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Biomedical subjects

T Kanamori

Publications and source records attributed to T Kanamori.

At least 19 recordsLinked to original sources
PubMed1992

Uncoupling of atrial natriuretic peptide extraction and cyclic guanosine monophosphate production in the pulmonary circulation in patients with severe heart failure.

OBJECTIVES: This study was designed to evaluate the role of endogenous atrial natriuretic peptide in the pulmonary circulation in patients with chronic heart failure. BACKGROUND: Plasma atrial natriuretic peptide concentrations in patients with heart failure have been reported to be higher than those in normal subjects and to increase as the severity of heart failure progresses. Although endogenous atrial natriuretic peptide is thought to improve the condition of patients with heart failure by reducing preload and afterload, recent findings have indicated that a high plasma atrial natriuretic peptide level is a prognostic predictor in patients with heart failure. METHODS: To evaluate the pathophysiologic role of endogenous atrial natriuretic peptide in the pulmonary circulation, plasma atrial natriuretic peptide and cyclic guanosine monophosphate (cGMP) levels were determined in the main pulmonary artery and pulmonary capillary wedge region in 80 patients with chronic congestive heart failure (New York Heart Association functional classes II to IV). RESULTS: The plasma atrial natriuretic peptide level decreased significantly from the main pulmonary artery to the pulmonary capillary wedge region, whereas the plasma cGMP level increased significantly from the main pulmonary artery to the pulmonary capillary wedge region. In patients with mild chronic heart failure (n = 50), the plasma atrial natriuretic peptide level correlated with the cGMP level in the main pulmonary artery (gamma = 0.71, p less than 0.001). The atrial natriuretic peptide extraction level, calculated as (Atrial natriuretic peptide in the main pulmonary artery--Atrial natriuretic peptide in the pulmonary capillary wedge region) x Cardiac output x (1-hematocrit/100) (ng/min), also correlated with the cyclic guanosine monophosphate production level, calculated as (cGMP in the pulmonary capillary wedge region--cGMP in the main pulmonary artery) x Cardiac output x (1-hematocrit/100) (nmol/min) (gamma = 0.78, p less than 0.001). In contrast, such correlations were not found in patients with severe chronic heart failure (n = 30). In these patients, the atrial natriuretic peptide extraction level was significantly higher but there was no significant difference in the cGMP production level between the two groups (mild and severe chronic heart failure). Therefore, the molar ratio of cGMP production to atrial natriuretic peptide extraction in the pulmonary circulation was significantly lower in patients with severe chronic heart failure (88 +/- 16 vs. 480 +/- 41, p less than 0.001). CONCLUSIONS: These results indicate that down-regulation of atrial natriuretic peptide receptors coupled to guanylate cyclase may occur in the pulmonary vascular beds of patients with severe chronic heart failure.

Adolescent↗
PubMed1992

Molecular cloning and partial characterization of a novel collagen chain, alpha 1(XVI), consisting of repetitive collagenous domains and cysteine-containing non-collagenous segments.

In an effort to identify new members of the collagen family, we screened a human placenta cDNA library with a collagenous probe. A novel 3.7 kb cDNA was identified encoding an open reading frame of 1,186 amino acids and containing a termination codon. The predicted polypeptide consists of 9 repetitive collagenous (stretches of Gly-X-Y) and several non-collagenous segments. Two cysteinyl residues separated by two amino acid residues (Cys-X-X-Cys) are regularly located in the N-terminal region of each non-collagenous segment. The deduced amino acid sequence described above is distinct from those of known types of collagen. Therefore, this novel collagen chain is designated alpha 1(XVI). Northern blot analysis revealed an alpha 1(XVI) mRNA of 5.2 kb, indicating that the overlapping cDNA clones isolated in this study covered nearly three-fourths of the mRNA. As a tool for further study on the expression of type XVI collagen, we prepared an antibody against the nonadecapeptide CFLSLERPRAEEARGDNSE, derived from the putative translation product of the cDNA. In immunoblot analysis, the antibody recognized a 160 kDa protein, which was bacterial collagenase-sensitive. Immunohistochemical stainings of human placental tissues with anti-peptide antibody revealed a positive reaction with amnion, the membranous tissue lining the amniotic cavity. The gene of alpha 1(XVI) chain, COL16A1, is mapped on the short arm of human chromosome 1 (1p13-p34).

Amino Acid Sequence↗
PubMed1992

Limitations of compensation by endogenous atrial natriuretic peptide in heart failure.

To evaluate the role of endogenous atrial natriuretic peptide (ANP) in patients with congestive heart failure (CHF), the relationship between plasma ANP and cyclic guanosine monophosphate (cGMP) levels and the prognosis of patients with CHF was examined. In patients with chronic mild to moderate CHF, there was a positive correlation between plasma ANP and cGMP levels (r = 0.81, p less than 0.001). However, there was no significant correlation between these plasma levels in patients with chronic severe CHF, in whom the cGMP concentration reached a plateau in spite of high levels of ANP. The ANP extraction level and the cGMP production level in the pulmonary and systemic circulation correlated significantly in patients with mild CHF. In contrast, there was no significant correlation between the 2 parameters in patients with severe CHF, and the molar ratios of cGMP production to ANP extraction in the pulmonary and systemic circulation were significantly lower than those in patients with mild CHF. In 44 patients with chronic severe CHF who were followed up over 2 years, plasma ANP levels provided more sensitive and specific prognostic information than any other parameters. These results indicate that ANP receptors coupled to guanylate cyclase may be down-regulated in patients with chronic severe CHF, suggesting that high plasma ANP levels as a prognostic predictor may be associated with limitations of compensation by endogenous ANP.

Atrial Natriuretic Factor↗
PubMed1992

Increased uncoupling of beta-, beta 1- and beta 2-adrenoceptor to myocardial contraction in failing human myocardium.

Coupling of myocardial beta-, beta 1-, beta 2- and alpha-adrenoceptors (AR) to myocardial contraction was investigated in patients with various degrees of heart failure. With the use of delta Vcfc, a load independent parameter of myocardial contraction, AR mediated contraction was evaluated. beta-AR mediated contraction, delta Vcfc by infusion of a beta-AR agonist, isoproterenol, declined with the advancement of heart failure from 0.41 Circ/sec (NYHA I) to 0.31 (NYHA II), 0.22 (NYHA III) and 0.12 (NYHA IV). Dobutamine, a beta 1-AR full agonist, mediated delta Vcfc was 92-97% of that of isoproterenol. On the other hand, terbutaline sulfate, a full agonist to beta 2-AR, increased delta Vcfc partially in comparison with isoproterenol; 51% in NYHA I, 52% in NYHA II, 36% in NYHA III and 17% in NYHA IV. An alpha 1-AR agonist, methoxamine had little effect on myocardial contractility beta-AR and alpha-AR densities were analyzed by saturation binding isotherms of myocardial membrane fraction with 125I-Iodocyanopindolol (ICYP) and 3H-Bunazosin, respectively. beta-1 and beta 2-ARs were separated by competition binding of 125ICYP with a highly selective beta 1 AR antagonist, CGP20712A. There was a progressive down regulation of beta, beta 1- and beta 2-ARs with the advancement of heart failure. A new index was used to examine coupling of ARs to myocardial contraction; Coupling Index. The index was slightly decreased in NYHA II in beta- and beta 1-ARs. In beta 2-AR, the coupling index declined as heart failure advanced from NYHA I to NYHA IV.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Stable expression of human tissue-type plasminogen activator regulated by beta-actin promoter in three human cell lines: HeLa, WI-38 VA13 and KMS-5.

A high-level and stable expression system of human tissue-type plasminogen activator (t-PA) was accomplished in human cells by selecting a promoter and a host cell line. First, we have constructed two types of t-PA expression plasmids containing 3 kb of the human beta-actin promoter region or 0.3 kb of SV40 early promoter region and these plasmids were transfected into HeLa cells, respectively, and the resulting transfectants were found to secrete various amounts of t-PA derived from the plasmids to the culture media. Southern blot analysis revealed that the beta-actin promoter was more efficient than the SV40 early promoter with regard to the expression level per single copy of the t-PA gene in the transfected HeLa cells. Next, the t-PA expression plasmid containing the beta-actin promoter was also transfected into WI-38 VA13 cells, a human fibroblastic cell line, and KMS-5 cells, a human lymphoid cell line, in order to compare the expression ability of the promoter among these three cell lines. Some of the transfectants from both cell lines were also found to produce t-PA. It was also found that the expression levels in HeLa and WI-38 VA13 seemed to be more efficient than that in KMS-5.

Actins↗
PubMed1989

A case of the pathogenesis of choledochocele in relation to dysfunction of the sphincter of Oddi.

A 47-year-old woman was admitted for evaluation of pain in the right upper quadrant of the abdomen. Seventeen years previously, she had undergone cholecystectomy for cholelithiasis. Endoscopic retrograde cholangiopancreatography (ERCP) showed a cystic dilatation of the terminal portion of the common bile duct (CBD) protruding into the duodenal lumen and delaying the drainage of contrast medium. In this patient the CBD and the pancreatic duct appeared to be unimportant in the formation of the cyst. Repeated changes in the radius of the cyst suggested dysfunction of the ampullary component of the sphincter of Oddi, with maintenance of normal function of the common duct component. The pathogenesis of the choledochocele in this patient is discussed in relation to dysfunction of the sphincter of Oddi. In addition, 2 criteria for the diagnosis of choledochocele by ERCP are proposed: [1] cystic dilatation of the terminal portion of the CBD protruding into the duodenal lumen, and [2] absence of the narrow segment of the CBD.

Ampulla of Vater↗
PubMed1989

In vivo antitumor mechanism of natural human tumor necrosis factor involving a T cell-mediated immunological route.

We have investigated the in vivo antitumor mechanism of natural human tumor necrosis factor (n-TNF) isolated from a culture of human leukemic B cell line (BALL-1), especially its action as an immunomodulator, and found that the in vivo antitumor effect of n-TNF on Meth A sarcoma implanted in BALB/c mice pretreated with monoclonal antibody against T cell-specific surface antigen (Thy-1) was significantly diminished. Furthermore, when BALB/c mice were treated with T cell subset-specific monoclonal antibodies, anti-L3T4 or anti-Lyt-2.2, the antitumor effect of n-TNF on Meth A sarcoma was significantly reduced. Therefore, it was suggested that the in vivo antitumor mechanism of n-TNF might involve a T cell-mediated immunological route.

Animals↗
PubMed1989

[A case of carcinoma of the ileum diagnosed as an adenocarcinoma].

A 65-year-old female with a history of cancer of the uterine body and a strong family history of cancer, was admitted with abdominal pain and anemia. During roentgenographic examination of the small intestine, a tumor was recognized about 25 cm from the ileocecal valve, leading us to suspect a carcinoma of the ileum. A colonoscopy demonstrated a constricting, ulcerated lesion, with a round wall: and a subsequent biopsy proved that the patient had a moderately differentiated adenocarcinoma. At surgery, a tumor, measuring 52 x 50 mm, was found to have infiltrated the serosa with a metastasis to the mesenteric lymph node.

Adenocarcinoma↗
PubMed1988

Expression and excretion of human pancreatic secretory trypsin inhibitor in lipoprotein-deletion mutant of Escherichia coli.

We constructed a gene coding for the 56-amino acid human pancreatic secretory trypsin inhibitor (PSTI), and ligated it on a plasmid downstream from the trp promoter and the signal peptide sequence of alkaline phosphatase. The resulting plasmid was transfected into a lipoprotein deletion mutant (Escherichia coli JE5505) and the plasmid-carrying cells were induced with 3-indoleacrylic acid. A considerable amount (50 micrograms/ml culture) of the mature PSTI protein was detected in the culture supernatant. The excreted PSTI was identical to the natural PSTI protein with respect to the trypsin-inhibiting activity, the N-terminal and the C-terminal amino acid sequences and the amino acid composition.

Base Sequence↗
PubMed1987

Ion-exchange chromatography of ionic detergent-solubilized proteins: application to purification of rat parotid gland phosphoproteins including ribosomal protein S6.

A method is described for separation of ionic detergent-solubilized proteins by ion-exchange chromatography. This method has been developed for purification of two phosphoproteins (Mr 19,000 and 30,000) from 32Pi-prelabeled, isoproterenol-stimulated rat parotid tissue and is based on the observation that, in the presence of urea and Nonidet-P40, ionic detergent-solubilized proteins can be adsorbed by ion exchangers according to their own charge. After adsorption, proteins were eluted with a stepwise gradient of NaCl in a urea-containing buffer. By the procedure described, the 30 kDa phosphoprotein was freed from other 32P-labeled substances; and it was identified as ribosomal protein S6 that was phosphorylated at some serine residues. The method is generally applicable and especially suited for preliminary purification of hydrophobic proteins subjected to analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Animals↗
PubMed1987

The inhibition of neoplastic cell proliferation with human natural tumor necrosis factor.

Purified human natural tumor necrosis factor (n-TNF) was prepared by stimulating human leukemic B cell line (BALL-1) with Sendai virus. The colony formations of all of 18 human cancer-derived abnormal cell lines were suppressed by 10(1)-10(6) U/ml of n-TNF, while n-TNF was nontoxic to all human normal fibroblast cells. This in vitro inhibition of cell growth was reversible. In breast adenocarcinoma MCF7 cells treated with n-TNF a specific decrease of DNA synthesis was observed, and DNA histograms showed a block at G1 in the cell cycle. In vivo studies revealed that n-TNF suppressed the tumor growth of murine Meth A sarcoma, human renal adenocarcinoma (ACHN), malignant melanoma (SK-MEL-28) and glioblastoma (U-373 MG). Isobologram analysis showed that n-TNF synergistically inhibited cell growth in combination with human natural interferon (IFN)-a. In vivo synergism of n-TNF and IFN-a was also found in the U-373 MG tumor model implanted into nude mice.

Animals↗
PubMed1986

[Basic study on human interferon-beta: Part III. The mechanisms of its antitumor effect].

The mechanisms of the direct and indirect antitumor effects of human interferon-beta (IFN-beta, MR-21) were examined. IFN-beta suppressed DNA, RNA and protein synthesis in cells derived from human tumor. The expression of cellular oncogenes (c-Ha-ras and c-myc) in tumor-originated cells was also suppressed by IFN-beta. These results suggest that such suppression is one possible mechanism of the direct anticellular effect induced by IFN-beta. IFN-beta augmented NK cell activity and the ADCC activity of human peripheral blood lymphocytes. It is also suggested that these are two of the immune system-mediated mechanisms responsible for the indirect antitumor effect of IFN-beta in vivo.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1986

The expression of human tumor necrosis factor in E. coli.

cDNA of human natural TNF (n-TNF) obtained by stimulating human leukemic B cell line (Ball-1) with Sendai virus was cloned. Valine-started-TNF (V-TNF) gene was constructed from the cDNA and expressed in E.coli HB101 under the control of a trp promoter by the induction of 3-indoleacrylic acid. The expression level of V-TNF clone was about 10% of the total E.coli protein. On the other hand, the expression level of glutamine started-TNF (Q-TNF) gene having the same SD-ATG sequence which was constructed from V-TNF gene was as low as about 1/20 of that of V-TNF. The nucleotide sequence around ATG (-4 approximately +12) of Q-TNF gene was randomly changed without modifying the coded amino acid sequence, resulting to obtain high expression clones as similar TNF protein yield as that of V-TNF. These clones possessed A residue rich sequence around the initiation codon ATG. These results show that some correlation might exist between the high expression rate and A residue rich sequence around the initiation codon.

Amino Acid Sequence↗
PubMed1986

[Basic study on human interferon-beta: Part I. Antiviral effect].

A study was performed on the antiviral effects of human interferon-beta (IFN-beta, MR-21) produced by a normal human diploid fibroblast cell strain. Of 4 DNA and 9 RNA viruses used in this study, all were inhibited by the IFN-beta and the IC90S obtained were approximately 10(1)-10(3) IU/ml. Results showed that IFN-beta had a very wide antiviral spectrum. The IFN-beta was able to induce 2',5'-oligo A synthetase activity in RSa, HeLa S3 and M08 cell lines but not in HEC-1C cell line lacking receptors for IFN-beta. This strongly suggests that one of the antiviral mechanisms might function through the induction of 2',5'-oligo A synthetase activity through the IFN-beta receptor.

2',5'-Oligoadenylate Synthetase↗