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Biomedical subjects

K Kubo

Publications and source records attributed to K Kubo.

At least 451 records · Page 25Linked to original sources
PubMed1993

Diuretic and renal protective effects of 8-(noradamantan-3-yl)-1,3-dipropylxanthine (KW-3902), a novel adenosine A1-receptor antagonist, via pertussis toxin insensitive mechanism.

KW-3902 [8-(noradamantan-3-yl)-1,3-dipropylxanthine] is a novel potent and selective adenosine A1-receptor antagonist. In anesthetized rats, KW-3902 (0.1 and 1 mg/kg p.o.) antagonized the 5'-N-ethylcarboxamidoadenosine (NECA) induced bradycardic response, which is thought to be mediated via adenosine A1-receptors. However, the hypotensive response to NECA, which is predominantly due to adenosine A2-receptor activation, was not affected by KW-3902. Diuretic and renal protective effects of KW-3902 were investigated in normal and pertussis toxin (IAP; 10 micrograms/kg i.v.)-treated rats. KW-3902 (0.001-1 mg/kg p.o.) caused significant increases of urine volume and sodium excretion with little change of potassium excretion in saline-loaded normal rats. In anesthetized normal rats, KW-3902 (0.01 and 0.1 mg/kg i.v.) caused significant diuresis and natriuresis with no change in renal plasma flow and glomerular filtration rate. These findings suggest that KW-3902 caused the diuretic effect not by the change in the renal hemodynamics, but by the inhibition of water and sodium reabsorption in tubular sites. KW-3902 (0.01-1 mg/kg p.o.) significantly attenuated increases of serum creatinine and urea nitrogen and renal tubular damage in glycerol-induced acute renal failure rats. Neither diuretic nor renal protective effects of KW-3902 were affected by pretreatment of rats with IAP, which totally abolished the bradycardic response to NECA. These results are compatible with the hypothesis that diuretic and renal protective effects by adenosine A1-receptor blockade are mediated via IAP-insensitive mechanism.

Absorption↗
PubMed1993

[Analysis of bronchoalveolar lavage fluid in a case of high altitude pulmonary edema].

A 29-year-old male climber developed high altitude pulmonary edema (HAPE), progressing from headache and dyspnea to disturbance of consciousness in the Japan Alps. He was admitted to Shinshu University Hospital. Physical examination on admission revealed a cyanotic patient with coarse crackles and wheezes in bilateral lungs. Chest X-ray film showed bilateral patchy infiltrates. Arterial blood gases indicated severe hypoxemia, and respiratory alkalosis; pH 7.452, PO2 35.5 Torr, PCO2 31.6 Torr. Right heart catheterization showed noncardiogenic pulmonary edema, analysis of bronchoalveolar lavage (BAL) fluid was as follows; cells 2.05 x 10(5)/ml (alveolar macrophages 61.5%, neutrophils 25.5%, lymphocytes 13.0%), protein concentration 91 mg/dl. Cellular and protein analysis of BAL has been shown to be of value to clarify the pathogenesis of the permeability edema in patients with HAPE.

Adult↗
PubMed1993

[Intravascular ultrasound imaging on the endarterectomized coronary arteries in two patients].

Intravascular ultrasound imaging on the endarterectomized coronary arteries in two patients are reported with a review of the literature. Case 1, a 62-year-old male and case 2, a 64-year-old male underwent endarterectomy of the right coronary artery (#3--#4PD, 4AV) combined with coronary arterial bypass grafting. Coronary arteriography (CAG) and intravascular ultrasound imaging (IVUS) were performed one month after operation. CAG revealed bypass grafts and endarterectomized coronary arteries to be patent together, and IVUS revealed endarterectomized coronary arteries had two layers, outer layer to be hyperechoic and inner layer to be heterogenously echoic in both cases. The histological examination of specimens suggests this heterogenously echoic area represents media, thrombus and irregularly proliferated intima. Therefore, anticoagulant therapy after endarterectomy should be strictly performed.

Coronary Artery Bypass↗
PubMed1993

[Nutritional assessment of patients on continuous ambulatory peritoneal dialysis].

Nutritional status was assessed in 214 CAPD patients from eight centers in Japan. All patients were receiving adequate dialysis, as indicated by KT/Vurea and Karnofsky's activity scale. Subjective global assessment indicated that 25% of 83 female patients and 27% of 131 male patients were, at least, moderately malnourished. Mid-arm muscle circumference was lower in malnourished male patients than in well-nourished patients, however, in female patients none of the anthropometric variables reflected nutritional status. Lower serum albumin level was observed in malnourished male patients, but not in female patients. Daily protein intake, estimated from protein catabolic rate (PCR) was approximately 0.8 g/Kg BW in both males and females. This value is similar to those reported in literatures for CAPD patients. In our well-rehabilitated patients, PCR did not reflect the nutritional status as indicated by subjective global assessment. The data suggest that low protein intake was not always the major cause of malnutrition in these patients and that other factors, such as endocrine disorder, may also have contributed to malnutrition.

Adult↗
PubMed1993

Predominant expression of nPKC eta, a Ca(2+)-independent isoform of protein kinase C in epithelial tissues, in association with epithelial differentiation.

Of the nine known members of the protein kinase C (PKC) family, we found that novel (n-) PKC eta, a newly isolated Ca(2+)-independent isoform, was expressed at the highest level in the epidermis of mouse skin and epithelia of the digestive and respiratory tracts including the tongue, esophagus, forestomach, glandular stomach, intestine, colon, trachea, and bronchus. Expression of nPKC eta mRNA in these epithelial tissues was 3-10 times that in the brain and was especially high in squamous epithelium. Two other PKC isoforms, conventional (c-) PKC alpha and nPKC delta, were also expressed in these epithelial tissues, but no cPKC gamma was detected. In situ hybridization and immunohistochemical analyses demonstrated the localization of nPKC eta in suprabasal layers of the skin, tongue, esophagus, and forestomach. In the intestine, it was expressed in the epithelial cells of villi, but not of crypts. In the lung, only bronchial epithelium expressed nPKC eta. The localization of nPKC eta in differentiating or differentiated epithelial cells, rather than in proliferating basal cells, suggests the involvement of nPKC eta in epithelial differentiation.

Amino Acid Sequence↗
PubMed1993

[Emergency operation for complete papillary muscle rupture after myocardial infarction--a case report of 81-year-old patient].

Mitral regurgitation due to complete rupture of the papillary muscles after myocardial infarction has a very poor prognosis, even if diagnosed and operated on at an early phase. Recently, we performed an emergency operation for mitral regurgitation due to complete papillary muscle rupture after myocardial infarction in an 81-year-old patient. This is probably the oldest case in Japan. Operation revealed complete rupture of the posterior papillary muscle, and valve replacement with a Carpentier-Edwards bioprosthesis was performed.

Aged↗
PubMed1992

Non-prostanoid thromboxane A2 receptor antagonists with a dibenzoxepin ring system. 1.

A series of 11-[[2-[(arylsulfonyl)amino]ethyl]thio]-6,11- dihydrodibenz[b,e]oxepin-2-carboxylic acids and related derivatives were synthesized. The compounds were tested for their antagonizing effects on guinea pig platelet TXA2/PGH2 receptors. Structure-activity relationships are discussed. (+/-)-11-[[2-[(Styrylsulfonyl)amino]ethyl]-thio]-6,11- dihydrodibenz[b,e]oxepin-2-carboxylic acid (41) and (+/-)-11-[[2-[(phenylsulfonyl)amino]ethyl]thio]-6,11- dihydrodibenz[b,e]thiepin-2-carboxylic acid (4af) were the most promising compounds with K(i) values of 6.5 +/- 0.29 and 3.7 +/- 0.31 nM, respectively, for the TXA2/PGH2 receptor. These compounds also significantly inhibited U-46619-induced guinea pig platelet aggregation ex vivo (10 mg/kg po). Compound 41 was resolved into its optically active form. The (-)-isomer was 60-fold more potent than the (+)-isomer in the TXA2/PGH2 receptor binding assay. Some compounds tested in this study showed both TXA2/PGH2 receptor antagonizing and TXA2 synthase inhibitory effects.

Animals↗
PubMed1992

Non-prostanoid thromboxane A2 receptor antagonists with a dibenzoxepin ring system. 2.

A series of 11-[2-(1-benzimidazolyl)ethylidene]-6,11-dihydrodibenz[b,e]oxep in-2- carboxylic acid derivatives and related compounds were synthesized and found to be potent TXA2/PGH2 receptor antagonists. Each compound synthesized was tested for its ability to displace [3H]U-46619 binding from guinea pig platelet TXA2/PGH2 receptors. Structure-activity relationship studies revealed that the following key elements were required for enhanced activities: (1) an (E)-2-(1-benzimidazolyl)ethylidene side chain in the 11-position of the dibenzoxepin ring system and (2) a carboxyl group in the 2-position of the dibenzoxepin ring system. The studies also indicated that the TXA2/PGH2 receptor binding affinities of this series of compounds in guinea pig platelet were poorly correlated with those in human platelet. Introduction of substituent(s) to the benzimidazole moiety was effective and sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl)ethylidene]- 6,11-dihydrodibenz[b,e]oxepin-2-carboxylate monohydrate (57) recorded the highest affinity for human platelet TXA2/PGH2 receptor with a K(i) value of 1.2 +/- 0.14 nM. It demonstrated potent inhibitory effects on U-46619-induced guinea pig platelet aggregation (in vitro and ex vivo) and human platelet aggregation (in vitro). Compound 57, now designated as KW-3635, is a novel, orally active, and specific TXA2/PGH2 receptor antagonist with neither TXA2/PGH2 receptor agonistic nor TXA2 synthase inhibitory effects. It is now under clinical evaluation.

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

The particle SSV1 from the extremely thermophilic archaeon Sulfolobus is a virus: demonstration of infectivity and of transfection with viral DNA.

The lemon-shaped "virus-like" particle SSV1 produced by the thermophilic archaeon Sulfolobus shibatae has not previously been observed to infect any host. Using a plaque assay suitable for the extreme growth conditions of this archaeon, we have shown infection of Sulfolobus solfataricus by SSV1. Upon infection, the viral genome was always found integrated into a tRNA gene of the host chromosome, a situation similar to that in S. shibatae, proving that site-specific integration is involved in establishing the lysogenic state. As in S. shibatae, UV-irradiation of lysogenized S. solfataricus led to virus production apparently not accompanied by cell lysis. We have also demonstrated the efficient uptake of exogenous DNA and its expression in Sulfolobus by transfecting S. solfataricus with SSV1 DNA by electroporation. Transfection efficiencies of up to 10(6) transfectants per microgram of DNA were obtained.

Bacteriophages↗
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

Hyaluronate synthesized by cultured skin fibroblasts derived from patients with Werner's syndrome.

Hyaluronate in cultured skin fibroblasts derived from patients with Werner's syndrome, who excrete large amounts of urinary hyaluronate, was investigated. The amount of hyaluronate secreted into the medium by Werner's fibroblasts was 2-3-times that of normal fibroblasts, whereas no difference in enzyme activities related to the degradation of hyaluronate was found. Werner's fibroblasts were then cultured in the presence of [3H]glucosamine, and the amount of [3H]hyaluronate and its chain lengths in the medium and matrix (trypsinate) fractions were compared with those of normal cells. No significant difference in the chain length of hyaluronate was observed between normal and Werner's fibroblasts. On the other hand, a significant increase of hyaluronate was found in the matrix fraction of Werner's fibroblasts when the cells reached confluency. In addition, a hyaluronate of small chain length was found in the matrix fraction of Werner's fibroblasts, although this was absent from that of normal cells. It was concluded that the constituents of the extracellular matrix of Werner's fibroblasts differed from those of normal cells, characterized by the presence of a large amount of hyaluronate and a relatively small hyaluronate chain.

Adult↗
PubMed1992

[MR imaging of hilar cholangiocarcinoma--comparative study with CT].

Magnetic resonance (MR) images of 18 cases of hilar cholangiocarcinoma were evaluated to compare the effectiveness of Gd-DTPA with that of high dose contrast enhancement computed tomography (HCE-CT) in detecting the primary tumor. The primary tumor was demonstrated as having slightly low intensity compared with liver parenchyma and high intensity compared with the dilated bile duct on T1 weighted images. In contrast, MRI using Gd-DTPA, which was carried out in five cases, revealed intense enhancement of the tumor. As the differentiation between cholangiocarcinoma and dilated bile duct was difficult, it was concluded that the use of Gd-DTPA improves the efficacy of MRI in diagnosing cholangiocarcinoma. Gd-DTPA was also effective in differentiating the growth pattern of the tumor: the infiltrating type was demonstrated as thickening of the wall of the bile duct, the polypoid type as a soft tissue mass in the bile duct. Contrast MRI study is effective for the detection of cholangiocarcinoma. It is also expected to be effective in the staging diagnosis of cholangiocarcinoma.

Adenoma, Bile Duct↗
PubMed1992

A novel, sensitive, and specific assay for abasic sites, the most commonly produced DNA lesion.

Free radicals produce a wide spectrum of damages; among these are DNA base damages and abasic (AP) sites. Although several methods have been used to detect and quantify AP sites, they either are relatively laborious or require the use of radioactivity. A novel reagent for detecting abasic sites in DNA was prepared by reacting O-(carboxymethyl)hydroxylamine with biotin hydrazide in the presence of carbodiimide. This reagent, called Aldehyde Reactive Probe (ARP), specifically tagged AP sites in DNA with biotin residues. The number of biotin-tagged AP sites was then determined colorimetrically by an ELISA-like assay using avidin/biotin complex conjugated to horseradish peroxidase as the indicator enzyme. With heat/acid-depurinated calf thymus or bacteriophage f1 DNA, ARP detected femtomoles of AP sites in DNA. Using this assay, DNA damages generated in calf thymus, phi X174 RF, and f1 single-stranded DNA, X-irradiated in phosphate buffer, were easily detectable at 10 rad (0.1 Gy). Furthermore, ARP sites were detectable in DNA isolated from heat-inactivated X-irradiated (10 Gy) and methyl methanesulfonate (MMS)-treated (5 microM) Escherichia coli cells. The rate of production of ARP sites was proportional to the X-ray dose as well as to the concentration of MMS. Thus, the sensitivity and simplicity of the ARP assay should provide a potentially powerful method for the quantitation of AP sites or other DNA lesions containing an aldehyde group.

Animals↗