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Biomedical subjects

Y Takayama

Publications and source records attributed to Y Takayama.

At least 19 recordsLinked to original sources

Structures of cDNAs encoding chum salmon pituitary-specific transcription factor, Pit-1/GHF-1.

Pit-1/GHF-1, a POU family transcription factor, was originally isolated as a protein that contributes to the pituitary-specific expression of the mammalian growth hormone(GH)-encoding gene. Pit-1/GHF-1 has been recently implicated in the development of three types of hormone-producing cells which secrete GH, prolactin (PRL) and thyroid-stimulating hormone. A presumed pituitary hormone, somatolactin (SL) which belongs to the GH/PRL family, was previously isolated from fish. As the first step for determining the possible involvement of the Pit-1 protein in the pituitary-specific expression of the SL gene and/or in the development of SL-producing cells, chum salmon Pit-1 cDNA clones were isolated. Chum salmon Pit-1 mRNAs were mainly 2 kb and 3 kb in size, and specifically expressed in the pituitaries. They encoded a 365-amino acid (aa) protein, which was 74 aa larger than that found in mammals. The identity of aa sequences between salmon and rat Pit-1 was 69%. These proteins were highly conserved in the region specific for the POU family. Salmon Pit-1 had two additional sequences each consisting of about 30 aa in the N-terminal region. The sequence involved in transcriptional activation is considered to be located in the region including the above sequences, and thus, salmon Pit-1 may possibly have novel functions distinct from those of rat Pit-1.

Amino Acid Sequence

Clinical significance of serum colloid osmotic pressure in relation to pulmonary edema and coronary instability in patients with unstable angina.

Several investigators demonstrated that severe reduction of colloid osmotic pressure (COP) predicts a fatal outcome in patients with cardiopulmonary failure. To evaluate the clinical significance of COP in relation to pulmonary edema, we studied 117 patients with unstable angina admitted in the hospital within 24 h after the chest pain. The mean COP of all 117 patients was 24.8 +/- 3.7 mmHg. COP was significantly lower in patients with pulmonary edema, according to the chest x-ray findings, compared with the patients without it. Among 26 patients with emergency coronary arteriography, a fairly good correlation was observed between coronary jeopardy score and COP (r = -0.57, p less than 0.005). Furthermore, COP in patients who survived 26 months after the hospital discharge was significantly higher than that of the nonsurvivors. Thus, measurement of COP is advised for monitoring patients with unstable angina.

Angina, Unstable

Difference in the residual left ventricular pump function between anterior and inferior myocardial infarctions.

To evaluate the left ventricular regional ejection fraction (EF) of noninfarcted area in relation to the left ventricular end-diastolic volume (EDV) in patients with recent myocardial infarction (MI), 75 patients with Q-wave MI (anterior: 51 patients; inferior; 24 patients) were studied. The regional EF of noninfarcted area was obtained by radionuclide angiocardiography 4 weeks after the onset of MI and was used to estimate the left ventricular regional function of the noninfarcted area. Peak creatine kinase and QRS scores were not significantly different between anterior and inferior MI in each left ventricular EDV (EDV < or = 100, 101-139 and > or = 140 ml). Global EF and regional EF of noninfarcted area in anterior MI with left ventricular EDV > or = 140 ml was significantly lower than in those with EDV < or = 139 ml (p < 0.01), whereas there were no significant differences in global EF and regional EF of noninfarcted area in the three groups of left ventricular EDV in inferior MI. Thus, the effect of left ventricular EDV on regional EF of noninfarcted area and on the total cardiac performance was more important in anterior than in inferior MI, because a similar degree of left ventricular dilatation resulted in more severe derangements after anterior MI.

Adult

Disturbance of pulmonary gas exchange in patients with right ventricular infarction.

To evaluate the difference in pulmonary gas exchange in patients with and without right ventricular infarction, 147 consecutive patients with their first inferior wall Q-wave acute myocardial infarction were studied. Thirty-nine patients (group 1) had electrocardiographic evidence of right ventricular infarction and it was absent in 108 patients (group 2). A significantly wider alveolar arterial oxygen difference and higher roentgenographic scores were observed in group 1 compared with group 2. Although there were no significant differences in pulmonary artery wedge pressure and colloid osmotic pressure between groups 1 and 2, mean right atrial pressure was significantly higher, while cardiac output and mixed venous oxygen saturation were lower in group 1 compared with group 2. Patients in group 1 had significantly more left ventricular segments with advanced asynergy and higher incidence of proximal right coronary artery lesions than those in group 2. Thus, our data suggest that disorder of pulmonary gas exchange in patients with right ventricular infarction may be explained by increased permeability of the alveolar capillary membrane secondary to larger extent of ischemic myocardium and by hemodynamic abnormalities associated with right ventricular infarction.

Catheterization, Swan-Ganz

Role of platelet-activating factor in pulmonary edema after coronary ligation in dogs.

To evaluate whether PAF is related to the precipitation of pulmonary edema after myocardial ischemia, we studied the effect of a specific PAF antagonist, CV-6209, on the extravascular lung water level measured by the thermal-dye double indicator dilution method, ETV, after coronary ligation in dogs. Eight dogs served as sham control animals (group 1). The proximal left anterior descending coronary artery was ligated for 45 min in eight dogs (group 2), and the coronary artery was ligated after pretreatment with CV-6209 (1 mg/kg) in eight dogs (group 3). The ETV increased significantly after coronary ligation in groups 2 and 3. The amount of increase in ETV in group 2 was significantly larger than in group 3. Thus, CV-6209 can prevent the accumulation of extravascular lung water after coronary ligation without producing changes in pulmonary vascular dynamics, indicating that PAF may play an important role in pulmonary edema after myocardial ischemia.

Animals

[Clinical characteristics of pulmonary edema in patients with unstable angina].

To elucidate the clinical characteristics of pulmonary edema in unstable angina, 120 patients with unstable angina who admitted to the hospital within 6 hours after the onset of chest pain were studied. The criteria for the diagnosis of pulmonary edema included interstitial pulmonary edema and diffuse alveolar edema. Pulmonary edema was present in 24 patients. In these patients, the duration of chest pain was relatively longer, and the incidences of diabetes mellitus, emergency coronary revascularization and multiple-vessel coronary artery disease were higher than in those without pulmonary edema. In addition, in-hospital mortality rate in patients with pulmonary edema was higher than in those without it (21 vs 1%, p < 0.001), which is probably due to a large area of myocardial ischemia. For these patients, therefore, early diagnosis and appropriate therapy to save viable segments of the myocardium are mandatory.

Aged

Insulin-like growth factor I rapidly induces tyrosine phosphorylation of a Mr 150,000 and a Mr 160,000 protein in highly metastatic mouse colon carcinoma 26 NL-17 cells.

Insulin-like growth factor I (IGF-I) stimulates the proliferation of highly metastatic NL-17 cells to a greater extent than poorly metastatic NL-44 cells, both of which are derived from mouse colon carcinoma 26. The NL-17 cells have been compared with NL-44 cells for the signal transduction pathway of IGF-I. IGF-I receptors of both cell types were identified by affinity labeling, and there was no significant difference between the two cell types in the amount or the autophosphorylation activity of the IGF-I receptors. However, when IGF-I-dependent tyrosine phosphorylation of cellular components was examined, remarkable tyrosine phosphorylation of proteins with molecular weights of 150,000 (pp150) and 160,000 (pp160) was found in NL-17 cells. In contrast, this phosphorylation stayed at significantly lower levels in NL-44 cells than in NL-17 cells. The phosphorylation of pp150 and pp160 was induced within 10 s after the addition of IGF-I and reached its maximal level by 30 s. After the removal of IGF-I, the phosphorylation of pp150 and pp160 was reduced to the basal level within 30 min. This phosphorylation was not induced by platelet-derived or epidermal growth factor. The pp150 and pp160 were not absorbed by wheat germ agglutinin-agarose. They were found in the soluble fraction of cytoplasm but not in the membrane or the cytoskeleton. The pp150 and pp160 might be endogenous substrates of IGF-I receptor kinase. These results suggest that tyrosine phosphorylation of pp150 and pp160 mediates the higher proliferative response of NL-17 cells to IGF-I.

Animals

Application of a metal capillary column in gas chromatographic determination of catechol-o-methyltransferase activity.

The utility of a deactivated metal capillary column, Rascot, in the measurement of an enzymatic reaction, in this case measurement of rat catechol-O-methyltransferase activity, was examined. 3,4-Dihydroxybenzaldehyde, 3,4-dihydroxybenzylalcohol and 3,4-dihydroxybenzoic acid were used as substrates and the m- and p-O-methylated products were separated by using Rascot after derivatization. The peaks on the chromatograms were symmetrical. The data obtained were compared with those reported in previously published papers. Good agreement with previous results proved that Rascot is able to withstand practical use in biological materials.

Animals

Conformational structure of a monoclonal anti-idiotypic antibody to the monoclonal anti-adenocarcinoma-associated carbohydrate antibody YH206.

The mAb AI206 (IgG1) is an anti-Id antibody of mAb YH206 (IgM) to adenocarcinoma-associated carbohydrate Ag and inhibits the reaction of mAb YH206 to YH206 Ag at low concentrations. By Western blot analysis, mAb AI206 only reacted with unreduced mAb YH206, whereas it did not react with reduced mAb YH206. Furthermore, mAb AI206 reacted with IgM subunit (180 kDa), F(ab')2 (110 kDa), and F(ab) (50 kDa) of pepsin-treated unreduced mAb YH206. Thus, mAb AI206 recognized the structure of F(ab) of mAb YH206. The mAb YH206 reacted with unreduced mAb AI206, F(ab')2 (110 kDa), and F(ab) (50 kDa) of pepsin-treated unreduced mAb AI206. It is presumed that mAb YH206 and mAb AI206 recognize each other in an unreduced condition but not a reduced condition. The recognition of such a conformational Id on F(ab) is important. Because mAb YH206 recognized the carbohydrate on YH206 Ag as well as the peptide on mAb AI206, the conformation on F(ab) of mAb AI206 may mimic the carbohydrate structure on YH206 Ag. In fact, YH206 antibody activity was induced in syngeneic mouse serum immunized with mAb AI206. These observations suggest that the internal image of YH206 carbohydrate Ag is preserved within the conformational Id on F(ab) of mAb AI206.

Adenocarcinoma

Mixed venous oxygen saturation as a guide to tissue oxygenation and prognosis in patients with acute myocardial infarction.

The relation of mixed venous oxygen saturation and the cardiac index to tissue oxygenation and prognosis was investigated in 119 patients with acute myocardial infarction. There was a positive correlation between mixed venous oxygen saturation and the cardiac index in 97 survivors and 22 nonsurvivors, but a significantly lower mixed venous oxygen saturation level at the same level of cardiac index was observed in nonsurvivors compared with survivors. Results of multivariate analysis with mixed venous oxygen saturation and the cardiac index indicated that only mixed venous oxygen saturation was significantly related to survival and to hyperlactacidemia. Oxygen delivery to tissues declined significantly in nonsurvivors because of a lower cardiac index and a lower hemoglobin concentration in these patients than in survivors. However, at the same level of oxygen delivery to tissues, nonsurvivors had a significantly higher rate of oxygen consumption leading to a correspondingly greater decrease in mixed venous oxygen saturation, suggesting that a greater increase in oxygen demand was also observed in nonsurvivors than in survivors. Thus mixed venous oxygen saturation after acute myocardial infarction is a better predictor of hyperlactacidemia and survival than the cardiac index, and this may be associated with an increased oxygen demand and an impaired oxygen transport system in seriously ill patients.

Aged

A novel enzyme immunoassay for serodiagnosis of Helicobacter pylori infection.

Helicobacter pylori has recently been implicated as an etiologic agent of gastroduodenal disorders. Comparing the antibody to H. pylori in the sera of patients with that of normal controls by Western blot analysis, a unique antibody was detected in the sera of patients, which reacted with the 25-kilodalton antigen of H. pylori. On the other hand, monoclonal antibody CP3 prepared in the authors' laboratory also recognized the 25-kilodalton antigen of H. pylori. Whether the serum antibody of the patient recognized the CP3 antigen purified by monoclonal antibody CP3 was then examined. Western blot analysis showed that the patient's serum reacted strongly with the affinity-purified CP3 antigen. Using monoclonal antibody CP3, an enzyme-linked immunosorbent assay to detect CP3 antibody in sera was established. In patients with chronic gastritis and gastric ulcers, the titer of CP3 antibody was significantly higher than in normal controls and correlated with the histological grade of antral gastritis. The detection of CP3 antibody in sera is useful in the diagnosis of chronic gastritis and gastric ulcer associated with H. pylori infection and also in evaluation of the grade of gastritis.

Animals

Greater conservation of somatolactin, a presumed pituitary hormone of the growth hormone/prolactin family, than of growth hormone in teleost fish.

From pituitary cDNA libraries of Atlantic cod and chum salmon, cDNA clones coding for somatolactin (SL), a presumed pituitary hormone belonging to the growth hormone (GH)/prolactin (PRL) family, were isolated and characterized. The 1.3-kb cod SL mRNA was composed of a greater than 0.25-kb 5' untranslated region, a coding region for the precursor of 235 amino acids (aa), a 0.14-kb 3' untranslated region, and a poly(A) tail. The 2.5-kb salmon SL mRNA had a less than 0.1-kb 5' untranslated region, a precursor (233 aa) coding region, a 1.6-kb 3' untranslated region, and a poly(A) tail. A signal peptide of 26 and 24 aa was found in the SL precursor of cod and salmon, respectively. Thus, the mature SLs of these fish are composed of 209 aa. Two potential N-glycosylation sites were identified in cod SL, whereas no site could be found in the salmon. A comparison of amino acid sequences of the three SLs so far isolated indicated six Cys residues to be in homologous positions to those in GH and PRL, and one Cys residue to be characteristically present in SL. Among cod, salmon, and flounder, greater colinearity of amino acid sequences was noted in SLs than in GHs. The identities of the SL amino acid sequences were between 73 and 81% as compared to 58-62% for the corresponding GHs, indicating greater conservation of SL than GH.

Amino Acid Sequence

Increased extravascular lung water in patients with low pulmonary artery occlusion pressure after acute myocardial infarction.

OBJECTIVE: To evaluate the clinical characteristics of increased extravascular lung water (EVLW) in patients with low pulmonary artery occlusion pressure (PAOP) in the early phase of acute myocardial infarction. DESIGN: Consecutive sample for descriptions of the clinical features of medical disorders. SETTING: A general medicine group practice in a university hospital. PATIENTS: Sixteen patients with low PAOP (less than 18 mm Hg) on the initial measurement obtained within 12 hr of chest pain onset. MEASUREMENTS AND MAIN RESULTS: EVLW was measured by the thermal indocyanine green dye double-indicator dilution method. QRS score was obtained on hospital day 7 from the Selvester's QRS Scoring System. Eleven (69%) patients had increased EVLW greater than 7 mL/kg despite low PAOP. EVLW had no significant correlation with PAOP and the difference between plasma colloid osmotic pressure and PAOP, but did have a significant correlation with pulmonary vascular resistance index (r2 = .31, p less than .05), and QRS score (r2 = .45, p less than .005). CONCLUSIONS: Larger infarcts led to increased EVLW even with low PAOP, and the accumulation of increased EVLW around the small arterioles might have led to increased pulmonary vascular resistance.

Blood Pressure

Colonization of Helicobacter pylori in the gastric mucosa of Mongolian gerbils.

Helicobacter pylori was orally inoculated into Mongolian gerbils. The organisms were able to colonize in the gastro-mucosal layer of the gerbils, especially in those gerbils which had mucosal lesions caused by indomethacin treatment. The pathological changes developed by H. pylori infection were restricted to the stomachs, and only slightly inflammatory cells were observed.

Animals

Stage-specific expression of intracisternal A-particle sequences in murine myelomonocytic leukemia cell lines and normal myelomonocytic differentiation.

The levels of intracisternal A-particle (IAP) mRNA were analyzed in a variety of myelomonocytic leukemia cell lines, peritoneally derived macrophages, and normal hemopoietic progenitors induced to differentiate. In both normal and leukemic cells, the highest level of IAP message was found in cells at an intermediate stage of myelomonocytic differentiation, namely, the promyelomonocyte. These results indicate that IAP sequence transcription is regulated differentially during myelomonocytic cell development and that in general, the expression pattern is preserved in leukemic cell lines in vitro. In addition, Northern (RNA) analysis detected only type I IAP transcripts as the major IAP message and the expressed IAP subtypes varied in certain cell lines. This is the first comprehensive study of IAP expression in the myelomonocytic lineage and provides a useful system to study the biology of IAPs.

Animals

Gene structure of chum salmon somatolactin, a presumed pituitary hormone of the growth hormone/prolactin family.

From a chum salmon genomic DNA library, clones coding for somatolactin (SL), a presumed pituitary hormone belonging to the GH/PRL family, were isolated and analyzed. The salmon SL gene was 16 kilobases (kb) in length, this being the largest among mammalian GH (approximately 2 kb) and PRL (approximately 10 kb) and fish GH (approximately 4 kb) genes. As in the case of mammalian GH/PRL genes, the salmon SL gene was comprised of five exons in contrast to rainbow trout and Atlantic salmon GH genes, which each have six exons. Upstream from the transcriptional initiation site were found one TATA box identical to those of mammalian PRL genes and four consensus sequences corresponding to the Pit-1/GHF-1 binding element which is essential to the expression of mammalian GH and/or PRL genes. The similarity in amino acid sequences and organization of the SL gene with mammalian GH/PRL genes indicates that the SL gene is quite likely produced from an ancestral gene common to GH/PRL genes by gene duplication. Based on these considerations, an evolutionary model for the GH/PRL/SL gene family was made and shows the common ancestral gene to originate not from duplication of a primordial gene but from shuffling of independent exons and a regulatory sequence.

Amino Acid Sequence

Pulmonary gas exchange in acute myocardial infarction with low pulmonary capillary wedge pressure.

To evaluate the clinical characteristic of pulmonary gas exchange in patients with low pulmonary capillary wedge pressure (PCW less than 18 mmHg) in the early phase of acute myocardial infarction, we investigated 48 patients admitted within 24h from the onset of chest pain. The alveolar-arterial oxygen tension difference (AaDO2) and arterial blood gas parameters were obtained while breathing room air on admission. The disturbance of pulmonary gas exchange, as revealed by the high value of AaDO2, existed without left ventricular dysfunction, and AaDO2 had no significant relationship with any of the hemodynamic parameters including the difference between plasma colloid osmotic pressure and PCW. Multiple regression analysis was performed using 9 variables related to pulmonary gas exchange, to identify those which were important. As a result, QRS score (p less than 0.01) and age (p less than 0.05) were identified as significant variables related to AaDO2. Thus, the disturbance of pulmonary gas exchange in patients with low PCW was caused by mechanisms other than left ventricular failure which may reflect the extent of ischemic myocardium.

Aged