic lymph nodes. FLP therapy combined with cisplatin (50 mg/m2 drip i.v., day 1-8), 5-fluorouracil (333 mg/m2 drip i.v.) and leucovorin (30 mg/body i.v., day 1-8) was planned for neoadjuvant chemotherapy (NAC) in order to reduce or eliminate the tumor and increase curability. After two cycles of the FLP therapy, the tumor size shrunk remarkably and the enlargement of the para-aortic lymph nodes disappeared. Distal gastrectomy with extended lymphadenectomy and cholecystectomy was performed. The histological findings of the primary tumor and metastatic lymph nodes demonstrated massive cancer cell degeneration such as pycnosis and vacuolation, xanthogranulomatous inflammation and dense fibrosis. The effect of NAC was judged to be grade 2 histologically. FLP therapy is an effective and safe regimen for NAC.

Adenocarcinoma↗

Pharmacokinetics of bisoprolol and its effect on dialysis refractory hypertension.

The efficacy, safety, and pharmacokinetics of bisoprolol were investigated following oral administration once daily for 12 weeks in hyperreninemic patients with dialysis-refractory hypertension. Mean blood pressure rapidly fell from 132 to 112 mmHg in the 5.0-mg/day (n = 6) and from 142 to 128 mmHg in the 2.5-mg/day patients (n = 5), which were accompanied by a fall in plasma renin activity. On nondialysis days, Cmax and T1/2 were significantly higher in patients than in healthy control subjects. However, Cmax in the 2.5-mg/day patients was almost equal to that in healthy control subjects receiving 5.0 mg/day of bisoprolol. Plasma bisoprolol was dialyzable. During the course of the study, dialysis hypotension and bradycardia occurred in two patients receiving 5.0 mg/day of bisoprolol. In conclusion, a daily dose of 2.5 mg bisoprolol seems to be an adequate and relatively effective dose in our patients with dialysis-refractory hypertension.

Administration, Oral↗

An effective method for recovering CD34 positive progenitor cells from peripheral blood stem cell apheresis products cryopreserved with simplified method.

The use of small volume collection chamber (SVCC) during peripheral blood stem cell (PBSC) apheresis, combined with simplified cryopreservation without rate-controlled freezing, have successfully been applied to clinical PBSC transplantation following myeloablative chemotherapies. However, the method to effectively select CD34+ progenitor cells from frozen apheresis products obtained with these simplified methods has not been reported. For this goal, after washing the thawed apheresis products with medium containing Dnase I, two different approaches to purify CD34+ progenitor cells from washed WBCs were compared. In method I, CD34+ cells were purified on the same day using immunomagnetic method. In method II, the cells after wash were cultured for overnight in RPMI-1640/10% FCS containing SCF and IL-3, followed by enrichment of CD34+ cells as in method I on the next day. In both methods, CD34+ cells were recovered with high viability. However, subsequent liquid culture revealed that the cells obtained from method II have clearly higher growth potential compared with the cells from method I. In addition, these CD34+ cells from method II well-tolerated to further refreeze and thaw. Thus, allowing to "rest" overnight after thaw may be critical for processing of the simply cryopreserved apheresis products as in method II.

Adult↗

Nephrotoxic effects of allopurinol in dinitrofluorobenzene-sensitized mice: comparative studies on TEI-6720.

Allopurinol is widely used and generally well-tolerated. However, when used in patients with renal insufficiency it may have life-threatening toxic effects known as allopurinol hypersensitivity syndrome (AHS). We previously found that allopurinol increased ear swelling and mortality in a DNFB-induced contact hypersensitivity mouse model. In the present study, we investigated the toxic effect of allopurinol on DNFB-sensitized mice in order to clarify the mechanism responsible for the lethal effect of allopurinol. Allopurinol increased plasma GPT and GOT in DNFB-sensitized mice and markedly increased plasma creatinine and BUN. The increase in plasma GPT and GOT was moderate and declined time-dependently. In contrast, the increase in plasma creatinine and BUN was striking and continued until 18 hr after administration of allopurinol at 100 mg/kg/day. Although allopurinol increased GOT and GPT in DNFB-sensitized mice, no effect was observed in non-sensitized mice even at 100 mg/kg/day, indicating that allopurinol essentially has no toxic effect on the liver. A high dose of allopurinol induced renal impairment even in non-sensitized mice. These observations indicate that there is some biological interaction between allopurinol and DNFB, and suggest that allopurinol may modulate or enhance the inflammatory reactions induced by DNFB, and/or that DNFB may cause metabolic changes via inflammation, leading to the enhanced toxicity of allopurinol. In contrast, TEI-6720, a newly synthesized XOD/XDH inhibitor, had almost no effect on DNFB-sensitized mice. TEI-6720 at 1 mg/kg, in terms of hypouricemic effect, appeared to be more potent than allopurinol at 3 mg/kg. Therefore, the nephrotoxic effect of allopurinol observed in the present study may not be related to XOD/XDH inhibitory activity.

Acute Kidney Injury↗

Differential diagnosis of linear corneal images on confocal microscopy.

PURPOSE: This study aimed to detect corneal conditions presenting with linear images on white light confocal microscopy and to analyze their distinguishing characteristics. METHODS: In 1996 and 1997, 153 eyes of 110 patients with various corneal conditions were examined. In vivo examination of the cornea was performed by using a white-light tandem scanning confocal microscope. Images were captured by using a video camera and stored on S-VHS video tapes. In this retrospective study, patient charts and confocal microscopic video records were reviewed. Conditions with linear images were looked for, and the images were analyzed and compared. RESULTS: The only structures presenting as linear images on confocal microscopy in normal subjects consisted of corneal nerves. The following pathologic conditions also had linear images on confocal microscopy: corneal vascularization, mycotic keratitis, lattice corneal dystrophy, and posterior polymorphous dystrophy. Each condition could be identified based on its reflectivity, delineation, size, branching pattern, and location in the cornea. CONCLUSION: Different corneal conditions present with linear images on confocal microscopy. Correct identification is critical to avoid misdiagnosis.

Cornea↗

4-(trans-4-Methylcyclohexyl)-4-oxobutyric acid (JTT-608). A new class of antidiabetic agent.

During an investigation of drugs for improving the beta-cell response to glucose, we found that 4-cyclohexyl-4-oxobutyric acid selectively improved glucose-stimulated insulin release and glucose tolerance in both normal and diabetic rats. A series of 4-cycloalkyl-4-oxobutyric acids and related compounds were synthesized and evaluated for their effects on the glucose tolerance test and fasting euglycemia. This study elucidated the structural requirements for drug activity and determined that the optimum compound was 4-(trans-4-methylcyclohexyl)-4-oxobutyric acid 7 (JTT-608). This compound improved glucose tolerance from an oral dose of 3 mg/kg and did not change fasting euglycemia even at an oral dose of 30 mg/kg. Selective improvement of glucose-induced insulin secretion was observed in studies using neonatal streptozotocin rats (nSTZ rats) and perfused pancreases isolated from nSTZ rats.

Animals↗

Engineering of S2 site of aqualysin I; alteration of P2 specificity by excluding P2 side chain.

Gly101, one of the conserved amino acid residues which was expected to be comprised in half-sphere-shaped S2 site small pocket of aqualysin I, a microbial thermophilic alkaline serine protease, was replaced by alanine, valine, or leucine to alterate the P2 specificity of the enzyme by excluding bulky P2 side chain of the substrate. By the mutation of G101A, the catalytic efficiencies of the enzyme for bulky amino acid residues in P2 site such as valine and leucine drastically decreased by excluding the P2 side chain. By the mutation of G101V, even the side chain of the methyl group of the alanine and the side chain of proline were excluded, while the catalytic efficiency toward glycine residue was retained. The enzyme was altered to be glycine preferable. The mutation of G101L reduced catalytic efficiencies for any substrate including glycine which is corresponding to the main chain of the peptide substrate. The strategies we have adopted in this paper are applicable to all subtilisin-related enzymes.

Alanine↗