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Biomedical subjects

Y Takeuchi

Publications and source records attributed to Y Takeuchi.

At least 559 records · Page 31Linked to original sources

[Clinical evaluation of granisetron injection against nausea and vomiting induced by anticancer drugs including cisplatin].

The antiemetic effect and safety of granisetron injection on nausea and vomiting induced by anticancer drugs were studied in the patients treated with anticancer drugs including 50 mg/m2 or more of cisplatin (CDDP). Granisetron is already on the market, and drip infusion of granisetron at 40 micrograms/kg has been used widely in clinical practice. In this clinical investigation, a simpler administration method of its slow (30 to 60 seconds) intravenous injection at 40 micrograms/kg just before CDDP administration was used. The clinical efficacy, safety and usefulness against nausea and vomiting were investigated in 22 patients, and the study medication was assessed as "remarkably effective" or "effective" in 16 patients (72.7%). Neither adverse experience nor abnormal laboratory test value was reported. In the usefulness rating, the study medication was assessed as "extremely useful" or "useful" in 16 out of 22 patients (72.7%). The above results have shown that the slow intravenous injection of granisetron has an excellent antiemetic effect on nausea and vomiting induced by anticancer drugs including CDDP and a high degree of safety.

Adult↗

[Zonisamide monotherapy against absence attacks: report of two cases].

We report two cases of absence seizures, in which zonisamide monotherapy was effective. In one case the attacks recurred 6 months after the beginning of zonisamide therapy but ceased again with an increase of the dosage. The EEG prior to treatment showed 3 Hz generalized spike-wave patterns and 3 Hz high voltage slow wave burst in the right occipital area in one case, and 3.5-4 Hz generalized spike-wave patterns and focal spike-wave complexes in the left frontal to central areas in the other. One of the generalized spike-wave patterns were preceded by right occipital delta wave burst in one case, and bilateral occipital sharp-wave complex in the other. It is suggested that zonisamide monotherapy may be effective against absence seizures with focal paroxysmal discharges.

Child↗

[Clinical characteristics of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) in adult].

Hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) were originally described as separate disease entities. Recently, HUS and TTP have been considered a single disease, because of the identical microangiopathic lesion. In the present study, we investigated the clinical and histological characteristics of HUS/TTP. Eleven patients with a definite diagnosis of HUS/TTP were found from a cohort of adult patients who were admitted to Kitasato University Hospital in the past two decades. Their clinical and histological characteristics were retrospectively analyzed. All of the 11 patients with HUS/TTP were sporadic and non-diarrheal cases with a mean age of 49 years +/- 10. Preceding episodes of flu-like syndrome and the administration of mitomycin C were observed in 3 and 5 patients, respectively. On admission, two of 10 patients with renal dysfunction required dialysis treatment, while none developed nephrotic syndrome. Six patients showed CNS manifestation, such as consciousness disturbance and convulsion. Three patients with severe hypertension did not show consciousness disturbance. As for the final outcome, 6 patients recovered and the remaining 5 died. Two died after 60 hospital days. In the histopathological investigation, renal biopsy specimen showed narrowing of the capillary loops in the glomeruli due to swelling of the endothelial cells, double contour of the glomerular basement membrane, or mesangial cell necrosis and sclerosis. In the autopsy specimen, internal organ infarction with fibrin thrombi in small arteries was observed in multiple organs, such as brain, kidneys, hearts, lungs, jejunum, liver, pancreas, adrenal glands and pituitary gland. A circumferential myocardial infarction with hyaline thrombi in the medial layer of myocardium was characteristic of HUS/TTP. In conclusion, microangiopathic lesions with infarction spread widely throughout various organs in HUS/TTP. Involvement of internal organs, not to mention kidneys and brain, is lethal and their prognosis remains poor.

Adult↗

Long-term outcome of myocardial revascularization in patients with Kawasaki coronary artery disease. A multicenter cooperative study.

The long-term outcome of myocardial revascularization by coronary artery bypass grafting in patients with severe coronary obstruction caused by Kawasaki disease is largely unknown. A multicenter follow-up study was performed in 1991. A total of 168 patients with Kawasaki disease (127 male [75.6%] and 41 female patients [24.4%]) who had undergone coronary bypass grafting were enrolled. Obstructive coronary artery disease affected the left main trunk in 11.8%, the right coronary artery in 77.6%, the left anterior descending in 87.6%, and the left circumflex in 25.9%. Old myocardial infarction was noted in 46.0% of the patients. Fifty-four patients (32%, 12.4 +/- 9.8 years) underwent bypass grafting with saphenous vein grafts alone. The remaining 114 patients (68%, 9.8 +/- 7.1 years) received at least one internal thoracic artery graft to the left anterior descending coronary artery. Gastroepiploic artery grafts were used in 12 patients. There were no significant differences between the saphenous vein and internal thoracic artery groups in the mean age at operation (12.4 versus 9.8 years), female ratio (22% versus 25%), the number of patients over 20 years of age (9.3% versus 9.6%), previous history of infarction (51.9% versus 41.2%), impaired left ventricular function (ejection fraction < 0.5) (13.0 versus 11.4%), left main trunk disease (11.1% versus 10.5%), the number of vessels involved (2.2 +/- 0.8 versus 2.0 +/- 0.6 per patient), or the mean number of grafts used (1.7 +/- 0.7 versus 1.7 +/- 0.7 per patient). The operative death rate was also the same in the two groups (1.9% versus 0%), but the late cardiac death rate was significantly higher in the saphenous vein graft group (13.0%) than in the internal thoracic artery group (0.9%) (p < 0.003). Actuarial analysis showed a significantly higher survival in the internal thoracic artery group (98.7% +/- 1.2% versus 81.6% +/- 7.0%, p < 0.05) at 90 months after the operation. Late death was strongly related to the absence of an internal thoracic artery graft (p < 0.003) and to the age at the time of operation (p < 0.05). The actuarial patency rate was significantly higher for arterial grafts (77.1% +/- 1.1%, n = 151) than for vein grafts (46.2% +/- 6.3%, n = 126) 85 months after the operation (p < 0.003). Arterial grafts were used for the non-left anterior descending coronary arteries in only 41 of 155 grafts (26.5%); in contrast, vein grafts were used in 85 of 133 grafts (63.9%) (p < 0.005 to 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗

Characterization of CD4+ single positive cells that lack CD3 in the human thymus.

In the thymus of experimental animals, single positive cells that lack surface CD3 expression (CD3-CD4+CD8- or CD3-CD4-CD8+) have been reported to have intermediate characteristics between the CD4-CD8- cells and CD4+CD8+ cells. Here we show the presence of single positive cells in the human thymus that lack CD3 by means of three-color flow cytometric analysis. CD3- cells constitute 12 +/- 7.5% of CD4 single positive cells in 10 normal thymus samples. CD8 single positive cells, on the other hand, contained only 1.5 +/- 2.2% CD3- cells. Seventeen percent of these CD3-4+8- thymocytes were in S+G2/M phase, while only 4.3% of CD4+CD8- thymocytes were in S+G2/M. The surface antigen phenotype of CD3-CD4+CD8- thymocytes was CD1(low), CD2+, alpha beta TCR-, CD29(high), LFA-1+, ICAM-1-, IL-2R-, CD45common (low), CD45RA-, and CD45R0(low). They expressed cytoplasmic CD3+ and 28% of them expressed cytoplasmic CD3 and cytoplasmic alpha beta TCR. The levels of CD2, CD29, CD45R0, cytoplasmic CD3, and cytoplasmic alpha beta TCR expression were intermediate between the CD3-4-8- and CD4+8+ populations. These results indicate that CD3-CD4+CD8- thymocytes constitute a minor but significant population in the human thymus. Their surface antigen phenotype and the high incidence of dividing cells suggest that they are immature and probably on their way to the CD4+8+ double positive thymocytes.

Adolescent↗

Induction of renal pelvic carcinoma by phenacetin in hydronephrosis-bearing rats of the SD/cShi strain.

Carcinogenicity of phenacetin (PH) to the urinary tract was tested with the use of spontaneously hydronephrosis-bearing rats. In Experiment 1, 55 SD/cShi male rats were fed with 2% PH-containing diet for 85 weeks, and 32 SD/cShi male rats fed basal diet for 85 weeks served as controls. Forty-three of 53 rats fed with PH had renal pelvic carcinoma with lung metastases in three. The mean induction time was 78 weeks. Ureteral carcinoma and urinary bladder carcinoma were observed in 2 and 6 of 53 rats given PH, respectively. No urinary tract carcinoma was found in control animals. In Experiment 2, early lesions of the kidney affected by PH were also evaluated with the use of SD/cShi and Sprague-Dawley (SD) rats. Two groups of animals containing 6 SD/cShi or 6 SD male rats per group were fed 2% PH-containing diet for 8 weeks. Control animals containing 6 SD/cShi rats or 6 SD rats were fed basal diet for 8 weeks. Simple hyperplasia was found in 5 of 6 SD/cShi rats given PH and 2 of 6 SD/cShi control rats. Papillary necrosis was seen in 4 of 6 SD/cShi and 2 of 6 SD rats given PH. SD/cShi rats, especially those treated with PH, showed higher but not significant 5-bromo-2'-deoxyuridine labeling indices in the covering epithelium of the renal pelvis and papillae. In this short term experiment PH and its metabolites, N-hydroxyphenacetin and N-acetyl-p-aminophenol, were measured in urine and plasma by using high performance liquid chromatography. Significantly higher PH and slightly higher metabolites were detected in urine and plasma of SD/cShi rats compared to SD rats. These results indicated that the renal pelvis of SD/cShi rats had more sensitivity to PH carcinogenicity. This paper provides experimental proof of PH carcinogenicity toward the renal pelvis in an animal model.

Animals↗

Site-directed mutagenesis of human tissue transglutaminase: Cys-277 is essential for transglutaminase activity but not for GTPase activity.

Transglutaminases (EC 2.3.2.13) catalyze an acyl-transfer reaction between peptide-bound glutamine residues and primary amines, including the epsilon-amino group of lysine residues in protein. Purified human erythrocyte transglutaminase was found to have another activity, i.e., GTP hydrolysis. Treatment of the enzyme with iodoacetamide, a cysteine-directed reagent, caused a 94% loss of TGase activity within 8 min, but no significant loss of GTPase activity. Cys-277, a known residue which is selectively modified by iodoacetamide, was replaced with Ser by site-directed mutagenesis to assess the role of the Cys-277 in the transglutaminase/GTPase activities. Wild-type cDNA, coding for human endothelial cell transglutaminase, and its C277S-mutated cDNA were cloned into a plasmid vector that contained a promoter from phage T7, and then expressed in Escherichia coli. The wild-type recombinant enzyme was indistinguishable from human erythrocyte transglutaminase in mobility on a SDS-polyacrylamide gel, immunoreactivity and catalytic activities for transglutaminase and GTPase. However, the recombinant enzyme was not blocked at the N-terminal alanine residue, as is the case in the naturally occurring erythrocyte enzyme. The C277S mutant enzyme showed no transglutaminase activity, but had Km and kcat values for GTPase activity that were comparable to those of wild-type recombinant and natural erythrocyte enzymes. These results demonstrate that Cys-277 is essential for transglutaminase activity, but not for GTPase activity, and that N-terminal blocking of tissue-type transglutaminase is not critical for either transglutaminase or GTPase activities.

Binding Sites↗

Classical acetylcholine receptors do not play a direct role in neuronal transmission of photic information in the suprachiasmatic nucleus in rats.

Acetylcholine is said to be involved in the neuronal transmission of photic information in the suprachiasmatic nucleus (SCN). The purpose of this study was to specify what subtypes of acetylcholine receptors play a major role using in vivo system and to examine the interaction of acetylcholine and excitatory amino acid receptors. To evaluate the effect of a selective agonist or antagonist for the nicotinic or muscarinic receptor on the neuronal transmission in the SCNT, N-acetyltransferase (NAT) activity in the pineal gland was measured after microinjection at this site. In the case of pretreatment with an antagonist, light stimulation was given after 20 min. Carbamilcholine chloride (carbachol) mimicked and only alpha-bungarotoxin (alpha-BTX) blocked the light effect; however, more selective agonists or antagonists were not effective. As for the interaction of these two cholinergic agents with an agonist or antagonist for N-methyl-D-aspartate (NMDA) receptor, alpha-BTX or D-2-amino-5-phosphonovalerate (D-APV) significantly blocked the suppressive effect of NMDA or carbachol, respectively. These data suggest that classical acetylcholine receptors do not play a direct role in neuronal transmission of photic information in the SCN in rats.

2-Amino-5-phosphonovalerate↗

[Three-dimensional MR angiography of the celiac artery with single breath holding].

We performed a three-dimensional MR angiography of the celiac artery with single breath holding. The measuring time was just twenty-three seconds. In four healthy volunteers, celiac arteries were visualized clearly, moved cephalad with expiration and caudad with inspiration. In two patients with the median arcuate ligament compression of the celiac artery, the degree of stenosis increased with deep expiration and decreased with deep inspiration. Using this technique, we obtained different vascular images with each respiratory phase. This technique is considered to be a useful three-dimensional MR angiography in the abdominal region without respiratory artifacts.

Celiac Artery↗

Experimental study of the therapeutic effects of folate, vitamin A, and vitamin B12 on squamous metaplasia of the bronchial epithelium.

BACKGROUND: Vitamin deficiency may be related to carcinogenesis. Cytologic examinations of sputum have already found that the administration of folate and vitamin B12 suppressed the development of squamous metaplasia and atypia in smokers' airways. The authors investigated the effect of folic acid, vitamin B12, and vitamin A on the formation of metaplasia and hyperplasia in methylcholanthrene (MCA)-treated rats. METHODS: The SD strain of rats received 10 mg of MCA intratracheally and was divided into six groups as follows: (1) vitamin A; (2) folic acid; (3) vitamin B12; (4) vitamin B12 with folic acid; (5) a combination of vitamin A, folic acid, and vitamin B12; and (6) no vitamins. The Lower respiratory tract epithelia of the rats were examined histologically 20, 32, and 36 weeks after MCA administration and at the end of the experiment. RESULTS: A clear difference was detected between the group receiving folic acid and that receiving vitamin A. In the former group, metaplasia was found in only one rat, atypia was not found, and hyperplasia with marked changes was present in less than 50% of other groups. In the latter group, atypia was found in all of the metaplastic foci. CONCLUSIONS: It was suggested that the epithelial hyperplasia and metaplasia of respiratory tract induced by MCA can be suppressed by the administration of folic acid.

Animals↗

Estrogen stimulates the elaboration of cell/matrix surface-associated inhibitory factor of osteoclastic bone resorption from osteoblastic cells.

Osteoblast-like UMR106 cells secreted bone resorption-stimulating activity (BRSA) under stimulation by human parathyroid hormone 1-34. Most of BRSA was associated with cell/matrix surface and could be extracted by 2 M NaCl. Pretreatment with 17 beta-estradiol (E2) reduced BRSA by enhancing the elaboration of an inhibitory factor of BRSA in a dose-dependent manner, and 10(-9) M 17 beta-E2 showed a significant effect. Neither 17 alpha-E2 nor dihydrotestosterone showed a similar effect. The inhibitory factor of BRSA was also bound to cell/matrix surface, showed affinity for heparin, and was trypsin- and heat-sensitive. Furthermore, this factor could also inhibit resorption pit formation stimulated by 1,25-dihydroxyvitamin D3, interleukin (IL)-1 alpha and IL-6. Elaboration of such an inhibitory factor of bone resorption from osteoblasts may play an important role in the protective effect of estrogen against bone resorption.

Animals↗

Determination of N-acetylneuraminic acid and N-glycolylneuraminic acid in glycoproteins by high-performance liquid chromatography without derivatization.

A simple and sensitive method for the determination of N-acetylneuraminic acid and N-glycolylneuraminic acid in glycoproteins by high-performance liquid chromatography has been investigated. The best condition to release sialic acid from glycoproteins involved incubation at 80 degrees C for 1 h in vacuo in 0.01 M hydrochloric acid with removal of the hydrochloric acid by evaporation without decomposing the sialic acids. Of the substances examined, N-acetylglycine was the best internal standard, because it is absent from glycoproteins, has an appropriate retention time on high-performance liquid chromatography (HPLC) and is stable during the procedures. The sample solution containing the internal standard was analysed directly by isocratic HPLC without pre-column or post-column labelling, and elution was monitored by ultraviolet absorbance at 205 nm. This method can determine 0.08-10 nmol of sialic acid accurately within 12 min and was successfully applied to bovine vitronectin.

Animals↗

Age-related accumulation of LFA-1high cells in a CD8+CD45RAhigh T cell population.

The differential expression of CD45 isoforms has been suggested as a marker for stages of post-thymic T cell development, that is, CD45RA+CD45R0-T cells and CD45RA-CD45R0+ T cells are supposed to be virgin and memory cells respectively. Recently, several adhesion molecules have been shown to be up-regulated on the cell surface of memory T cells, and have been suggested to serve as a memory marker. In this study, we investigated the levels of LFA-1 expression on T cells in various subpopulations defined by CD45 isoform expression in donors of various ages. In CD4+ T cells, the proportion of LFA-1high cells among CD45RAhighCD45R0- T cells remained low in all age groups and did not show significant accumulation with age. CD4+CD45RA-CD45R0high T cells expressed LFA-1 at a higher level than CD4+CD45RAhighCD45R0- T cells. Thus, the currently prevailing view that CD45RA and CD45R0 can be markers for virgin and primed cells was consistent with LFA-1 expression in CD4+ T cell population. In CD8+ T cells, however, CD45RAhighCD45R0- T cells consisted of two distinct subpopulations, LFA-1low and LFA-1high cells, whereas CD45RA-CD45R0high T cells were almost exclusively LFA-1high. When CD29 expression was examined in place of LFA-1 expression, similar results were obtained; CD45RAhigh CD45R0- T cells consisted of two distinct subpopulations, CD29-to low and CD29high cells, while CD45RA-CD45R0high T cells were mostly CD29high. The proportion of LFA-1high cells in the CD8+CD45RAhigh T cell subpopulation increased significantly as a function of age (r = 0.9, p < 0.001). It ranged from 8% in a 14-year-old donor to 94% in a 79-year-old donor. Furthermore, the proportion of CD8+CD45RAhighLFA-1high cells in the CD8+ T cell population increased significantly as a function of age (r = 0.85, p < 0.001). On the other hand the proportion of LFA-1high cells in CD8+CD45RA- T cell subpopulation exceeded 90% in most donors irrespective of age. These results indicate that the CD8+CD45RAhighCD45R0- T cell subpopulation contains a considerable number of LFA-1high cells and CD29high cells, phenotypically similar to previously activated cells. Thus, in terms of LFA-1 and CD29 expressions, the simple scheme that CD45RA is a marker of virgin cells is not applicable to the CD8+ T cell population.

Adolescent↗

Effects of transforming growth factor beta 1 and L-ascorbate on synthesis and distribution of proteoglycans in murine osteoblast-like cells.

Proteoglycans synthesized by osteoblasts are incorporated into bone matrix and thought to play a role in bone metabolism. Transforming growth factor (TGF) beta affects the synthesis of matrix proteins, including proteoglycans, in various stromal cells, and proteoglycans, especially decorin, are associated with matrix collagen. In the present study, the effects of TGF-beta 1 and L-ascorbate, a factor essential for collagen synthesis, on the synthesis and distribution of proteoglycans were examined using murine osteoblast-like MC3T3-E1 cells. TGF-beta 1 stimulated the synthesis of proteoglycans in MC3T3-E1 cells. Among various proteoglycans, the synthesis of decorin was preferentially enhanced by TGF-beta 1, and the effect was more pronounced on secreted decorin compared to that associated with the cell/matrix layer. TGF-beta 1 also stimulated the initiation and elongation of the dermatan sulfate glycosaminoglycan chain, resulting in a larger molecular size of decorin. TGF-beta 1 influenced the synthesis of a heparan sulfate proteoglycan only slightly. L-ascorbate had no effect on the synthesis of proteoglycans, but increased those associated with the cell/matrix layer. Furthermore, when L-ascorbate was added to the culture along with TGF-beta 1, the percentage of proteoglycans associated with the cell/matrix layer increased from 25.8 +/- 1.0 to 41.0 +/- 0.5%. These data demonstrate that TGF-beta 1 markedly stimulates the synthesis of proteoglycans, especially decorin, mainly as a secreting form, that the accumulation of decorin into matrix is enhanced by L-ascorbate, and that the effects of TGF-beta 1 and L-ascorbate are additive.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗

n-hexane polyneuropathy in Japan: a review of n-hexane poisoning and its preventive measures.

n-Hexane is used in industry as a solvent for adhesive, dry cleaning, and vegetable oil extraction. In 1963, the first case of severe polyneuropathy suspected to be caused by n-hexane was referred to us. Case studies, animal experiments, and field surveys on n-hexane poisoning were conducted, and preventive measures like threshold limit value revision and biological monitoring were also studied. I review a brief history of our investigations on n-hexane poisoning and its preventive measures in Japan. n-Hexane could cause overt polyneuropathy in workers exposed to more than 100 ppm time-weighted average concentrations [TWA]. The present threshold limit value of 40 ppm in Japan is considered low enough to prevent subclinical impairment of peripheral nerve caused by n-hexane. Urinary 2,5-hexanedione could be a good indicator for biological monitoring of n-hexane exposure. About 2.2 mg/liter of 2,5-hexanedione measured by our improved method corresponds to exposure of 40 ppm (TWA) of n-hexane.

Animals↗