Biomedical subjects

H Okumura

Publications and source records attributed to H Okumura.

At least 19 recordsLinked to original sources

PubMed2000

Functional comparison between YCF1 and MRP1 expressed in Sf21 insect cells.

YCF1 is a yeast vacuole membrane transporter involved in resistance to Cd(2+) and to exogenous glutathione S-conjugate precursors. MRP1 contributes to multidrug resistance (MDR) in tumor cells. MRP1 and YCF1 have extensive amino acid sequence homology (63% amino acid similarity). We expressed MRP1 or YCF1 in insect cell membranes and compared their functions to know more about their structure-function relationships. YCF1 and MRP1 with His epitopes were expressed in Sf21 insect cells; both of them in the plasma membrane. The ATP-dependent transport of [(3)H]LTC(4) in Sf/YCF1-His vesicles was osmotically sensitive and showed saturable kinetics with an apparent K(m) of 758 nM for LTC(4) and 94 microM for ATP which were similar to those in yeast cells. The K(m) of YCF1 for LTC(4) (758 nM) was sevenfold higher than that of MRP1 (108 nM). MK-571 and ONO-1078, reversing agents for MRP1-mediated MDR, considerably inhibited the transport of LTC(4) by both YCF1 and MRP1. However, PAK-104P, a pyridine analog that reverses MDR associated with P-gp and MRP1, inhibited the transporting activity of MRP1 stronger than that of YCF1. KE1, another MDR reversing agent, moderately inhibited the transport of LTC(4) by MRP1 but not that of YCF1. In conclusion, we successfully expressed yeast YCF1 in Sf21 insect cells and found that the localization of the protein was different from that in yeast. The function of YCF1 in Sf21 insect cells was similar but not identical to that of MRP1.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Clinical results of coronary artery bypass grafting with use of the internal thoracic artery under low free flow conditions.

OBJECTIVE: Even when left internal thoracic artery flow is very low, we have used the artery for grafting without any further maneuvers. In this study, we investigated the clinical results of coronary bypass surgery using the left internal thoracic artery with low free flow. METHODS: A total of 163 patients were divided into 2 groups: group L (n = 43) had free flow of 20 mL/min or less and group H (n = 120) had free flow of more than 20 mL/min. We performed a comparative study on the basis of coronary angiography and pulsed Doppler echocardiography. Furthermore, 12 months' postoperative graft angiography was carried out in 11 patients from group L. RESULTS: No patient had low output syndrome or perioperative myocardial infarction. One month after the operation, 3 cases of graft occlusion and 9 cases of the "string sign" were identified in group H. However, group L had no graft occlusion and only 1 case of the "string sign." The 1-month postoperative Doppler echocardiographic study showed no significant differences in the diastolic fraction of velocity time integrals and the diastolic/systolic peak velocity ratio of the grafts. In the 11 patients undergoing angiography after 1 year, graft patency was excellent. Moreover, the graft diameter was significantly larger than it was 1 month after the operation. CONCLUSION: These results suggest that the left internal thoracic artery can be used for coronary artery bypass grafting even when the flow is less than 20 mL/min.

Blood Flow Velocity↗

PubMed2000

A clinical use of the Kyocera Gyro C1E3 centrifugal pump.

The Kyocera Gyro C1E3 centrifugal blood pump was clinically applied for a cardiopulmonary bypass (CPB) of coronary artery bypass grafting (CABG). The patient was 72-year-old male with postinfarction unstable angina. The surgery was carried out on November 20, 1998. The air inside the pump was easily and quickly removed, and its controllability was excellent. The pump flow during operation was maintained 2.2 L/m2. Total CPB time was 173 min. Perioperative parameters of hemolysis and cytotoxicity were not remarkably changed. Macroscopically and microscopically, there were no thrombi inside the pump after usage. This is the first reported case of clinical use of the Kyocera Gyro C1E3 pump.

Aged↗

PubMed2000

Cemented total hip arthroplasty with acetabular bone graft for developmental dysplasia. Long-term results and survivorship analysis.

Although the technique of autogenous acetabular bone grafting has been widely used to augment containment of the acetabulum in total hip arthroplasty (THA) for developmental dysplasia, the role of this technique in improving long-term results remains controversial. We present the long-term results of cemented THA with acetabular bone grafting in 112 patients (133 hips) in order to clarify the factors which affect the outcome. The mean follow-up was for 12.3 years (8 to 24). Kaplan-Meier survivorship analysis predicted a rate of survival of the acetabular component at 15 years of 96% (95% confidence interval (CI) 92 to 99) with revision for aseptic loosening as the endpoint, and of 75% (95% CI 65 to 85) when radiological loosening was used. Parametric survivorship analysis using the Cox proportional-hazards model indicated that trochanteric nonunion, lateral placement of the socket, and delayed trabecular reorientation of the bone graft were risk factors for loosening of the acetabular component. Our findings have shown that autologous acetabular bone grafting is of value for long-term success provided that the risk factors are reduced.

Acetabulum↗

PubMed2000

Mid-term results of ATS open pivot bileaflet mechanical prosthetic heart valve.

We investigated mid-term results of the patients with an ATS bileaflet valve in our institution. In the past 6 years, 69 patients received valve replacement with an ATS valve. We assessed the changes of serum lactate dehydrogenase (LDH) level in the hospital, and the valve's closing sound. The serum LDH level had almost normalized one week postoperatively and they have maintained normal levels since then. According to the questionnaire about the valvular sound at a random period after surgery, it was unnoticeable in 61 (88.4%) of the patients with ATS valve. In the 8 patients (12.6%) who recognized the valve sound, 7 of them were reoperation cases. As to the frequency analysis for the valve's closing sound, the sound peak was indicated at around 1.2 kHz in the patients with ATS valves. In patients with St. Jude Medical (SJM) valves, it appeared not only around 1.2 kHz but also around 2 to 7 kHz. Postoperative cerebral infarction was complicated in one patient. Mortality occurred in 4 (5.7%) of the patients with ATS valves. The follow up periods were from one to 66 months. Thromboembolic event free and actuarial survival rate in the patients with ATS valves were 98.6% and 94.2%, respectively. These results indicated that the ATS valve is considered to be a safe valve and mid-term follow-up shows excellent results in terms of the patients quality of life.

Female↗

PubMed1999

Substance P regulates the function of rabbit cultured osteoclast; increase of intracellular free calcium concentration and enhancement of bone resorption.

The effects of substance P on cultured rabbit osteoclasts were investigated. The intracellular Ca(2+) concentration ([Ca(2+)](i)) which was monitored by the microfluorometric technique using fura-2, in osteoclasts elevated by the addition of substance P (0.3-5 microM). The EC(50) value of substance P was about 200 nM. This substance P-evoked [Ca(2+)](i) elevation was not observed in the Ca(2+)-free medium. Simultaneous application of spantide, a substance P receptor antagonist, blocked the Ca(2+) response. The addition of substance P (0.1-10 microM) to cultured osteoclasts enhanced their bone resorption activity which was evaluated by the pit formation assay. Maximum enhancement of the pit formation by substance P (5 microM) peaked at about 170% of the control level. The addition of substance P receptor antagonists also inhibited the enhancement of the bone resorption by substance P addition. Substance P possibly stimulates the bone remodeling by osteoclasts via the [Ca(2+)](i) elevation.

Analysis of Variance↗

PubMed1999

Comparative study of antiplatelet drugs in vitro: distinct effects of cAMP-elevating drugs and GPIIb/IIIa antagonists on thrombin-induced platelet responses.

Among various categories of antiplatelet drugs, cAMP-elevating agents and GP IIb/IIIa antagonists have been reported to inhibit platelet aggregation stimulated by a wide variety of platelet agonists. To clarify the qualitative difference between these two agents, their effects on various platelet responses in washed platelets evoked by thrombin (0.05 U/mL) were compared in vitro. Two types of cAMP-elevating drugs, cilostazol (a phosphodiesterase III inhibitor) and prostaglandin E1 (an adenylate cyclase activator), both inhibited platelet aggregation, thromboxane A2 formation, and platelet factor 4 release in a concentration-dependent manner. In addition, both agents suppressed intracellular Ca++ elevation induced by thrombin. However, two classes of GP IIb/IIIa antagonists, abciximab (Fab fragment of antibody) and tirofiban (a synthetic compound), showed no inhibitory effects against thromboxane A2 formation and platelet factor 4 release, although these drugs inhibited platelet aggregation. Essentially the same results were obtained in platelet-rich plasma stimulated with high concentration (100 microM) of thrombin receptor activating peptide. In contrast to these different profiles on thromboxane A2 formation and release reaction, both cAMP-elevating agents and GP IIb/IIIa antagonists potently suppressed procoagulant activity in thrombin-stimulated platelets. These results suggest that the development of platelet procoagulant activity induced by thrombin is exclusively dependent on platelet aggregation or aggregation-dependent processes. These observations also indicate that cAMP-elevating agents possess wider inhibitory effects on platelet responses evoked by strong agonists than GP IIb/IIIa antagonists.

Abciximab↗

PubMed1999

Morphologic limitations of posterior decompression by midsagittal splitting method for myelopathy caused by ossification of the posterior longitudinal ligament in the cervical spine.

STUDY DESIGN: This is a retrospective study of the morphologic limitations of posterior decompression for ossification of the posterior longitudinal ligament in the cervical spine. OBJECTIVES: To determine the morphologic limitations of the posterior approach in the management of ossification of the posterior longitudinal ligament. SUMMARY OF BACKGROUND DATA: Thirty-eight patients who underwent laminoplasty by midsagittal splitting for ossification of the posterior longitudinal ligament were reviewed. Fifteen patients were included in the noncontact group, in which the spinal cord was free of the ossified lesion after posterior decompression. Twenty-three patients were included in the contact group, in which the spinal cord was not free of the ossified lesion even after posterior decompression. METHODS: The preoperative sagittal alignment of the cervical spine and preoperative maximal thickness of ossification were compared between the two groups. In addition, the morphologic limitations of posterior decompression for ossification of the posterior longitudinal ligament were investigated. RESULTS: The following factors were found to contribute significantly to contact between the spinal cord and ossification of the posterior longitudinal ligament after posterior decompression: 1) lordosis of less than 10 degrees or kyphosis in the preoperative sagittal alignment, and 2) preoperative maximal thickness of ossification of more than 7 mm. CONCLUSIONS: Patients who exhibit significant risk factors for continued contact of the spinal cord should be morphologically considered for anterior decompression.

Adult↗

PubMed1999

Clinical analysis and TPO levels in three patients with refractory thrombocytopenia.

Refractory thrombocytopenia (RTC) is a counter-concept to refractory anemia, which is characterized by isolated thrombocytopenia associated with clonal chromosomal abnormality. The diagnosis of RTC is difficult to establish based on morphologic features alone. And steroid therapy for RTC is often ineffective. We examined 3 patients with RTC to identify its characteristics and measured serum thrombopoietin levels. The mean platelet count was 5.1 x 10(4)/microl and the mean age was 64 years. None of our patients had clinical nor laboratory evidence of liver dysfunction, renal disease or disseminated intravascular coagulation. All patients were negative for antiplatelet antibody, PA-IgG and anticardiolipin-beta2GPI antibody. Leukocyte alkaline phosphatase level was low in two patients. Clonal chromosomal abnormalities of different types were detected in all patients. Bone marrow smears showed micromegakaryocytes. But there were no apparent morphological abnormalities of erythroid and granuloid series. Thrombopoietin levels, as determined by enzyme-linked immunosorbent assay, varied from <0.2 to 1.40 fmol/ml. We could not find the screening tool of RTC. In conclusion, there is a need to identify RTC from isolated thrombocytopenia because the patients with RTC don't have good prognosis as patients with isolated thrombocytopenia. Cytogenetic analysis is necessary to establish the diagnosis of RTC. We recommend that a patient above 50 years of age presenting with isolated thrombocytopenia and a low leukocyte alkaline phosphatase score should be suspected of having RTC.

Aged↗

PubMed1999

Identification of peak bone mass QTL in a spontaneously osteoporotic mouse strain.

The whole genome scan for quantitative trait loci (QTLs) specifying peak bone mass was performed with the F2 intercrosses of SAMP6, an established murine model of senile osteoporosis, exhibiting a significantly lower peak bone mass, and SAMP2, exhibiting a higher peak bone mass. Cortical thickness index (CTI), a parameter of bone mass of femurs, was measured in 488 F2 progeny at 4 months of age, when the animals attained peak bone mass by microphotodensitometry. Genetic markers were typed at 90 loci spanning all chromosomes except the Y. By interval mapping of 246 male F2 mice, two loci were identified with significant linkage to peak bone mass, one on Chromosome (Chr) 11 and another on Chr 13, with a maximum lod score of 10.8 (22.2% of the total variance) and 5.8 (10.0%), respectively. Another locus on the X Chr was suggestive of a QTL associated oppositely with a low peak bone mass to the SAMP2 allele. This association was consistent with the distribution of peak bone mass in the F1 and F2. These findings should be useful to elucidate the genetics of osteoporosis.

Animals↗

PubMed1999

Capillary changes with fenestrations in the contralateral soleus muscle of the rat following unilateral limb immobilization.

Using electron microscopy, we examined structural changes in the capillaries of the immobilized and contralateral soleus muscles in the rat after the unilateral limb had been immobilized for 4 weeks. Individual contralateral muscle fibers showed a normal structure, compared with the structure in the immobilized muscle fibers. Most capillaries in the contralateral muscle were of the continuous type. However, about 5% of the examined capillaries in these muscles in each rat had fenestrations. The non-nuclear portions of the endothelial cells in these capillaries were extremely thin and were perforated by several fenestrations that were bridged by a single-layered diaphragm. The fenestration of capillaries in the contralateral muscle may have been caused by some the unilateral limb immobilization.

Animals↗

PubMed1999

Three-dimensional virtual imaging of facial skeleton and dental morphologic condition for treatment planning in orthognathic surgery.

The improvement of esthetics and function, including the occlusal relationship, needs to be carefully considered in treatment planning for the success of orthognathic surgery. Conventional lateral cephalograms and dental study casts have been used usually for the assessment of skeletal morphologic condition and occlusion, respectively, in planning procedures. However, these traditional techniques do not allow for simultaneous evaluation of the skeletal morphologic condition and the occlusal harmony. A new technique has been developed that combines the conventional clinical diagnostic materials, cephalograms, and dental study casts to produce a 3-dimensional virtual image for routine practice. A 3-dimensional graphic image of dental study casts was generated with a laser surface scanner. A 3-dimensional skeletal image was constructed based on the coordinates of anatomic landmarks registered on frontal and lateral cephalograms. The image of the study cast was then set up with the 3-dimensional skeletal image to create a 3-dimensional dataset of the virtual image. The 3-dimensional virtual image, combining the cephalometric and the dental study cast information, permits simultaneous display of skeletal morphologic condition and occlusal relationship. This 3-dimensional virtual imaging can be helpful in planning orthodontic-surgical treatment and in providing graphic information to the patient. This article describes the technique and outline. A clinical application with this imaging technique is also demonstrated.

Cephalometry↗

PubMed1999

Growth-stimulating effects of tumor necrosis factor-alpha on simian virus 40-transformed human keratinocytes is linked to phosphorylation of retinoblastoma protein.

In this report, we show that tumor necrosis factor-alpha (TNF-alpha) has a strong growth-stimulating effect on simian virus 40 (SV40)-transformed keratinocytes, while it exerts a potent growth-inhibitory effect on normal human keratinocytes. Addition of TNF-alpha to SV40-transformed keratinocytes stimulated cell growth by 216, 246, or 248% at 25, 50, or 250 ng/ml after 4 days culture compared with untreated cells, while addition to normal human keratinocytes reduced growth to 65, 38, and 32% at the same concentrations, respectively. Cell cycle analysis by flow cytometry showed that treatment of SV40-transformed keratinocytes with 250 ng/ml TNF-alpha for 48 h increased the S-phase cells from 19.8 +/- 0.3 to 49.7 +/- 2.4%. The percentage of G1/G0 phase cells decreased from 62.6 +/- 1.6 to 32.4 +/- 3.3%. We also demonstrated by immunofluorescent staining that SV40 large T antigen was enhanced by TNF-alpha incubation. Additionally, we examined the hyper and hypo-phosphorylated state of retinoblastoma protein (pRB), the cell cycle regulatory protein. TNF-alpha induced hyperphosphorylated pRB in SV40-transformed keratinocytes. On the other hand, TNF-alpha suppressed it in normal keratinocytes. We hypothesize that the enhancement of SV40 large T antigen and hyperphosphorylated pRB is involved in the mechanism of growth stimulation of SV40-transformed keratinocytes by TNF-alpha.

Cell Division↗

PubMed1999

Cytokine and endothelial damage in pulsatile and nonpulsatile cardiopulmonary bypass.

Recently, several types of centrifugal pumps have been widely used as the main pumps for cardiopulmonary bypass (CPB). However, according to the results of our experimental studies, after cardiogenic shock, pulsatile flow was effective in maintaining the functions and microcirculations of end organs, especially those of the liver and kidney. To estimate the effectiveness of pulsatility during CPB, cytokine and endothelin and other metabolic parameters were measured in clinical pulsatile and nonpulsatile CPB cases. From March to May 1997, CPB was performed in 18 elective cases (14 ischemic and 4 valvular disease). In 9 cases, pulsatile perfusion was achieved by the Jostra HL20, which is a newly developed CPB pump (Group P). A nonpulsatile centrifugal pump was used in 9 patients (Group NP). In both groups, as chemical and metabolic mediators, interleukin-8 (IL-8), endothelin-1 (ET-1), and plasma free hemoglobin were measured before and during CPB, and 0.5, 3, 6, 9, 18 h after weaning from CPB. This pulsatile CPB pump could be very simply and easily controlled and could easily produce pulsatile flow. There were no significant differences in CPB time (CPBT), aortic cross clamp time (ACCT), mean aortic pressure, or pump flow during CPB between the both groups. The ET-1 level of Group P was significantly (p < 0.05) lower than that of Group NP 9 h after CPB weaning. The IL-8 level of Group P also showed a lower value than that of Group NP. As for plasma free hemoglobin, there were no significant differences between the groups. These results suggested that even in conventional CPB, pulsatility was effective to reduce endothelial damage and suppress cytokine activation. It may play a important role in maintaining the functions and microcirculations of end organs during CPB.

Aged↗

PubMed1999

Effects of phosphodiesterase inhibitors after coronary artery bypass grafting.

The aim of this study was to estimate the postoperative effects of phosphodiesterase (PDE) inhibitors (milrinone and olprinone) after coronary artery bypass grafting (CABG). To prevent hypotension caused by the PDE inhibitors, low dose of catecholamines were used concomitantly. A total of 34 elective CABG cases were tested. In 12 cases, 0.25 microg kg(-1) min(-1) of milrinone, 3 microg kg(-1) min(-1) of dobutamine (DOB) and dopamine (DOA) were used concomitantly (Group-M). In another 10 patients, 0.1 microg kg(-1) min(-1) of olprinone and the same doses of the catecholamines were infused (Group-O). As a control, the same doses of DOA and DOB only were administered in 12 patients (Group-C). When the pump flow of the cardiopulmonary bypass (CPB) decreased to half, these drugs were given in all groups. Hemodynamics were recorded before CPB, just after the operation, and 3, 6, 12, 24, 48 and 72 h after the operation. Both milrinone and olprinone increased the cardiac index and decreased systemic vascular resistance to almost the same degree. Olprinone decreased mean aortic and pulmonary artery pressures, and also significantly reduced the preload of both right and left heart compared with milrinone. Significant hypotension was not detected due to the concomitant usage of low-dose catecholamines. This concomitant usage of PDE inhibitors and catecholamines allowed easy weaning from CPB, demonstrating excellent hemodynamics after CABG. Good oxygen demand and supply balance were maintained in peripheral tissue. These results suggest that these new PDE inhibitors may be effective not only for weaning from CPB but also for post-cardiotomy cardiogenic shock.

Aged↗

PubMed1999

Should use of the internal thoracic artery be avoided under conditions of low free flow? Postoperative hemodynamic assessment using pulsed Doppler echocardiography.

There are cases in which it is thought advisable to avoid the use of the left internal thoracic artery (LITA) in coronary artery bypass grafting (CABG) due to its low free flow (FF). However, even though the LITA flow is very low, anastomosis without any further maneuvers intraluminally is recommended. The present study investigated the clinical results of CABG, using a LITA with low FF. The 60 cases of CABG were divided into 2 groups: (i) Group L (n = 23), in which LITA FF was less than 20 ml/min; and (ii) Group H (n = 37) in which it was more than 20 ml/min. A comparative study on the basis of coronary angiography and pulsed Doppler echocardiography was performed. In both groups, no LITA graft occlusion was identified, and the 'string sign' was also absent. In the LITA blood waveform, all cases exhibited a biphasic pattern with a higher mid-diastolic and a lower end-systolic component. There were no significant differences in the LITA flow diastolic peak velocity, velocity time integrals and the diastolic/systolic peak velocity ratios. These results suggest that the LITA can be used for CABG even when the free flow is less than 20 ml/min.

Aged↗

PubMed1999

Doppler features of occlusion of the internal thoracic artery due to preoperative branch embolization.

A 61-year-old male was referred to the surgical ward by cardiologists because of a diagnosis of unstable angina with 3-vessel disease. On preoperative left internal thoracic arteriography, a large first intercostal branch was found at the proximal portion. Selective arterial embolization of the branch of the left internal thoracic artery (LITA) was carried out preoperatively. At 2 days after embolization, the Doppler peak flow velocity and diameter of the LITA were increased and enlarged compared with before the procedure. However, a large reverse wave following after the first systolic peak flow of the LITA was newly detected after embolization. Upon operation, the LITA was found to be occluded at the 2nd intercostal space due to thrombus formation. Therefore, the right internal thoracic artery was anastomosed to the left anterior descending artery and coronary reversed saphenous vein grafts were joined to segment 4PD of the right coronary artery. The postoperative course was uneventful. There has been no previous report of an LITA branch being embolized preoperatively. It was possible to diagnose the graft problem by detecting the altered Doppler wave form of the LITA.

Angina Pectoris↗

PubMed1999

Morphologic changes in the perioral soft tissues in patients with mandibular hyperplasia using a laser system for three-dimensional surface measurement.

Soft tissue changes following correction of mandibular hyperplasia were studied using a laser system for three-dimensional (3-D) surface measurement. Twelve subjects (7 men and 5 women; age 17-48 years) were included in this study. Bilateral sagittal split ramus osteotomies were performed in ten patients and intraoral vertical ramus osteotomies in two patients. Pre- and postoperative images, obtained with the laser system, were superimposed to determine distribution of changes in the perioral soft tissue. Mean volume changes were 1032.3 mm3 in the Subnasale-UL area and 8700.9 mm3 in the LL-Menton area. Changes in both areas were symmetrical around the mid-sagittal plane in some patients and asymmetrical in others. This measurement system provided a simple method of determining 3-D changes in soft tissue following surgery and might be useful for clinical purposes.

Adolescent↗