Biomedical subjects
Publications and source records attributed to H Yasui.
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Between January 1995 and March 1997, 78 Helicobacter pylori strains were isolated from patients with gastritis and gastric ulcer and their drug-susceptibilities to 8 antimicrobial agents and 3 anti-ulcer drugs were determined. Imipenem was the most active agent and its MICs to all the strains tested were lower than 0.013 microgram/ml. Amoxicillin, cefaclor and minocycline were active against H. pylori with MIC90s of 0.05 microgram/ml, 0.78 microgram/ml and 0.39 microgram/ml, respectively, and no resistant strains against these drugs were isolated. However, resistant strains to clarithromycin (isolation frequency: 9%), erythromycin (13%), ofloxacin (8%) and metronidazole (13%) were isolated. Triple, double and single resistant strains to above 4 antimicrobial agents were noted. No quadruple resistant strain was isolated. Frequencies of those resistance patterns were 14.3% (triple), 28.6% (double), and 57.1% (single), respectively. Seven erythromycin-resistant strains were shown to be cross-resistant to clarithromycin but 3 erythromycin-resistant strains were susceptible to clarithromycin. It seems likely that this phenomenon is caused by the fact that clarithromycin is more active to H. pylori than erythromycin. The MIC90 value of lansoprazole was lower than those of omeprazole and famotidine.
We analyzed immunoreactive hCG/hCGbeta (IR-beta) in the sera and urine of patients with trophoblastic diseases and non-trophoblastic tumors by using enzyme immunoassays (EIAs) specific for intact hCG, free hCG beta, and beta-core fragment of hCG (beta-CF). In trophoblastic diseases, while intact hCG and free hCGbeta were contained in both serum and urine, the beta-CF could be detected only in the urine of the patients. The relative contribution of the beta-CF to the total urinary IR-beta accounted for about 30-50% in normal early pregnancy and hydatidiform mole, and more than 60% in choriocarcinoma. We conclude that intact hCG should be measured in the serum rather than in the urine as a tumor marker for trophoblastic diseases, and suggested that the ratios of intact hCG, free hCGbeta, and beta-CF to each other may be useful indices in the differential diagnosis of trophoblastic diseases. Ectopic IR-beta was also investigated in the sera and urine of the patients with cervical, endometrial, ovarian, lung, and bladder carcinomas. We found that even when IR-beta could not be detected in the serum, the urine of the same patients with cancer often contained the significant amounts of IR-beta. The chromatographic study indicated that these urinary IR-beta were essentially attributed to beta-CF, leading to the evaluation of urinary beta-CF as a tumor marker. The positive rated of urinary beta-CF were 48% for cervical, 38% for endometrial, and 84% for ovarian, 40% for lung, and 42% for bladder carcinomas. We conclude that ectopic production of hCG beta by non-trophoblastic tumors is not a rare phenomenon and it can be recognized as a tumor marker when beta -CF is measured in urine of the patients.
BACKGROUND: The method for mouse vascularized heart transplantation have been described using suture and cuff techniques. Technical problems have limited its widespread use. Here, we describe our method of modified cervical heterotopic transplantation with the cuff technique. METHODS: By using a smaller Teflon cuff (external diameter 0.6 mm, internal diameter 0.4 mm) and superfine-tip forceps, it became possible to directly pull the edge of the carotid artery and evert the proximal end of the artery over the cuff. Similarly, the external jugular vein could be easily everted over a 22-gauge cuff with this direct pulling method. RESULTS: By these modifications, the operation time was reduced. It usually takes 20 min for the donor harvest, 15 min for preparation of the cervical vessels, and 15 min for anastomosis. All procedures from the donor harvest through skin closure of the recipient mice can be completed within 1 hr, and ischemic time is within 25-40 min. CONCLUSIONS: This method can be used to investigate cyclophosphamide-induced tolerance and mechanisms of reperfusion injury.
Carboxyamidotriazole (CAI) is a calcium influx inhibitor that has both antiproliferative and antimetastatic activities. Pretreatment of human T-cells with micromolar concentrations of CAI causes a near complete inhibition of calcium-regulated mitogen-induced transcription from the human immunodeficiency virus (HIV) long terminal repeat (LTR). This inhibition is selective since other mitogen-activated gene regulatory elements, such as the 12-O-tetradecanoylphorbol-13-acetate response element, are not influenced by the drug. HIV LTR transcription inhibition is maximal at 1.0 microM CAI, requires a pretreatment interval of at least 8 h for optimum inhibition, and shows no acute interference with the growth properties of the cells. Moreover, the inhibition is rapidly reversible upon removal of the drug from the medium. Studies to identify enhancer elements within the HIV LTR that are functionally sensitive to low-dose long-term pretreatment with CAI indicate that the NF-kappaB-binding sites are among the major targets of drug action. In vitro DNA binding studies with nuclear extracts prepared from mitogen-induced T-cells stimulated in the presence of CAI indicate that the drug differentially influences the calcium-regulated downstream signal transduction pathways necessary for specific NF-kappaB DNA binding activity at the two kappaB sites within the HIV LTR. Studies with ionomycin and thapsigargin show that repression is specific for selected modes of inducible calcium entry and indicate that, in T-cells, a major mechanism of CAI action is to modulate calcium influx at a level that is proximal to the regulated release of calcium from intracellular stores. Measurement of calcium influx in CAI-treated cells reveals a dramatic and reversible inhibition of mitogen-induced calcium influx. These results indicate that CAI can be an important and effective pharmacological tool for analysis of the calcium-dependent modulation of HIV LTR transcription.
BACKGROUND: Injection of allo-spleen cells (SC) followed by a single dose of cyclophosphamide (CP) can induce tolerance of tumor and/or skin allografts in mice. To minimize the damage caused by CP, fractionation of CP that can establish long-lasting skin graft survival, stable mixed chimerism, and intrathymic clonal deletion in the host was investigated in the present study. METHODS: Allo-SC (10(8)) were given intravenously on day 0. CP at 200 mg/kg was given intraperitoneally on day 2 in a single dose (CP 200x1 group). CP at 100, 66, 50, 40, and 33 mg/kg was given daily from day 1 through days 2, 3, 4, 5 and 6, respectively, in the fractionated doses (CP 100x2, 66x3, 50x4, 40x5, and 33x6 groups; total dose=200 mg/kg). Allografting was performed on day 14. RESULTS: In a fully allogeneic combination of C57BL/6 (H2b)-->AKR (H2k, Mls-1a), an EL-4 tumor (H2b) was specifically accepted to kill the AKR mice in all of the SC+CP 200x1, 100x2, 66x3, 50x4, 40x5, and 33x6 groups (n=6), but C57BL/6 skin graft survival was not prolonged in any of the tumor-tolerant groups. In an H2-identical combination of AKR-->C3H (H2k, Mls-1b), AKR skin graft survival was prolonged remarkably (80-90 days) in the SC+CP 200x1, 100x2, and 66x3 groups (n=5-11), but was prolonged moderately (20-60 days) in the SC+CP 50x4 and 40x5 groups. In both of the SC+CP 200x1 and 66x3 groups in the AKR-->C3H combination, mixed chimerism was maintained for as long as 100 days after tolerance induction in both the spleen and thymus, associated with intrathymic clonal deletion of Vbeta6+ T cells. The decreases in leukocyte count, hemoglobin level, spleen weight, SC count, and body weight were significantly smaller in the SC+CP 66x3 group than in the SC+CP 200x1 group. CONCLUSIONS: Fractionated CP is effective in ameliorating the compromised state induced by a single dose of CP. To induce a long-lasting skin allograft survival associated with stable mixed chimerism and intrathymic clonal deletion in an H2-identical combination, 200 mg/kg of CP can be divided into three or fewer fractions.
To confirm the ectopic production of human chorionic gonadotropin (hCG) in lung cancer, we attempted to detect the presence of mRNA transcripts of the alpha and beta genes for hCG in lung cancer tissues obtained from surgical operations. Although we were able to show the presence of hCG beta mRNA transcripts in lung cancer tissue by Northern blot, the sensitivity of the assay was too low for a precise analysis of hCG beta mRNA transcripts in most lung cancers. Using reverse transcription PCR (RT-PCR) and Southern blot analysis, however, various amounts of mRNA transcripts of hCG beta genes 3, 5, 7 and 8 were demonstrated in 9 of the 14 lung cancer tissues examined, while no mRNA transcripts were detectable in 12 normal lung tissues from the same patients. Our results are consistent with a clear difference in serum and urinary hCG beta levels observed between normal subjects and lung cancer patients. The expression of the hCG alpha gene, however, was detected in normal lung tissues more frequently than in lung cancer tissues using RT-PCR Southern blot. Our results strongly suggest the production of hCG beta as being part of the phenotype of malignantly transformed lung cells and further strengthen its superior specificity over intact hCG or hCG alpha as a tumor marker for lung cancers.
It has been reported that all-trans retinoic acid induces transposition of the great arteries (TGA) at 80-90% in ICR mice. The authors revealed that retinoic acid affects the initial formation of the conus cushions leading to a loss of spirality in the cardiac outflow tract. However, the aberrant process of septation has not been precisely defined. In this study, we observed the hearts of live embryos using a video system followed by scanning electron microscopic examination. First, we found that, in the retinoic acid-treated embryos, the proximal outflow tract cushions, in addition to hypoplasia and dysplasia, did not establish the continuity with the distal outflow tract cushions and could not contribute to the outflow septation. Second, the distal outflow tract did not rotate counter-clockwise, retaining the outflow septum anlage in the superoinferior position. Third, a tongue-like mesenchymal tissue had developed on the right anterior rim of the muscular interventricular septum and was incorporated into the interventricular septum. Altogether, these processes contributed to establishing a reversed relationship between the outflow septum anlage and the ventricular septum anlage. On the other hand, right-ward deviation of one or both of the distal outflow tract cushions, relative to the mesenchymal tissue, gave rise to variable degrees of overriding of the pulmonary artery orifice. We conclude that, due to hypoplasia and dysplasia of the proximal outflow tract cushions and lack of distal outflow tract rotation, the outflow septum anlage took an inverted relationship with the ventricular septum anlage. Various types of rightward shift of the outflow tract cushions produced a morphological spectrum of TGA-type cono-truncal anomalies.
Complete transposition of the great arteries (TGA) is inducible by treatment with all-trans retinoic acid in the ICR mouse. In this model, hypoplasia and dysplasia of the proximal outflow tract cushion tissue lead to non-spiral septation. In order to evaluate the effect of retinoic acid on the extracellular matrix of the cardiac outflow tract, we examined the distribution of collagen type I and hyaluronic acid, immunohistochemically, on days 8-9 of gestation. In controls, collagen type I fibrils ran mainly in a radial direction, extending towards the endocardium in the cardiac jelly of the proximal outflow tract. Also, a pair of longitudinal fiber bundles were formed stretching to the distal outflow tract. As for hyaluronic acid, intense staining was observed in the submyocardial and intermyocardial space of the outer curvature of the heart. On the other hand, in retinoic acid-treated embryos, the submyocardial radial fibrils or longitudinal fiber bundles of collagen type I were diminished, and irregular and dense deposits of collagen type I were observed along the endocardium. Furthermore, hyaluronic acid showed a loss of differential localization between the outer and inner curvature. Instead, irregular and intense staining was observed uniformly along the outflow myocardium. Thus, retinoic acid appeared to have perturbed the differentiation in the proximal outflow tract causing an altered organization of multiple extracellular matrix molecules, including collagen type I and hyaluronic acid, which led to an abnormal molecular network of the cardiac jelly in the cardiac outflow tract, abnormal septation and, further, to TGA or TGA-type anomalies.
BACKGROUND: Steroid use during cardiac operations may reduce the risk of postperfusion lung syndrome, but both cardiopulmonary bypass and steroids are immunosuppressive. The synergistic effects of the bypass and steroids on patients' immunologic activities, hemodynamics, and metabolisms during and after heart operations have not been clarified systematically. METHODS: Twenty-four patients undergoing valve replacement were studied in a randomized, double-blind trial. Twelve of these patients (S group) received bolus methylprednisolone, 20 mg/kg body weight, and the remaining 12 patients (C group) received a placebo intravenously before and after bypass. Blood cell count, C-reactive protein, lymphocyte surface markers (CD3, CD4, CD8, CD16, and CD20), phytohemagglutinin response, interleukin-2 production, and natural killer cell activity were examined on admission through day 7. Cardiac output, blood gas, electrolyte, lactate, and serum glucose levels were examined perioperatively. RESULTS: The peak white blood cell count in the S group was higher than that in the C group (analysis of variance: p [group] = 0.0436). The peak C-reactive protein level was higher in the C group than in the S group (p [group] < 0.0001). From the analysis of the surface markers, the steroid increased the natural killer cells before and soon after bypass (p [group] = 0.0117), and later tended to increase the CD4+ T and B cells during the postoperative recovery period. The phytohemagglutinin response in both groups decreased after bypass (p [time] < 0.0001), but the steroid caused exaggerated decreases before (p < 0.01 by Student's t test) and soon after (p < 0.001) bypass in the S group (analysis of variance: p [group] = 0.0127). The interleukin-2 production was suppressed by bypass alone after the bypass in the C group, but was further suppressed by the steroid before and after bypass in the S group (p [group] = 0.0446). The cardiac index, water balance, electrolytes, arterial oxygen tension, and timing of extubation were not different between the groups. In contrast, the glucose (p [group] = 0.0486) and lactate (p [group] = 0.0525) levels were higher in the S group than those in the C group. CONCLUSIONS: T-cell functions are synergistically suppressed by cardiopulmonary bypass and high-dose methylprednisolone in heart operations. The hemodynamic benefits of the steroid are negligible, whereas glucose tolerance is worsened by the steroid during bypass.
Double-orifice mitral valve is an unusual condition of importance to surgeons, and usually associated with other cardiac anomalies. This article reports a case of isolated double-outlet mitral valve with torn chordae in which we successfully performed mitral valvuloplasty by placement of artificial chordae. The mitral valve was divided into anterolateral and posteromedial orifices by vertical bridging tissue. Two torn chordae at the posteromedial scallop surrounding the posteromedial mitral orifice were replaced with artificial chordae of two pairs of expanded polytetrafluoroethylene sutures. Because replacement of torn chordae with artificial chordae was not complicated and seemed to preserve very fine relationships among leaflet tissues, bridging tissue, chordae, and papillary muscles, we suggest this method may be used to reconstruct various kinds of mitral lesions causing mitral regurgitation.
The responsiveness of melanophores of the medaka fish (wild type, Oryzias latipes) to a neurotransmitter and hormones is changed differentially after long-term adaptation to a black or white background. In the present study, we further examined whether this phenomenon involved some change in the intracellular signaling system. Using a permeabilized melanophore model, in which pigment granules could be dispersed by exogenously applied cAMP, the requirement of cAMP for pigment-dispersing reaction was revealed to be higher in melanophores of fish adapted to a black background (B cells) than in those of white background-adapted fish (W cells). Specific inhibitors of cAMP-dependent protein kinase (PKA) and cyclic nucleotide phosphodiesterase did not reduce the difference in the pigment dispersion level between B and W cells. A similar result was obtained with the free catalytic subunit of PKA. In contrast, the inhibition of protein phosphatase activity by okadaic acid diminished the difference in the responsiveness between B and W cells. These results suggest that the activity of protein phosphatase in B cell is higher than that in W cells, and that the change in the melanophore responsiveness by long-term chromatic adaptation to a background involves the change in the enzyme activity in the intracellular signaling system.
Kinetics of immunological parameters such as natural killer (NK) cell activity and tritium-thymidine uptake rate of T lymphocytes by phytohemagglutinin stimulation were investigated using peripheral leukocyte fractions of melanoma patients treated with hyperthermic isolated limb perfusion (HILP). Also, serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) were quantified during and after HILP. It was found that NK cell activity was augmented during HILP, and T lymphocyte function was stimulated 24 h and 1 week after HILP with statistical significance. NK cell activities in the cells isolated from perfused and non-perfused circulations were equally augmented during HILP in two patients examined. Serum concentrations of sICAM-1 in the patients who received HILP also increased 24 h or even 1 week after HILP. The stimulation of these immune competent cells and upregulation of sICAM-1 by HILP were independent of the stages of melanoma patients at the time of HILP or the doses of agents which were used for the infusion during HILP. The origin of cells which shed sICAM-1 into the serum of the patients who received HILP remains to be further investigated.
STUDY OBJECTIVE: To evaluate a new method for removal of retained air at the end of cardiopulmonary bypass (CPB) by end-tidal CO2 pressure (PETCO2) and pulmonary arterial pressure (PAP) monitoring, and transesophageal two-dimensional echocardiography (TEE). DESIGN: Prospective study. SETTING: Cardiac surgery unit at a university hospital. PATIENTS: 36 ASA physical status I, II, III patients for open heart surgery. INTERVENTIONS: The CPB reservoir was gradually raised to decrease venous drainage. Accordingly, the right heart began to receive the venous blood and eject it to the pulmonary artery. The vent existing in the left ventricle or the left atrium then collected any whole blood containing air bubbles that came from the pulmonary circulation. The air bubbles were confirmed by TEE to be removed and not to eject from the left ventricle to te systemic circulation. MEASUREMENTS AND MAIN RESULTS: Levels of PETCO2, PaCO2, PAP, and the duration of the removal procedure were measured when a sufficient pulmonary circulation was established and the removal of retained air was considered to be satisfactorily accomplished by the absence of air bubbles, confirmed by TEE for more than 30 seconds. PETCO2 reached 28 +/- 4 mmHg during the removal of air, while PaCO2 reached 35 +/- 6 mmHg (p < 0.05). Mean PAP during removal of air reached 18 +/- 4 mmHg, which was approximately 90% of that before CPB. The duration time of removal of air was 9 +/- 2 min. CONCLUSIONS: PETCO2 and PAP are useful indicators of pulmonary circulation during this procedure for removal of air. PETCO2 of 25 to 30 mmHg and PAP of 90% of the prebypass level have been found to be necessary for the removal of air. Our technique for removal of air using PETCO2, PAP, and TEE enables us to satisfactorily eliminate residual air.
During cardiac surgery abrupt hypotension sometimes occurs by the atrium being pulled, though the hypotensive mechanism is not known. The effects of mechanical stretching of the right atrium on haemodynamics and renal sympathetic nerve activity in the anesthetized rabbit was investigated. During stretching of the right atrial appendage with a metal weight (right atrial stretch), both mean arterial pressure (mAP) and renal sympathetic nerve activity significantly decreased. Bilateral vagotomy significantly reduced the change in mean arterial pressure with right atrial stretch (P < 0.01), and significantly increased renal sympathetic nerve activity (P < 0.01). The duration of the decreases of mean arterial pressure with right atrial stretch was significantly shortened after vagotomy. Decreases of blood flow of the descending aorta with right atrial stretch were observed and not affected by vagotomy. These results suggest that hypotension with mechanical stimulation of the right atrium is not only due to the decrease in cardiac output but also to sympathetic inhibition through the vagus via cardiac baroreflex.
Large amounts of homogeneous cells are not always available for in vitro studies of inflammatory skin disorders. Here we demonstrate that a novel cell line, termed YAA, has been established from peripheral blood mononuclear cells, which were separated by the Ficoll method, of a patient with atopic dermatitis. YAA cells were grown in suspension culture. The cytochemical staining showed a positive reaction for alpha-naphthyl butyrate esterase, which was completely inhibited by sodium fluoride, but a negative result for periodic acid-Schiff, peroxidase and alkaline phosphatase. A large population of YAA cells exhibited phenotype of CD33 and CD56 but neither of CD2 nor CD3. The phorbol ester-stimulated YAA cells produced a considerable amount of tumor necrosis factor-alpha. These findings suggest that YAA might be a monocytoid line with an additional phenotype specific for natural killer cells.
BACKGROUND: The peripheral blood concentrations of several proteases of the clotting system have been shown to predict survival in patients with malignancy. A study was undertaken to investigate the independent value of the plasma levels of the D-dimer degradation product of fibrin before treatment for predicting prognosis in patients with lung cancer. METHODS: The study comprised 70 patients with lung cancer (49 non-small cell lung cancer and 21 small cell lung cancer). Plasma levels of D-dimer were measured using an enzyme immunoassay kit. Multivariate statistical analysis was carried out using the Cox's proportional hazards model. RESULTS: The median value of the plasma level of D-dimer differentiated two groups of patients with different outcomes: a group with a D-dimer level of < 150 ng/ml (low DD group) and those with D-dimer levels of > or = 150 ng/ml (high DD group). Survival time was significantly better in patients in the low DD group than in those in the high DD group in all patients (hazard ratio for high DD group = 4.7; 95% confidence interval (CI) 1.8 to 11.7). The plasma levels of D-dimer predicted survival independently from the clinical stage of disease, histological type, performance status, and tumour size (hazard ratio = 3.9; 95% CI 1.6 to 9.2). CONCLUSIONS: These results suggest that plasma levels of D-dimer might be useful for predicting the clinical outcome in patients with lung cancer. However, further prospective studies are needed in a larger population to confirm these findings.