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Biomedical subjects

K Kubo

Publications and source records attributed to K Kubo.

At least 541 records · Page 30Linked to original sources
PubMed1990

Existence of a low-affinity ATP-binding site in the unphosphorylated Ca2(+)-ATPase of sarcoplasmic reticulum vesicles: evidence from binding of 2',3'-O-(2,4,6-trinitrocyclohexadienylidene)-[3H]AMP and -[3H]ATP.

ATP-binding sites in the unphosphorylated Ca2(+)-ATPase of sarcoplasmic reticulum vesicles were titrated with 2',3'-O-(2,4,6-trinitrocyclohexadienylidene)-[3H]AMP (TNP-AMP) or -[3H]ATP (TNP-ATP) in the absence of Ca2+ at pH 7.0 and 0 degrees C by using a centrifugation procedure. In some measurements, the bound TNP-nucleotides were chased with ATP. The data were analyzed by best-fit computer programs as well as by Scatchard plots. The results showed the existence of 1 mol of TNP-AMP binding sites with high affinity (Kd = 7.62 nM) per mole of phosphorylatable sites. The affinity of these sites for ATP (Kd = 10.1 microM) agreed with that of catalytic sites for ATP in the absence of Ca2+. The results further showed the existence of 2 mol of TNP-ATP binding sites with uniform affinity (Kd = 156 nM) per mole of phosphorylatable sites. Half of the bound TNP-ATP was fully chased by low concentrations of ATP. The affinity of this class of the sites for ATP (Kd = 8.9 microM) again agreed with that of catalytic sites for ATP. The other half of the bound TNP-ATP was fully chased only by much higher concentrations of ATP. Thus, the affinity of this class of the sites for ATP (Kd = 791 microM) was much lower than that of catalytic sites for ATP. Similar measurements were performed with sarcoplasmic reticulum vesicles pretreated by N-(iodoacetyl)-N'-(5-sulfo-1-naphthyl)ethylenediamine. Although the affinities for TNP-ATP and for ATP were appreciably altered by this pretreatment, the results were essentially the same as those obtained with native vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Monophosphate↗
PubMed1990

[Treatment results of maxillary sinus carcinoma. A retrospective study].

The treatment results of a total of 617 cases with maxillary sinus carcinoma mainly treated by radiotherapy at the Department of Radiology, Osaka University Hospital between 1967 and 1983 were reviewed. The overall actuarial 5-year survival rate was 36.2%. The cases were divided into 3 groups by period of the treatment modalities corresponding each 5-year survival rate of 24.1% on 217 patients for 1967 to 1971, 40.0% on 155 patients for 1972 to 1975, and 44.6% on 245 patients for 1976 to 1983. The treatment results have improved in 5-year survival rate as modifying treatment modality. The actuarial 5-year local control rate was 60.0% for T1 on 9 patients, 43.1% for T2 on 181 patients, 31.7% for T3 on 246 patients, and 19.2% for T4 on 181 patients, respectively. For more detailed analysis of the results, the cases were divided into 4 groups according to the initial treatment; the group 1 was treated by radiotherapy alone (RT), the group 2 by radiotherapy combined with intra-arterial infusion of 5-fluorouracil (RT + 5-FU), the group 3 by radiotherapy combined with surgical removal of the tumor mass through curettage under the general anesthesia (RT + OP) and the group 4 by multidisciplinary procedure combined with radiotherapy, 5-FU regional infusion and curettage (RT + 5-FU + OP). In the T2 cases, the 5-year actuarial local control rate was 25.5% for RT on 51 patients, 45.0% for RT + 5-FU on 55 patients, 58.2% for RT + OP on 23 patients and 51.5% for RT + 5-FU + OP on 52 patients, respectively. In the T3 cases, the rate was 13.2% for RT on 85 patients, 33.6% for RT + 5-FU on 78 patients, 52.3% for RT + OP on 31 patients and 45.9% for RT + 5-FU + OP on 52 patients, respectively. In the T4 cases, the rate was 7.6% for RT on 77 patients, 27.2% for RT + 5-FU on 52 patients, 17.8% for RT + OP on 20 patients and 31.5% for RT + 5-FU + OP on 32 patients, respectively. The combination therapy with 5-FU regional infusion and/or curettage had successfully improved the local control rate. On the T2 and T3 cases of RT + OP, an additive effect of 5-FU infusion was not significant, and also on the T4 cases of RT + 5-FU, any usefulness of curettage could not be found.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

A new type of exo-beta-glucuronidase acting only on non-sulfated glycosaminoglycans.

Using chondroitin as a substrate, a new type of exo-beta-glucuronidase (EC 3.2.1.31) from rabbit liver was purified using a combination of ammonium sulfate fractionation, DEAE-cellulose chromatography, gel filtration on Sephracryl S-300, affinity chromatography through heparin-Sepharose CL-6B, and preparative polyacrylamide gel electrophoresis. This enzyme acts only on non-sulfated glycosaminoglycans and their oligosaccharides and was shown to be quite different from exo-beta-glucuronidase, which does act on p-nitro-phenyl-beta-D-glucuronide with regard to the following properties. 1) Neither sulfated glycosaminoglycanoligosaccharides nor p-nitrophenyl-beta-D-glucuronide were substrates for the enzyme. 2) The molecular weight was found to be about 130,000 by gel filtration, compared with a molecular weight of 280,000-300,000 for beta-glucuronidase, which acts on p-nitro-phenyl-beta-D-glucuronide. 3) The enzyme showed maximal activity at pH 5.0, compared with an optimum pH of 4.5 for beta-glucuronidase, which acts on p-nitro-phenyl-beta-D-glucuronide. 4) The enzyme showed maximal activity in 0.075 M NaCl but no activity above 0.25 M NaCl. 5) The enzyme was inhibited strongly by compounds bearing a sulfate group. 6) The enzyme did not react with an antibody against beta-glucuronidase acting on p-nitrophenyl-D-glucuronide. It is suggested that the enzyme may be involved in the catabolism of glycosaminoglycans, acting especially on chondroitin after the desulfation reaction and/or hyaluronic acid, but showing little involvement with the detoxification system.

Ammonium Sulfate↗
PubMed1990

Recombinant human erythropoietin corrects anemia of blood loss: a study in the dog.

In order to evaluate the possibility of using recombinant human erythropoietin (rhEpo) for the prevention and correction of anemia due to blood loss and as an adjuvant for autologous blood transfusion, its preventive and therapeutic effects were evaluated in beagles in which anemia was induced by repeated phlebotomies. Two hundred U/kg of rhEpo were administered i.v. four or nine times every two weeks for six weeks. Phlebotomies (25 ml/kg of body weight) were conducted three times at two-week intervals. rhEpo was found to successfully prevent and correct anemia caused by the phlebotomies. Concurrent administration of iron increased efficacy. The findings obtained in the present study suggest that rhEpo is useful both for the treatment of anemia caused by blood loss due to surgery and as an adjuvant therapy for pre-deposit autologous blood transfusion.

Anemia↗
PubMed1990

Effect of cyclic guanosine monophosphate on hypoxic and angiotensin-II-induced pulmonary vasoconstriction.

We examined, in isolated blood perfused rat lungs, the effect of the cell permeable 8-bromo derivative of cGMP on pulmonary vasoconstriction induced by either alveolar hypoxia or angiotensin II. 8-Bromo cGMP dose-dependently reduced both hypoxia-(IC50 = 2.2 X 10(-5) M) and angiotensin-II-induced pulmonary vasoconstriction (IC50 = 5.0 X 10(-5) M). This effect of 8-bromo cGMP on pulmonary vasoconstriction was not affected by cyclooxygenase blockade. M & B 22948 (0.1 mM), an inhibitor of cGMP-phosphodiesterase, reduced synergistically with 8-bromo cGMP the hypoxia or angiotensin-II-induced vasoconstriction. The cGMP-phosphodiesterase inhibitor M & B 22948, by itself, selectively reduced hypoxia-induced vasoconstriction, suggesting a modulating effect of endogenous cGMP during hypoxic vasoconstriction.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1990

Signal transduction mechanisms of Ia induction in B cells by interleukin 4 and immunoglobulin receptors.

Molecular mechanisms of signal transduction through receptors for interleukin 4 (IL-4) are still largely unknown. To elucidate the second messenger(s) of IL-4 action in mature B cells, we performed blocking experiments with inhibitors of various aspects of cellular responses, using Ia-inducing activity of IL-4 as a readout system. In the event, only agents that are shown to inhibit calcium ion (Ca2+) release from intracellular stores, such as 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8) and ryanodine, could block the IL-4 action in a dose-dependent fashion. These results suggest that the process leading to the final expression of IL-4 action may be mediated, at some point, by the release of Ca2+ from intracellular stores. In the parallel experiments with antiimmunoglobulin (Ig) antibody, we found that amiloride, an inhibitor of Na+/H+ pump, blocks the Ia induction by anti-IgM antibody. Thus the Na+/H+ exchange system activated by anti-Ig antibody may be present in mature B cells.

Animals↗
PubMed1990

Modification of noradrenergic innervation in the cerebellum of mutant rats with Purkinje cell degeneration (jaundiced Gunn rats).

In heterozygous (Jj) and homozygous Gunn rats (jj), cerebellar noradrenergic innervation was examined using immunohistochemical, neurochemical and electrophysiological techniques. Immunohistochemical analysis using an antiserum against tyrosine hydroxylase (TH) revealed a marked enhancement in immunoreactivity largely in the granular layer and the whole nuclei in the jj cerebellum, resulting from an increase in TH-immunoreactive varicose fibers forming synapse-like structures on the somata and dendrites of granule cells or nuclear neurons. The concentration of norepinephrine in both the cortical and nuclear regions of the jj cerebellum was significantly higher than that in the control, whereas no significant difference of this total amount was observed between the jj and Jj cerebella. Injection of norepinephrine into the Jj cerebellar nuclei reduced the firing rate of spontaneous unitary discharges of neurons in the interpositus nucleus. These findings suggest that the the jj cerebellum causes an enhancement of the noradrenergic innervation which may possibly be one of its characteristic alterations.

Animals↗
PubMed1990

Internal jugular phlebectasia in two siblings: manometric and histopathologic studies of the pathogenesis.

Two brothers, 4 years and 6 years of age, presented with a swelling in the right side of the neck. Ultrasonography and venography confirmed a diagnosis of phlebectasia of the right internal jugular vein (IJV). In an attempt to elucidate the etiology of this rare lesion, venous pressures in both the dilated right IJV and in the left IJV were taken under general anesthesia with intratracheal intubation at the time of surgery in each patient. No significant difference in pressure elevation with increase of intrathoracic pressure by overinflating the breathing bag was observed between the right and left IJV, suggesting that there would be no mechanical obstructive process generated on exertion, in each case. Microscopic examinations of a dissected portion of the dilated IJV showed paucity of muscle layer of the vein wall in the younger patient, and absence of that in the elder. Therefore, we assume that congenital muscle defect of the right IJV wall, rather than mechanical obstruction in the lower neck or the mediastinum, might cause phlebectasia. To our knowledge, this is the first report of IJV phlebectasia in siblings.

Child↗
PubMed1990

Synthesis and antiarrhythmic activity of 5,11-dihydro[1]benzoxepino[3,4-b]pyridines.

During further modification of the new antiulcer agent 5 (KW-5805), a 5,11-dihydro[1]benzoxepino[3,4-b]pyridine derivative, we found that some new derivatives had antiarrhythmic activity. So we continued synthesis and evaluation of a series of 5-substituted 5,11-dihydro[1]benzoxepino[3,4-b]pyridines for antiarrhythmic activity in chloroform-induced ventricular arrhythmias in mice and in ouabain-induced ventricular arrhythmias in dogs. In chloroform-induced ventricular arrhythmias, the 7-methoxy group played an important role in activity and the type of terminal side chain at position 5 had not obvious effect on potency. On the other hand, in ouabain-induced ventricular arrhythmias, the structure-activity relationship was highly specific and only four compounds, 9, 30, 34, and 35, were effective. Compound 9,5-[[2-(diethylamino)ethyl]amino]-7-methoxy-5,11-dihydro[1] benzoxepino[3,4-b]pyridine 1.5-fumarate, which exhibited low affinity for muscarinic acetylcholine receptors and a high ED100(mydriasis)/ED50(antiarrhythmic activity) ratio, was selected for further development and clinical evaluation as KW-3407. The synthesis and antiarrhythmic activity of optically active 9 is described. The order of potency of antiarrhythmic activity in ouabain-induced ventricular arrhythmias in dogs was (-)-9, (+/-)-9, and (+)-9.

Animals↗
PubMed1990

Studies on cardiotonic agents. III. Synthesis of 1-[1-(6,7-dimethoxy-4-quinazolinyl)-4-piperidinyl]-3-substituted 2-imidazolidinone and 2-imidazolidinethione derivatives.

A series of 1-[1-(6,7-dimethoxy-4-quinazolinyl)-4-piperidinyl]-3-substituted 2-imidazolidinone and 2-imidazolidinethione derivatives was synthesized and examined for cardiotonic activity in anesthetized dogs. Alkylation of the 2-imidazolidinone (1) afforded the N-alkylated products, while alkylation of the 2-imidazolidinethione (12) afforded the S-alkylated derivatives accompanied with a small quantity of the N-alkylated products. The N-alkylated derivatives showed generally potent activity, and the S-alkylated ones exhibited weak activity. Insertion of an alkyl group between the piperidine and the imidazolidinone moiety generally resulted in a fall in activity.

Animals↗
PubMed1990

Synthesis of 2-[[(4-fluoroalkoxy-2-pyridyl)methyl]sulfinyl]-1H- benzimidazoles as antiulcer agents.

Many 2-[[(4-fluoroalkoxy-2-pyridyl)methyl]sulfinyl]-1H-benzimidazoles were synthesized and tested for anti-secretory, antiulcer, and cytoprotective activities. Most of these compounds were superior to omeprazole in anti-secretory and antiulcer potencies, and especially in protecting the gastric mucosa from ethanol-induced damage. Among these compounds, 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]sulfinyl] - 1H-benzimidazole, AG-1749 (lansoprazole) (6f), was selected for further development and clinical evaluation.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1990

Studies on cardiotonic agents. IV. Synthesis of novel 1-(6,7-dimethoxy-4-quinazolinyl)piperidine derivatives carrying substituted hydantoin and 2-thiohydantoin rings.

A series of novel 1-(6,7-dimethoxy-4-quinazolinyl)piperidines carrying substituted hydantoin and 2-thiohydantoin rings was synthesized and examined for cardiotonic activity in anesthetized dogs. Introduction of isopropyl and sec-butyl group at the 5-position of the hydantoin and thiohydantoin rings led to potent inotropic activity. Effects of insertion of an alkyl chain between the piperidine and the hydantoin rings were also examined. The structural requirements necessary for optimal cardiotonic activity within the series were investigated.

Animals↗
PubMed1990

Protection by benidipine hydrochloride (KW-3049), a calcium antagonist, of ischemic kidney in rats via inhibitions of Ca-overload, ATP-decline and lipid peroxidation.

Renal failure was produced in rats by unilateral clamping of the left renal artery for 60 min, followed by reperfusion and contralateral nephrectomy. Prophylactic administrations of benidipine (10, 30 micrograms/kg, i.v.) significantly ameliorated the development of renal failure as estimated by histological examination as well as by the measurements of serum creatinine and blood urea nitrogen. ATP content of the ischemic kidney dropped immediately after renal ischemia, and this decline persisted for more than 48 hr after reperfusion. The content of lipid peroxide in the kidney was increased 15 min after reperfusion following renal ischemia. Calcium content of the kidney progressively increased after reperfusion and reached the peak level 24 hr after reperfusion, whereas calcium content scarcely changed during 60 min of renal ischemia. The decline of ATP, the lipid peroxidation, and the increase in calcium content of the kidney observed after reperfusion were significantly inhibited by pretreatment of the rats with benidipine (30 micrograms/kg, i.v.). These results suggest that lipid peroxidation and Ca-overload play causative roles in the pathogenesis of acute ischemic renal failure and that benidipine protects the ischemic kidney by inhibiting these deteriorating consequences.

Adenosine Triphosphate↗
PubMed1990

Pocket depth reduction by tooth types and sites after initial treatment.

Differences in pockets depth reduction rates were compared between different tooth types and sites after initial treatment in 41 adult periodontitis patients whose O'Leary plaque records were maintained at less than 10% during initial treatment. Pocket depths were significantly reduced after initial treatment. Response to treatment was good at 15, 25, 14, 24, 33, 43, 31, 41, 34 and 44; but was poor in 11, 21, 17, 27, 37 and 47. Response to treatment was poor on the mesiopalatal surfaces; midpalatal surfaces of 16 and 26; the distolingual surfaces of 17, 27, 37 and 47; and the mesiopalatal surfaces of 11 and 21; but was good on the distobuccal and midpalatal surfaces of 14 and 24, the mesio- and distal-buccal surfaces of 15 and 25; and the mesiolingual surfaces of 34 and 44. The tooth types and root surfaces that require careful attention during treatment were clarified.

Adult↗
PubMed1990

[A case of marked effectiveness using medroxyprogesterone acetate (MPA) in lung metastases of cancer of the uterine body].

This case is a 71-year-old female. As hormonotherapy, 400 mg/day of MPA alone was orally administered in a lung metastatic case of cancer of the uterine body in the IV stage. Although progressing for 2 years and 1 month after the initial administration, lung metastatic foci disappeared, and recurrence was not noted, and serious side effect by using MPA was also not noted. Progesterone therapy such this case is considered as one of therapeutic methods which can be expected remarkably effective rate in the lu metastatic foci of cancer of the uterine body.

Administration, Oral↗