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Biomedical subjects

R Sakai

Publications and source records attributed to R Sakai.

At least 145 records · Page 8Linked to original sources
PubMed1991

Mutations of the p53 gene in lymphoid leukemia.

p53 is currently considered to be a tumor suppressor gene product, and its alterations are suggested to be involved in several human malignancies. Here we show evidence of the possible involvement of p53 gene mutations in lymphoid leukemias studied by reverse transcriptase-polymerase chain reaction, single strand conformation polymorphism analysis, and nucleotide sequencing. Fourteen patients with various leukemias were examined and two with acute lymphoblastic leukemia and one with Waldenström's macroglobulinemia were identified to have mutations in the coding region of the p53 gene. These mutations included point mutation, triplet deletion, and single nucleotide insertion. Furthermore, expression of the wild-type p53 mRNA was not detected in the samples from these three patients. In one of them, chromosome 17p was deleted, suggesting the absence of the nonmutated p53 gene, whereas in the other two patients, chromosome 17p seemed to be intact by cytogenetic analysis. Our results suggest that alterations of the p53 gene may have a role in the genesis of some leukemias.

Base Sequence↗
PubMed1991

Role of activated c-H-ras oncogene in the induction and progression of immortal liver epithelial cell lines derived from normal C3H mice.

The nature of 15 immortal mouse liver epithelial cell (MLEC) lines established from normal C3H mice was investigated specifically in terms of ras oncogene activation. Neither transforming activity nor point mutation within codon 61 of c-H-ras could be demonstrated in any of the cell lines by DNA transfection in a NIH/3T3 cell system or by the direct sequencing method after polymerase chain reaction, respectively. Acrylamide gel migration analysis of ras p21 products did not show any shift from the normal. Transplantation experiments demonstrated only 2 out of the 15 lines to be tumorigenic in nude mice. When 4 of the non-tumorigenic MLEC lines were transfected with cloned activated c-H-ras containing a point mutation within codon 61, they all became tumorigenic, the resultant neoplasms being hepatocellular carcinomas often associated with albumin mRNA expression. Our results thus indicate that ras activation is not necessary for immortalization or even for transformation of mouse liver cells in culture, and that ras activation may be an event during the progression process in mouse hepatocarcinogenesis in vivo.

Animals↗
PubMed1991

Ki-ras activation in pancreatic carcinomas of Syrian hamsters induced by N-nitrosobis(2-hydroxypropyl)amine.

Five pancreatic carcinomas induced by N-nitrosobis(2-hydroxypropyl)amine in Syrian golden hamsters were analyzed for activation of Ki-ras at codons 12 and 13, using the polymerase chain reaction and direct sequencing. The Ki-ras gene was shown to be activated in four of the five carcinomas, and the results were further confirmed by subcloning and sequencing. All the mutations involved a G-to-A transition at the second position of codon 12, which resulted in a change at the amino acid level from glycine to aspartic acid. This mutation is identical with that reported for pancreatic tumors of Syrian hamsters induced by N-nitrosobis(2-oxopropyl)amine.

Animals↗
PubMed1991

Rapid accumulation of plasma acid-stable trypsin inhibitor in experimental acute renal injury.

Acid-stable trypsin inhibitor (ASTI) activity was measured during experimental acute renal tubular dysfunction and glomerulonephritis in rats. A marked elevation of ASTI activity occurred at a very early stage of acute renal tubular damage, and the changes were observed prior to histological abnormalities or elevation of blood creatinine. No alteration in ASTI activity was observed at an early stage of experimental glomerulonephritis. The data obtained confirm that ASTI is excreted through the renal tubules and that the plasma ASTI concentration is very sensitive to renal tubular dysfunction.

Animals↗
PubMed1991

Effects of gomisin A on hepatocarcinogenesis by 3'-methyl-4-dimethylaminoazobenzene in rats.

We examined the effects of gomisin A on tumor promotion in the liver after a short-term feeding of 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) to rats, compared with the effects of phenobarbital. Male Donryu rats were fed ad libitum a diet containing 0.06% 3'-MeDAB and 0.03% or 0.01% gomisin A or water containing 0.05% phenobarbital. Gomisin A and phenobarbital did not cause any proliferative and neoplastic lesions by themselves in 40 weeks of feeding. Altered foci in the liver increased with a peak at 12 weeks after the rats were fed 3'-MeDAB. Gomisin A decreased the number of hepatic altered foci such as the clear cell and basophilic cell type foci in the early stages. Phenobarbital enhanced neoplastic alterations so that the number and size of the foci were much larger in the phenobarbital-combined group than in the 3'-MeDAB-control group. Thus, phenobarbital acted as a promoter of cells initiated by 3'-MeDAB; on the other hand, gomisin A showed a weak suppressive effect on tumor promotion.

Animals↗
PubMed1991

Complete sacral agenesis--a case report.

We report a case of a girl with complete sacral agenesis associated with arthrogrypotic-like deformity. This case demonstrates that a posterior knee release and braces following operation are effective treatment for knee-flexion contractures. Accordingly it is suggested that a supracondylar osteotomy is not required for mild or moderate recurrence of knee-flexion contractures.

Contracture↗
PubMed1991

Anticoagulant therapy in a congenital antithrombin III (ATIII)-deficient patient with chronic renal failure undergoing regular hemodialysis.

We describe a 43-year-old male patient with congenital antithrombin III deficiency requiring hemodialysis due to extension of venous thrombus from recurrent deep vein thrombosis. During dialysis with adequate heparinization, the patient often revealed clot formation in the extracorporeal circuit resulting in unexpected discontinuation of dialysis. When either a combination of antithrombin III concentrate + heparin or the newly developed synthetic antithrombin preparation, MD805, was administered during dialysis, he could be uneventfully dialyzed with either of the two regimens.

Adult↗
PubMed1990

Studies on responsiveness of hepatoma cells to catecholamines. V. Loss of adrenergic response of glycogen phosphorylase in rat ascites hepatoma AH130 cells.

The beta-adrenoceptor-cyclic adenosine monophosphate (AMP) dependent glycogenolytic cascade was examined in normal rat hepatocytes and rat ascites hepatoma AH130 cells. The cyclic AMP content in AH130 cells was half of that in normal hepatocytes, and the cyclic AMP levels in both kinds of cells were clearly increased by isoproterenol (IPN). Cyclic AMP-dependent protein kinase activity was higher in AH130 cells than in normal hepatocytes. Phosphorylase kinase activities in 10000 x g supernatant of normal hepatocytes and AH130 cells were also increased in the presence of cyclic AMP. Phosphorylase a activities in the supernatant of both kinds of cells gradually decreased during incubation with 40 mM glucose at 37 degrees C, and the enzyme activity of normal hepatocytes was completely restored by the addition of Mg2(+)-adenosine triphosphate (ATP), but in the case of the hepatoma cells the recovery was small. The decreased phosphorylase a activity in the hepatoma cells was increased by additional glycogen but did not exceed the level before the incubation. In the case of normal hepatocytes it was not affected by glycogen. This indicates that glycogen contained in the cells influences the activation of phosphorylase; the glycogen content in AH130 cells was far less than in normal hepatocytes. On the other hand, when intact cells were incubated with a high concentration of glucose, phosphorylase a activity in the homogenate of normal hepatocytes was decreased and could be restored by IPN and dibutyryl cyclic AMP, but the enzyme activity in the homogenate of AH130 cells was very low and hardly changed after the incubation and treatment with these agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[A study on LH- and FSH-RIA kits by immunoradiometric assay].

An evaluation of LH- and FSH-RIA BEAD kits based on IRMA was carried out. The results obtained with the methods characterized by the use of monoclonal antibodies, i.e., one is linked to solid phase, and another is isotopically labeled, were compared with those determined by the Daiichi LH- and FSH-kits. Intra- and inter-assay precision, recovery, linearity, and specificity of both methods were favorable without exceptions. The cross reactivity of the LH kit to 5,000 mIU/ml hCG revealed within the range of less than 3 mIU/ml. Significant correlations were observed between the results derived from conventional Daiichi LH- and FSH-kits. The results from the conventional kits exhibited 30 to 40% of those from the Daiichi kits, considered to be mainly due to the difference in standard calibrations used. Among the individuals within the normal menstrual cycle, the serum LH- and FSH-levels determined by the present kits gave a typical pattern with a peak in the preovulatory phase. On the other hand, the LH- and FSH-values of individuals in normal pregnancy revealed strikingly decreased in comparison with those of non-pregnant women.

Adult↗
PubMed1990

[Electrophysiological effects of flecainide acetate on guinea-pig left atrial cells].

Using conventional glass microelectrode technique, electrophysiological effects of flecainide acetate on guinea-pig left atrial muscle fibers were examined. Resting membrane potential was not affected by flecainide at any concentrations tested (10(-7) M-3 X 10(-5) M), although overshoot potential was significantly decreased at the concentration over 3 X 10(-6) M. Effective refractory period significantly increased at 10(-5) M. The reduction of Vmax was about 25% and 50% by 3 X 10(-6) M and 10(-5) M, respectively at 1 Hz. At 3 X 10(-6) M, Vmax decreased by about 10%, 15%, 22%, 33%, and 34% at 0.2, 0.5, 1, 2, and 3 Hz respectively. Flecainide, decreased Vmax of atrial muscle fibers in a dose and frequency dependent manner. It is suggested that flecainide might be effective in the treatment of atrial tachyarrhythmias.

Action Potentials↗
PubMed1990

[A polypoidal adenosquamous cell carcinoma of the esophagus with a pseudosarcomatous stromal reaction].

A case of a polypoidal carcinoma with a pseudosarcomatous stromal reaction is presented. Histologically, the polypoidal tumor of the lower esophagus was revealed to be an adenosquamous cell carcinoma associated with the proliferation of atypical stromal cells, osteoclastic-like giant cells, and histiocytes. Using an immunohistochemical stain, these stromal atypical cells were found to be positive for vimentin, with some cells positive for alpha 1-antichymotrypsin. However these atypical cells proved negative as epithelial markers (keratin and EMA). Thus, it was felt that such atypical stromal cells may be a reactive proliferation of the stromal cells to an adenosquamous cell carcinoma.

Adenocarcinoma↗
PubMed1989

In vivo treatment with erythroid differentiation factor (EDF/activin A) increases erythroid precursors (CFU-E and BFU-E) in mice.

The in vivo effect of human EDF on erythroid precursors (CFU-E and BFU-E) was investigated in normal and bled mice. In anemic (bled) mice, EDF treatment led to significant dose-dependent rises in the CFU-E and BFU-E levels of bone marrow. An elevation in the level of CFU-E was also seen in the spleen. In normal mice, a significant elevation in the level of bone marrow BFU-E was observed. Thus, EDF has an effect on erythropoiesis in anemic and normal mice in vivo.

Activins↗
PubMed1989

1-Oleoyl-2-acetylglycerol promotes immunoglobulin production independent of cell proliferation in human peripheral blood mononuclear cells.

1-Oleoyl-2-acetylglycerol (OAG) stimulated IgG and IgM production in a dose-dependent manner in human peripheral blood mononuclear cells (PBM) but not PBM proliferation. 12-O-Tetradecanoyl phorbol-13-acetate (TPA) did not stimulate Ig production. OAG did not stimulate an increase in IL-2 generation or IL-2 receptor expression. H-7, a protein kinase C blocker completely inhibited OAG-stimulated Ig production. The results suggest that OAG stimulation of Ig production is independent of cell proliferation; a generalized increase in T-cell activation does not appear to be necessary in the OAG stimulation of Ig production. Finally, PBMs respond differently to OAG and TPA although both are protein kinase C activators.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1989

1,25-Dihydroxyvitamin-D3 regulation of interleukin-2 and interleukin-2 receptor levels and gene expression in human T cells.

1,25-Dihydroxyvitamin-D3 (1,25-D3) is known to inhibit DNA synthesis, immunoglobulin and lymphokine production [interleukin-2 (IL-2), gamma interferon (G-IFN), and granulocyte-monocyte colony-stimulating factor (GM-CSF)] by mitogen-stimulated human peripheral blood mononuclear cells (PBMCs). Recent data suggest these inhibitory effects are mediated at the gene level through inhibition of mRNA accumulation of specific lymphokines in the activated cells. In previous studies, we have demonstrated the CD8+ T cell population was less sensitive to the anti-proliferative actions of 1,25-D3 than CD4+ T cells. The purpose of this investigation was to further assess ability of 1,25-D3 to regulate CD4+ and CD8+ T cell functions. Initial experiments showed that 1,25-D3 inhibited both IL-2 production and mRNA accumulation in mitogen-stimulated PBMC. However, IL-2 receptor (IL-2R) expression and mRNA accumulation in stimulated PBMC was not affected by 1,25-D3. Both FACS sorted CD4+ and CD8+ T cells expressed IL-2R equally upon stimulation and neither showed an inhibitory effect on this expression by 1,25-D3. Human CD4+ and CD8+ T cells showed a stimulus-specific production of IL-2. CD4+ cells stimulated with mitogen and HLA-DR positive accessory cells produced measurable levels of IL-2 that were completely inhibited by 1,25-D3. CD8+ T cells did not generate measurable amounts of IL-2 in this system. However, CD4+ and CD8+ T cells produced large amounts of IL-2 when stimulated with mitogen and a protein kinase C activator, phorbol myristate acetate (PMA). Under these circumstances, both CD4+ and CD8+ T cell IL-2 production was inhibited completely by 1,25-D3. These data suggest that IL-2R expression in PBMCs and T cell subsets is equal and unaffected by 1,25-D3 while IL-2 production in T cell subsets is stimulus-specific and completely inhibited by 1,25-D3.

Adult↗
PubMed1989

Effect of chlordane on hepatic mitochondrial respiration.

In order to clarify the cytotoxicity of chlordane, an industrial product used as an insecticide, its effect on oxidative phosphorylation in rat hepatic mitochondria was studied. The respiration rate, RCI and ADP/O ratios were inhibited by chlordane-related compounds; the degree of inhibition was in the descending order of trans-chlordane, cis-chlordane, heptachlor and heptachlorepoxide. Of the indices indicating various respiratory activities, state 3 respiration was the most sensitively inhibited by these compounds, suggesting that they inhibit energy transfer. However, electron transport was inhibited also by high concentrations of chlordane constituents. The inhibitory effect of the chlordane constituents on respiratory activity varied depending on the species of respiratory substrate, suggesting site-specificity of these compounds. The release of K+ ions paralleled the results of the respiratory activity study. Heptachlorepoxide, a metabolic product of heptachlor, had less effect on mitochondria than heptachlor.

Animals↗