Search PubMed⌕ Search

Biomedical subjects

K Sakamoto

Publications and source records attributed to K Sakamoto.

At least 559 records · Page 31Linked to original sources
PubMed1993

Growth inhibition and differentiation of HT-29 cells in vitro by inositol hexaphosphate (phytic acid).

Inositol hexaphosphate (InsP6 or phytic acid) has been shown to have antineoplastic action in in vivo models of colon carcinogenesis. We therefore investigated its effect on proliferation and differentiation of the human colon cancer cell line HT-29 in vitro. Proliferation was evaluated by neutral red incorporation assay, and differentiation was assessed by expression of the markers, cytokeratin, carcinoembryonic antigen (CEA) and beta-D-galactose-[1-->3]-N-acetyl-galactosamine (Gal-GalNAc). InsP6 in the culture media (0.66-10 mM) inhibited cell proliferation in a dose-dependent manner (P < 0.001), while inositol or inositol hexasulfate used as controls or media without InsP6 did not show any suppressive effect. The expression of the tumor marker, Gal-GalNac, was augmented (100.7% increase) by low dose (0.66 mM) of InsP6 but was subsequently suppressed with higher concentrations of InsP6. The expression of cytokeratin and CEA were both augmented by either InsP6 or inositol at all concentrations tested, although the degree of augmentation was milder with inositol than with InsP6. The combination of InsP6 and inositol (both 0.66 mm) resulted in augmentation (P < 0.001) of cytokeratin expression, while that of CEA remained unchanged. The inhibitory effect of InsP6 on cell proliferation was not altered by combination with additional inositol at any concentrations tested. Our results show that InsP6 inhibits cell proliferation and concomitantly increases differentiation and is therefore a candidate chemopreventive and chemotherapeutic agent for human large intestinal cancer.

Adenocarcinoma↗
PubMed1993

[3H]phytic acid (inositol hexaphosphate) is absorbed and distributed to various tissues in rats.

To understand the mechanism of antineoplastic action of phytic acid, we investigated the absorption and distribution of myo-[inositol-2-3H(N)] hexakisphosphate in rats. The radioactivity was measured in urine, feces, blood, gastrointestinal tract contents and various organs and tissues at 1 and 24 h after intragastric administration. Of the total radioactivity, 79.0 +/- 10.0% was absorbed and at least 26.6% was degraded during the 24-h period following ingestion. The absorption was rapid; 11.0 +/- 2.6% of the radioactivity was detected in the wall of the stomach (4.4 +/- 3.7%) and upper small intestine (6.6 +/- 1.9%), 6.5 +/- 2.6% in the skeletal muscle and 4.0 +/- 1.5% in the skin after 1 h. Much of the radioactivity after 24 h was in the liver (4.0 +/- 0.9%), kidneys (2.2 +/- 1.1%), muscle (18.1 +/- 3.4%) and skin (10.1 +/- 3.3%). Analysis of plasma and urine demonstrated that most of the radioactivity was due to myo-inositol and small amounts of inositol monophosphate (InsP1). Gastric epithelial cells, however, contained inositol and various inositol phosphates (InsP1-6). Our data suggest that soluble InsP6 when administered in drinking water is rapidly absorbed through the stomach and upper small intestine, becomes quickly dephosphorylated within the mucosal cells and is distributed to various organs as inositol and InsP1.

Animals↗
PubMed1993

A nationwide survey of seasonal affective disorder at 53 outpatient university clinics in Japan.

A nationwide survey of seasonal affective disorder (SAD) was performed from autumn 1990 to spring 1991 with the cooperation of 53 outpatient university psychiatric clinics in Japan. Forty-six SAD patients were identified among 5265 depressed outpatients. SAD was generally reported to occur in 1-3% of the depressed outpatients newly attending each facility. Hours of sunshine were found to be a more relevant variable influencing the prevalence of SAD than latitude or the mean temperature in December. The unexpectedly low percentage (20-30%) of SAD patients with atypical vegetative symptoms suggests that SAD patients who have no prior knowledge of SAD and those who are recruited via the media have different vegetative symptom profiles.

Adult↗
PubMed1993

Hypoxic brain damage: cortical laminar necrosis and delayed changes in white matter at sequential MR imaging.

PURPOSE: To report the findings of sequential magnetic resonance (MR) imaging in hypoxic encephalopathy. MATERIALS AND METHODS: Three women and three men underwent repeated MR imaging studies. Sequential changes in signal intensity and morphologic features of the brain were evaluated. RESULTS: Involvement of the watershed zones in the parietooccipitotemporal cortex was more frequent and more severe than that in the basal ganglia, thalami, hippocampus, pons, and cerebellum. Cerebral edema was seen in the acute stage. Enhanced T1-weighted images showed cortical laminar enhancement in the early subacute stage; unenhanced T1-weighted images revealed characteristic laminar hyperintense lesions of the cerebral cortex in the late subacute stage. Both of these findings seemed to reflect the progression of cortical laminar necrosis. In the chronic stage, cortical atrophy and delayed but progressive white matter changes were seen. CONCLUSION: Changes in MR imaging features of hypoxic brain damage are complex but distinct. Cortical laminar necrosis, delayed white matter degeneration, and, probably, increased iron deposition in the white matter can be delineated.

Adult↗
PubMed1993

GP2, the homologue to the renal cast protein uromodulin, is a major component of intraductal plugs in chronic pancreatitis.

Protein plug obstruction of the pancreatic duct is one of the early events in chronic pancreatitis yet little is known about its pathogenesis. GP2, a protein in the exocrine pancreas, is a glycosyl phosphatidylinositol-anchored protein that is cleaved from the zymogen granule membrane and secreted into pancreatic juice. Since its homologue, uromodulin, is involved in renal cast formation, we asked the question whether GP2 might play a similar role in plug formation in chronic pancreatitis. The protein composition of intraductal plugs from patients with noncalcific chronic pancreatitis was examined. Plugs purified from pancreatic juice obtained by endoscopic cannulation were analyzed by SDS-PAGE. A 97-kD protein was found not only to be a reproducible constituent but also enriched within intraductal plugs. This protein was confirmed as GP2 by its localization to zymogen granule membranes, its isoelectric point, and by Western blotting. Although the pancreatic stone protein was identified in plugs, it was not a major reproducible component. These results demonstrate that GP2 is an integral component of plugs in pancreatic juice and suggest that GP2 may play a role in pancreatic plug formation that is analogous to the role played by uromodulin in the pathogenesis of renal casts.

Cytoplasmic Granules↗
PubMed1993

Reverse interference method for measurement of hog cholera virus (HCV) and anti-HCV antibody.

A new procedure was developed for the assay of the hog cholera virus (HCV) and anti-HCV antibody. Initially, the suppression effect of HCV on interferon (IFN) by HCV production was confirmed. Swine kidney cell cultures preinfected with HCV produced no IFN, even following the addition of IFN inducers. However the sensitivity of the cell to IFN was not influenced by the infection with this virus. Based on these results, a new method, named reverse interference method, was established. In this method, infective titer of HCV was determined by the appearance of cell pathogenic effects (CPE) induced by vesicular stomatitis virus (VSV), which is caused by the suppression effect on the heterologous interference of GPE- strain of HCV against VSV infection in swine kidney cell cultures. This method showed nearly the same sensitivity as the END method. There was no difference in the infective titer of HCV and antibody titer against HCV as estimated by this method and the END method. The reverse interference method had advantages in rapidity and objectivity compared with the END method.

Animals↗
PubMed1993

Establishment of inbred strain of long-haired golden hamster.

Features of a long-haired mutant and inheritance of mutation were investigated in the golden hamster (Mesocricetus auratus). The hair of adult long-haired hamsters was longest at the rump and flanks (approximately 70 mm) and was also unusually long at the neck (45 to 50mm). The hair length of males was more striking than that of females. Mating experiments indicated that an autosomal recessive gene is responsible for the inheritance of long hair. An albino long-haired hamster strain was established by continuous full-sib mating from F2 hybrids, descendants of (acromelanic albino x agouti long-haired) F1 progeny, and genetic homogeneity was confirmed by DNA fingerprinting. The long-haired strain was characterised by the fact that males grew larger than females, in contrast to the other strains of hamsters.

Animals↗
PubMed1993

Prognostic significance of CT scan in malignant glioma.

In 91 malignant gliomas treated with radiation therapy, CT scan which was taken before treatment was reviewed to examine the significance as a prognostic indicator. The irradiation methods and the surgical resectability did not affect the survival. Similarly, the tumor location and the grade of the low density area (LDA) surrounding the contrast enhanced area (CEA) had no significance on the prognosis. As a result of the multi-variate analysis, the histopathologic diagnosis, the CEA size and the CEA pattern were significantly important prognostic factors. Astrocytoma grade III, a CEA diameter of under 4 cm and a homogeneous CEA were favorable indicators of the malignant gliomas. Tumors with a heterogeneous or a ring-like CEA in the diameter of more than 4 cm have the worse prognosis and should be treated extensively by radiation therapy.

Adolescent↗
PubMed1993

Glucose sensitivity of ATP-sensitive K+ channels is impaired in beta-cells of the GK rat. A new genetic model of NIDDM.

In the Goto-Kakizaki rat, a new genetic model of NIDDM, insulin response to glucose is selectively impaired. To elucidate the mechanism of this abnormality, we studied the properties of ATP-sensitive K+ channels, the inhibition of which is a key step of insulin secretion induced by fuel substrates, using the patch-clamp technique. The glucose-sensitivity of KATP channels was considerably reduced in GK rats. However, the inhibitory effects of ATP on channel activity and unitary conductance were not significantly different between control and GK rats. Thus, it appears that the impaired insulinotropic action of glucose in beta-cells of GK rats is attributable to insufficient closure of the KATP channels, probably because of deficient ATP production by impaired glucose metabolism. KATP-channel activities in both control and diabetic beta-cells were found to be equally suppressed by glyceraldehyde and 2-ketoisocaproate. These results strongly suggest that the step responsible for the metabolic dysfunction of diabetic beta-cells is located within the glycolytic pathway before glyceraldehyde-3-phosphate or in the glycerol phosphate shuttle.

Adenosine Triphosphate↗
PubMed1993

Urinary metabolites of pinacidil: I. Isolation and identification of the metabolites in rat urine.

1. The urinary metabolites of pinacidil administered orally to rats, were analysed by h.p.l.c. Seven metabolites were isolated from rat urine following fractionation on an HP-20 column and purified by t.l.c. 2. The major metabolite was pinacidil-pyridine-N-oxide (M-1). omega-Hydroxypinacidil (M-2) and dealkylpinacidil (M-3) were less abundant metabolites, and minor metabolites were the M-2-aldehyde, in which an intramolecular ring had formed (M-4), M-2-pyridine-N-oxide (M-5), carbamoyl-pinacidil (M-7) and M-7-pyridine-N-oxide (M-6). 3. Metabolic pathways of pinacidil in rats were postulated from the isolated metabolites.

Animals↗
PubMed1993

Urinary metabolites of pinacidil. II. Species difference in the metabolism of pinacidil.

1. Pinacidil was given orally to rabbit (10 mg/kg), dog (10 mg/kg), monkey (10 mg/kg) and mouse (150 mg/kg), the urinary metabolites were separated by h.p.l.c. and their structures determined by mass spectrometry. 2. Three new metabolites, namely, omega-hydroxy-pinacidil-O-glucuronide (M-8), pinacidil-pyridine-N-oxide-O-glucuronide (M-9) and pinacidil-pyridine-N-glucuronide (M-10) were isolated from rabbit urine, and one new metabolite, namely, pinacidil-pyridine-phenolic-glucuronide (M-11) was isolated from mouse urine. 3. M-9 is a unique glucuronide because the glucuronic acid is linked to the oxygen of pyridine-N-oxide. 4. In man, similar to rat, dog and mouse, pinacidil-pyridine-N-oxide (M-1) was the main urinary metabolite, with pyridine-N-oxidation being the major metabolic pathway. On the other hand, M-8 and M-9 were the most abundant metabolites in monkey and rabbit urine, respectively. Therefore, rat, dog and mouse have similar metabolism of pinacidil to man, but monkey and rabbit are significantly different in their metabolism of the drug.

Adult↗
PubMed1993

FR901459, a novel immunosuppressant isolated from Stachybotrys chartarum No. 19392. Taxonomy of the producing organism, fermentation, isolation, physico-chemical properties and biological activities.

FR901459, a novel immunosuppressant, has been isolated from the fermentation broth of Stachybotrys chartarum No. 19392. The molecular formula of FR901459 was determined as C62H111N11O13. FR901459 was found to be a member of the cyclosporin family. However, it is structurally distinct from any other cyclosporins discovered so far, in that Leu is present at position 5 instead of Val. FR901459 was capable of prolonging the survival time of skin allografts in rats with one third the potency of cyclosporin A.

Amino Acid Sequence↗
PubMed1993

[Laboratory diagnosis of left atrial thrombi in patients with mitral stenosis].

Left atrial (LA) thrombi sometimes occur in patients with mitral stenosis (MS) and may cause systemic embolization resulting in serious and fatal complications. Several clinical techniques are used to detect the presence of LA thrombi, but even echocardiography, the most widely used, has some drawbacks depending on the sizes and locations of the thrombi. This study evaluated D-dimer, fibrinopeptide A(FPA), and thrombin-antithrombin III complex (TAT) as molecular markers for diagnosing the presence of LA thrombi in 26 patients with MS who underwent cardiac surgery. Atrial fibrillation was detected in all patients. Patients with episodes of obvious thromboembolic diseases were excluded. Blood was obtained from the brachial vein before the surgery (3 +/- 1 days; mean +/- SD). The presence or absence of thrombi was confirmed at surgery in all patients. Levels of both D-dimer and TAT were significantly higher in patients with thrombi than in those without thrombi or in normal subjects. FPA levels did not differ significantly between the three groups. The levels of D-dimer and TAT correlated significantly with the weights of the LA thrombi. LA thrombi (ca > or = 2 g) were always confirmed at surgery in patients with levels of D-dimer higher than 200 ng/ml and/or levels of TAT higher than 4 ng/ml. These results indicate that D-dimer and TAT are simple and useful diagnostic markers for determining LA thrombi in patients with MS.

Antithrombin III↗