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Biomedical subjects

Y Tsuchiya

Publications and source records attributed to Y Tsuchiya.

At least 19 recordsLinked to original sources
PubMed1992

Synthesis and structure-activity relationships of acetylcholinesterase inhibitors: 1-benzyl-4-(2-phthalimidoethyl)piperidine and related derivatives.

Following the discovery of a new series of 1-benzyl-4-[2-(N-benzoyl-N-methylamino)ethyl]piperidine (2) derivatives with a potent anti-acetylcholinesterase (anti-AChE) activity, we extended the structure-activity relationships (SAR) to rigid analogues (4) and 1-benzyl-4-[2-(N-benzoyl-N-phenylamino)ethyl]piperidine derivatives (3). Introduction of a phenyl group on the nitrogen atom of the amide moieties resulted in enhanced activity. The rigid analogue containing isoindolone (9) was found to exhibit potent anti-AChE activity comparable to that of 2. Furthermore, replacement of the isoindolone with other heterobicyclic ring systems was examined. Among the compounds prepared in these series, 1-benzyl-4-[2-[4-(benzoylamino)phthalimido]ethyl]piperidine hydrochloride (19) (IC50 = 1.2 nM) is one of the most potent inhibitors of AChE. Compound 19 showed a definite selectivity to AChE over the BuChE (about 34700-fold) and, at dosages of 10-50 mg/kg, exerted a dose-dependent inhibitory effect on AChE in rat brain.

Acetylcholinesterase↗
PubMed1992

Diagnosis of portal vein tumor thrombus by pulsed Doppler ultrasonography.

The blood flow of portal vein thrombus was studied by pulsed Doppler ultrasonography in 21 patients with tumor thrombus and 14 with blood clot thrombus. Pulsatile waves were observed in 19 of the 21 with tumor thrombus, with backward continuous waves in 3, and forward/backward continuous waves in 2. In contrast, forward continuous waves were observed in 2 of the 14 with blood clot thrombus. By color imaging, the blood flow could be observed in 9 of 14 with tumor thrombus, but in 1 of 7 with blood clot thrombus. Pulsatile and backward continuous waves were characteristic of tumor thrombus.

Adult↗
PubMed1992

Fructose and glucagon loading in siblings with fructose-1,6-diphosphatase deficiency in fed state.

Hypoglycaemia induced by fructose administration is one of the diagnostic clues to fructose-1,6-diphosphatase (FDPase) deficiency (McKusick 229700). However, the pathological mechanism of this reactive hypoglycaemia is not fully known. This paper describes two siblings with FDPase deficiency, diagnosed enzymatically in leukocytes, who failed to correct reactive hypoglycaemia after glucagon administration even in the fed state, supporting a possibility that disturbed hepatic phosphorylase activity may be a main cause of reactive hypoglycaemia.

Blood Glucose↗
PubMed1992

Relationship between gallium 67 citrate scanning and transferrin receptor expression in lung diseases.

The uptake of gallium 67 (67Ga) into cells is postulated to be through transferrin receptors (TFR) of 67Ga combined with transferrin. We studied the relationship between gallium 67 citrate scanning (67Ga scan) and immunohistochemical TFR expression in lungs of nine patients with lung cancer and eight patients with diffuse interstitial lung diseases. We found that lung cancer tissues of positive 67Ga scan expressed TFR, but those of a negative scan did not. In all of the five patients with idiopathic pulmonary fibrosis (IPF), TFR were expressed on the membrane of alveolar macrophages that formed clusters. However, TFR were not expressed in lymphocytes, neutrophils, type 2 alveolar epithelial cells, and endothelial cells. In two patients with sarcoidosis and a patient with pneumoconiosis, TFR were expressed positively only on the membrane of foamy alveolar macrophages and epithelioid cells of granuloma. These findings suggest that 67Ga-citrate initially combines with transferrin in the blood and then the complex is incorporated into cells through TFR. Therefore, 67Ga scan could be positive when cells have TFR and one should be able to observe cancer cells, clusters of alveolar macrophages, and epithelioid cells through the imaging of 67Ga scan in lung cancer and diffuse interstitial lung diseases.

Citrates↗
PubMed1992

Western ligand blot assay for human growth hormone-dependent insulin-like growth factor binding protein (IGFBP-3): the serum levels in patients with classical growth hormone deficiency.

The insulin-like growth factors I and II (IGFs), important growth factors both in vivo and in vitro, are known to have at least six binding proteins (IGFBP-1-6). In human serum, IGFBP-3 is a major binding protein and is considered to be GH-IGF-I-dependent. We have established a Western Ligand Blot (WLB) assay for IGFBP-3. The method is a densitometric analysis of IGFBP-3 bands on a film of WLB. The IGFBP-3 levels of patients with classical growth hormone deficiency (GHD, 5 isolated and 10 multiple hormone deficiencies with appropriate therapy) were studied. Before puberty there is no overlap between control (n = 31) and the patients with GHD (n = 10). However, IGFBP-3 levels of two of five pubertal patients with GHD were within the normal range (n = 16). We think that measurement of serum IGFBP-3 is a useful diagnostic marker for GHD, especially before puberty.

Adolescent↗
PubMed1992

Gradual progress of ACTH deficiency in a child with panhypopituitarism associated with pituitary stalk transection.

We present here a 13-year-old male with hypopituitarism which accompanied an insidious and gradual progress of ACTH deficiency. ACTH deficiency finally led to an overt crisis of adrenal insufficiency at the age of 12 years and 7 months. This patient is unique because the insidious and gradual progress has been proved by not only the laboratory results but also the clinical course for over 13 years. The cause of panhypopituitarism including ACTH deficiency is thought to have existed before or at the delivery because of the stalk transection seen on the magnetic resonance image (MRI). At the crisis, his laboratory results suggested that he had secondary adrenal insufficiency, whereas he showed normal adrenal function proved by the insulin tolerance test (ITT) at the age of 4 years. Abrupt crisis of secondary adrenal insufficiency developed at the age of 12 years, although he had been well until the crisis.

Adolescent↗
PubMed1992

Usefulness and limitation of measurement of insulin-like growth factor binding protein-3 (IGFBP-3) for diagnosis of growth hormone deficiency.

To analyze the utility of insulin-like growth factor binding protein-3 (IGFBP-3) radioimmunoassay for diagnosis of growth hormone deficiency (GHD) we measured IGFBP-3 in sera from normal children, short children and patients with GHD. The sensitivity (true positive ratio) of IGFBP-3 for complete GHD (cGHD) was 93%, while the specificity (true negative ratio) for normal short children (NS) was 88%. In contrast, the sensitivity of IGFBP-3 for partial GHD (pGHD) was only 43%. The poor discrimination between patients with pGHD and NS may be the result of their relatively similar GH level, as compared to cGHD, or due to the limitations of GH stimulation tests. The specificity of IGFBP-3 for NS was excellent in children of all ages: less than 10 years old (87%) and older than 10 (88%). However, sensitivity for GHD was good for children less than 10 years old (84%) but poor for children older than 10 (64%). IGFBP-3 may be less sensitive for diagnosing GHD in older children because IGFBP-3 levels may also increase during puberty due to mechanisms independent of the GH-IGF-I axis.

Adolescent↗
PubMed1992

Spontaneous growth hormone secretion in healthy prepubertal children of normal stature.

To evaluate the dynamics of growth hormone (GH) secretion in healthy prepubertal children of normal stature, we determined spontaneous GH secretion by measuring GH every 30 min in 21 Japanese subjects, age: 5.4 +/- 2.3 (1.6-10.6) years; height: -1.4 +/- 1.1 (-1.98-1.77) SD. The 24-h mean GH concentration was 4.8 +/- 1.5 ng/ml. The 24-h mean GH was similar in boys and girls (mean +/- SD: 4.8 +/- 1.7 vs 4.7 +/- 1.1 ng/ml). No correlation was found between chronological age and the 24-h mean GH. The 24-h mean GH was closely correlated with GH pulse amplitude (r = 0.94; P less than 0.001), but not with the number of GH pulses. The 24-h mean GH was also highly correlated with 3-h mean GH after sleep and 3-h peak GH after sleep (r = 0.86; P less than 0.001 and r = 0.72; P less than 0.001, respectively). Our data suggest that in healthy prepubertal children of normal stature, (1) spontaneous GH secretion is independent of sex and age, (2) the amount of spontaneous GH secretion is controlled by pulse amplitude, not by number of pulses. (3) 3-h mean GH and 3-h peak GH after sleep might represent 24-h total spontaneous GH secretion.

Body Height↗
PubMed1992

Occurrence of a novel 350-kDa serine proteinase in the fluid of porcine ovarian follicles and its increase during their maturation.

Porcine ovary was found to contain enzyme activities hydrolyzing peptide 4-methylcoumaryl-7-amide (MCA) substrates with a preference for Arg-MCA bond. The activities were shown to be present almost exclusively in the follicular fluid and to increase several times during follicular maturation. The enzyme responsible for these activities is thought to be a serine proteinase as judged from its strong inhibition by diisopropylfluorophosphate (DFP), leupeptin and antipain. The molecular weight of the native enzyme was electrophoretically estimated to be approximately 350,000, the result indicating that the enzyme is clearly distinct from plasmin (M(r) = 80,000) and collagenase (M(r) = 30,000-65,000), both of which are thought to be involved in ovulatory process. The substrate specificity of the partially purified enzyme was qualitatively different from that of plasmin. These results suggest that the enzyme is a novel type of serine proteinase.

Amino Acid Sequence↗
PubMed1992

[Treatment of acute cholecystitis by direct-puncture bile aspiration with ultrasound-image control].

We carried out ultrasound guided direct-puncture bile aspiration (DPBA) in 58 patients with acute cholecystitis. Symptoms and laboratory findings of acute cholecystitis were rapidly improved after DPBA. NO serious complications were seen during and after the DPBA procedure. It was concluded that DPBA is practical and safe treatment of acute cholecystitis. Furthermore long follow up study revealed that this therapeutic method would be useful and reliable for elder patients and patients with systemic complication.

Acute Disease↗
PubMed1991

A correlation between GM-CSF gene expression and metastases in murine tumors.

Using 14 transplantable murine tumors, we investigated a possible correlation between their ability to produce the cytokine GM-CSF and the spontaneous metastatic potential when mice were subcutaneously inoculated. The following results were obtained: (1) seven tumors, which produced severe pulmonary metastases and metastatic swelling of lymph nodes, exhibited the ability to produce GM-CSF activity in culture. The cell population analysis revealed that the cells producing GM-CSF were tumor cells themselves, but that contaminating macrophages/granulocytes and T lymphocytes did not produce GM-CSF. The mRNA for GM-CSF was also found in all of these highly metastatic tumors tested. In mice inoculated with a highly metastatic tumor, the GM-CSF mRNA was also found in lungs; (2) in 3 other tumors, which produced histological but not macroscopical pulmonary metastases, no GM-CSF activity could be detected in the culture fluids. GM-CSF mRNA was, however, detected in the tumor cells in the presence of an mRNA-stabilizing agent, cycloheximide, suggesting the possibility that the tumor cells of this type were transcribing GM-CSF gene, and secreting it in undetectable levels; (3) in culture of the 4 remaining poorly or non-metastatic tumors, neither CSF activity nor GM-CSF mRNA could be detected even in the presence of cycloheximide. GM-CSF mRNA was also not found in lungs of tumor-bearing mice. Our results indicate that there may be a correlation between GM-CSF gene expression in tumor cells and spontaneous metastases.

Animals↗
PubMed1991

Effect of a glucan, sizofiran, on natural-killer activity of 5-fluorouracil-treated murine bone marrow cells.

The number of bone marrow cells in C3H/He mice was reduced 3-4 days after treatment with 130 mg/kg intraperitoneal 5-fluorouracil (5-FU). Higher rates of spontaneous proliferation and natural killer (NK) activity, accompanied by an increase in asialoGM1-positive cells, were observed in treated mice. When sizofiran at a dose of 200 micrograms/animal was intramuscularly injected after 5-FU treatment, the rates of proliferation and NK activity of bone marrow cells were higher than with 5-FU alone. The cell number was not influenced by sizofiran alone. These results indicate that all precursors of the various mature cell types (including NK cells) differentiate and regenerate rapidly to replace cells damaged by 5-FU treatment, and that sizofiran has the potential to assist this recovery. These results suggest that administration of sizofiran after chemotherapy may be useful in cancer patients.

Animals↗
PubMed1991

Hypolipidemic effects of NB-598 in dogs.

NB-598, a new inhibitor of mammalian squalene epoxidase, was found to be a potent inhibitor of microsomal squalene epoxidase from dog liver. Hypolipidemic effects of NB-598 were compared with those of simvastatin (MK-733, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) in dogs. NB-598 was found to decrease serum total cholesterol levels and increase serum squalene levels in a dose-dependent manner. MK-733 decreased serum total cholesterol and squalene levels. Both NB-598 and MK-733 decreased all classes of lipoprotein cholesterol, and they decreased low density lipoprotein cholesterol most potently. Both drugs decreased phospholipid levels in parallel with cholesterol levels. NB-598 also decreased triacylglycerol levels. After termination of drug administration, these levels returned to the control levels. The potency of NB-598 is thought to be as great or greater than that of MK-733. Moreover, NB-598 increased squalene concentrations in the feces and gallbladder bile, but it did not affect neutral sterol and bile acid concentrations. NB-598 did not affect the lithogenic index.

Animals↗
PubMed1991

Establishment and characterisation of human carcinoembryonic antigen transgenic mice.

We have produced human CEA transgenic mice which were found to express CEA mRNA in all tissues. By immunoblot analysis using anti-CEA polyclonal antibody, we also detected CEA protein in all tissues. However, the molecular size of CEA in the brain was different from that in other tissues, although the mRNA size was same and no deletion nor rearrangement was detected at the DNA level. Immunohistochemical analysis of the lung and the colon showed that the expression sites were the bronchial epithelial cells of the lung and the columnar epithelial cells of the colon. Interestingly, the expression of CEA protein in the transgenic mice was polarised to the luminal side of epithelial cells similar to the normal CEA expression in human tissues. We also detected cell surface expression of human CEA on thymocytes and spleen cells and CEA expression was greatly reduced by the phosphatidylinositol-specific phospholipase C (PI-PLC) treatment.

Animals↗
PubMed1991

Effect of Clostridium perfringens alpha toxin on contraction of isolated guinea-pig diaphragm.

The effect of Clostridium perfringens alpha toxin on contraction induced by electric stimulation of isolated guinea-pig diaphragm was investigated. The toxin inhibited electrically stimulated contraction of the tissue in a dose- and incubation time-dependent manner. Tetrodotoxin resulted in no effect of the action of the toxin. Nifedipine dose-dependently delayed the action of the toxin, but verapamil and diltiazem did not. On the other hand, treatment of the toxin with N-acetylimidazole caused significant reduction of the inhibitory activity of the toxin on contraction, but did not cause significant loss of phospholipase C activity (PN activity) as measured by hydrolysis of p-nitrophenylphosphorylcholine. The data showed that the toxin impairs contraction of isolated guinea-pig diaphragm.

Animals↗
PubMed1991

EEC syndrome (ectrodactyly, ectodermal dysplasia and cleft lip/palate) with a balanced reciprocal translocation between 7q11.21 and 9p12 (or 7p11.2 and 9q12) in three generations.

Familial cases (a grandfather, a father and a daughter) of the EEC syndrome (ectrodactyly, ectodermal dysplasia and cleft lip/palate) are reported. All of them have a balanced reciprocal translocation (46,XY or XX, t(7;9) (q11.21;p12) or (46,XY or XX, t(7;9) (p11.2;q12)), but no other members of the family have either the EEC syndrome or chromosome abnormalities. This indicates that one of the chromosome sites 7q11.21, 9p12, 7p11.2 and 9q12 is a candidate for gene locus of the EEC syndrome.

Adult↗
PubMed1991

Early carcinoma of the gallbladder: macroscopic features and US findings.

To facilitate early detection of carcinoma of the gallbladder, a comparative study of macroscopic forms and ultrasonographic (US) features of stage I (TNM staging system) gallbladder cancer was carried out retrospectively in 71 cases of such carcinomas that were resected surgically. Macroscopic forms of the lesions were classified into four types: pedunculated (eight cases), sessile (15 cases), superficial raised (25 cases), and flat (23 cases). Among 71 cases, only 20 were diagnosed preoperatively by means of US. US patterns of the lesions were also classified into four types: fungating mass, lumen filling, smooth raised, and thickening of mucosa. US features corresponded well to the macroscopic forms. No flat lesion was identified preoperatively. For early detection of carcinoma of the gallbladder, it seemed essential to pay careful attention to mild mucosal change, as more than 50% of early cancers did not show apparently protruding lesions.

Adenocarcinoma↗