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Biomedical subjects

N Nishimura

Publications and source records attributed to N Nishimura.

At least 163 records · Page 9Linked to original sources

Inhibition of DNA synthesis by protein kinase C-activating phorbol esters in NIH/3T3 cells.

Fibroblast growth factor (FGF) plus insulin induced DNA synthesis in and proliferation of NIH/3T3 cells. The protein kinase C-activating phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), inhibited both the DNA synthesis and cell proliferation induced by FGF plus insulin. The concentration of TPA required for 50% inhibition of the DNA synthesis was about 5 nM. Phorbol-12,13-dibutyrate, another protein kinase C-activating phorbol ester, also inhibited the DNA synthesis but 4 alpha-phorbol-12,13-didecanoate, known to be inactive for this enzyme, was ineffective. DNA synthesis started at about 12 h after the addition of FGF plus insulin. The inhibitory action of TPA on the DNA synthesis was observed when it was added within 12 h after the addition of FGF plus insulin. These results suggest that phorbol esters exhibit an antiproliferative action through protein kinase C activation in NIH/3T3 cells, and that this action of phorbol esters is due to inhibition of the progression from the late G1 to the S phase of the cell cycle.

Animals

General pharmacology of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazole difumarate. 2nd communication: Effects on the circulation and the other systems.

Effects of 1-(2-ethoxyethyl)-2(4-methyl-1-homopiperazinyl)benzimidazole difumarate (KB-2413) on the circulation and the other systems were compared with those of ketotifen and chlorpheniramine. 1. Among the effects on the circulation and the respiratory system, KB-2413 as well as ketotifen and chlorpheniramine transiently inhibited respiration at 3 mg/kg i.v. and slightly decreased blood pressure in dogs. KB-2413 slightly decreased heart rate in dogs, but ketotifen slightly increased it. 2. KB-2413 at 100 mg/kg p.o. slightly decreased the volume of gastric juice in rats and dose-dependently increased biliary secretion in rats in the dose range of 10-100 mg/kg i.d. On the other hand, ketotifen and chlorpheniramine decreased biliary secretion. 3. KB-2413 inhibited the spontaneous movements of various isolated smooth muscles at a high concentration of 10(-4) g/ml. 4. The autonomic system in cats and the motor nervous system in rats were not influenced by KB-2413 at 3 mg/kg i.v. 5. The blood clotting system, blood sugar level, urine volume and urinary electrolytes in rats were not affected by KB-2413 in the dose range of 10-100 mg/kg p.o. 6. KB-2413 inhibited carrageenin-induced rat paw edema at 100 mg/kg p.o. In conclusion, KB-2413 showed a less potent effect on the circulation and the other systems than ketotifen and chlorpheniramine, and no results suggested serious side effects of KB-2413.

Animals

The mechanism of cadmium-induced lysozyme enhancement in rabbit kidney.

The effect of cadmium on the renal lysozyme level was examined by injecting male albino rabbits subcutaneously with 1 mg cadmium/kg body weight three times a week for 1 or 3 months. The lysozyme level in the renal brush border membrane of the cadmium-treated animals was elevated ten-fold. The lysozyme activity in the liver and small intestine tissue homogenates of rabbits was elevated by a 1-month treatment with cadmium, markedly elevated in the kidney, but markedly reduced in the spleen and lungs. Exposure to cadmium for 3 months produced an essentially similar effect on the enzyme level in the tissue, except for the lungs in which the lysozyme level returned to the preinjection level. This marked increase in the lysozyme level in the kidney of cadmium-treated rabbits was confirmed by an indirect immunofluorescent antibody technique. In control animals, intracellular distribution of the enzyme was selectively distributed to only a small number of proximal tubules, with none distributed in the medulla or glomerulus. However, after expose to cadmium, the renal tubules showed strongly positive lysozyme staining. In addition to an increase in intensity of the specific fluorescence, this enzyme was widely distributed not only in the proximal convoluted portion, but also in the straight portion of the proximal tubules, which essentially showed no enzyme activity under normal conditions. The enzyme in these cells was evenly distributed throughout the cytoplasm. The plasma lysozyme level increased immediately after the administration of cadmium, and detectable amounts of the enzyme began to appear in urine from the 3rd week after the first injection, with a 1-week lag after the maximum level of lysozyme in the plasma. This high level of plasma lysozyme, varied two-to four-fold over the control, and lysozymuria continued throughout the experiment. The concentration of cadmium in the renal cortex was 141 micrograms/g wet tissue at 1 month, and 208 micrograms at 3 months. In conclusion, the cadmium-induced enhancement of the lysozyme level in the renal cortex may be due primarily to the elevation of the lysozyme level in plasma by cadmium. The enzymatic high net positive charge, characteristic of lysozyme, may contribute greatly to this mechanism. In addition, the excretion of a large amount of lysozyme into the urine observed in a later stage may be due to the concomitant occurrence of leakage from the destroyed tubular cells and reduced tubular reabsorption of filtered enzyme, whereas lysozymuria at an early stage may be solely due to excess amounts of plasma lysozyme.

Animals

Increased production of aspartase in Escherichia coli K-12 by use of stabilized aspA recombinant plasmid.

Recombinant plasmid pYT471, which consists of the aspartase gene (aspA) and the multicopy vector pBR322, was lost from cells of Escherichia coli K-12 at high frequencies in medium in which aspartase was abundantly formed due to release from catabolite repression. This plasmid loss was not completely prevented by the selective pressure of antibiotic addition. To increase the stability of the aspA plasmid, pNK101 (pBR322::aspA-par) was constructed by using the partition locus (par) derived from the low-copy vector pSC101. In E. coli K-12 cells, pNK101 was lost at a frequency as low as 0.4% per cell generation in nonselective medium, whereas pYT471 was lost at a frequency as high as 8.5%. Cells harboring this stable plasmid produced ca. 30-fold more aspartase than did cells harboring the unstable plasmid after 30 cell generations. Thus, we could increase aspartase production by stabilizing the aspA recombinant plasmid.

Ammonia-Lyases

[Anti-allergic effects of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazole fumarate (KB-2413)].

The effects of KB-2413 on four types of allergic reactions classified by Coombs and Gell were investigated. KB-2413 inhibited homologous passive cutaneous anaphylaxis and passive anaphylactic bronchoconstriction in guinea pigs mediated by IgE-like antibody, and ED50 values were 0.0017 mg/kg, p.o., and 0.022 mg/kg, p.o., respectively. KB-2413 also inhibited IgG-mediated anaphylactic bronchoconstriction in guinea pigs actively sensitized with egg albumin. Both complement-dependent immune hemolysis and complement-independent hypotonic hemolysis were inhibited by KB-2413 in a concentration-dependent manner. KB-2413 had no effect on the Forssman systemic reaction. The passive Arthus reaction in guinea pigs sensitized with anti-egg albumin rabbit serum was unaffected by KB-2413. However, the early stage of the active Arthus reaction in rabbits sensitized with egg albumin was inhibited. KB-2413 had an inhibitory effect on the efferent phase of delayed-type hypersensitivity induced by picryl chloride (PC-DTH) in mice. On the other hand, the afferent phase of PC-DTH in mice was unaffected. These results suggest that KB-2413 strongly suppresses type I allergic reactions, and it slightly suppresses type II, III and IV allergic reactions.

Animals

Inhibition of chemical mediator release from human leukocytes and lung in vitro by a novel antiallergic agent, KB-2413.

The effect of KB-2413 on IgE-mediated histamine and LTC4 release from leukocytes obtained from asthmatic patients who were sensitive to mites, and from human lung tissues passively sensitized with IgE myeloma serum was studied. KB-2413 inhibited the IgE-mediated chemical mediator release concentration dependently at a range of 10(-4) to 3 x 10(-3) M. KB-2413 did not enhance histamine release at a higher concentration unlike ketotifen. These findings suggest that the inhibitory effect of KB-2413 on the release of chemical mediators contributes to the anti-allergic activity of this compound.

Benzimidazoles

[Histological study of muscle in the experimental hypophosphatemic rat].

Using hypophosphatemic rat maintained on a low phosphate diet as a model for human rickets and osteomalacia, the skeletal muscle was histochemically and electron microscopically examined, in comparison with specimens obtained from normal control animals. In muscles obtained from hypophosphatemic animals, the type 2 muscle fibers were increased in number, and the type 1 fibers were atrophic. Electron microscopic studies revealed some atypical structures of mitochondria with fusion of cristae in the muscle spindles of intrafusal muscle fibers. The presynapse, the secondary cleft, and the endplate plasm were significantly atrophic in the extrafusal neuromuscular junction. Mitochondrial vacuolization was observed in the presynapse. These results indicated the presence of immature muscle fibers, dysfunction of the energy metabolism of the mitochondria and neurogenic disorders in hypophosphatemic muscles.

Animals

[Usefulness of caerulein in suppressing post-TAE complications of the gallbladder].

While transcatheter hepatic arterial embolization (TAE) has been extensively performed as a form of treatment for nonresectable malignant hepatic tumors, complications, such as abdominal pain, fever or leukocytosis due to gallbladder infarction by embolic materials frequently occur and have not yet been overcome. We devised a new procedure for reducing the incidence of gallbladder infarction by administering caerulein prior to TAE. Between 1984 and 1986, 63 patients with hepatocellular carcinoma were treated by TAE with the use of Gelfoam. These patients were divided into 3 groups. Fourteen patients underwent TAE in which the tip of the catheter was placed in the right hepatic artery distal to the origin of the cystic artery (group A). In the other patients the tip of the catheter was placed proximal to the origin of the cystic artery; 40 patients were not treated by caerulein (group B); 9 patients were administered caerulein 20 micrograms intramuscularly 15 to 30 minutes prior to TAE. The incidence of complications after TAE, such as abdominal pain, fever over 38 degrees C, leukocytosis and ultrasonographical abnormalities of the gallbladder was compared in these 3 groups. The results showed that in group C (TAE after administration of caerulein), the incidence of complications was significantly decreased compared with group B(TAE without caerulein). The authors suggest that post-TAE infarction of the gallbladder is effectively diminished by contracting it with caerulein.

Carcinoma, Hepatocellular

Urinary trehalase as an early indicator of cadmium-induced renal tubular damage in rabbit.

The significance of urinary trehalase as a possible early indicator of renal disorder was examined using Cd-treated rabbits, which received 1 mg/kg Cd thrice weekly for 3 months subcutaneously. The results showed that urinary trehalase increased significantly from 1 week after treatment, earlier than LAP, ALP, proteinuria and glucosuria, with no changes in plasma trehalase level. A marked decrease in trehalase activity in renal brush border membranes prepared from Cd-treated rabbits was observed. It was also confirmed by immunohistological techniques that Cd treatment resulted in a marked decrease in specific fluorescence compared with controls. Ouchterlony double diffusion analysis demonstrated that urine and renal brush border extracts formed precipitation lines against anti-renal trehalase IgG, indicating that urinary trehalase and renal trehalase had the same antigenicity. Therefore, the facts presented here would suggest that urinary trehalase originated from the renal brush border, indicating its superiority as a diagnostic tool over other indicative indicating its superiority as a diagnostic tool over other indicative enzymes like LAP and ALP in detecting injury to renal proximal tubular cells in the early stage.

Animals

Spontaneous renal subcapsular hematoma in a patient undergoing hemodialysis.

We describe a patient on hemodialysis in whom a spontaneous renal subcapsular hematoma developed. The diagnosis was confirmed by computerized tomography and angiography, and the patient was treated conservatively. We recommend conservative management in such cases based on radiological findings that rule out underlying pathological changes.

Adult