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Biomedical subjects

T Wada

Publications and source records attributed to T Wada.

At least 649 records · Page 36Linked to original sources

Effects of DN-2327, a new anxiolytic, diazepam and buspirone on exploratory activity of the rat in an elevated plus-maze.

In the present study, the effects of a new anxiolytic, DN-2327, were compared to those of diazepam and buspirone in rats in the elevated plus-maze test. Two indices of anxiety were obtained in this test: the number of entries into the open arms expressed as a percentage of the total number of arm entries and the percentage of time spent on the open arms. Both a typical anxiolytic, diazepam, at 2.5, 5 and 10 mg/kg, PO and a new anxiolytic, DN-2327, at 2.5 and 5 mg/kg, PO dose-dependently increased the two indices: the percentage of time spent on the open arms and the percentage of open-arm entries. On the other hand, pentylenetetrazol (PTZ) at 10 and 20 mg/kg, IP decreased the two indices dose dependently as did yohimbine at 1.5 and 3 mg/kg, IP. DN-2327 at 2.5 and 5 mg/kg, PO and diazepam at 5 and 10 mg/kg, PO dose dependently and significantly increased the two indices that were suppressed following administration of PTZ at 10 mg/kg, IP. The effects of both DN-2327, 5 mg/kg, PO, and diazepam, 10 mg/kg, PO, on the two indices were significantly antagonized by the benzodiazepine (BZD) receptor antagonist flumazenil, 20 mg/kg, IP. Buspirone (2.5-20 mg/kg, PO) did not affect either of the two responses but dose dependently decreased the number of rearings, although in the Vogel conflict test, the anti-conflict activity of buspirone was equipotent to that of diazepam and DN-2327 at the minimum effective dose (10 mg/kg, PO) of each drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The immunosuppressive effect of hepatocytes in rats--assessment by heart allograft survival and delayed-type-hypersensitivity reactions.

The immunosuppressive effect of hepatocytes was examined experimentally by heart allograft and delayed-type-hypersensitivity (DTH) reactions. The hepatocyte inoculation (1 X 10(7) of BDE (of the major histocompatibility complex haplotype RT1u), LEW (RT1l), and DA (RT1a) into the spleens of LEW rats significantly prolonged the survival of BDE heart allografts to 14.3 +/- 2.7 (mean +/- SD), 9.2 +/- 0.8, and 10.8 +/- 2.3 days respectively, compared with 6.7 +/- 0.8 days in controls (p less than 0.01). Moreover, the BDE hepatocytes had a significantly prolonged survival compared to the LEW (p less than 0.01) and DA (0.02 less than p less than 0.05) groups. BDE hepatocyte (donor specific) inoculation 4 and 7 days before priming with the spleen cells reduced DTH responses in the LEW rats to 44.6 +/- 4.8 per cent, and 74.2 +/- 8.0 per cent, respectively. DA hepatocyte inoculation (third party) 4 and 7 days prior to priming reduced DTH responses to 72.5 +/- 11.5 per cent, and 76.5 +/- 11.9 per cent, respectively. All DTH responses were significantly suppressed after hepatocyte inoculation compared to 100 per cent in the controls (p less than 0.01). Moreover, the inoculation of BDE hepatocytes (donor specific) 4 days prior to the priming significantly reduced DTH responses compared to the group primed 7 days before (p less than 0.01). From these results we concluded that hepatocytes produced not only non-specific but also donor specific immunosuppressive effects through T cell immune reaction. Moreover, donor specific immunosuppressive effects were induced at least 4 to 7 days after hepatocyte inoculation.

Animals↗

Evaluation of initial hepatic allograft function with changes of free plasma amino acids in canine orthotopic liver transplantation.

We investigated the correlation between amino acid level and hepatic graft function. Plasma amino acid levels were measured at three time periods during canine orthotopic liver transplantation. During the anhepatic phase, plasma amino acid levels rose except for tryptophan. Cystine and alanine (Ala) increased significantly to 210 +/- 28% (n = 20, mean +/- SEM) and 203 +/- 11% from preoperative values (100%), respectively. In animals successfully surviving without hepatic insufficiency after transplantation of fresh livers (n = 7), plasma amino acid levels were restored to preoperative values within 3 hr following reperfusion. On the other hand, in animals that died from hepatic insufficiency within 5 days after grafting of warm ischemically damaged livers (n = 8), plasma amino acids, especially Ala, phenylalanine, total free plasma amino acids, and aromatic amino acids progressively increased to 216 +/- 25, 274 +/- 36, 152 +/- 15, and 152 +/- 15% at 3 hr after reperfusion. These were significantly higher compared to those of the group of animals transplanted with fresh livers (P less than 0.01-0.05). Furthermore, higher values were found in those dogs transplanted with warm ischemically damaged livers surviving for shorter periods. Also in dogs that died from hepatic insufficiency within 8 hr after grafting of livers preserved for 24 hr (n = 5), amino acid levels were at high values at 3 hr. These results suggest that in animals having good graft function, plasma amino acid levels are restored to preoperative values by 3 hr after reperfusion. In other cases, primary nonfunction should be strongly suspected after liver transplantation.

Amino Acids↗

Collagen metabolism in cutis laxa fibroblasts: increased collagenase gene expression associated with unaltered expression of type I and type III collagen.

Collagen metabolism was studied in cutis laxa by analyzing collagen and collagenase gene expression in three dermal fibroblast strains from patients with congenital cutis laxa and comparing them with fibroblasts obtained from age-matched healthy subjects. Normal collagen synthetic activity was observed in the cutis laxa fibroblasts. An increased level of collagenase mRNA and unaltered levels of alpha 1(I) and alpha 1(III) collagen mRNA were found in all cutis laxa cell strains by dot blot hybridization. Reduced levels of elastin mRNA were also detected in these strains. However, no qualitative differences in these mRNA transcripts were detected between the control and cutis laxa fibroblasts by Northern blot analysis. Collagenase activity in fibroblast culture supernatants was then measured using fluorescein isothiocyanate (FITC)-labeled type I collagen. Increased collagenolytic activity in cutis laxa fibroblast culture supernatants was also found. These data suggest that increased collagenase expression of fibroblasts is related to the structural abnormality of dermal connective tissue in cutis laxa.

Collagen↗

Detection of bone-type alkaline phosphatase by monoclonal antibodies reacting with human osteosarcoma-associated antigen.

The antigen detected by monoclonal antibodies reacting with human osteosarcoma-associated antigen was shown to be a phosphatidyl-inositol (PI)-glycan-anchored protein, which can be released from the cell surface by PI-specific phospholipase C-treatment. The antigen detected by 2D3 and 2H10 antibodies exhibited alkaline phosphatase activity. Both antibodies strongly reacted with bone-type alkaline phosphatase. However, importantly, immunohistochemical analysis demonstrated that 2D3 and 2H10 did not react with alkaline phosphatase present in kidney or liver. In addition, neither placental nor intestinal alkaline phosphatase was recognized by 2D3 and 2H10 antibodies. These results indicated that two monoclonal antibodies, 2D3 and 2H10, are highly specific for bone-type alkaline phosphatase and can distinguish bone alkaline phosphatase from liver alkaline phosphatase in spite of the fact that liver and bone alkaline phosphatase are encoded by the same gene.

Alkaline Phosphatase↗

Different biological activities of the hetero- and homodimers formed by the 47- and 43-kilodalton proteins of transcription factor ATF/E4TF3.

The transcription factor ATF/E4TF3 stimulates transcription from the adenovirus early region 4 (E4) promoter by binding to specific promoter elements. Among the multiple forms of ATF/E4TF3, two forms with molecular masses of 47 and 43 kDa, which are most active in transcription in vitro from the E4 promoter, have been purified to homogeneity from HeLa cells by sequence-specific DNA affinity chromatography and biochemically characterized. Each purified protein formed a homodimer. These two homodimers were easily altered into a heterodimer when mixed together in the absence, but not in the presence, of the specific DNA sequence. All of these dimers were able to activate transcription in vitro from the E4 promoter by binding to the specific DNA sequence. Their activities to bind to DNA or stimulate transcription were different. The ability of the 47-kDa homodimer to stimulate transcription in vitro from the E4 promoter was approximately nine and three times higher than the abilities of the 43 kDa homodimer and the heterodimer, respectively, at the same level of DNA-binding activity. However, the affinity of the 47-kDa homodimer for DNA was lower than that of the 43-kDa homodimer, and the heterodimer had intermediate affinity. These results are the first to show differential binding and transcriptional activation activities of the different dimers of ATF/E4TF3, using purified cellular proteins rather than cloned gene products.

Activating Transcription Factors↗

Correlation of common carotid flow volume measured by ultrasonic quantitative flowmeter with pathological findings.

To evaluate the possibility of quantitatively diagnosing carotid and cerebral atherosclerosis noninvasively, we measured common carotid flow volume in 60 sides (30 patients), using an ultrasonic quantitative flowmeter, and then compared these findings to the severity score of carotid and cerebral atherosclerosis as determined at autopsy. Stenosis decreased common carotid flow volume in the carotid and cerebral arteries. Increases in the severity score varied inversely with reduced flow volume, which was high in inverse correlation (r = -0.696). Patients with flow volumes of 8.5 ml/sec or greater did not have stenosis greater than or equal to 75%, whereas all patients with flow volumes of 6.4 ml/sec or less had stenosis greater than or equal to 50%, with 45% of these having stenosis greater than or equal to 75%. These pathological findings confirm that the common carotid flow volume reflects the degree of carotid and cerebral atherosclerosis present and that the lower limit of common carotid flow volume in healthy subjects is 6.5 ml/sec.

Arteriosclerosis↗

Effects of calcium channel agonists (BAY K 8644, CGP28392 and YC-170) on 45Ca uptake by rat uterine segments.

The characteristics of the stimulating effects of the calcium channel agonists BAY K 8644, CGP28392 and YC-170 on 45Ca uptake by rat uterine segments were investigated. BAY K 8644, CGP28392 and YC-170 caused about 150, 100 and 150% increase, respectively in the 45Ca uptake induced by 20 mM KCl. The ED50 values of BAY K 8644, CGP28392 and YC-170 were 1.8 X 10(-9), 2.5 X 10(-8) and 9.8 X 10(-9) M, respectively. These agonists had little effect on the 45Ca uptake induced by 10(-6) M acetylcholine. They also did not affect the basal 45Ca uptake. Their enhancing effects were blocked by the Ca channel antagonist nitrendipine. We conclude that rat uterine segments have voltage-sensitive Ca channels that are stimulated by Ca channel agonists (BAY K 8644, CGP28392 and YC-170) under depolarizing conditions and that the characteristics of the stimulating effects of CGP28392 and YC-170 on 45Ca uptake by rat uterine segments are qualitatively the same as those of BAY K 8644.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Organ doses to atomic bomb survivors during photofluorography, fluoroscopy and computed tomography.

Doses to the salivary glands, thyroid gland, breast, lung, stomach and colon during mass radiological gastric screening, mass radiographic chest screening, upper gastrointestinal series and computed tomography were determined by exposing a female human phantom to simulated radiological X-ray examinations as performed in community hospitals. The doses were measured using thermoluminescent dosimeters, and the results will be used to document organ doses received by participants in the Atomic Bomb Casualty Commission/Radiation Effects Research Foundation Adult Health Study.

Adult↗

Effect of size of region of interest on precision of bone mineral measurements of the mandible by quantitative computed tomography.

The effect of size and shape of the region of interest (ROI) on the precision of the measurements of bone mineral content of mandibular bone by quantitative computed tomography (QCT) has been studied. A dry mandible and a series of calcium carbonate rods (density: 119.6 mg cm-3, 461.2 mg cm-3 and 939.0 mg cm-3) were used. The precision of measurements of the ROI for sizes less than 1 cm2 was very low, but the shape did not have any influence on the precision if the material examined was either homogeneous or if it was heterogeneous from always the same area. Higher precision was found when the ROI was more than 1 cm2. The size of ROI is a critical factor in the measurement of bone mineral content in the mandible by QCT.

Bone Density↗

Image salvage in panoramic radiography using histogram optimization.

Optical density and contrast recovery from poor quality panoramic radiographs was studied using the histogram modification technique. A series of experimental images of varying density and contrast were obtained by exposing a phantom in 4 kV steps between 50 and 94 kV. A standard of good image quality was selected by 10 observers grading the radiographs. Images were processed using the histogram specification technique and re-evaluated. All the processed images were found to be of acceptable quality. This technique was also shown to be applicable for salvaging unacceptable clinical radiographs.

Humans↗

[Angiographic analysis of intratumoral Pt concentration on intra-arterial infusion therapy for bladder cancer].

Eleven patients with advanced bladder cancers (T2-4) were treated by intra-arterial CDDP infusion therapy and intratumoral Pt concentrations were measured. The following results and suggestions were obtained by comparing the histological effects and intratumoral Pt conc. 1) By calculating cross section areas from diameter of blood vessels, the blood flow distributions of tumor feeding arteries were estimated. Based on this distributions, the distributed CDDP dosage flowed into the tumor feeding arteries was calculated. The distributed CDDP dosage of histologically effective group (N = 5, Grade IIb less than by Shimosato histological evaluation) were significantly higher than that of ineffective group (N = 6, Grade IIa greater than). (p less than 0.02, Student t test). 2) A good correlation was obtained between the revised intratumoral Pt value by distributed CDDP dosages and intervals from intra-arterial infusion therapies to operations. (r = -0.90, p less than 0.001). Intratumoral Pt conc. declined with a half life of 12 weeks. 3) Based on the declined linear line calculated from 2), theoretical intratumoral Pt conc. which was presumed value on day 0 (just after intra-arterial infusion therapy) were calculated. Theoretical Pt conc. of effective group were significantly higher than that of ineffective group (p less than 0.01), although no significant difference was seen between two groups compared by net intratumoral Pt conc. 4) A good correlation was seen between theoretical intratumoral Pt conc. and distributed CDDP dosage (r = 0.89, p less than 0.01). 5) Five of 6 cases with above 5 micrograms/g of theoretical intratumoral Pt conc. were histologically effective, and 5 micrograms/g of theoretical Pt conc. corresponded to 31 mg of distributed CDDP dosage.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[A clinical study of associated bladder cancer in patients with renal pelvic and ureteral cancer].

Retrospective study on the frequency of associated bladder cancer and the influence on the prognosis was carried out in 170 cases of renal pelvic and ureteral cancer. The number of cases of associated bladder cancer coexistent with renal pelvic and ureteral cancer was 31 (18.2%), and the number of subsequent cases 3 (19.4%). The frequency of occurrence of the primary tumor site was 27.2% in the renal pelvis, 45.6% in the ureter and 58.3% in both renal pelvis and ureter. Multiple tumors occurring in the renal pelvis and ureter occupy a high percentage. As for the degree of differentiation, many cases were subsequent to G1. As for the stage, a few cases with bladder cancer were subsequent to T4, but there was no definite tendency in the occurrence of bladder cancer. The prognosis of renal pelvic and ureteral cancer: the 10-year survival rate was 93.3% for G1, 66.6% for G2 and 12.4% for G3. As can be seen, there was good correlation with the pathological gradings. It must be remembered, however, that 5-year survival rates in cases of associated bladder cancer of coexistent type, in cases of subsequent type and in cases without associated bladder cancer were 56.2%, 72.7% and 64.8%, respectively: there was no significant difference. Bladder cancer associated with renal pelvic and ureteral cancer makes the therapy troublesome, but no influence on the prognosis was observed. Therapy in conformity with the pathological grading and stage is regarded as particularly important in cases of associated bladder cancer.

Adult↗

[Tolerance to a sustained release form of isosorbide dinitrate: comparison between 20 mg four times and 40 mg twice-daily administrations].

Attenuation of antianginal effects of oral isosorbide dinitrate in a sustained release from (ISDN-SR) were studied using the treadmill exercise test in eleven patients with stable exertional angina and a positive exercise test. We compared the four-time-daily administration of 20 mg with a twice-daily regimen of 40 mg for 10 days using the double-blind, crossover method. On the 1st day of the administration, with both regimens, the treadmill walking time, the time to 1mm and 2mm ST depression, and several hemodynamic parameters increased significantly. These improvements were reduced gradually on day 5 and day 10 after the administration. In the comparison between the four-time-daily and two-time-daily regimens, the former application showed clearer antianginal and hemodynamic effects than the latter regimen, but these effects were attenuated more markedly in the four-time daily administration. With both dosage regimens, the plasma ISDN concentrations increased gradually. With the long-term four-time-daily regimen, the time-to-time changes of the ISDN concentration were smaller each day. These data suggest that tolerance to oral ISDN-SR exists even if it is applied only two time daily, but its degree is less than when a four-time-daily dose in administered.

Administration, Oral↗