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K Kojima

Publications and source records attributed to K Kojima.

At least 631 records · Page 35Linked to original sources
PubMed1985

A sensitive and specific assay for dipeptidyl-aminopeptidase II in serum and tissues by liquid chromatography-fluorometry.

A highly sensitive and specific method for the assay of dipeptidyl-aminopeptidase II (DAP II) in crude enzyme preparations such as serum and tissue homogenates has been established by using a newly synthesized fluorogenic substrate, 7-Lys-Ala-4-methylcoumarinamide. The enzymatically formed 7-amino-4-methylcoumarin was determined by high-performance liquid chromatography with fluorescence detection. The activities of other aminopeptidases in human serum and rat brain homogenates were completely inhibited by o-phenanthroline without any effect on DAP II activity to permit specific determination of DAP II. The limit of sensitivity for DAP II activity was about 300 fmol/30 min. DAP II activity was found to be increased in sera from cancer patients, in contrast to the decrease in serum DAP IV activity. DAP II activity was found to be unequally distributed in rat brain regions, and the highest activity was found in the hypothalamus.

Animals↗
PubMed1985

Intracellular calcium and adenosine 3',5'-cyclic monophosphate as mediators of potassium-induced aldosterone secretion.

We compared the action of K+ on aldosterone secretion from isolated bovine adrenal glomerulosa cells with that of ionophore A23187. Addition of either 50 nM-A23187 or 8 mM-K+ to perifused cells induces a similar initial aldosterone-secretory responses, and a similar sustained increases in Ca2+ entry. However, K+-induced secretion is more sustained than is A23187-induced secretion, even though each agonist appears to act by increasing Ca2+ entry into the cells. When [3H]inositol-labelled cells are stimulated by 8 mM-K+, a small decrease in phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] is observed. This decrease is not accompanied by an increase in inositol trisphosphate (InsP3) concentration. Also, if [3H]arachidonic acid-labelled cells are exposed to 8 mM-K+, there is no increase in [3H]diacylglycerol production. When [3H]inositol-labelled cells are stimulated by 50 nM-A23187, a small decrease in PtdIns(4,5)P2 is observed. This decrease is not accompanied by an increase in InsP3. The cyclic AMP content of K+-treated cells was approximately twice that in A23187-treated cells. If cells are perifused simultaneously with 50 nM-forskolin and 50 nM-A23187, the initial aldosterone-secretory response is similar to that induced by A23187 alone, and the response is sustained rather than transient, and is similar to that seen during perifusion of cells with 8 mM-K+. This dose of forskolin (50 nM) causes an elevation of cyclic AMP concentration in A23187-treated cells, to a value similar to that in K+-treated cells. These results indicate that, in K+-treated cells, a rise in cyclic AMP content serves as a positive sensitivity modulator of the Ca2+ message, and plays a key role in mediating the sustained aldosterone-secretory response.

Adrenal Glands↗
PubMed1985

Collagenase-like peptidase activity in serum from patients with rheumatoid arthritis.

The activities of collagenase-like peptidase, estimated by using (succinyl-Gly-Pro-Leu-Gly-Pro-Leu-Gly-Pro)-4-methylcoumaryl-7-amide as substrate, and of dipeptidyl-aminopeptidase IV were decreased in the sera from patients with rheumatoid arthritis. Both enzymes bring about the degradation of peptides derived from collagen. A significant positive correlation was observed between the activities of the two serum peptidases.

Arthritis, Rheumatoid↗
PubMed1985

Role of calcium and cAMP in the action of adrenocorticotropin on aldosterone secretion.

When the dose-response curve of adrenocorticotropin (ACTH)-induced aldosterone secretion is compared to that of ACTH-induced intracellular cAMP, the ED50 for intracellular cAMP is more than 10 times as high as that for aldosterone production. In contrast, the dose-response curve of forskolin-induced aldosterone secretion correlates well with that for forskolin-induced intracellular cAMP. ACTH, but not forskolin, increases calcium influx into glomerulosa cells without inducing the mobilization of calcium from an intracellular pool. The effect of ACTH on calcium influx is dose-dependent and ED50 is 3.5 X 10(-11) M. In a perifusion system, the effect of 1 nM ACTH on aldosterone secretion is much greater than that of 1 microM forskolin, even though these two stimulators induce identical increases in the intracellular cAMP. Perifusion with combined A23187 (50 nM) and forskolin (1 microM) stimulates aldosterone secretion to a value comparable to that induced by 1 nM ACTH. Likewise, BAY K 8644 (1 nM), which induces a comparable increase in calcium influx, potentiates the effect of 1 microM forskolin. When the intracellular [Ca2+] is fixed at either 100 or 300 nM, forskolin-stimulated intracellular cAMP content is identical, but ACTH-stimulated intracellular cAMP content at 100 nM [Ca2+]i is 60% of that at 300 nM [Ca2+]i. Both the ACTH- and forskolin-induced aldosterone secretion rate is higher at 300 nM than at 100 nM [Ca2+]i. These results indicate that ACTH stimulates calcium influx, that calcium potentiates ACTH-induced but not forskolin-induced cAMP generation, and that Ca2+ and cAMP act as synarchic messengers in ACTH-mediated aldosterone secretion.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

[Establishment of anti-thyroglobulin antibody-producing cell line by EB virus transformation].

We established an anti-thyroglobulin antibody-producing cell line using the peripheral lymphocytes from a patient with chronic thyroiditis. The method was based on preselection by "panning", transformation by EB virus and twice clonings by "limiting dilution". The cells of the cloned cell line (Yo3CTX10) had neither E-receptor nor IgG X Fc-receptor but had C3-receptor as shown by rosetting. We could not detect surface immunoglobulin, but we could detect cytoplasmic immunoglobulin (IgG lambda) with FITC-stainings. This cell line has continuously secreted anti-thyroglobulin antibody for 8 months, which was IgG lambda as shown by immunoelectrophoresis and solid phase radioimmunoassay. The pattern obtained using the purified antibody showed two sharp bands (H, L-chains) in SDS polyacrylamide gel electrophoresis, but it showed six sharp bands in isoelectric focusing electrophoresis. Thus we could establish an oligoclonal cell line producing IgG lambda anti-thyroglobulin antibody.

Antibody-Producing Cells↗
PubMed1985

Aromatic L-amino acid decarboxylase activities in human lung tissues: comparison between normal lung and lung carcinomas.

We measured the activity of aromatic L-amino acid decarboxylase with L-dihydroxyphenylalanine as a substrate (DOPA decarboxylase) in normal lung tissues and lung tumors obtained fresh at surgery. The activity in control human lung tissues was low and variable: 3.50 +/- 0.42 pmole/min/mg protein (n = 56, mean +/- SE, range 0.01-15), indicating the wide individual variations. Most of small cell carcinoma specimens showed very high activity, as compared with both control lung tissues and with other types of non-SCC lung cancers. Similar results were also obtained in the athymic mice heterotransplants of SCC. High activity was also observed using 5-L-hydroxytryptophan as a substrate (5-HTP decarboxylase) in nine SCC samples. Serotonin was not detected in any control lung tissues, but was detected in all the nine SCC samples, but dopamine was detected only in three out of nine SCC samples.

Animals↗
PubMed1985

Expression of meta-vinculin associated with differentiation of chicken embryonal muscle cells.

We confirmed the existence of meta-vinculin, which cross-reacts immunologically with vinculin and has a slightly higher molecular weight than the latter. The immunological cross-reactivity between meta-vinculin and vinculin was confirmed with monoclonal antibodies against vinculin. Furthermore, we found that this protein is present only in either smooth or striated muscle, but is absent in non-muscular tissues and that the expression of this protein is associated with a differentiation of muscle cells either in vivo or in vitro. Microinjection experiments of fluorescently labelled vinculin and/or meta-vinculin into the cytoplasm of cultured myotubes suggested that meta-vinculin may be localized at sites similar to vinculin in muscle cells.

Animals↗
PubMed1985

Lipid composition of the plasma membrane isolated from hyperplastic nodules of rat liver.

Hyperplastic nodules and hepatomas were induced in livers of rats fed a diet containing 0.05% N-2-fluorenylacetamide (2-FAA). The lipid contents, and phospholipid and fatty acid compositions were analyzed in plasma membranes (PM's) isolated from these tissues and normal rat liver, and the following trends were observed. The molar ratio of cholesterol to phospholipid-phosphorus (phospholipid-P) increased in the order: hepatoma less than normal liver less than hyperplastic nodules. The molar percentage of plasmalogen to phospholipid-P decreased in the order: hepatoma = hyperplastic nodules greater than normal liver. The percentages of choline phosphoglycerides (sum of phosphatidylcholine and lysophosphatidylcholine) and ethanolamine phosphoglycerides (sum of phosphatidylethanolamine and lysophosphatidylethanolamine) both decreased in the order: hepatoma greater than hyperplastic nodules greater than normal liver. On the other hand, the percentages of sphingomyelin and phosphatidylserine both increased in the order: hepatoma less than hyperplastic nodules less than normal liver. As regards fatty acid composition, the percentages of both 18:1 and 18:2 decreased in the order: hepatoma greater than hyperplastic nodules greater than normal liver. Those of 18:0 and 20:4 increased in the order: hepatoma less than hyperplastic nodules less than normal liver. These results suggested that the lipid bilayer in PM of hyperplastic nodules has characteristics roughly intermediate between those of hepatoma and liver PM's, although the molar ratio of cholesterol to phospholipid-P in hyperplastic nodules PM was not intermediate.

Animals↗
PubMed1985

Thermophilic microspheres of peptide-like polymers and silicates formed at 250 degrees C.

We examined the possibility of chemical evolution in superheated hydrothermal environments and found the formation of microspheres at 250 degrees C and above from a mixture of glycine, alanine, valine, and aspartic acid. The microspheres did not form at lower temperatures and consisted of silicates and peptide-like polymers that contained imide bonds and amino acid residues having an abundance of valine. The results show the possibility of thermophilic cellular structures, which might be adopted by the extremely thermophilic organisms, if they exist, reported by Baross and Deming.

Amino Acids↗
PubMed1985

Effects of ANG II and K+ on Ca efflux and aldosterone production in adrenal glomerulosa cells.

A comparison was made of the effects of angiotensin II (ANG II) and K+ on aldosterone secretion and calcium efflux from porcine adrenal glomerulosa cells. In the presence of 1.25 mM Ca2+ in the perifusion medium, both 1 x 10(-9) M ANG II and 12 mM K+ caused a 3-fold increase in rate of aldosterone secretion. ANG II caused a 3.5-fold increase in the fractional efflux ratios of radiocalcium from cells prelabeled with 45Ca, but K+ caused only a 1.5-fold increase. When the perifusate contained no Ca2+ or the Ca2+ was replaced by 0.6 mM Sr2+, the effects of K+ on both 45Ca efflux and aldosterone production were abolished. On the other hand, ANG II still caused approximately the same increase in the fractional efflux ratio of radiocalcium and 25-50% of the normal increase in aldosterone production rate. When the perifusate contained 1.25 mM calcium and 25 microM dantrolene, K+ produced the same 1.5-fold increase in calcium efflux and the same maximal rate of aldosterone production as seen in the absence of dantrolene. In contrast, dantrolene greatly inhibited ANG II-induced increase in the fractional efflux ratio of calcium, 1.5-fold compared with 3.5-fold in the absence of dantrolene. Likewise, dantrolene delayed the onset of the ANG II-induced increase in aldosterone secretion and reduced the maximal rate of secretion to 50%. Cells incubated with both dantrolene and media containing no Ca2+ or containing Sr2+ in place of Ca2+ showed no response to ANG II either in terms of calcium efflux or aldosterone production.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1985

Possible role of phospholipase A2 action and arachidonic acid metabolism in angiotensin II-mediated aldosterone secretion.

When [3H]arachidonic acid-labeled calf adrenal glomerulosa cells are stimulated by angiotensin II (AII), free [3H]arachidonic acid is released. AII treatment significantly decreases radioactivity in phosphatidylinositol but not in other phospholipids. Inhibitors of phospholipase A2 (PL-A2) activity, quinacrine and p-bromophenacyl bromide, inhibit AII-stimulated aldosterone secretion from glomerulosa cells in a dose-dependent manner. The effect of these inhibitors is irreversible when used at high concentration, but not when employed at lower concentration. Exogenous PL-A2 as well as arachidonic acid stimulates both radiocalcium efflux and aldosterone secretion. Unlike AII, stimulation of aldosterone secretion by PL-A2 is only transient. Radiocalcium efflux induced by PL-A2 is greater than that induced by AII and is not inhibited by either nitrendipine or dantrolene. Pretreatment with PL-A2 abolishes the radiocalcium efflux response to subsequent AII, whereas AII pretreatment does not abolish the subsequent PL-A2-mediated radiocalcium efflux response. The aldosterone secretory response to AII is not affected by 0.3 microM indomethacin but is inhibited by either of three compounds which inhibit lipoxygenase activity; 5,8,11,14-eicosatetraynoic acid, BW755c, or caffeic acid. In a static incubation system, AII-stimulated aldosterone secretion is inhibited 40-50% by any of these lipoxygenase inhibitors. In a perifusion system, BW755c partially inhibits only the sustained phase of AII-stimulated aldosterone secretion. However, BW755c has no effect on the secretion of aldosterone in response to combined A23187 plus 12-O-tetradecanoyl-phorbol-13-acetate. These results suggest that PL-A2 action is not obligatory in AII-induced aldosterone secretion and that lipoxygenase, but not cyclooxygenase, products of arachidonic acid metabolism may play a role in AII action as positive feed forward mediators.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1985

No elevated cell surface charge at mitosis in X-ray-irradiated mammalian cells.

Rounded mitotic cells showed 30% enhanced electrophoretic mobility (EPM) when compared to spindle-formed interphase cells. This increase in EPM that was not present in interphase cells that had been rounded chemically by EDTA is considered to reflect a structural change in the cell membrane during mitosis. X-ray irradiation induced a dose-dependent EPM decrease in both interphase and mitotic cells during a 4-hour period. During the next 20 h of incubation, EPM recovery took place in cells irradiated with 250R, but not in cells exposed to 1000R. EPM was enhanced during mitosis in cells irradiated with low doses, but was absent in cells irradiated with 1000R. The ratio of colony-forming cells and of electrophoretically recovered mitotic cells after 24 h of exposure showed a good statistical correlation. These results indicate that unrepaired membrane damage contributes to mitotic cell death after irradiation.

Animals↗
PubMed1985

Pharmacokinetics of spironolactone and potassium canrenoate in humans.

Plasma concentrations and urinary excretion of canrenone (III), canrenoic acid (IV) and canrenoic acid glucuronide (V) were determined by means of high performance liquid chromatography (HPLC) and fluorometry after oral administration of spironolactone (I) and potassium canrenoate (II) to human subjects. Comparison of both assays for III in plasma as well as in urine after administration of I showed marked differences. Plasma concentrations of III were significantly higher after administration of II than I, Cmax and AUC from II being 3--5 times larger than those from I by means of HPLC assay, while the fluorometrically determined values for III in plasma after administration of I and II did not differ as much from each other. On the other hand, in contrast to plasma, the amount of III excreted in urine after administration of I was much larger than that after II, i.e. 3--4 times greater by means of HPLC and over 10 times greater by means of fluorometry. These results strongly suggest that precursors of III are formed which have a higher renal clearance than that for III alone after oral administration of I. Considering the relative biological potency ratio of I and II, it is presumed that their pharmacological activities may relate to the urinary excretion of III. Plasma concentrations of IV were definitely higher after administration of II compared to those after I. Canrenoic acid (IV) was excreted mainly as glucuronide (V) in urine.

Adult↗
PubMed1985

[Receptor macroautoradiography of 3H-spiroperidol binding in the rat brain].

The kinetic and pharmacological characteristics of 3H-spiroperidol binding sites were studied in slide mounted sections of rat forebrain, and optical binding conditions were defined. Using the receptor macroautoradiographic techniques with tritium-sensitive LKB sheet film, the distribution of dopamine (D2) receptor was determined in slices including striatum of rat brain. The autoradiograms were analyzed using Video Digitizer System combined with video camera and minicomputer, and the subtraction images were obtained. These studies suggest that this quantitative receptor macroautoradiography might be useful in the explanation of etiology in the field of neuro-psychiatric diseases and the fundamental studies of positron emission computed tomography, since this method has several advantages over in vivo autoradiography and in vitro receptor assay.

Animals↗
PubMed1985

[Treatment of hepatocellular carcinoma with esophageal varices].

This report describes 53 patients with hepatocellular carcinoma (HCC) complicated with esophageal varices. Esophageal varices were due to cirrhosis of the liver in all cases. Hepatic resection and blocking operations such as Sugiura procedure, transabdominal esophageal transection or Hassab's operation were performed for the treatment of HCC and esophageal varices in 6 cases with satisfactory results. Non-operative treatments such as TAE or arterial infusion chemotherapy for HCC and blocking operations for esophageal varices were performed in 17 cases. Late deaths were recognized in 10 cases. Causes of late deaths were carcinoma of the liver in 7 cases and ruptured varices in only 1 case. In 13 cases with severe hepatic failure, only endoscopic sclerotherapy was performed for the treatment of esophageal varices. However 8 cases of 13 had rebleeding from esophageal varices and died after sclerotherapy. We concluded that effective treatments for HCC complicated with esophageal varices were to perform both the hepatic resection and the blocking operation and these treatments prolong the long-term survival of patients with HCC with esophageal varices.

Aged↗
PubMed1985

Effects of aldose reductase inhibitor on retinal microangiopathy in streptozotocin-diabetic rats.

Wistar strain rats were made diabetic by injection of streptozotocin and divided into three groups fed on different diets: conventional solid foods, a fructose-rich diet and a fructose-rich diet mixed with ONO 2235, an aldose reductase inhibitor. The retinas of these rats were examined in flat mount preparations after trypsinization. Microvascular changes such as capillary tortuosity, microaneurysms, pericyte loss, that are typical of diabetic retinal microangiopathy, were seen most frequently in the rats fed on the fructose-rich diet. The rats fed on the fructose-rich diet with ONO 2235 showed much less vascular change than the diabetic rats fed on the conventional food. Electron microscopy of the retina revealed localized thickening of the basement membrane of the retinal capillaries, and this was most frequent in the fructose-fed rats. However, in rats fed on fructose with ONO 2235 the changes of the basement membrane were slight. It was concluded that the aldose reductase inhibitor, ONO 2235, prevented development of diabetic microangiopathy, probably by suppressing the enzymatic activation of aldose reductase in the retina.

Aldehyde Reductase↗