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Biomedical subjects

N Kuno

Publications and source records attributed to N Kuno.

At least 19 recordsLinked to original sources

The concentration of hepatocyte growth factor (HGF) in human amniotic fluid at second trimester: relation to fetal birth weight.

Hepatocyte growth factor (HGF) was measured in 28 samples of amniotic fluid, 1 of fetal urine and 5 of first neonatal urine. The mean level of HGF was 12.4 +/- 4.5 ng/ml (second trimester) and 10.5 +/- 6.6 ng/ml (third trimester). These values were extremely high compared to that in plasma from normal subjects and greater than the plasma levels from patients with acute hepatitis. The concentration of amniotic HGF at second trimester showed a significant inverse correlation both with birth weight (r = 0.47; p < 0.05) and birth weight deviation (r = 0.54; p < 0.02). The level of HGF in fetal urine (0.10 ng/ml) and in the first neonatal urine (0.08 +/- 0.02 ng/ml) were much less than that in amniotic fluid. HGF stimulated DNA synthesis of human fetal liver cells in vitro. While the effect was dose dependent, a maximal response was reached with about 0.2 ng/ml, attaining a 1.3-fold stimulation. The presence of extremely high levels of HGF in the amniotic fluid may be involved not in fetal growth, but rather in maturation of fetal organs such as the lung and the digestive tract.

Amniotic Fluid

Effectiveness of multivariate analysis of tumor markers in diagnosis of pancreatic carcinoma: a prospective study in multiinstitutions.

In 403 patients suspected of having pancreatic cancer, we prospectively studied a combination assay of various serum tumor markers: CA19-9, DUPAN2, tissue polypeptide antigen, elastase 1, gamma-glutamyltranspeptidase, lactate dehydrogenase, lipase, amylase, and alkaline phosphatase. The diagnostic value of each marker was compared with a multivariate analysis (computer-aided multivariate and pattern analysis system for pancreatic cancer examine-1: CAMPAS-PX1). Pancreatic cancer was subsequently identified in 47 patients. CAMPAS-PX1 had higher negative in health and positive predictability than those of each marker used alone in the diagnosis of pancreatic cancer. CAMPAS-PX1 proved the most effective marker for diagnosing pancreatic cancer, but in terms of its cost/benefit ration CAMPAS-PX1 was not superior to CA19-9 used alone. In this prospective trial, we experienced poor generalizability in the statistical models (CAMPAS-PX1). We believe that selection bias was present in samples used for model building. Based on this study a new model has been designed.

Aged

[Early detection of pancreatic cancer by serum markers].

Serum markers such as pancreatic enzymes and tumor markers are useful for the diagnosis of pancreatic cancer. Among 40 cases of pancreatic cancer, elevated values were observed for immunoreactive elastase (IRE) in 70% and for CA19-9 in 73%. Elevated serum IRE was observed more frequently in head cancer and resectable cancer, whereas elevation in CA19-9 occurred more often in body-tail cancer and unresectable cancer. Elevation of serum IRE and CA19-9 are useful for diagnosis of pancreatic cancer but it is not specific for pancreatic cancer. Therefore, we studied the clinical usefulness of a combination assay of various serum markers such as CA19-9, lipase, serum iron, amylase, albumin globulin ratio, tissue polypeptide antigen, immunoreactive trypsin, and CA125 using the logistic regression analysis. This assay showed higher sensitivity and high specificity for pancreatic cancer than CA19-9. This combination assay may be very useful for the diagnosis of pancreatic cancer.

Amylases

Overproduction of biologically-active human nerve growth factor in Escherichia coli.

A gene coding for human nerve growth factor (hNGF) was constructed for expression under control of the trp promoter in E. coli. The plasmid pTRSNGF contained a synthetic hNGF gene fused, in frame, to the region encoding the beta-lactamase signal peptide. The plasmid pTRLNGF contained the same coding sequence as hNGF attached downstream from the N-terminal fragment of the trp L gene. E. coli cells harboring pTRSNGF produced an amount of hNGF constituting 4% of the total cellular protein, and removed the beta-lactamase signal peptide. The mature protein hNGF was biologically active in the PC12h bioassay for neurite outgrowth. This biological activity was comparable to that of authentic mouse NGF. E. coli cells harboring pTRLNGF produced an amount of fusion protein hNGF constituting 25% of the total cellular protein. Although the fusion protein hNGF formed inclusion bodies in cells, dissolved fusion protein hNGF was active in neurite outgrowth from PC12h cells.

Amino Acid Sequence

Binding of [3H]p-aminoclonidine to two sites, alpha 2-adrenoceptors and imidazoline binding sites: distribution of imidazoline binding sites in rat brain.

Binding sites labeled by [3H]p-aminoclonidine [( 3H]PAC) were investigated by the competitive analysis with imidazoline and non-imidazoline derivatives. Phenylethylamine derivatives displaced only the part of specific sites for [3H]PAC, which was considered as alpha 2-adrenoceptor, whereas imidazoline derivatives, such as clonidine and tolazoline, competed for a further specific binding of [3H]PAC to the non-adrenergic sites, in addition to the alpha 2-adrenoceptor. Because the non-adrenergic sites were specific for the imidazoline structure, they were termed imidazoline sites. The imidazoline sites were not distributed uniformly among rat brain regions. In striatum, hippocampus and medulla oblongata, they occupied 39.6, 33.0 and 36.5% of the specific binding of [3H]PAC, respectively. Saturation isotherms revealed that Kd and Bmax of imidazoline sites for [3H]PAC were 3.09 +/- 0.59 nM, 27.4 +/- 1.7 fmol/mg protein and 2.23 +/- 0.29 nM, 21.0 +/- 1.5 fmol/mg protein in striatum and hippocampus, respectively. Because imidazoline binding sites also displayed weak affinities for imidazole compounds, such as histamine and cimetidine, the imidazoline site may be a subtype of histamine H2-receptor.

Animals

Inhibition of cyclic AMP accumulation by alpha 2-adrenoceptors in the rat cerebral cortex.

The effects of alpha 2-adrenoceptor agonist and antagonists on the accumulation of cyclic AMP were examined in rat cerebral cortex slices. Norepinephrine (10(-4) M) caused a 123 +/- 11% increase in the cyclic AMP concentration in the cortical slices, which was greater than the increase (89 +/- 7% increase) caused by isoproterenol (10(-4) M) alone. However, the cyclic AMP response to norepinephrine was completely inhibited by propranolol (10(-4) M), a beta-adrenoceptor antagonist. Yohimbine (10(-7)-10(-5) M), an alpha 2-adrenoceptor antagonist, intensified the cyclic AMP response to norepinephrine by 30%, whereas, clonidine, an alpha 2-adrenoceptor agonist, decreased the response. Treatment with reserpine (3.0 mg/kg) reduced the density of [3H]p-aminoclonidine binding sites (Bmax, 93.8 +/- 18.4 fmol/mg protein) compared to the density in non-treated rats (154.4 +/- 33.5 fmol/mg protein). The potentiating effect of yohimbine and the inhibitory effect of clonidine on the cyclic AMP response to norepinephrine were also reduced. These results suggest that alpha 2-adrenoceptors regulate the accumulation of cyclic AMP in the rat cerebral cortex in an inhibitory fashion. The results also suggest that the accumulation is mediated through beta-adrenoceptors and that this response is intensified by alpha 1-adrenoceptor stimulation.

Adenylyl Cyclases

L-threo-3,4-dihydroxyphenylserine (DOPS) aldolase: a new enzyme cleaving DOPS into protocatechualdehyde and glycine.

An enzyme which cleaves L-threo-3,4-dihydroxyphenylserine into protocatechualdehyde and glycine was demonstrated in extracts of human brains. Equimolar production of protocachualdehyde and glycine was quantitatively confirmed using high-performance liquid chromatography. In subcellular fractions of the brain, the highest enzyme activity was found in cytosol and soluble fraction. L-threo-DOPS proved to be the best substrate for this enzyme. The L-erythroisomer was less active and D-threo- and D-erythro-isomers were essentially inactive. The enzyme activity has an optimal pH around 7.4, and requires pyridoxal phosphate for maximal activity.

Aldehyde Dehydrogenase

Correlation between endoscopic retrograde pancreatogram and postmortem.

Endoscopic retrograde pancreatogram and postmortem pancreatograms were compared in 6 dogs. The main duct, branches and acini of the pancreas were opacified adequately in that order with infusion of each 1 ml of contrast medium on 4 occasions in endoscopic retrograde pancreatography, and infusion of each 0.1 ml of the contrast medium on 4 occasions in postmortem pancreatography, respectively. The two pancreatograms were almost identical to the appearance of the main duct, branches and acini. The results suggest that a postmortem retrograde pancreatogram in order to investigate the correlation between the pancreatogram and the histological findings of the pancreas.

Animals