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Biomedical subjects

Y Inagaki

Publications and source records attributed to Y Inagaki.

At least 19 recordsLinked to original sources
PubMed1992

Effect of phosphoramidon on big endothelin-2 conversion into endothelin-2 in human renal adenocarcinoma (ACHN) cells. Analysis of endothelin-2 biosynthetic pathway.

The biosynthetic pathway of endothelin (ET)-2 was analyzed in cultured ACHN cells. In the supernatant, we detected three ET-2-related peptides, ET-2, big ET-2(1-38) and big ET-2(22-38). Phosphoramidon decreased the amount of ET-2 and increased that of big ET-2(1-38) dose-dependently. The amount of big ET-2(1-37) did not significantly change. These results suggest that big ET-2 is composed of 38 and not 37 amino acid residues, and that a putative ET-2-converting enzyme (ECE-2) should be classified as a phosphoramidon-sensitive neutral metalloprotease, bearing a resemblance to the putative ET-1-converting enzyme (ECE-1) in endothelial cells.

Adenocarcinoma↗
PubMed1992

Identification of an upstream regulatory region essential for cell type-specific transcription of the pro-alpha 2(V) collagen gene (COL5A2).

The transcriptional features of the human alpha 2(V) collagen gene (COL5A2) were examined by transfection experiments coupled to various DNA binding assays. This approach identified an upstream region essential for the cell type-specific expression of the COL5A2 promoter. Within this region are two nuclear factor-binding sites, FP-A and FP-B, responsible for the formation of distinct DNA-protein complexes. Mutations introduced across each of the two binding sites eliminated the formation of the cognate complex and decreased promoter activity by about 3-fold (FP-A) and 40-fold (FP-B) in transfection experiments. Competition experiments using recognition sequences for known transcription factors exhibiting some similarity to the FP-A- and FP-B-binding sites failed to inhibit COL5A2/protein interactions. Thus, COL5A2 expression appears to be under the positive control of a short regulatory sequence likely to harbor two novel nuclear factor-binding sites.

Base Sequence↗
PubMed1992

Chimeric HU-IHF proteins that alter DNA-binding ability.

Chimeric proteins between Escherichia coli histone-like HU and IHF were constructed by genetic engineering, in which part of the arm region was replaced by the corresponding region of IHF alpha (designated as HupANhimA) or IHF beta (HupANhimD); alternatively, an alpha-helix 2-beta 1 region was replaced by the corresponding region of IHF alpha (HupAXhimA) or IHF beta (HupAXhimD) (symbols N and X indicate NotI and XhoI junctions). These proteins were synthesized in a hupA-hupB double-deletion mutant. HupANhimA exhibited marked reduction in nonspecific DNA binding in vitro, and a drastic loss of HU activity in replicative transposition of Mu phage in vivo. HupANhimD also showed a significant reduction in the ability for DNA binding, though this protein supported Mu phage development. In contrast, the other two chimeric HU proteins showed only slight changes in nonspecific DNA-binding ability: they retained activities for transposition of Mu phage in vivo. These observations confirm that the flexible arm of HU-2, a domain proposed for DNA binding [Tanaka et al., Nature 310 (1984) 376-381; Goshima et al., Gene 96 (1990) 141-145], plays an important role in the physiological function of this protein. The results indicate that a unique conformation of the arm structure of HU protein, particularly the N-terminal half of a two-strand antiparallel beta-ribbon of the structure, is important for the DNA-binding ability of this protein.

Amino Acid Sequence↗
PubMed1992

Clearance of HBsAg in seven patients with chronic hepatitis B.

The natural history of chronic hepatitis B patients who spontaneously cleared serum HBsAg was investigated. A total of 351 patients with chronic hepatitis B were observed in our hospital for at least 3 yr. Seven of these patients became HBsAg negative during the follow-up period. HBsAg disappeared within 6 mo (range = 11 to 169 days, mean = 70 days) after acute elevation of ALT. ALT levels as high as 500 IU were found in three patients, whereas such elevation was not demonstrated in the other four patients. After the disappearance of HBsAg, ALT levels returned to normal in all patients. With one exception, all patients seroconverted to antibody to HBsAg; however, hepatitis B virus DNA remained detectable in serum using the polymerase chain reaction in five patients. The titer of percent inhibition of antibody to HBcAg gradually decreased to less than 70% when a 1:200 dilution of the serum of six patients was used. Four of the patients had active liver disease develop: two had chronic active hepatitis and two had cirrhosis. Three of these four patients subsequently had hepatocellular carcinoma develop. These findings suggest that patients may suffer complications of chronic hepatitis even after normalization of transaminase activities and after the clearance of HBsAg. Thus hepatitis B virus should be considered as a possible factor associated with hepatocellular carcinoma even in the absence of HBsAg, particularly if serum hepatitis B virus DNA persists.

Base Sequence↗
PubMed1992

Reverse redistribution on Tl-201 SPECT images after reperfusion therapy for acute myocardial infarction: possible mechanism and prognostic implications.

So-called reverse redistribution on stress Tl-201 imaging has been reported previously, but its significance and clinical implications are not well understood. In patients who received reperfusion therapy for acute myocardial infarction, we frequently observed reverse redistribution on stress Tl-201 images. To investigate the significance of reverse redistribution, 61 patients who underwent reperfusion within 4 h of the onset of chest pain underwent submaximal exercise Tl-201 imaging 3 weeks later. We performed simultaneous coronary arteriography and left ventriculography. We divided these 61 patients into three groups based on the pattern of Tl-201 images. Reverse redistribution was found in 19 patients (Group A), 12 patients had redistribution (Group B), and 30 patients had nonreversible defects (Group C). All patients in Group A had less residual stenosis than those in the other groups, and showed significant improvement of left ventricular function. Furthermore, 12 patients (Group A) demonstrated reverse redistribution or a normal pattern in a follow-up study performed 12 months later. However, in the delayed images the defect was smaller than that shown in the previous study. None of the patients had any symptoms and all returned to their previous occupations. In conclusion, reverse redistribution was common in patients undergoing reperfusion therapy for acute myocardial infarction, especially those with little residual stenosis. Reverse redistribution appears to indicate improved regional wall function in such patients.

Aged↗
PubMed1992

Evaluation of morphological changes of the atherosclerotic aorta by enhanced computed tomography.

Enhanced and non-enhanced computed tomography (CT) were performed in 405 subjects (222 men; 183 women; mean age 57 years). Intimal atherosclerotic changes of the aorta were quantified by enhanced CT, revealing the atheromatous intima to be projecting and thick-walled, while non-enhanced CT demonstrated aortic calcification. We measured the degree of aortic intimal changes at various segments of the aorta. In 224 cases, CT was performed from the aortic root to the bifurcation of the abdominal aorta. Intimal changes were found predominantly at the aortic arch, the middle descending thoracic and the infrarenal abdominal aorta. As for the intimal changes, aortic calcification and aortic pulse wave velocity were significant atherosclerotic characteristics. The aortic diameter did not show a significant association with intimal change. Among the various atherosclerotic risk factors, intimal change was significantly associated with age, systolic blood pressure, serum total cholesterol and diabetes mellitus, whereas gender, diastolic blood pressure, relative weight and cigarette use were not significantly related. For coronary artery disease and arteriosclerosis obliterans, aortic intimal changes constituted a significant atherosclerotic feature. In cerebrovascular disease, however, aortic intimal change did not play a significant role.

Adolescent↗
PubMed1992

Type 1 pili enhance the invasion of Salmonella braenderup and Salmonella typhimurium to HeLa cells.

The relationship between type 1 pili-associated adhesion and invasion to HeLa cells by Salmonella braenderup and S. typhimurium was studied. When the clinical isolates of these strains were grown in L-broth, they showed both type 1 pili formation and mannose-sensitive adhesion to HeLa cells. On the other hand, the type 1 pili-defective mutants, which were obtained either by repeated subcultures on L-agar plates or by the transposon Tn1-insertion mutagenesis of the S. braenderup and S. typhimurium strains, concomitantly lost mannose-sensitive adhesion to HeLa cells. When the HeLa cells were incubated with Salmonella, the type 1 piliated strains invaded the HeLa cells with much higher infection rate than did the type 1 pili-defective strains. The invasion of type 1 piliated strains to HeLa cells was markedly inhibited in the presence of D-mannose. The infectivity of the strain, which lost type 1 pili but still had mannose-resistant adhesion, was slightly higher than that of the strains defective in both mannose-sensitive and mannose-resistant adhesion. These results suggested that type 1 pili have a role in enhancing the invasion of S. braenderup and S. typhimurium to HeLa cells.

Acute Disease↗
PubMed1992

Primary hepatocellular carcinoma with severe hypoglycemia: involvement of insulin-like growth factors.

We report a case of severe hypoglycemia and hepatic masses suspected to be an insulin-like growth factor-II (IGF-II)-producing hepatocellular carcinoma. A 62-year-old man presented with mental disorder in the night and early morning associated with extremely low blood sugar levels (less than 21 mg/dl). Computerized axial tomography and ultrasonography revealed a massive tumor in the right lobe of the liver with multiple secondary nodules, and a tumor thrombus in the portal vein. At autopsy 107 days after admission, the liver weighed 3070 g, histologically showing an Edmondson type II tumor with liver cirrhosis. IGF-II in plasma (899 ng/ml) and tumor tissue (2.4 micrograms/g) was higher than that in normal plasma (374-804 ng/ml) and non-tumor liver tissue (0.2 micrograms/ml), while IGF-I (14 ng/ml) was significantly reduced. IGF-II, probably produced by the liver tumor, appeared to be involved in the mechanism of hypoglycemia.

Carcinoma, Hepatocellular↗
PubMed1992

[In vitro antimicrobial activity of DR-3355, a new quinolone antibacterial agent, against clinical isolates of enteritis-causing bacteria].

We determined the minimum inhibitory concentration (MIC) of DR-3355, a newly developed quinolone-derivative antibacterial agent, against clinical isolates of various bacterial species from enteritis patients, and compared them with those of ofloxacin (OFLX), ciprofloxacin (CPFX), nalidixic acid (NA), ampicillin (ABPC), kanamycin (KM). MIC90 of DR-3355 against 94 strains of Shigella spp. and 5 strains of Escherichia coli, 36 strains of Salmonella spp., 22 strains of Vibrio cholerae, 5 strains of Vibrio parahaemolyticus, and 19 strains of Campylobacter jejuni were 0.05, 0.10, 0.0025, 0.39, and 0.78 micrograms/ml, respectively. These values were 1/2 of that of OFLX, and two times of that of CPFX. MIC90 of DR-3355, OFLX and CPFX against C. jejuni were 0.78 micrograms/ml. MIC90 of DR-3355 against isolates from enteritis patients except for Vibrio spp., were 1/30 to 1/60 of those of NA, ABPC, and KM.

Bacteria↗
PubMed1992

Prolongation of canine epidural anesthesia by liposome encapsulation of lidocaine.

The purpose of our study was to produce a long-acting lidocaine by using a liposome that would entrap the drug. Egg yolk phosphatidylcholine and cholesterol were used as liposome materials. After epidural administration, the pharmacodynamics and pharmacokinetics of liposomal and free lidocaine were studied in 20 dogs. Two percent liposomal or free lidocaine (3.0 mL) was injected into the lumbar epidural space. Nerve blocking effects were estimated by measuring somatosensory evoked potentials. Recovery time from the epidural block in the liposomal lidocaine group (170 +/- 49.5 min) was approximately three times longer than that in the free lidocaine group (61 +/- 18.1 min). The areas under the drug concentration-time curves (AUC0-infinity) and time to maximal concentration (Tmax) in the liposomal lidocaine group were significantly larger than those in the free lidocaine group. These results suggest that the prolongation of epidural blockade by liposomal lidocaine is caused by a slow release of the drug from liposomes. The present study suggests that liposomal lidocaine can be used as a long-acting local anesthetic.

Amines↗
PubMed1992

Segmental analgesic effect and reduction of halothane MAC from epidural fentanyl in humans.

To clarify the site of action of epidural fentanyl, we compared the effects of epidural and intravenous fentanyl on the change in pressure pain threshold (PPT) and the minimum alveolar concentration (MAC) of halothane. Seventy patients who underwent gastrectomy in the PPT study group and 84 female patients who underwent hysterectomy in the MAC study group were assigned randomly to seven groups in each study. The seven groups each received a bolus injection of 1, 2, or 4 micrograms/kg of fentanyl, either intravenously or epidurally, and of saline solution epidurally. Compared with intravenous fentanyl, epidural fentanyl significantly increased (P less than 0.01) PPT around surgical incisions by approximately 50%, 100%, and 150% of preadministration levels 1 h after administration of 1, 2, and 4 micrograms/kg, respectively, and significantly reduced (P less than 0.05) halothane MAC at the same doses. These data suggest that the more potent analgesic and anesthetic effects of epidural fentanyl, compared with intravenous fentanyl, are due mainly to the segmental analgesia produced by its spinal analgesic action.

Adult↗
PubMed1992

High-energy phosphate metabolism of the myocardium in normal subjects and patients with various cardiomyopathies--the study using ECG gated MR spectroscopy with a localization technique.

Nuclear magnetic resonance spectroscopy (MRS) is a new technique for the evaluation of myocardial metabolism. Recently, localized MRS has been clinically available to measure by a non-invasive method the relative concentrations of the high-energy phosphate metabolites in the myocardium. We performed ECG gated P-31 MRS using ISIS (image-selected in vivo spectroscopy) in 15 normal volunteers, 12 patients with hypertrophic cardiomyopathy, 12 with left ventricular hypertrophy, 6 with dilated cardiomyopathy and 11 with specific heart muscle disease. Myocardial peak height ratios of PCr/gamma-ATP, Pi/gamma-ATP and PCr/Pi were measured. Myocardial P-31 MRS demonstrated a significant decrease in the ratio PCr/ATP in patients with hypertrophic cardiomyopathy and specific heart muscle disease as compared with normal subjects, indicating myocardial metabolic disturbance in these patients. The ratio of PCr/ATP in patients with dilated cardiomyopathy did not differ significantly from that of normal subjects. However, exercise MRS revealed a marked decrease of PCr peak in an asymptomatic patient with dilated cardiomyopathy, which may indicate a latent metabolic disturbance in the myocardium of dilated cardiomyopathy.

Adenosine Triphosphate↗
PubMed1992

Expansion rate of thoracic aortic aneurysms and influencing factors.

The risk of rupture of an aortic aneurysm increases with size and rapid expansion rate. We studied the expansion rate of thoracic aortic aneurysms and the factors influencing expansion rate, and compared the results with those of abdominal aortic aneurysms. Forty thoracic aortic aneurysms and 25 abdominal aortic aneurysms were serially examined with enhanced and nonenhanced computed tomography. The mean expansion rate of thoracic aortic aneurysms was 1.3 +/- 1.2 mm/yr and was significantly lower than 3.9 +/- 3.2 mm/yr of abdominal aortic aneurysms. The factors increasing expansion rate of thoracic aortic aneurysms were initial size of aneurysms, diastolic blood pressure, and presence of renal failure by univariate analysis. Multivariate analysis concerning the entire aortic aneurysms also revealed that the large size of the aneurysm and the presence of the aortic aneurysm in the abdomen increased expansion rate of aneurysms.

Aged↗
PubMed1992

Unoperated thoracic aortic aneurysms: survival rates of the patients and determinants of prognosis.

The purpose of this study was to evaluate the long-term prognosis of unoperated thoracic aortic aneurysms, and to detect the risk factors which determine the prognosis of unoperated patients. The subjects were 52 unoperated patients with 58 thoracic aortic aneurysms (22 of the ascending aorta, 36 of the descending aorta or the aortic arch) and 38 with abdominal aortic aneurysms. The survival rates of the patients with ascending aortic aneurysms at 3 years and 5 years and those of the patients with descending aortic aneurysms at 5 years were significantly higher than those of the patients with abdominal aortic aneurysms. The risk factors for rupture of thoracic aortic aneurysms were the large size of aneurysms and non-management by the cardiologist and the risk factors for death unrelated to the aneurysms were patient age, male gender and non-management by the cardiologist.

Age Factors↗
PubMed1992

[Left ventricular trabeculae evaluated with MRI in dilated cardiomyopathy and old myocardial infarction].

The morphological examination of the left ventricular trabeculae was performed using MRI (0.5T) in 14 normal volunteers, 12 patients with dilated cardiomyopathy (DCM), and 9 patients with old myocardial infarction (OMI). Left ventricular trabeculae were observed at the free walls of the left ventricle in all subjects, but not at the septal wall. Left ventricular trabeculae were larger in DCM than in the normals. The trabeculae were scarce in OMI and inner sides of the infarcted myocardium were very smooth. The development of the left ventricular trabeculae was graded as diminished, ordinary, and marked. Ordinary trabeculae were seen in 86% of the normals, whereas; marked trabeculae in 75% of DCM, and diminished trabeculae in 78% of OMI. In patients with DCM, the mean area of the left ventricle with marked trabeculae was greater than that with ordinary trabeculae. The more dilated left ventricle, the thinner the anterior wall was and the lower the ejection fraction was in DCM and OMI, though there were no significant differences in values of these 3 items between DCM and OMI. The MRI findings on the development of the trabeculae were confirmed in patients with DCM at autopsy. Thus, the MRI findings were very useful in the differential diagnosis between DCM and OMI.

Adult↗