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Biomedical subjects

Y Ohashi

Publications and source records attributed to Y Ohashi.

At least 289 records · Page 16Linked to original sources

PCF1 and PCF2 specifically bind to cis elements in the rice proliferating cell nuclear antigen gene.

We have previously defined the promoter elements, sites IIa and IIb, in the rice proliferating cell nuclear antigen (PCNA) gene that are essential for meristematic tissue-specific expression. In this study, we isolated and characterized cDNAs encoding proteins that specifically bind to sites IIa and IIb. The two DNA binding proteins, designated PCF1 and PCF2, share > 70% homology in common conserved sequences at the N-terminal regions. The conserved regions are responsible for DNA binding and homodimer and heterodimer formation, and they contain a putative basic helix-loop-helix (bHLH) motif. The structure and DNA binding specificity of the bHLH motif are distinguishable from those of other known bHLH proteins that bind to the E-box. The motif is > 70% homologous to several expressed sequence tags from Arabidopsis and rice, suggesting that PCF1 and PCF2 are members of a novel family of proteins that are conserved in monocotyledons and dicotyledons. A supershift assay using an anti-PCF2 antibody showed the involvement of PCF2 in site IIa (site IIb) binding activities in rice nuclear extracts, particularly in meristematic tissues. PCF1 and PCF2 were also more likely to form heterodimers than homodimers. Our results suggest that PCF1 and PCF2 are involved in meristematic tissue-specific expression of the rice PCNA gene through binding to sites IIa and IIb and formation of homodimers or heterodimers.

Amino Acid Sequence↗

Preoperative endocrine therapy for clinical stage A2, B, and C prostate cancer: an interim report on short-term effects. Prostate Cancer Study Group.

BACKGROUND: Preoperative endocrine therapy has been suggested to improve surgical radicality and/or patient prognosis in prostate cancer. METHODS: Patients with clinical stage A2, B, and C prostate cancer were randomized to either group I (n = 113) or group II (n = 111). Group I patients were to receive preoperative endocrine therapy consisting of leuprolide and chlormadinone for 3 months, followed by radical prostatectomy with lymph node dissection. Group II patients were to undergo the surgery before endocrine therapy. RESULTS: Group I patients showed a remarkable decrease in prostate-specific antigen (PSA) (mean +/- SE: 41.8 +/- 8.6 ng/mL to 2.7 +/- 0.7 ng/mL) and prostate volume (29.8 +/- 1.7 mL to 21.2 +/- 1.6 mL) during the preoperative therapy. Histopathologic analysis showed a significant difference in the rates of down-staging (19.1% in group I versus 3.3% in group II), positive surgical margins (63.8% versus 81.3%) and positive lymph node metastasis (20.7% versus 36.5%). No significant difference was detected in operating features. Subgroup analyses indicated that beneficial effects were correlated positively with degree of histologic differentiation and negatively with the basal PSA level. CONCLUSIONS: Preoperative endocrine therapy reduced local extension of prostate cancer, and the effects depended on histologic differentiation and PSA level. Long-term follow-up data are needed to determine the effects on the patient prognosis.

Aged↗

The effect of respiration on the performance of the total artificial heart.

An electromechanical driven pusher plate type total artificial heart (TAH) has been developed in the Department of Surgery at Baylor College of Medicine. The control of this TAH is based upon Frank-Starling's law, and the output is likely to be affected by the respiration cycle. The necessity of an averaging system for the pumping to avoid this drifting of the output has been discussed in several papers. In this study, the effect of respiration on the performance of the TAH was evaluated in both in vitro and in vivo conditions. This TAH was driven without an averaging system in its control system. The results indicated that the mean output pressure was stable with minute changes in both the heart rate and outflow. This verifies that the electromechanical driven pusher plate type TAH, which is under development in our laboratory, compensated for the effect of respiration without an averaging system.

Animals↗

Effects of pulsatile flow on gas transfer of membrane oxygenator: MENOX EL-4000 and Gyro C1-E3 pulsatile mode.

It is acknowledged that pulsatile flow enhances the gas exchange performance of membrane oxygenators. However, the data for currently developed oxygenators are limited. In this study, the effect of pulsatile flow was assessed utilizing the MENOX EL-4000 oxygenator. The in vitro test was performed following the Association for the Advancement of Medical Instrumentation (AAMI) standards. Pulsatile flow was produced by the Gyro C1-E3 centrifugal pump with periodical changing of the impeller speed. In Study 1, the following 3 groups were created and examined: nonpulsatile flow, pulsatile flow of 40 bpm, and pulsatile flow of 60 bpm. The blood flow rate was maintained at 3 L/min, and the V/Q ratio was 1. In Study 2, four groups were examined, nonpulsatile flow with V/Q = 1, nonpulsatile with V/Q = 2, pulsatile with V/Q = 1, and pulsatile with V/Q = 2. The blood flow rate was maintained at 4 L/min, and the pulse frequency was set at 40 bpm. In study 1, although O2 transfer was not enhanced, CO2 transfer was significantly improved (40-50%) by pulsatile flow, regardless of pulse frequency. Study 2 demonstrated that pulsatile flow resulted in improved CO2 transfer as did higher ventilation (V/Q = 2). Furthermore, even after applying higher ventilation, the pulsatile mode enhanced CO2 transfer more than the nonpulsatile mode. It was considered that the pulsatile mode induced an active secondary flow and enhanced mixing effects, and consequently CO2 transfer was improved. In conclusion, the pulsatile flow significantly enhanced the CO2 transfer of the MENOX oxygenator. It is indicated that applying the pulsatile mode is a unique and effective method to improve the gas exchange performance for a current membrane oxygenator.

Analysis of Variance↗

Anatomical consideration for an implantable centrifugal biventricular assist system.

A miniaturized pivot bearing-supported centrifugal blood pump (Gyro PI) has been developed as a long-term biventricular assist system (BiVAS). In this study we determined the anatomical configuration of this system using a bovine model. Under general anesthesia, a left lateral thoracotomy was performed to open the chest. Two Gyro PI-601 pumps for left and right assists were placed in the preperitoneal pocket by a subcostal abdominal incision. The left pump could be placed along the dome of the diaphragm just beneath the apex of the left ventricle. The right pump could be placed next to the left pump. The inlet and outlet ports of both pumps penetrated the diaphragm. The inlet port of the left pump, with a length of 55 mm, was inserted directly into the apex of the left ventricle. A woven Dacron graft (150 mm long, 11 mm inner diameter) was placed between the outlet port of the left pump and the descending aorta. As for the right pump, a 100 mm long and 120 degree angled inflow conduit was placed between the inlet port and the right ventricular infundibulum. The outlet port of the right pump was connected to the main trunk of the pulmonary artery using a 90 mm long, 11 mm inner diameter Dacron graft. We could perform biventricular assistance to confirm the anatomical feasibility of the Gyro implantable centrifugal BiVAS.

Animals↗

Hemolysis test of a centrifugal pump in a pulsatile mode: the effect of pulse rate and RPM variance.

Centrifugal pumps are generally employed as nonpulsatile blood flow pumps; however, these pumps can produce pulsatile flow by periodically alternating the impeller rotation speed. This study investigates blood trauma due to the effect of pulse frequency and various ranges of pump speed. The hemolysis tests were conducted using the Gyro C1E3 pump. The study was divided into the following categories: Group 1 in a nonpulsatile mode; Group 2 operated at 40 bpm with 30% of speed variance; Group 3, 60 bpm with 30% of speed variance; Group 4, 40 bpm with 70% of speed variance; and Group 5, 60 bpm with 70% of speed variance. A flow rate of 3 L/min and a total pressure head of 200 mm Hg were employed in all groups to simulate a percutaneous cardiopulmonary support condition. There were no significant differences in the hemolysis levels among Groups 1, 2, and 3. However, Groups 4 and 5 exhibited a significantly higher hemolysis rate compared to the other groups. These results indicate that a high rate of speed variance increases hemolysis; however, a range of less than 30% does not affect hemolysis. The pulse rate has no significant effect on hemolysis. In conclusion, the higher speed variance increases the hemolysis level when a pulsatile mode is applied with a centrifugal pump at the given test conditions. However, a speed variance of less than 30% or a pulse rate of less than 60 bpm does not affect hemolysis.

Analysis of Variance↗

Estimation of the minimum pump speed to prevent regurgitation in the continuous flow left ventricular assist device: left ventricular drainage versus left atrial drainage.

Due to the fact that centrifugal and axial pumps do not require valves, there is a possibility of back flow when the pump speed is low. To estimate the minimum required pump speed to prevent this regurgitation, an in vitro simulation test was conducted. A pulsatile pump simulated the natural heart while a centrifugal pump simulated the continuous flow left ventricular assist device (LVAD). The LVAD flow was attained from the left atrial (LA) drainage or left ventricular (LV) drainage. The minimum or regurgitate flow was observed in the systolic phase with LA drainage and in the diastolic phase with LV drainage. LV drainage always provided higher flow than LA drainage at the same pump speed. These differences are due to the various total pressure heads of the LVAD. To prevent the regurgitation, the LVAD should maintain a certain pump speed which can create positive flow against the aortic systolic pressure with LA drainage and against the aortic diastolic pressure with LV drainage. These required pump speeds can be identified by the LVAD flow-pressure curve.

Aortic Valve Insufficiency↗

Control system modification of an electromechanical pulsatile total artificial heart.

A reliable control system is one of the most important characteristics of the electromechanical pulsatile total artificial heart (TAH). Obtaining an error-free procedure is essential for a successful in vivo implantation. To avoid any malfunction of the electrical control system, a modification of the previously designed controller was made to ensure stable pumping without the Hall effect sensor missensing. The installation position of the Hall effect sensor was changed from the top of the housing to the central piece with small magnets being installed in the stabilizer rods. The usage of the Hall effect sensor was chosen as an electrical switch. An in vitro one month running test of the TAH demonstrated adequate hydrodynamic performance with a completely error-free pumping characteristic. The total efficiency of the TAH was 12.6 +/- 1.4% at an 8 L/min outflow and 10.7 +/- 1.0% at a 6 L/min outflow condition.

Electricity↗

The hemolysis test of the Gyro C1E3 pump in pulsatile mode.

While a centrifugal pump is generally used for nonpulsatile blood flow, it can also produce a pulsatile flow by alternating the impeller rotational speed (rpm) periodically. However, there is a concern that this centrifugal pump pulsatile mode may induce added hemolysis as a result of the repeated acceleration and deceleration of rpm. Thus, a hemolysis study of the pulsatile modes of the Gyro C1E3 centrifugal pump (Gyro-P) was conducted. The results were then compared with the nonpulsatile mode of the same pump (Gyro-N) and the nonpulsatile BioMedicus BP-80 (Bio-N) pump. Three different conditions were simulated: left ventricular assist device (LVAD), cardiopulmonary bypass (CPB), and percutaneous cardiopulmonary support (PCPS). The beating rate of the Gyro-P was set at 40 bpm, with repetition of two different impeller speed (the lower being 70% of the higher speed). The 2 impeller speeds were set to obtain the same average flow as that of the nonpulsatile mode. The hemolysis results of the Gyro-P were comparable to or better than those of Bio-N, and no excessive hemolysis was observed, compared to the Gyro-N. In conclusion, The Gyro-P had an excellent hemolytic characteristic and generated no excessive hemolysis in most clinical usage conditions. With the concern of hemolysis eliminated, this pulsatile mode may have various possible mode advantages.

Analysis of Variance↗

Flow visualization studies to improve the spiral pump design.

The spiral pump (SP) uses centrifugal and axial pumping principles simultaneously, through a conical shaped impeller with threads in its surface. Flow visualization studies were performed in critical areas of the SP. A closed circuit loop was filled with glycerin-water solution (40%). Amberlite particles (80 mesh) were illuminated by a planar helium-neon laser light (7 mW). The particle velocities were recorded with Kodak (TMAX-400) black and white film, and the flow behavior was studied with a micro video camera and color video printer. The flow visualization studies showed no turbulence or stagnant areas in the inlet and outlet ports of the SP. When using the impeller with one lead, at the top of the threads some recirculation appeared when the total pressure head increased. Two new impellers were made. One of them had the same conical shape with a thread having 2 leads. The second had a thread with 2 leads, but it also had a bigger cone angle. These modifications improved the pump hydrodynamic performance, decreasing the recirculation in pumping conditions that require pressures over 200 mm Hg.

Centrifugation↗

Comparison of the Gyro C1E3 and BioMedicus centrifugal pump performances during cardiopulmonary bypass.

The compact eccentric inlet port (C1E3) centrifugal blood pump was developed as a cardiopulmonary bypass (CPB) pump. The C1E3 pump incorporated a sealless design with a blood stagnation free structure. The pump impeller was magnetically coupled to the driver magnet in a sealless manner. To develop an atraumatic and antithrombogenic centrifugal pump without a shaft seal junction, a double pivot bearing system was introduced. Recently, a mass production model of the C1E3 was fabricated and evaluated. The ratio of the normalized index of hemolysis (NIH) of the C1E3 was 0.007 g/ 100 L, in comparison to the NIH of the BP-80, 0.018 g/ 100 L, each in a CPB condition of 5 L/min against 325 mm Hg. Both pumps were compared in identical in vitro circuits. To further evaluate the pumps during cardiopulmonary bypass for reliability and function, 6 h of CPB was performed on each of 8 bovines using either the C1E3 or BP-80 centrifugal pump. The BP-80 and C1E3 provided pump flows of 50-60 ml/kg/min without incident. The hemodynamics were stable, and the hematology and biochemistry data were within normal ranges. There were no statistically significant differences between the 2 groups. Concerning the plasma free hemoglobin values, a mass production model of the C1E3 pump had the same hemolysis levels as the BP-80. Our preliminary studies reveal that the C1E3 pump is reliable. Also, the C1E3 will satisfy clinical requirements as a cardiopulmonary bypass pump.

Alanine Transaminase↗

Nitric oxide inhibits neutrophil adhesion to cytokine-activated cardiac myocytes.

Neutrophils play important roles in myocardial injury in which an inflammatory reaction ensues. We investigated the role of nitric oxide (NO) in neutrophil adhesion to cardiac myocytes. Isolated adult rat myocytes were coincubated with human neutrophils, and the number of neutrophils adherent to myocytes was microscopically counted. The adhesion increased up to 2.4-fold when both myocytes and neutrophils were activated by interleukin-1 beta (IL-1 beta) and platelet-activating factor (PAF), respectively. The NO donors, S-nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside (SNP), inhibited the adhesion by 50% when administered to neutrophils before activation. However, when activated neutrophils were added to myocytes that had been incubated with NO donors during IL-1 beta stimulation, the inhibition of adhesion was not observed. Pretreatment of neutrophils with SNAP or 8-bromoguanosine 3',5'-cyclic monophosphate did not reduce PAF-induced CD11b/CD18 expression determined by flow cytometry, nor did simultaneous treatment of myocytes with IL-1 beta and SNAP decrease IL-1 beta-induced intercellular adhesion molecule-1 expression determined by immunofluorescence staining and enzyme-linked immunosorbent assay. Thus NO inhibits neutrophil-myocyte adhesion, mainly acting on neutrophils without quantitatively affecting the upregulation of CD11b/CD18.

Animals↗

Effect of retinol palmitate as a treatment for dry eye: a cytological evaluation.

Vitamin A is known to regulate the proliferation and differentiation of corneal epithelial cells and preserved conjunctival goblet cells and has been used in the treatment of disease of the eye such as dry eye and superior limbic keratoconjunctivitis for some time. This study was undertaken in order to evaluate the efficacy of retinol palmitate aqueous ophthalmic solution under development for the treatment of dry eye failing to respond to the conventional therapy with artificial tears or cornea-protective drugs. Retinol palmitate ophthalmic solution was applied repeatedly for 4 consecutive weeks. Before and after instillation therapy, brush cytology (Cytobrush-S) was performed and cytodiagnosis was made for keratinized cells, nonkeratinized cells, goblet cells and inflammatory cells on samples prepared using an automated smear apparatus (ThinPrep). In dry eye, an increase in goblet cells (1.3+/-2.6-->2.1+/-1.8 cells/slides), a decrease in keratinized cells (11.2+/-16.5-->5.2+/-10.9 cells/300 cells) and, hence, an increase in nonkeratinized cells (287.3+/-16.6-->293.4+/-11.4/300 cells) were found after treatment with retinol palmitate. As to inflammatory cells, there was no change from the pretreatment baseline (1.4+/-1.4-->1.4+/-1.3 cells/300 cells). These results demonstrate that brush cytology suggests the efficacy of retinol palmitate ophthalmic solution in dry eye treatment.

Administration, Topical↗

Treatment of herpetic keratitis with acyclovir: benefits and problems.

Since the introduction of acyclovir in the last decade, the visual prognosis of herpetic keratitis has improved dramatically. Benefits with this superb agent include rapid resolution of epithelial keratitis, reduction of disturbances in ocular surface epithelia, and a decreased incidence of necrotizing keratitis or subsequent corneal melting. On the other hand, persistent superficial punctate keratopathy associated with topical usage, emergence of an acyclovir-resistant strain of herpes simplex virus, and a gradual increase in progressive corneal endotheliitis comprise the problems to be resolved.

Acyclovir↗

Significant correlation between symptom score and IgG4 antibody titer following long-term immunotherapy for perennial allergic rhinitis.

Although there is evidence of some measure of clinical benefit as well as immunologic change during the early phase of immunotherapy, a sustained clinical response is only possible with prolonged therapy. Immunotherapy has to be administered for about 3 to 5 years for such sustained clinical efficacy. This study aimed at investigating the dynamics of IgE and IgG4 antibodies after more than 5 years of immunotherapy, to examine the statistical correlation between these antibodies and symptom scores. Our study demonstrated that the allergen-specific IgE antibody level significantly decreases and the IgG4 antibody level significantly increases following immunotherapy. However, the percent decrease in IgE antibodies did not correlate with the percent decrease in symptom scores. On the other hand, the percent increase in IgG4 antibodies correlated with the percent decrease in symptom scores. We infer that an elevation of IgG4 antibodies is not simply an epiphenomenon unrelated to the underlying working mechanism of clinically successful immunotherapy, but probably makes an active contribution to symptom relief.

Adolescent↗

Effect of immunotherapy on serum levels of eosinophil cationic protein in perennial allergic rhinitis.

Eosinophil cationic protein (ECP) levels in the serum of clotted blood could reflect the rate of activation of circulating eosinophils. We investigated the serum ECP levels in patients with perennial allergic rhinitis, with special reference to the effect of immunotherapy on the serum ECP levels. Serum ECP levels in untreated patients with perennial allergic rhinitis are significantly higher than those of nonatopic volunteers. Therefore, this elevation in the untreated patients represents an ongoing inflammation occurring in allergic rhinitis. The mean serum ECP level of a 1-year immunotherapy group was significantly higher than that of the nonatopic group, and was not different from that of the untreated group. In contrast, the mean serum ECP level in patients who had more than 2 years of immunotherapy was significantly lower than that of the untreated group, and was not different from that of the nonatopic group. Additionally, serum ECP levels were significantly correlated with the duration of immunotherapy. These findings suggest that activation of circulating eosinophils decreases gradually during immunotherapy, but this inhibition becomes apparent only after 2 years of immunotherapy. The control of circulating eosinophil activation might be one of the important working mechanisms behind the clinical effect of immunotherapy.

Adolescent↗

Human urinary macrophage colony-stimulating factor reduces the incidence and duration of febrile neutropenia and shortens the period required to finish three courses of intensive consolidation therapy in acute myeloid leukemia: a double-blind controlled study.

PURPOSE: To determine whether macrophage colony-stimulating factor (M-CSF) reduces the incidence and duration of febrile neutropenia during three courses of intensive consolidation therapy and whether it shortens time to complete consolidation therapy. PATIENTS AND METHODS: In 198 adult patients with acute myeloid leukemia (AML) in complete remission (CR), M-CSF (8 x 10(6) U/d) or placebo was administered from 1 day after the end of each consolidation chemotherapy for 14 days. RESULTS: The duration and incidence of febrile neutropenia was significantly reduced by 34% (P = .00285) and 17% (P = .02065), respectively, in 88 assessable patients in the M-CSF group compared with those in 94 assessable patients in the placebo group. Patients in the M-CSF group had 565 days and 133 episodes of febrile neutropenia during 7,901 days at risk, while patients in the placebo group had 977 days and 185 episodes during 9,077 days at risk. The median period required to finish the three courses of consolidation therapy was 93 days in the M-CSF group, which was significantly shorter than 110 days in placebo group (P = .0050). In the M-CSF group, the recovery of neutrophils and platelets was significantly faster (P = .0348 and P = 0.0364, respectively), the administration of systemic antimicrobial agents tended to be less (P = .0839), and the frequency of platelet transfusion (P = .0259) and the total volume of transfused platelets (P = .0292) were significantly less. However, there was no significant difference in the disease-free survival. CONCLUSION: M-CSF significantly reduced the incidence and duration of febrile neutropenia during the intensive consolidation therapy, and shortened the time to complete consolidation chemotherapy in AML.

Acute Disease↗

Immunopotentiating activity of the water-soluble lignin rich fraction prepared from LEM--the extract of the solid culture medium of Lentinus edodes mycelia.

The water-soluble lignin in LEM (the extract of the solid culture medium of Lentinus edodes mycelia) has been known to have antiviral and immunopotentiating activities in vivo and in vitro. The water-soluble lignin rich fraction (JLS-18) was prepared from LEM using ultrafiltration and hydrophobic column chromatography. JLS-18 showed about 70 times higher antiviral activity than LEM in vitro. JLS-18 activated the cytotoxicity of NK cells and macrophages, and activated T cells in vitro. JLS-18 also induced interleukin 6 (IL-6) secretion from human leukocytes infected with Sendai virus in vitro. These data showed that JLS-18, the water-soluble rich fraction of LEM, had antiviral and immunopotentiating activities.

Adjuvants, Immunologic↗