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Biomedical subjects

K Wada

Publications and source records attributed to K Wada.

At least 667 records · Page 37Linked to original sources

Antihypertensive effect of NKY-722, a new water-soluble 1,4-dihydropyridine derivative, on conscious spontaneously hypertensive rats.

3-(4-Allyl-1-piperazinyl)-2,2-dimethylpropyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine dicarboxylate dihydrochloride (NKY-722) produced a dose-dependent antihypertensive effect in conscious spontaneously hypertensive rats (SHR). In this respect NKY-722 was more potent and longer-acting than nicardipine. In canine isolated mesenteric arteries, exposed to a Ca2+-free medium containing high K+, NKY-722 inhibited Ca2+-induced contraction in concentration-dependent manner, suggesting the calcium antagonism as the mechanism of action.

Animals↗

Osseous xanthomatosis and a pathologic fracture in a patient with hyperlipidemia. A case report.

Osseous xanthomatosis and a pathologic fracture of the femoral neck associated with hyperlipoproteinemia occurred in a 48-year-old woman. Widely distributed skeletal lesions suggested a primary neoplasm such as malignant lymphoma or multiple myeloma; however, needle aspiration cytology of the fracture site, cutaneous manifestations, and abnormally high concentrations of lipoproteins established a diagnosis of intraosseous xanthomatosis associated with hyperlipidemia. Histologically, the excised femoral head showed a dense aggregate of lipid-laden macrophages and depletion of normal bone trabeculae. The hyperlipidemia is classified as Type IIb hyperlipoproteinemia.

Bone Diseases↗

Hydrogen bonding of sulfur ligands in blue copper and iron-sulfur proteins: detection by resonance Raman spectroscopy.

The resonance Raman spectrum of the blue copper protein azurin from Alcaligenes denitrificans exhibits nine vibrational modes between 330 and 460 cm-1, seven of which shift 0.4-3.0 cm-1 to lower energy after incubation of the protein in D2O. These deuterium-dependent shifts have been previously ascribed to exchangeable protons on imidazole ligands [Nestor, L., Larrabee, J. A., Woolery, G., Reinhammar, B., & Spiro, T. G. (1984) Biochemistry 23, 1084] or to exchangeable protons on amide groups which are hydrogen bonded to the cysteine thiolate ligands (a feature common to all blue copper proteins of known structure). In order to distinguish between these two possibilities, a systematic investigation of Fe2S2(Cys)4-containing proteins was undertaken. Extensive hydrogen bonding between sulfur ligands and the polypeptide backbone had been observed in the crystal structure of ferredoxin from Spirulina platensis. The resonance Raman spectrum of this protein is typical of a chloroplast-type ferredoxin and exhibits deuterium-dependent shifts of -0.3 to -0.5 cm-1 in the Fe-S modes at 283, 367, and 394 cm-1 (assigned to the bridging sulfurs) and -0.6 to -0.8 cm-1 in the Fe-S modes at 328 and 341 cm-1 (assigned to the terminal cysteine thiolates). Considerably greater deuterium sensitivity is observed in the Raman spectra of spinach ferredoxin and bovine adrenodoxin, particularly for the symmetric stretching vibration of the Fe2S2 moiety at approximately 390 cm-1. This feature decreases by 0.8 and 1.1 cm-1, respectively, for the two oxidized proteins in D2O and by 1.8 cm-1 for reduced adrenodoxin in D2O.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

Two types of hormone-responsive adenylate cyclase in the rat liver.

We have demonstrated the existence of two types of hormone-responsive adenylate cyclase in the isolated perfused rat liver. One, less abundant, is linked to glycogenolysis and the other is not. Glucagon stimulates mainly the glycogenolysis-linked fraction and, to a lesser extent, the fraction which is not linked to glycogenolysis. The suppressive effect of insulin is specific for the glucagon-responsive adenylate cyclase and is inhibited by 3-isobutyl-1-methylxanthine (IBMX). However, this mechanism can explain only partly the ability of insulin to suppress glycogenolysis, and is not observed when cAMP is increased sufficiently by glucagon. Secretin-responsive adenylate cyclase is not linked to glycogenolysis and is suppressed specifically by oxymetazoline. The capacity of this suppressive effect is large and not inhibited by IBMX. These results suggest that there is a functional compartmentalization of cAMP within the hepatocyte or among hepatocytes.

1-Methyl-3-isobutylxanthine↗

Amino acid sequence of chicken liver cathepsin L.

The complete amino acid sequences of the heavy and light chains of chicken liver cathepsin L have been determined by automated gas-phase Edman degradation. The heavy and light chains contained 176 and 42 amino acid residues respectively. A glucosamine-based oligosaccharide group was attached to Asn-109 of the heavy chain. Chicken liver cathepsin L had high sequence homology with rat cathepsin H, but exhibited less similarity with rat cathepsin B. Comparisons of cathepsin L with plant cysteine proteinases, such as papain, actinidin and aleurain, reveal high degree of homology.

Amino Acid Sequence↗

Platelet aggregation induced by cryoprecipitate infusion in platelet-type von Willebrand's disease.

Platelet-type von Willebrand's disease (VWD) is a recently described bleeding disorder characterized by a heightened interaction between platelets and von Willebrand factor (vWF) as the result of an intrinsic platelet-membrane abnormality. Administration of cryoprecipitate into a patient with this disorder was followed by thrombocytopenia in vivo and "spontaneous" platelet aggregation in vitro. However, a prolonged bleeding time was shortened and sufficient haemostasis was achieved without thromboembolic complications. These results provide evidence that human vWF infused with cryoprecipitate directly interacts with platelet-type vWD platelets, causing thrombocytopenia in vivo, and suggest that impaired primary haemostasis is related to the depletion of the high-molecular-weight vWF multimers in the circulating plasma.

Hemostasis↗

Primary structure of the biotin-binding site of chicken liver acetyl-CoA carboxylase.

Limited proteolysis of chicken liver acetyl-CoA carboxylase by staphylococcal serine proteinase yielded a fragment of 31 kDa which contained the biotinyl active site. This polypeptide was purified by preparative polyacrylamide gel electrophoresis and characterized. The complete amino acid sequence of this polypeptide has been deduced from the nucleotide sequence of cloned DNA complementary to the chicken liver acetyl-CoA carboxylase mRNA. A highly conserved sequence of Met-Lys-Met was found in the biotin-binding site. Appreciable homology was observed among the sequences in close vicinity of the biotin sites of chicken liver acetyl-CoA carboxylase and other biotin-dependent carboxylases including biotin carboxyl carrier protein of Escherichia coli acetyl-CoA carboxylase.

Acetyl-CoA Carboxylase↗

A radiological population study on the ossification of the posterior longitudinal ligament in the spine.

This paper reports the results of a radiological population study on the ossification of the posterior longitudinal ligament (OPLL) in both the cervical and the thoracic spine among Japanese. The study was carried out in the Yachiho-mura district in the central part of Japan, where 5074 people were living. X-ray examinations were made of 1058 of the people; there were 440 men and 618 women, 50 or more years of age. The roentgenograms showed 34 cases of OPLL in the cervical spine (3.2%): 19 men (4.3%) and 15 women (2.4%). The condition was most frequently observed at the level of C-4. Radiological classification showed 18 cases of the segmental type, 11 of the continuous type, and five of a mixed type. There were eight cases of OPLL in the thoracic spine (0.8%), four in men (0.9%) and four in women (0.6%). OPLL in the thoracic spine was most frequently observed at the midthoracic levels. All eight cases showed a continuous type of ossification. There were three subjects with OPLL in both the cervical and the thoracic spine. Therefore, the number of subjects with OPLL in either the cervical or the thoracic spine was 39 (3.7%) total.

Aged↗

Morphological clues for the diagnosis of small hepatocellular carcinomas.

Histological features of 44 cases of small hepatocellular carcinoma (HCC) were examined and compared with those of large regenerative nodules. The highly differentiated type of HCC most often occurred in nodules which were less than 2 cm in diameter. Noticeably, in 9 out of 15 such cases (60.0%), tumour cells were arranged in trabeculae of almost normal thickness (normotrabecular pattern). These trabeculae, however, showed variable nuclear crowding, occasional microacinar formation, and increase in cytoplasmic basophilia. It is emphasized that the presence of this triad may be a very reliable indicator for the histological identification of early HCC, especially in examining limited material such as a biopsy specimen. However, cellular and structural atypia becomes more prominent in nodules which are larger than 2 cm.

Biopsy↗

Carcinoma and polyps of the gallbladder associated with Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome is a genetic condition characterized by mucocutaneous pigmentation and gastrointestinal polyposis. A variety of neoplasms have been found in the alimentary tract or elsewhere in patients with this entity. A 39-year-old female patient who had carcinoma and two polyps in the gallbladder in association with Peutz-Jeghers syndrome is described. Since the polyps consisted of the normal lining epithelium of the gallbladder and pseudopyloric gland-type metaplastic cells and obviously lacked cellular atypism, the authors would consider them hamartomatous. The carcinoma partly showing submucosal invasion existed in an area other than the polyps. This is the first documented case of the syndrome having gallbladder carcinoma.

Adenocarcinoma↗

A unique amino acid sequence of the B subunit of a heat-labile enterotoxin isolated from a human enterotoxigenic Escherichia coli.

The purified B subunit of heat-labile enterotoxin produced from a human strain, 240-3, of enterotoxigenic Escherichia coli (LTh(240-3] was carboxymethylated, succinylated, digested with chymotrypsin and subjected to high performance liquid chromatography (HPLC), and the amino acid compositions of the peptide peaks from the column were analyzed and compared with the data reported by Yamamoto and Yokota (J. Bacteriol. 155, 728.1983), who deduced the amino acid sequence of LTh(H10407) from the DNA sequence of a human strain H10407. Only one fraction differed in amino acid composition from that reported by them. This fraction was found to consist of peptides with the sequences Arg-Asn-Thr-Gln-Ile-Tyr and Arg-Ile-Ala-Tyr. Yamamoto and Yokota reported the sequence of the latter peptide as Arg-Ile-Thr*-Tyr, which corresponds to the peptide from 73rd to 76th from amino (N-) terminus. Thus amino acid residue 75 from the N-terminus of LTh-B(240-3) is alanine, not threonine. The B subunit of cholera toxin also has alanine at position 75. LTh(240-3) appeared similar to LTh(H10407) in an Ouchterlony test, vascular permeability test and GMI ganglioside ELISA. These data show that substitution of threonine for alanine at position 75 from the N-terminus does not affect the immunological and biological characteristics of LTh.

Amino Acid Sequence↗

Reduction of purothionin by the wheat seed thioredoxin system.

Thioredoxin h, the thioredoxin characteristic of heterotrophic plant tissues, was purified to homogeneity from wheat endosperm (flour) and found to resemble its counterpart from carrot cell cultures. In the presence of NADPH, homogeneous thioredoxin h and partially purified wheat endosperm thioredoxin reductase (NADPH), (EC 1.6.4.5), purothionin promoted the activation of chloroplast fructose-1,6-bisphosphatase (EC 3.1.3.11). Under these conditions, NADPH provided the reducing equivalents for a series of thiol reactions in which (a) thioredoxin reductase reduced thioredoxin h thereby converting it from disulfide (S-S) to sulfhydryl (SH) form; (b) the sulfhydryl form of thioredoxin h reduced the disulfide form of purothionin-a 5 kilodalton seed storage protein with 4 S-S bridges; and (c) the sulfhydryl form of purothionin reductively activated fructose-1,6-bisphosphatase. The results show that, since thioredoxin h does not react effectively with fructose-1,6-bisphosphatase, the thioredoxin system can activate an enzyme through purothionin by secondary thiol redox control. In a related type reaction, purothionin, inhibited the activity of either Escherichia coli or calf thymus ribonucleotide reductase with reduced thioredoxin as hydrogen donor. The results suggest that purothionin competes with ribonucleotide reductase for reducing equivalents from thioredoxin. Thus, inhibition of deoxyribonucleotide synthesis should be considered a possible mechanism when examining the toxic effects of purothionin on mammalian cells in S-phase.

Journal Article↗

Effect of angiotensin-converting enzyme inhibitor YS980 on prostaglandin synthesis in rabbit kidney medulla slices.

The effect of YS980, an angiotensin-converting enzyme inhibitor, on the generation of medullary prostaglandins E2 and F2 alpha was examined. At concentrations of 0.2 mM and below, YS980 enhanced prostaglandin F2 alpha synthesis at the expense of prostaglandin E2. At concentrations of 0.4 mM or more, YS980 inhibited synthesis of both prostaglandins E2 and F2 alpha markedly. These results suggest that YS980 has the potential to modulate prostaglandins E2 and F2 alpha synthesis by the kidney and that this effect may represent some pharmacological action of the drug.

3-Mercaptopropionic Acid↗

Heat-treated factor VIII/von Willebrand factor concentrate in platelet-type von Willebrand's disease.

Cryoprecipitate has proved to correct the hemostatic defects in von Willebrand's disease (vWD) and platelet-type vWD. However, recent studies have revealed that transmission of the AIDS retrovirus (HIV) occurs through exposure to blood products including cryoprecipitate. Treatment with heat-treated factor VIII/von Willebrand factor (vWf) concentrates may have certain advantages over treatment with nonheated products, if these preparations are efficacious in these disorders. We found that a commercially available factor VIII/vWf concentrate, Haemate P, contained the high-molecular-weight multimers of vWf and had a ratio of ristocetin cofactor (RCof) to vWf antigen (vWf:Ag) close to unity. In addition, its capacity to directly induce aggregation of platelet-type vWD platelets in vitro was similar to that for cryoprecipitate. When infused into a patient with platelet-type vWD, Haemate P shortened the prolonged bleeding time and caused spontaneous platelet aggregation in vitro with a mild diminution of platelet count. These results indicate that some of the heat-treated factor VIII/vWf concentrates may provide a safer, yet still effective, treatment for platelet-type vWD.

Factor VIII↗