Search PubMed⌕ Search

Biomedical subjects

H Nonaka

Publications and source records attributed to H Nonaka.

At least 73 records · Page 4Linked to original sources
PubMed1992

Adenosine A1 antagonists. 2. Structure-activity relationships on diuretic activities and protective effects against acute renal failure.

Diuretic activities of xanthine or nonxanthine adenosine antagonists and their ameliorative effects against glycerol-induced acute renal failure in rats were investigated in order to clarify the physiological and pathological function of adenosine receptors in the kidney. Diuretic and natriuretic activities of a variety of adenosine antagonists clarified systematically for the first time that the blockade of A1 receptors is more important than that of A2 receptors in sodium and water excretion and support the hypothesis that endogenous intrarenal levels of adenosine directly enhance tubular sodium readsorption. Studies of structure-activity relationships of 8-substituted xanthines in the acute renal failure demonstrated that the activation of adenosine A1 receptor was an important factor in developing such a renal failure. A series of 8-(3-noradamantyl)xanthines exhibited the extremely potent diuretic and natriuretic activities (24; 2.5 micrograms/kg, po, the ratio of urinary excretion value in treated rats to urinary excretion value in control rats = 1.69, the ratio of Na+/K+ in treated rats to Na+/K+ in control rats = 1.76) and potent ameliorative effects against glycerol-induced acute renal failure (24; 10 micrograms/kg, ip, 55% inhibition). From our detailed studies of structure-activity relationships, we can speculate that some tissue differences of the adenosine A1 receptor might exist between kidney and brain and sites of action for adenosine antagonists could be different between two renal pharmacological assays. 1,3-Dipropyl-8-(3-noradamantyl)xanthine, KW-3902 (24), was chosen for further studies and is under development as a drug for treating the acute renal failure.

Acute Kidney Injury↗
PubMed1992

The ES-242s, novel N-methyl-D-aspartate antagonists of microbial origin, interact with both the neurotransmitter recognition site and the ion channel domain.

ES-242-1 approximately 5 are novel microbial bioxanthracenes which do not contain nitrogen. The ES-242s inhibited the binding of [3H]TCP and [3H]CGS19755 to the N-methyl-D-aspartate (NMDA) receptor complex. They had no effect on the binding of the specific ligands for the non-NMDA receptor. The biochemical and pharmacological properties of ES-242-1 were fully examined since it is the most potent of the five compounds. ES-242-1 is highly specific for the NMDA receptor; it has no effect on other receptors. Kinetic analyses indicated that ES-242-1 inhibited the binding of [3H]TCP and [3H]CGS19755 in a competitive manner, respectively, suggesting that ES-242-1 interacts with both the transmitter recognition site and the channel domain. ES-242-1 selectively inhibited NMDA-induced Ca2+ influx in primary cultures of mouse hippocampal neurons. ES-242-1 also specifically blocked the increase in cyclic GMP accumulation induced by NMDA or L-glutamate in rat cerebellar slices. In a concentration range of 0.1-1.0 microM, ES-242-1 was as potent as MK-801 in preventing glutamate-induced neurotoxicity in primary cultures of mouse hippocampal neurons. These results show that ES-242-1 is a potent and specific antagonist for the NMDA receptor. The antagonistic properties of the ES-242s appear to be due to a novel mechanism of action at the NMDA receptor.

Animals↗
PubMed1992

8-Polycycloalkyl-1,3-dipropylxanthines as potent and selective antagonists for A1-adenosine receptors.

With the aim of characterizing the hydrophobic interactions between xanthines and the A1 receptor site, 1,3-dipropyl-8-substituted xanthines were synthesized. Introduction of a quaternary carbon and the conformationally restricted cyclopentyl moiety into the 8-position of xanthines enhanced the adenosine A1 antagonism. 1,3-Dipropyl-8-(3-noradamantyl)xanthine was identified to be a selective and the most potent A1 receptor antagonist reported to date. Under our structure-activity relationship, the 8-substituent of xanthine antagonists and the N6-substituent of adenosine agonists appears to bind to the same region of the A1 receptor.

Adenosine↗
PubMed1992

Muscarinic receptor subtypes in feline tracheal submucosal gland secretion.

To determine what muscarinic receptor subtype regulates [Ca2+]i mediating airway submucosal gland secretion, we examined the effects of atropine (Atr), pirenzepine (PZ), 11([2-(diethylamino)methyl-1-piperidinyl] acetyl)-5,11-dihydro-6H-pyrido (2,3-b)(1,4)-benzo-diazepin-6-one (AF-DX116) and 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP) on methacholine (MCh)-evoked [Ca2+]i rise in acinar cells, and compared this with mucus glycoprotein (MGP) and electrolyte secretion evoked by MCh from submucosal glands isolated from feline trachea. [Ca2+]i was measured with the Ca(2+)-sensitive fluorescent dye, fura 2. We determined MGP secretion by measuring TCA-precipitable 3H-labeled glycoconjugates and electrolyte secretion by the change in the rate constant of 22Na-efflux from isolated glands. Half-maximal inhibitory concentrations (IC50) of PZ, AF-DX116, 4-DAMP, and Atr against MCh-evoked [Ca2+]i rise were 10(-7) M, 6 x 10(-6) M, 8 x 10(-9) M, and 6 x 10(-9) M, respectively. IC50 of PZ, AF-DX116, 4-DAMP, and Atr against MCh-evoked MGP secretion were 10(-6) M, 2 x 10(-5) M, 8 x 10(-9) M, and 6 x 10(-9) M, respectively. MCh (10(-5) M)-evoked 22Na efflux was significantly inhibited by 10(-7) M 4-DAMP and 10(-7) M Atr (P less than 0.01, each) but not by 10(-7) M PZ. Receptor binding assays with [3H]quinuclidinyl benzilate showed that the Ki values for PZ, AF-D x 116, 4-DAMP and Atr were 2.2 x 10(-8) M, 6.6 x 10(-7) M, 6.2 x 10(-10) M, and 2.9 x 10(-10) M, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of KW-3635, a novel dibenzoxepin derivative of a selective thromboxane A2 antagonist, on human, guinea pig and rat platelets.

We examined the binding of [3H]U-46619, a thromboxane A2 agonist, to human and guinea pig platelets and the binding of [3H]SQ 29,548, a thromboxane A2 antagonist, to human, rat and guinea pig platelets. KW-3635 (sodium (E)-11-[2-(5,6-dimethyl-1- benzimidazolyl)ethylidene]-6,11-dihydrodibenz[b,e]oxepin-2-c arboxylate monohydrate) concentration-dependently inhibited the [3H]U-46619 binding to human and guinea pig platelets with inhibition constants of 1.2 nM and 2.7 nM, respectively. KW-3635 also potently inhibited the [3H]SQ 29,548 binding to human and guinea pig platelets with inhibition constants of 1.9 nM and 3.2 nM, respectively. In contrast, KW-3635 was less active against thromboxane A2/prostaglandin H2 receptors in rat platelets with an inhibition constant of 97 nM. KW-3635 at 10(-5) M did not antagonize various receptors including prostaglandin E2, prostaglandin I2 and neurotransmitters. In addition, 10(-5) M KW-3635 did not alter the prostaglandin D2-induced cAMP accumulation in EBTr cells. KW-3635 was inactive towards thromboxane synthase, cyclooxygenase and prostaglandin I2 synthase up to 10(-5) M. KW-3635 slightly inhibited 5-lipoxygenase with an IC50 value of 71 microM. These data indicate that KW-3635 is a potent and selective non-prostanoic thromboxane A2 antagonist, and it can recognize the species differences in thromboxane A2/prostaglandin H2 receptors.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1992

Effect of manidipine, a novel calcium channel blocker, on quality of life in hypertensive patients.

A multicenter open study was performed to evaluate manidipine monotherapy for 6 months on quality of life in hypertensive patients. One hundred and sixty-six patients with essential hypertension were enrolled. Of these, 2 were excluded because of violation of entry criteria, 4 withdrew from treatment because of side effects, and 12 for personal reasons. Manidipine treatment observed at a daily dose of 10 to 20 mg produced effective reduction in blood pressure during the course of the study. Adverse reactions such as palpitation or headache were experienced by 5 of 166 (3%) patients. Quality of life (QOL), assessed grossly by attending physicians, was rated as improved in 62% and unchanged in 36% of patients. Significant improvements in mean QOL scores were noted in general symptoms, physical symptoms and general well-being, work performance and satisfaction, sleep scale, emotional state, cognitive function, sexual function, and self-control. Elderly patients, age 60 years and older, achieved significant improvement in the same QOL items as in all cases; there was no difference between younger and older age groups. In conclusion, manidipine monotherapy is useful for treating patients, including the elderly, with essential hypertension, and this therapy improves their quality of life.

Adult↗
PubMed1992

[Sudden death due to bilateral pulmonary thromboembolism in a patient with multiple myeloma: an autopsy case report].

We encountered a patient with multiple myeloma who died suddenly, in whom bilateral pulmonary artery thrombosis was found at autopsy. The patient was a 50-year-old woman who had received chemotherapy for multiple myeloma at a local clinic for 4 years, and was transferred to our hospital because of recurrence of multiple myeloma in August 1990. Despite chemotherapy performed after admission, serum globulin level increased and her low back pain worsened, and she was generally restricted to bed. On October 21, she developed sudden dyspnea, became markedly cyanotic, lost consciousness, and then suffered a cardiopulmonary arrest. Autopsy revealed bilateral pulmonary artery thrombosis as well as thrombosis in the pelvic veins. Hyperviscosity due to multiple myeloma and long-term recumbency were the probable causes of pelvic venous thrombosis and subsequent pulmonary artery thrombosis. We report a rare case of bilateral pulmonary artery thrombosis which developed during the course of multiple myeloma and led to sudden death.

Death, Sudden↗
PubMed1992

[Basic studies of intra-arterial hyperthermic treatment].

Basic studies on intra-arterial hyperthermic treatment (1AHT) were conducted in rabbits implanted with VX2 tumor inside the thigh. For the purpose of determining the best temperature, saline added Adriamycin (ADM) (2 mg/body) that heated up to a predetermined objective temperature was injected. At 3 days after administration, the intratumor concentration of ADM (ITCA) and blood laboratory data were obtained. ITCA of the 53 degrees C group (1.13 +/- 0.41 micrograms/g) was significantly higher than those in the 23 degrees C group. In the 58 degrees C group, BUN, CPK, and creatinine were elevated. These data suggested that the best temperature of IAHT was about 53 degrees C. The treated rabbits were divided into 4 groups (heated saline added ADM, heated saline, non-heated saline added ADM, control) and the tumor growth rates after IAHT were investigated. The tumor size of the groups treated by heated saline was inhibited compared with that in the other two groups. There was no elevation of intratumor temperature in spite of IAHT. At 2 days after the IAHT, patho logically there were vacuolar degeneration in the arterial endothelial cells near the tumor, and narrowing of involved artery. These results suggest that the antitumor effect by IAHT is related with blood supply without hyperthermic effect.

Animals↗
PubMed1992

Molecular cloning of the human cDNA for a stimulatory GDP/GTP exchange protein for c-Ki-ras p21 and smg p21.

We have previously purified smg GDP dissociation stimulator (GDS) from bovine brain and isolated its cDNA from a bovine brain cDNA library. smg GDS stimulates the GDP/GTP exchange reaction of a group of small GTP-binding proteins (G proteins), including at least c-Ki-ras p21, smg p21A, smg p21B, rhoA p21 and rhoB p21, by stimulating the dissociation of GDP from and the subsequent binding of GTP to each small G protein. In this study, we have isolated and sequenced the cDNA of smg GDS from a human brain cDNA library using the cloned bovine smg GDS cDNA. The cDNA has an open reading frame encoding a protein of 558 amino acids with a calculated Mr value of 61,122. Human smg GDS shares 93% nucleotide and 96% amino acid sequence homologies with bovine smg GDS. The isolated cDNA is expressed in Escherichia coli, and the encoded protein shows the physical and functional properties similar to those of bovine smg GDS.

Amino Acid Sequence↗
PubMed1991

Tissue and subcellular distributions of an inhibitory GDP/GTP exchange protein (GDI) for the rho proteins by use of its specific antibody.

We have recently purified from bovine brain cytosol to near homogeneity a GDP/GTP exchange protein for the rho proteins, named rho GDI, that inhibits the dissociation of GDP from and the subsequent binding of GTP to the rho proteins. In the present study, we made a monoclonal antibody against rho GDI and studied its tissue distribution in rat and its subcellular distribution in rat cerebrum by use of this antibody. rho GDI was found in most rat tissues as described for the rho proteins. In rat cerebrum, rho GDI was mostly found in the cytosol of neuron body and synaptosome. In synaptosome, it was mainly found in the synaptic cytosol.

Animals↗
PubMed1991

Tissue and subcellular distributions of an inhibitory GDP/GTP exchange protein (GDI) for smg p25A by use of its antibody.

We have recently purified from bovine brain cytosol to near homogeneity a GDP/GTP exchange protein for smg p25A, named smg p25A GDI, that inhibits the dissociation of GDP from and the subsequent binding of GTP to smg p25A. In the present study, we made an antiserum against smg p25A GDI and studied its tissue distribution in rat and its subcellular distribution in rat cerebrum by use of this antiserum. smg p25A GDI was found in secretory cells with both regulated and constitutive secretion types. Since smg p25A was previously found in only secretory cells with a regulated secretion type, this result suggests that small GTP-binding proteins different from smg p25A but recognized by smg p25A GDI are present in secretory cells with a constitutive secretion type, and that smg p25A GDI is involved in both regulated and constitutive secretory processes. In subcellular fractionation analysis of rat cerebrum, smg p25A GDI was mostly found in the cytosol fraction of neuron body and synaptosome. In synaptosome, it was mainly found in the synaptic cytosol.

Animals↗
PubMed1991

Effects of dextran sulphate on renal dysfunctions induced by gentamicin as determined by the kidney perfusion technique in rats.

The effect of dextran sulphate on accumulation of gentamicin within the renal cortex and on renal functional changes induced by gentamicin has been investigated using the rat renal perfusion technique. Gentamicin accumulation decreased by the coadministration of dextran sulphate, the degree being proportional to dextran sulphate concentration. The filtered load of gentamicin was unaffected by dextran sulphate. The perfusion of kidney with gentamicin brought about a decrease in the reabsorption of Na+ and an increase in the rate of urine flow with no effect on that of glomerular filtration. The addition of dextran sulphate in the perfusate resulted in the resumption of these levels to those of the control. Dextran sulphate thus apparently interacts with gentamicin in the lumen of proximal tubules to inhibit the reabsorption of gentamicin by proximal tubular cells, and prevents the renal dysfunctions induced by gentamicin.

Animals↗
PubMed1991

[Positive rate of serum anti-HCV in various liver diseases and the clinico-pathological study of chronic liver disease in alcoholics].

The aim of this study was to elucidate the positive rate of serum anti-HCV in alcoholic (with negative HBsAg and without blood transfusion history) and non-alcoholic (type-B and type-NANB) patients with chronic liver diseases. The clinico-pathological difference between anti-HCV positive and negative alcoholic patients was also investigated. Anti-HCV (Chiron C-100-3) was assayed with Ortho EIA kit in 196 patients. Liver function tests and the histological findings were evaluated in 111 cases of chronic hepatitis (CH) and 39 of liver cirrhosis (LC). Following results were obtained. [1] Positive rate of serum anti-HCV in alcoholic patients was 40% in CH, 36% in LC and 100% in hepatocellular carcinoma. In non-alcoholic type-NANB group, it was 75%, 68% and 69%, respectively. [2] Serum GGT/ALT ratio was higher in anti-HCV negative patients than positive patients both in CH and LC alcoholics. In non-alcoholic group, it was higher in type-NANB patients than type-B patients. [3] Among the histological findings in CH alcoholics, lymph follicles in the portal area were characteristic in anti-HCV positive patients, while these were not seen in negative patients. [4] In LC alcoholics, regenerative nodules were irregular in size in anti-HCV positive patients, while these were even and small in negative patients. [5] Serum HCV-RNA was detected in two out of 14 anti-HCV negative patients. [6] A female alcoholic patient who showed positive serum anti-HCV and negative HCV-RNA was presented. [7] For the evaluation of the influence of HCV in alcoholics, further studies have to be continued with more sensitive HCV markers.

Adult↗
PubMed1991

[Studies on the mode of progression of alcoholic liver disease].

In order to elucidate the mode of progression of alcoholic liver disease, relationships among the drinking style, laboratory data, anti-HCV antibody and histological changes were investigated on 36 patients in whom the liver biopsy was repeatedly done. Following results were obtained (1) In the group of continuous drinking over 100g ethanol per day, histological progression was found in 11 of 13 patients (85%) regardless of positive anti-HCV. On the other hand, in the group of abstinence or temperance less than 60g daily alcohol intake, histological improvement was found in 6 of 11 patients (55%). (2) Histological improvement was predominantly seen by abstinence or temperance in the cases with lower levels of serum IgA and adenosine deaminase (ADA) on hospitalization and those with rapid decrease in serum gamma-GTP after hospitalization. In conclusion, the amount of ethanol was considered to be the most important factor to affect on a progression of alcoholic liver diseases. Assessment of laboratory data such as IgA and ADA on hospitalization and change in gamma-GTP after hospitalization were also thought to be useful in foreseeing the prognosis of alcoholic liver disease.

Alcohol Drinking↗
PubMed1991

[YAG laser contact therapy of ovarian endometriosis under laparoscopy].

Thirty-six patients with ovarian endometriosis were treated with Nd:YAG laser contact irradiation under laparoscopic control. Indications for laparoscopy were infertility (n = 20) and dysmenorrhea (n = 16). The laparoscopic procedures so far undertaken in our clinic include: Aspiration of chocolate cyst, removal of ovarian endometriosis, adhesion-lysis, uterine nerve ablation, coagulation of peritoneal endometriosis and irrigation. No complications were seen. After undergoing this procedure, eight of 20 patients achieved pregnancy and 15 of 16 patients obtained pain relief. Serum CA125 levels were significantly decreased postoperatively. We confirmed that contact irradiation with a cone-shaped sapphire probe provides adequate incision and lysis at lower power levels, and that this method is an effective treatment for ovarian endometriosis.

Adult↗