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Biomedical subjects

H Yamauchi

Publications and source records attributed to H Yamauchi.

At least 55 records · Page 3Linked to original sources

Characterization of the antitumor activities of IFN-alpha8 on renal cell carcinoma cells in vitro.

Interferon-alpha (IFN-alpha) has a number of therapeutic applications in the treatment of various human cancers and diseases of viral origin. IFN-alpha includes several subtypes, and little has been reported on the biologic properties of the individual subtypes. Here, we report on the individual antitumor effects of five IFN-alpha subtypes, alpha1, alpha2, alpha5, alpha8, and alpha10, against six renal cell carcinoma (RCC) cell lines in vitro. Among the subtypes, IFN-alpha8 most potently inhibited cell proliferation and delayed the G(1)/S transition. Synergistic induction of apoptosis was shown in two of the RCC cell lines when treated with the combination of IFN-alpha and IFN-gamma rather than with either IFN-alpha or IFN-gamma alone. IFN-alpha8 was most effective in the induction of apoptosis when combined with IFN-gamma. In addition, IFN-alpha8 had the strongest ability to upregulate HLA class II antigen expression in the subtypes examined. These data indicate that subtypes of IFN-alpha have disparate antitumor effects in vitro, and in vitro distinctions among the IFN-alpha subtypes should be appreciated more in clinical application.

Antineoplastic Agents↗

Analysis of the antiviral activities of natural IFN-alpha preparations and their subtype compositions.

Here we report on the antiviral effects of two commercially available natural interferon-alpha (IFN-alpha) preparations, their subtype compositions, and the effects of combinations of pairs of the subtypes on virally infected cells. Our results show that the antiviral effects of these preparations depend on the target cell and on the infecting virus. The component subtypes vary with the preparations, and combinations of pairs of IFN-alpha subtypes may have synergistic or competitive effects. Our results suggest that optimal preparations of synergistically acting subtypes may provide more therapeutic benefit to patients.

Antiviral Agents↗

Dissociable mechanisms of attentional control within the human prefrontal cortex.

Neuropsychological tests that require shifting an attentional set, such as the Wisconsin Card Sorting Test, are sensitive to frontal lobe damage. Although little information is available for humans, an animal experiment suggested that different regions of the prefrontal cortex may contribute to set shifting behavior at different levels of processing. Behavioral studies also suggest that set shifting trials are more time consuming than non-set shifting trials (i.e. switch cost) and that this may be underpinned by differences at the neural level. We determined whether there were differential neural responses associated with two different levels of shifting behavior, that of reversal of stimulus-response associations within a perceptual dimension or that of shifting an attentional set between different perceptual dimensions. Neural activity in the antero-dorsal prefrontal cortex increased only in attentional set shifting, in which switch costs were significant. Activity in the postero-ventral prefrontal cortex increased not only in set shifting but also in reversing stimulus-response associations, in which switch costs were absent. We conclude that these distinct regions in the human prefrontal cortex provide different levels of attention control in response selection. Thus, the antero-dorsal prefrontal cortex may be critical for higher order control of attention, i.e. attentional set shifting, whereas the postero-ventral area may be related to a lower level of shift, i.e. reorganizing stimulus-response associations.

Adult↗

New base analogs for the formation of non-natural triplexes.

Novel nucleoside analogs have been designed for selective formation of antiparallel triplexes including a TA or a CG interrupting site. The new compounds are constructed of a W-shape bicyclic nucleic acid (WNA) bearing an aromatic ring as a stacking motif and a guanine for the formation of Hoogesteen hydrogen bonds, and are expected to effect triplex stabilization by both stacking and complementary hydrogen bonds. Purine-rich triplex-forming oligodeoxynucleotide (TFO) incorporating the new analog, WNA-7 beta G, formed a stable triplex with high selectivity to the AT site.

DNA↗

Quantitative comparison of the bolus and steady-state methods for measurement of cerebral perfusion and oxygen metabolism: positron emission tomography study using 15O-gas and water.

To evaluate a new simplified bolus method for measurement of cerebral perfusion and metabolism, the parametric images with that method were compared with those obtained from the conventional steady-state method with 15O-gas. The new method also provided images of arterial blood volume (V0), which is a different parameter from cerebral blood volume (CBV) obtained using a C15O technique. Seven healthy volunteers and 10 patients with occlusive cerebrovascular diseases underwent positron emission tomography (PET) scans with both methods. Three-weighted integration was applied to calculate regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of oxygen (rCMRO2) in the bolus method. Global and regional CBF and CMRO2 in volunteers were compared between the two methods and used as control data. Regional values in patients also were evaluated to observe differences between the bilateral hemispheres. Both rCBF and rCMRO2 were linearly well correlated between the two methods, although global difference in CMRO2 was significant. The difference in each parametric image except for V0 was significant between the bilateral hemispheres in patients. The bolus method can simplify oxygen metabolism studies and yield parametric images comparable with those with the steady-state method, and can allow for evaluation of V0 simultaneously. Increase in CBV without a change in V0 suggested the increase might mainly be caused by venous dilatation in the ischemic regions.

Adult↗

Effects of acetazolamide on cerebral blood flow, blood volume, and oxygen metabolism: a positron emission tomography study with healthy volunteers.

To evaluate changes in cerebral hemodynamics and metabolism induced by acetazolamide in healthy subjects, positron emission tomography studies for measurement of cerebral perfusion and oxygen consumption were performed. Sixteen healthy volunteers underwent positron emission tomography studies with 15O-gas and water before and after intravenous administration of acetazolamide. Dynamic positron emission tomography data were acquired after bolus injection of H2[15O] and bolus inhalation of 15O2. Cerebral blood flow, metabolic rate of oxygen, and arterial-to-capillary blood volume images were calculated using the three-weighted integral method. The images of cerebral blood volume were calculated using the bolus inhalation technique of C[15O]. The scans for cerebral blood flow and volume and metabolic rate of oxygen after acetazolamide challenge were performed at 10, 20, and 30 minutes after drug injection. The parametric images obtained under the two conditions at baseline and after acetazolamide administration were compared. The global and regional values for cerebral blood flow and volume and arterial-to-capillary blood volume increased significantly after acetazolamide administration compared with the baseline condition, whereas no difference in metabolic rate of oxygen was observed. Acetazolamide-induced increases in both blood flow and volume in the normal brain occurred as a vasodilatory reaction of functioning vessels. The increase in arterial-to-capillary blood volume made the major contribution to the cerebral blood volume increase, indicating that the raise in cerebral blood flow during the acetazolamide challenge is closely related to arterial-to-capillary vasomotor responsiveness.

Acetazolamide↗

[The effects of kampo-formulation and the constituting crude drugs, prescribed for the treatment of peptic ulcer on H,K-ATPase activity].

We studied the effects of 17 kinds of Kampo-formulations prescribed for the treatment of peptic ulcer on H,K-ATPase activity. The activity was strongly inhibited by San-o-shashin-to ([symbol: see text], IC50 = 82 micrograms/ml), Bukuryo-in ([symbol: see text], IC50 = 110 micrograms/ml), Shakuyaku-kanzo-to ([symbol: see text], IC50 = 170 micrograms/ml), Hange-koboku-to ([symbol: see text], IC50 = 290 micrograms/ml), Dai-saiko-to ([symbol: see text], IC50 = 340 micrograms/ml), Irei-san ([symbol: see text], IC50 = 380 micrograms/ml) than other Kampo-formulations. Among the 17 kinds of crude drugs contained in these Kampo-formulation, Rhei Rhizoma, Coptidis Rhizoma, Glycyrrhiza Radix, Cinnamomi Cortex, and Poria have notable inhibitory effects (IC50 = 19-57 micrograms/ml). H,K-ATPase activity was inhibited by sennoside A (Rhei Rhizoma), sennoside B (Rhei Rhizoma), ergosterol (Poria), coptisine (Coptidis Rhizoma), glycyrrhizin (Glycyrrhiza Radix), glycyrrhetic acid (Glycyrrhiza Radix), gallic acid (Cinnamomi Cortex) in the 21 components of these crude drugs (IC50 = 1.6-7.9 x 10(-4) M). The inhibition of San-o-shashin-to and Bukuryo-in is considered to be mainly attributed to Rhei Rhizoma and Poria, respectively. The anti-gastric ulcer effects of San-o-shashin-to and Bukuryo-in may be ascribed to the inhibition of H,K-ATPase activity.

Anti-Ulcer Agents↗

Surgical repair of coronary artery aneurysm after percutaneous coronary intervention.

Two cases of coronary artery aneurysm after percutaneous coronary intervention are presented. In both cases, follow-up coronary angiography revealed an expanding saccular aneurysmal formation and restenosis or a new lesion. Consequently, surgical repair and revascularization were indicated. The intraoperative angioscope was used to identify the aneurysm, which had not been visible on the heart surface in one case. Its optic fiber light was a useful guide, but little information was obtained from direct vision because of the small caliber of the angioscope. Plication of the aneurysm and bypass grafting distal to the aneurysm were performed. A whitish and thick-walled aneurysm was easily found in one case, in which ligation of the aneurysm was attempted with added distal bypass. The postoperative course was uneventful in both cases, and follow-up angiography showed disappearance of the aneurysm with patent grafts. There was a fragile thrombus inside both the aneurysmal sacs, which might have caused myocardial infarction and, therefore, justified the surgical repair of the aneurysm with concomitant revascularization.

Aged↗

[Clinical characteristics of congenital heart disease diagnosed during neonatal period].

We have analyzed 43 newborn babies with congenital heart disease (CHD) over the last two years. The occurrence rate of CHD was 7.5 per 1,000 live births in our maternity hospital, and 4.5% of all babies admitted to our NICU. Low birth weight (<2,500g), and prematurity (<37 weeks of gestation) led to occurrence rates of 34% and 26%, respectively. Cardiac symptoms (heart murmur and cyanosis) accounted for 47% of all cases in which CHD was discovered, and extracardiac symptoms accounted for 40%. Prenatal diagnosis was made in two patients. Twenty babies were transferred to the pediatric cardiac care unit in the general hospital from our maternity hospital during their neonatal period. Dividing them into two categories by hemodynamic state, acyanotic type made up 72% of all patients; VSDs (Ventricular Septal Defects) were the most frequent anomaly. Cyanotic type made up only 28%, but included all 4 cases of neonatal death. Twelve babies underwent surgery during the study period, and 7 of them reached final anatomical correction. Early detection of the cardiac anomaly, including prenatal diagnosis, plays an important role in improving the prognosis of patients, and comprehensive therapeutic strategies are essential for neonatal CHD.

Cardiac Surgical Procedures↗

Development of interferon-alpha resistant subline from human chronic myelogenous leukemia cell line KT-1.

OBJECTIVE: Interferon-alpha (IFN-alpha) is one of the most effective therapeutic agents for a number of hematological malignancies, including chronic myelogenous leukemia (CML). Nevertheless, its efficacy is limited because of the development of resistance to IFN-alpha therapy. Previously, we established the novel human CML cell line KT-1, which is sensitive to the antiproliferative effects of IFN-alpha. Here, we report the establishment of an IFN-alpha-resistant subline, KT-1/A3R alpha 1000, by culturing KT-1/A3 cells (IFN-alpha-sensitive subline of KT-1) with increasing concentrations of IFN-alpha, in order to analyze the mechanism of acquisition of IFN-alpha resistance in CML cells after IFN-alpha therapy. SUBJECTS AND METHODS: We developed an IFN-alpha-resistant tumor cell variant, KT-1/A3R alpha 1000, from the KT-1/A3 cell line by culturing cells with increasing concentrations of IFN-alpha. This subline was examined for its ability to proliferate and its resistance to apoptosis in high concentrations of IFN-alpha. The induction of the ISGF3 complex in response to IFN-alpha alpha in KT-1/A3R alpha 1000 was compared with that in the parental cell. RESULTS: The levels of interferon-stimulated gene factor 3 components (STAT1, STAT2, and p48) proteins and STAT2 tyrosine phosphorylation induced after IFN-alpha treatment were unchanged, but formation of the ISGF3 complex was remarkably reduced in KT-1/A3R alpha 1000 cells compared to parental cells. CONCLUSION: The KT-1/A3R alpha 1000 subline is a useful model for studying the mechanism of IFN-alpha resistance after IFN-alpha therapy.

Antineoplastic Agents↗

A model for achievement motives, goal orientations, intrinsic interest, and academic achievement.

This study investigated the effects of approach and avoidance achievement motives (the motive to achieve success and the motive to avoid failure) on three goal orientations (mastery, performance-approach, performance-avoidance goals) and the effects of goal orientations on intrinsic interest in learning and academic achievement for 157 tenth and 135 eleventh grade students of a Japanese girls' high school. Structural equation modeling indicated that mastery goals arose mainly from the motive to achieve success; however, the positive relation between the motive to avoid failure and mastery goals was also found. Performance-approach goals were related both the motive to achieve success and the motive to avoid failure. Performance-avoidance goals arouse mainly from the motive to avoid failure; however, the positive relation between the motive to achieve success and these goals was found. Mastery goals positively correlated with intrinsic interest and academic achievement, and scores on both performance-approach goals and performance-avoidance goals had no significant effects on either intrinsic or academic achievement.

Achievement↗

[Low dose melphalan therapy was effective in an elderly patient with MDS-AML].

An 80-year-old man with MDS-refractory anemia (RA) suffered transformation to a leukemic state after 18 months. The karyotype of the bone marrow cells was 47, XY, +8 in 8 cells among 20 dividing cells analyzed. Combination therapy of 150 micrograms of granulocyte colony-stimulating factor (G-CSF) and 250 mg of cytarabine ocfosfate (SPAC) for 3 weeks had no beneficial effect. Then, the patient was subjected to low-dose (2 mg daily) melphalan therapy. Gradual and concurrent improvement in anemia, thrombocytopenia, and neutropenia occurred, and the patient became free of transfusions at 2 weeks after the treatment began. Since then, his performance status has improved from grade 4 on his diagnosis of AML to grade 2. Cytogenetic analysis was normal in all 20 dividing cells in the bone marrow examination and melphalan had no adverse effect. Recently, several reports of low dose chemotherapy for elderly patients or high risk leukemia have been described, and have sustained for the QOL therapy. In the present case, low-dose melphalan therapy was effective and, moreover the abnormal karyotype of trisomy eight had disappeared.

Aged↗

Diagnostic validity of computed tomography for mediastinitis after cardiac surgery.

BACKGROUND: Optimal treatment based on appropriate early diagnosis is essential in managing mediastinitis after cardiac surgery. We evaluated the accuracy of thoracic computerised tomography (CT) in the diagnosis of mediastinitis. METHODS: Forty-one patients in whom we performed CT after cardiac surgery were classified into two groups as follows; Six cases had mediastinitis requiring a redo surgical intervention (Group M). Thirty-five cases recovered without mediastinitis (Group C). Comparisons of CT findings in both groups were made retrospectively. RESULTS: In group M, CT and re-operations were performed 6.3+/-2.5 days and 8.0+/-5.2 days after previous operation, respectively. All but one of redo surgical procedures were mediastinal lavage and omental transplantation. Two patients died due to septic shock and multiple organ failure. CT in group M showed a soft tissue mass with contrast enhancement in 4 patients, bilateral pleural effusion in 5, free gas appearance in 4, and sternal dehiscence or destruction in 2 patients. Consequently, we regarded 4 of the 6 patients in this group as showing postoperative mediastinitis radiographically. In group C, CT performed 16.6+/-7.1 days after operations revealed findings suggestive of mediastinitis in 6 patients. Therefore, in terms of the validity of CT for the diagnosis of mediastinitis, the sensitivity was 67% and the specificity was 83%. CONCLUSION: The sensitivity of CT for diagnosis of mediastinitis after cardiac operations is unsatisfactory. Diagnosis by seeking infective changes in a multidisciplinary way is important in dealing with mediastinitis.

Aged↗

Circulating HER-2/erbB-2/c-neu (HER-2) extracellular domain as a prognostic factor in patients with metastatic breast cancer: Cancer and Leukemia Group B Study 8662.

PURPOSE: The HER-2/erbB-2/c-neu (HER-2) proto-oncogene is a M(r) 185,000 transmembrane tyrosine kinase that is amplified and/or overexpressed by 20-40% of breast cancers. HER-2 has been associated with worse prognosis and resistance or sensitivity to specific treatment. We evaluated circulating levels of extracellular domain of HER-2 (ECD/HER-2) in metastatic breast cancer patients and investigated the prognostic and predictive significance of circulating HER-2 levels regarding endocrine therapy or chemotherapy. EXPERIMENTAL DESIGN: Plasma samples from 242 patients were assayed for circulating ECD/HER-2 levels, using a sandwich enzyme immunoassay. ECD/HER-2 was correlated with clinical data gathered from these patients while they were participating in prospective Cancer and Leukemia Group B (CALGB) therapeutic protocols for metastatic breast cancer. RESULTS: Eighty-nine (37%) of 242 patients had elevated ECD/HER-2 levels (> or =10.5 ng/ml). ECD/HER-2 was significantly associated with tumor burden, progesterone receptor levels, and presence of visceral metastases. Patients with elevated pretreatment levels had a significantly shorter OS but not time-to-progression than did those with ECD/HER-2 levels <10.5 ng/ml in univariate analysis. In univariate but not multivariate subset analyses, among patients treated with endocrine therapy (megestrol acetate), elevated initial ECD/HER-2 was associated with worse OS compared with nonelevated patients. However, among patients treated with chemotherapy (mainly anthracycline-containing regimens), OS did not differ significantly. Rates of response to either endocrine therapy or chemotherapy were similar for patients with elevated and nonelevated ECD/HER-2 levels. CONCLUSIONS: ECD/HER-2 levels are elevated in 35-40% of patients with metastatic breast cancer. Elevated ECD/HER-2 levels are associated with a poorer prognosis in these patients. However, no predictive role for ECD/HER-2 was identified, either for endocrine therapy or for anthracycline-based chemotherapy in the metastatic setting.

Adult↗

[3 cases of polymyalgia rheumatica (PMR), in which serum amyloid A was a useful index of the disease activity].

We encountered 3 cases of polymyalgia rheumatica (PMR), in which serum amyloid A (SAA) levels were correlated with clinical pictures after normalization of ESR and CRP levels. Therefore, it is suggested that SAA may be a useful index for evaluating the severity of intractable PMR. Case 1: The patient was a 75-year-old man. Although ESR and CRP levels were normalized after the administration of PSL (20 mg/day), myalgia persisted. When the dose of PSL was reduced, PMR recurred, which was relieved by administering 15 mg/day of PSL. However, myalgia recurred again when the dose of PSL was reduced thereafter. The elevated SAA level (33.0 micrograms/ml) was normalized by continuous administration of PSL without reducing the dose, resulting in the relief of myalgia. Case 2: The patient was a 65-year-old woman. The administration of PSL was initiated at a dose of 15 mg/day. Although myalgia was relieved, the symptom and elevated SAA levels persisted for approximately 3 months. Thereafter, PMR recurred, and SAA levels were markedly increased to 78.2 micrograms/ml. However, the symptom of PMR was eliminated by continuously administering PSL without reducing the dose. Although the dose of PSL was then reduced after the decrease in SAA levels, PMR did not recur. Case 3: The patient was an 88-year-old woman. Although the symptom of PMR was relieved by administering 15 mg/day of PSL, myalgia persisted. Since SAA levels were increased to 106 micrograms/ml, PSL was continuously administered without reducing the dose, resulting in the disappearance of the symptom and normalization of SAA levels approximately 3 months later. Although the dose of PSL was then reduced to 12.5 mg/day, PMR did not recur.

Aged↗

Physiological effects of shift work on hospital nurses.

OBJECTIVE: The purpose of this study was to assess the physiological effects of shift work on the urinary excretion rates of norepinephrine, 6-sulfatoxymelatonin and estriol in hospital nurses. METHOD: Twenty-four hour urine specimens were examined on a daytime/nighttime basis for each work shift of pregnant and non-pregnant subjects. The urinary norepinephrine and 6-sulfatoxymelatonin were measured by enzyme-linked immunosorbent assay and estriol by radio-immunoassay. RESULTS: Urinary norepinephrine level during the night work was higher than the night levels of the days off and the day shift. Urinary 6-sulfatoxymelatonin level during the night work was lower than the night levels of the days off and the day shift. Urinary estriol level of pregnant subjects showed no differences among work shift and also between daytime and nighttime. CONCLUSIONS: Urinary excretion rates of norepinephrine and 6-sulfatoxymelatonin were affected by shift work both for non-pregnant and pregnant subjects. It was unlikely that urinary estriol levels in the pregnant subjects were significantly affected by shift work.

Adult↗