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Biomedical subjects

Y Fujimura

Publications and source records attributed to Y Fujimura.

At least 127 records · Page 7Linked to original sources
PubMed1997

Disrupted cholecystokinin type-A receptor (CCKAR) gene in OLETF rats.

OLETF rats develop hyperglycemia, hyperinsulinemia and mild obesity, which is characteristic of human non-insulin-dependent diabetes mellitus (NIDDM). We cloned and sequenced the cholecystokinin type-A receptor (CCKAR) gene in the rats. Comparing the DNA sequences of the OLETF CCKAR gene and LETO CCKAR gene, normal gene, we found a deletion in the OLETF gene, 6847 bases in length, which was flanked by two 3-base-pair direct repeats (5'-TGT-3') at positions -2407/-2405 and 4441/4443, numbered according to the LETO gene sequence, one of which was lost. The promoter region, the first and second exons were missing in the mutant. The region upstream and downstream of the deletion, including exons 3, 4 and 5, was conserved between the two strains, and did not contain any base changes. We found that the gene mapped to chromosome 14 in rats. OLETF rats are the naturally occurring knockout animals with the homozygously disrupted CCKAR gene.

Animals↗
PubMed1997

Characterization of the novel murine monoclonal anti-von Willebrand factor (vWf) antibody GUR76-23 which inhibits vWf interaction with alpha IIb beta 3 but not alpha v beta 3 integrin.

von Willebrand factor (vWf) is known to interact with the two beta 3 integrins, alpha IIb beta 3 and alpha v beta 3, in an RGD-dependent manner. We characterized a novel murine monoclonal antibody to human vWf, GUR76-23, which recognized a site within the carboxy-terminal half of the molecule containing the RGD sequence. This antibody inhibited high shear-induced platelet aggregation and blocked adhesion of ADP plus epinephrine-stimulated platelets to vWf, indicating that it interferes with the interaction with alpha IIb beta 3. Unlike antibodies against the RGD site, however, the antibody was without effect on adhesion of cultured human umbilical vein endothelial cells to vWf, a phenomenon known to involve the interaction with alpha v beta 3. GUR76-23 binding was not displaced by anti-RGD antibodies. These results suggest that the adhesive interaction of vWf with these two beta 3 integrins may be differentially modulated by a site(s) other than the common RGD module.

Animals↗
PubMed1997

High shear stress attenuates agonist-induced, glycoprotein IIb/IIIa-mediated platelet aggregation when von Willebrand factor binding to glycoprotein Ib/IX is blocked.

High shear stress facilitates von Willebrand factor (vWF) binding to platelet glycoprotein (GP) Ib/IX, causing activation of GPIIb/IIIa to induce platelet aggregation. Here we report that activated GPIIb/IIIa, even occupied by ligands, is not sufficient to mediate platelet aggregation under high shear stress conditions when vWF binding to GPIb/IX is blocked. Platelet rich plasma or washed platelet suspension supplemented with purified human fibrinogen at a concentration of 2 mg/mL were treated with an anti-vWF monoclonal antibody NMC-4 which blocks the binding of vWF to GPIb/IX. After addition of 10 mumol/L ADP, aggregation was continuously monitored under various shear stress conditions (0-108 dyne/cm2) using a cone-plate type aggregometer previously described (Ikeda Y et al J Clin Invest 1991; 87:1234). The extent of maximal aggregation of agonist-stimulated platelets in the presence of NMC-4 correlated inversely with the level of shear stress applied, with the virtual absence of aggregation at 108 dyne/cm2. Once aggregated by 10 mumol/L ADP under low shear stress (12 dyne/cm2), platelets could be disaggregated, in part, by the application of high shear stress (108 dyne/cm2), and reaggregated when shear stress was returned to 12 dyne/cm2. Flow cytometric analysis revealed that platelets stimulated with 10 mumol/L ADP at 108 dyne/cm2 bound fluorescein isothiocyanate (FITC)-labeled fibrinogen, although aggregation was absent in this experimental condition. These results demonstrate the dual effect of shear stress on platelet functions; a pro-aggregating activity that induces vWF-GPIb/IX interaction leading to platelet activation, and an anti-aggregating force to prevent the growth of platelet thrombi. It is suggested that the efficacy of vWF blockade is greater under high shear than low shear stress conditions, and that a selective inhibition of platelet functions can be possible.

Adenosine Diphosphate↗
PubMed1997

Inhibition of apoptosis by normal and aberrant Fli-1 and erg proteins involved in human solid tumors and leukemias.

Two ets family members, namely erg and Fli-1 are fused with two EWS family members namely EWS and TLS/FUS as a result of chromosome translocation in human solid tumors and leukemias. EWS-erg and EWS-Fli-1, which are involved in greater than 95% of Ewing family of tumors, were shown to function as transcriptional activators. TLS/FUS-erg, which is involved in human myeloid leukemias also functions as a transcriptional activator. Expression of these fusion proteins (EWS-erg and EWS-Fli-1) are shown to be essential for maintaining the oncogenic and tumorigenic properties of tumor cells. Cancer is thought to be caused not only by uncontrolled cell proliferation but also by deregulation of programmed cell death. Therefore, we have studied the role of normal (Fli-1 and erg) and aberrant fusion proteins (EWS-erg, EWS-Fli-1 and TLS/FUS-erg) in apoptosis. We have found that expression of normal (Fli-1 and erg) and aberrant fusion proteins inhibit the apoptosis of NIH3T3 cells induced by either serum deprivation or by treatment with calcium ionophore. We have also observed similar suppression of apoptosis in Ewing's sarcoma cells expressing EWS-Fli-1 and EWS-erg proteins suggesting that these fusion proteins may be responsible for the decreased ability of these tumor cells to undergo apoptosis. Inhibition of the expression of these aberrant fusion proteins by antisense RNA technique resulted in increased susceptibility to apoptosis leading to the death of tumor cells. Therefore, our results suggest that one can use therapeutic agents which can down regulate the expression of fusion proteins in combination with chemotherapeutic agents as an effective treatment for these human solid tumors and leukemias.

3T3 Cells↗
PubMed1997

Correlation of titer of antibody to principal neutralizing domain of HIVMN strain with disease progression in Japanese hemophiliacs seropositive for HIV type 1.

With the use of the principal neutralizing determinant (PND) peptide-based ELISA to measure anti-PND antibodies that specifically bound synthetic peptides derived from HIVIIIB, HIVMN, HIVRF, HIVSC, HIVWJM-2, HIVAf1l.con, or HIVAf2.con, type-specific antibodies to the HIVMN peptide were studied in 350 serum specimens from Japanese with hemophilia A who had been injected with known unheated factor VIII concentrates until 1985 and had been infected with HIV-1 subtype B. These antibodies were not found in any of the seronegative sera of hemophiliacs, patients with autoimmune diseases, or normal healthy controls. Further, all hemophiliacs rapidly progressing to AIDS and death among the 95 hemophiliacs in a restricted Nara area had antibody titers of less than 20 and their low levels preceded the rapid progression to the disease state. In contrast, slowly progressing hemophiliacs maintained an antibody titer of more than 100 from the initial stages of viral infection and remained asymptomatic. Sequence analysis of the V3 regions of HIV-1 indicated that the hemophiliacs who maintained a high anti-PNDMN antibody level showed a conserved MN sequence. In contrast, the HIV-infected hemophiliacs with nonreactivity in the ELISA showed sequence changes in the neutralizing epitopes of HIVMN. The dynamic of the serum anti-PNDMN antibody titer appear to be a characteristic indicator of the progression of the HIV-infected status in Japanese hemophiliacs seropositive for HIV-1.

Adult↗
PubMed1997

Long-term follow-up study of anterior decompression and fusion for thoracic myelopathy resulting from ossification of the posterior longitudinal ligament.

STUDY DESIGN: This was a retrospective study of the results of anterior decompression and fusion in patients with thoracic myelopathy secondary to ossification of the posterior longitudinal ligament with a minimum follow-up time of 5 years. OBJECTIVES: To clarify the effectiveness and limits of anterior decompression and fusion for thoracic ossification of the posterior longitudinal ligament. SUMMARY OF BACKGROUND DATA: Posterior decompression for the surgical management of thoracic ossification of the posterior longitudinal ligament has had an uncertain success record. Anterior decompression and fusion have been considered the treatment of choice however, there are few reports describing the long-term results. METHODS: The participants in this investigation were 33 patients whose cases were followed for an average period of 8 years and 2 months. The factors that were investigated included changes in the Japanese Orthopedic Association score and in recovery rates, postoperative complications, and radiographic findings of bone union and progression of ossification of the posterior longitudinal ligament within the area of anterior decompression. RESULTS: Although the recovery rates were relatively stable from 1-5 years after surgery, the rates declined thereafter. The average recovery rate at the final follow-up visit was 53.2%. Postoperative complications included three cases of deterioration of thoracic myelopathy and four cases of extrapleural cerebrospinal fluid leakage. Except for the one case of deterioration of thoracic myelopathy, the remainder of the complications were transient. CONCLUSIONS: Anterior decompression and fusion is an effective surgical procedure for thoracic ossification of the posterior longitudinal ligament with good, stable, long-term results; when thoracic ossification of the posterior longitudinal ligament was extensive or coincident with ossification of the intraspinal ligament, however, the results were not as predictable.

Adult↗
PubMed1997

Relationship between respiratory distress and cytokine response after cardiopulmonary bypass.

The influence of cytokines on the inflammatory response in surgery has recently been the subject of investigations. We measured tumor necrotic factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), interleukin 8 (IL-8), and granulocyte elastase (GEL) in 26 patients undergoing elective cardiac operations using cardiopulmonary bypass (CPB), preoperatively, immediately after CPB, and on post-operative days (PODs) 1, 3, and 6. To evaluate the effect of these cytokines on pulmonary function, the patients were divided according to whether the oxygenation index (OI) on POD 1 was > 250 or < 250, into groups A and B, respectively. TNF-alpha and IL-1 beta were undetectable and there were no significant differences in the preoperative IL-6, IL-8, and GEL levels. However, immediately following CPB, the mean IL-6, IL-8 and GEL levels in both groups were significantly higher than the preoperative levels (P < 0.01). Moreover, all these levels were significantly higher in group B than in group A, at 162 +/- 150 pg/ml vs 64 +/- 53 pg/ml (P < 0.05) for IL-6; 53 +/- pg/ ml vs 22 +/- 20 pg/ml (P < 0.01) for IL-8; and 2477 +/- 1642 mg/ l vs 1397 +/- 774 mg/l (P < 0.01) for GEL. The IL-6 levels returned to the preoperative values in both groups on POD 1; however, the GEL levels remained significantly higher in group B than in group A postoperatively, at 616 +/- 326 mg/l vs 378 +/- 70 mg/l on POD 1, and at 292 +/- 70 mg/l vs 218 +/- 62 mg/ l on POD 3 (P < 0.05). Thus high levels of cytokines such as IL-6, IL-8, and GEL may be detrimental to respiratory function.

Adult↗
PubMed1997

Modified Bentall operation with concomitant total aortic arch replacement for DeBakey type I aortic dissection: report of a case.

The successful implementation of a reoperative Bentall procedure with concomitant total aortic arch replacement after ascending aortic replacement for acute aortic dissection is infrequently reported. We performed a modified Bentall procedure with total replacement of the aortic arch in a patient suffering from worsening aortic regurgitation (AR) and residual dissection. Our strategy involved the button method for coronary reconstruction, selective cerebral perfusion, the use of a composite graft with four branches for aortic arch replacement, and the administration of high-dose aprotinin to decrease bleeding.

Acute Disease↗
PubMed1997

Immunological suppression after surgery in scoliosis patients.

This is a prospective study to analyze the postoperative immunological changes in scoliosis surgery. Twenty-eight patients who underwent Harrington instrumentation were analyzed. Seven patients who underwent arthroscopic surgery were analyzed as a control group. The objective of this study is to determine whether surgery and surgical stress (minor versus major surgery) changed the immune capability of patients as indicated by the ratio of lymphocyte cell types and interferon induction. Pre- and postoperative blood from scoliosis and knee arthroscopy patients was analyzed at various times using antisera and two-color flow cytometry with monoclonal antibodies. Both scoliosis and knee arthroscopy patients had a postoperative decrease in the population of B-lymphocytes (Leu 12+) and a transient increase in the natural killer cells (Leu 4-/Leu 19+) and the cytotoxic T-lymphocytes (Leu 2a++/Leu 15-). These changes were significantly greater in the scoliosis patients, who also experienced a prolonged decrease in the inducer T-lymphocytes (Leu 8+/Leu 3a+) for 3 weeks following surgery. Production of interferon-alpha and interferon-gamma by lymphocytes was suppressed postoperatively and returned to preoperative levels within 3 weeks. Immunological depressive changes occurred postoperatively and lasted at least 1 week. These effects are more pronounced with longer surgeries, suggesting greater postoperative vigilance for infections in these cases.

Adolescent↗
PubMed1997

A video-assisted thoracoscopic surgical technique for interruption of patent ductus arteriosus.

We describe herein a technique for patent ductus arteriosus (PDA) closure using a method of video-assisted thoracoscopic surgical (VATS) interruption derived from video-assisted endoscopic surgery. This technique of repair was performed on five patients with a mean age of 3 years and a mean weight of 13.7 kg during 1994 and 1995. Under general anesthesia, two 10-mm trocars and two or three 5-mm trocars were inserted through the left thoracic wall. A video camera and specially designed surgical tools including scissors, dissectors, and a clip applicator were then introduced. The ductus was dissected, and two titanium clips were applied to interrupt the ductus completely. Successful closure of the PDA by this video-assisted technique was achieved in all patients. The only complication which developed in one patient was hoarseness for 2 weeks postoperatively. The hospital stay ranged from 7 to 12 days and there were no serious complications or deaths. There results indicate that video-assisted thoracoscopic surgical interruption is a safe and effective technique for achieving closure of PDA.

Child, Preschool↗
PubMed1997

Evaluation of brain oxygenation during selective cerebral perfusion by near-infrared spectroscopy.

BACKGROUND: Although selective cerebral perfusion (SCP) has been used for cerebral protection in aortic arch operations, the appropriate perfusion conditions of SCP are unclear. METHODS: We used near-infrared spectroscopy, which evaluates brain ischemia noninvasively and continuously, to determine whether perfusion with SCP (core temperature, 20 degrees C; flow rate, 10 mL.kg-1.min-1) was acceptable in terms of oxyhemoglobin and deoxyhemoglobin in patients having SCP for aortic arch operations (SCP group, n = 6) versus patients having cardiopulmonary bypass (CPB) for coronary artery bypass grafting (CPB group, n = 6). RESULTS: There were no significant differences in age (65 +/- 10 versus 63 +/- 12 years), CPB time (199 +/- 67 versus 199 +/- 52 minutes), changes in hematocrit (-12.9% +/- 3.7% versus -12.5% +/- 6.0%), lowest blood pressure (43 +/- 7 versus 45 +/- 10 mm Hg), or highest central venous pressure (8 +/- 2 versus 9 +/- 4 mm Hg) between the SCP and CPB groups. In the SCP group, the maximum decrease in oxyhemoglobin level and the maximum increase in deoxyhemoglobin level were -5.0 to -11.4 mumol/L and -0.1 to 3.9 mumol/L, respectively; in the CPB group, the respective changes were -3.2 to -14.2 mumol/L and -0.4 to 3.6 mumol/L. Changes of oxyhemoglobin and deoxyhemoglobin levels in the SCP group were almost within the range of those in the CPB group. There were no brain complications in either group. CONCLUSIONS: As described here, SCP is acceptable and safe for brain protection in aortic arch procedures.

Adult↗
PubMed1997

Muscle reorganization following incomplete cervical spinal cord injury in rats.

This study on rats was designed to evaluate the change of biceps muscle fibers by enzyme histochemical examination and the change of distribution of motoneurons innervating biceps muscle fibers by retrograde tracer examination after incomplete spinal cord injury. Incomplete spinal cord injury was produced by placing a 20 g weight on exposed dura at the C6 level. The number of the labeled motoneurons of C6 segment significantly decreased compared with that in the control, but there were no significant changes in the other segments at 4 weeks after the injury. Moreover, there was type grouping of biceps muscle fibers at 4 weeks after the injury. These findings indicated that the incomplete cervical spinal cord injury at C6 level in rats caused the partial denervation and then reinnervation of biceps muscle fibers by the collateral sprouting of the remaining motoneurons which belonged to the same motoneuron pool of the injured motoneurons.

Animals↗
PubMed1997

Myelopathy secondary to ossification of the posterior longitudinal ligament of the thoracic spine treated by anterior decompression and bony fusion.

We examined the utility of anterior decompression and bony fusion via the extrapleural approach in the treatment of thoracic myelopathy secondary to ossification of the posterior longitudinal ligament (OPLL). Patient outcome and complications were analyzed in 48 patients treated with this procedure, with a follow-up of at least 2 years. The Japanese Orthopaedic Association score was used to evaluate the severity of the thoracic myelopathy, and the recovery rate was used to evaluate the surgical outcome. The outcome, postoperative complications, radiographic evaluations of bony union, and progression of OPLL within the area of anterior decompression were examined. The T3 vertebral body was the highest level to which anterior decompression was applied. The average follow-up period was 57 months with a recovery rate of 56.7% which stabilized 1 year after operation. However, the surgical outcome was less favorable in patients with long-standing myelopathy, extensive OPLL, or thoracic OPLL with coexisting intraspinal ligament ossification. Four patients experienced deterioration of their myelopathy, and seven patients had the postoperative complication of extraspinal leakage of cerebrospinal fluid. The myelopathy was transient in all but one patient. Radiographic studies showed that bony union was achieved and restenosis of the spinal canal due to progression of OPLL within the area of decompression did not occur. We conclude that anterior decompression and bony fusion using the extrapleural approach provides a good outcome and is useful in treating mid- and lower thoracic OPLL when performed carefully at an early stage of disease.

Adult↗
PubMed1997

Decreased choline acetyltransferase activity in the murine spinal cord motoneurons under chronic mechanical compression.

The tiptoe-walking Yoshimura (twy) mouse is a model of chronic spinal cord compression caused by ossification of intraspinal ligaments. Choline acetyltransferase (CAT), which is known to be a specific marker of cholinergic neurons, best reflects spinal motoneuron function. Changes in CAT immunoreactivity following chronic spinal cord compression in twy mice were investigated quantitatively in order to elucidate spinal motoneuron functional changes according to the degree and direction of compression. Thirty 24-week-old twy mice were used in this study. They were divided into three groups according to the direction of spinal cord compression (anterior, posterior, and lateral) and the CAT immunoreactivities in whole sections of their upper cervical spinal cords were investigated quantitatively using a fluorescence microphotometry system. The lateral compression group showed histological spinal motoneuron atrophy and loss on the compressed, but not the non-compressed, side. Spinal motoneuron atrophy and loss were observed when the severity of spinal canal stenosis due to the ossified lesion, expressed as the occupation rate, was 30% or more, but the spinal motoneurons appeared normal when it was below 30%. The CAT immunofluorescence intensity of the anterior horn showed a linear negative correlation with the degree of canal stenosis. When the occupation rate was below 20%, the CAT immunofluorescence intensities in the anterior horns of the compression and control groups did not differ significantly. The CAT immunofluorescence intensity of twy mice with occupation rates of 20% or more were significantly lower than that of those with occupation rates below 20%. Furthermore, the CAT immunofluorescence intensity was significantly lower on the compressed than the non-compressed side of the lateral compression group. Thus, our findings indicate that an occupation rate of about 20% may be the critical level for functional changes in the spinal motoneurons.

Animals↗
PubMed1997

Interaction of von Willebrand factor with the extracellular matrix and glycocalicin under static conditions.

The binding of human von Willebrand factor (vWF) to a variety of extracellular matrix components immobilized on plates and the binding of vWF to platelet glycoprotein Ib (GPIb) after interacting with these matrix components were examined by means of an enzyme-linked immunosorbent assay. vWF preferably bound to type III collagen, whereas it did not significantly bind to type I, IV, V, or VI collagen, fibronectin, laminin, elastin, or proteoglycans. Soluble type III collagen did not bind to vWF coated on plates and showed a little effect on the vWF binding to the immobilized collagen, suggesting that solid-phase collagen is important for the interaction with vWF. When glycocalicin, the N-terminal carbohydrate-rich extracellular domain of GPIb alpha exhibiting the vWF-binding activity, was added to vWF bound to collagen type III, no significant binding of glycocalicin was observed, but it bound to vWF in the presence of botrocetin, a vWF modulator protein isolated from Bothrops jararaca snake venom. These results indicate that vWF immobilized on collagen can interact with GPIb but that binding of vWF to the collagen matrix alone is insufficient for modulating vWF so that it interacts with GPIb under static conditions. Another unknown physiological modulator functionally mimicking botrocetin or high-shear stress may be involved in the platelet adhesion to extracellular matrix in the early stage of hemostasis.

Antibodies, Monoclonal↗
PubMed1997

Exercise-induced changes in enzymatic O-methylation of catecholestrogens by erythrocytes of eumenorrheic women.

The present study was designed to assess the effects of acute exercise and short-term intensive training on catechol-O-methyltransferase (COMT) activity. COMT inactivates catecholamines and converts primary catecholestrogens (CE) into their O-methylated form yielding the 2- (2-MeOE) and 4-methoxyestrogens (4-MeOE). Blood samples were obtained from 15 previously untrained eumenorrheic women (mean +/- SE, VO2max: 43.8 mL x kg-1 x min-1 +/- 0.6) before and after a 5-d intensive training period, at rest and during incremental exercise. COMT activity was determined in the erythrocytes (RBC-COMT) after incubation of blood lysate with primary CE. The formation of both 2- and 4-MeOE was significantly higher (P < 0.05) during the luteal (LPh) than during the follicular phase (FPh). The amount of 2-MeOE formed (FPh: 4.2 +/- 0.2%; LPh: 4.9 +/- 0.2%) was significantly greater than the produced amount of 4-MeOE (FPh: 1.4 +/- 0.1%; LPh: 1.5 +/- 0.1%) (P < 0.05). Both before and after training, incremental exercise did not significantly alter RBC-COMT activity although we observed a trend for RBC-COMT activity increasing proportionally with the exercise intensity. After a brief period of exhaustive training, during rest the formation of 2-MeOE (FPh: +16.7%, LPh: +15.7%) and 4-MeOE (FPh: +28.6%; LPh: +40%) was significantly (P < 0.05) increased. The results of the present study are consistent with earlier findings reporting increased plasma concentrations of O-methylated CE following training. It is concluded that RBC-COMT activity is increased by brief intensive training, but not by acute exercise. We speculate that an increase in COMT-catalyzed O-methylation of CE may indicate that less COMT is available to deactivate norepinephrine.

Adolescent↗
PubMed1997

Anterior decompression and fusion via the extrapleural approach for thoracic disc herniation causing myelopathy.

Anterior decompression and fusion via an extrapleural approach was performed for 33 patients with myelopathy arising from thoracic disc herniation and the clinical usefulness and problems related to this procedure were assessed on the basis of surgical results and complications. The severity of the myelopathy was evaluated by the Japanese Orthopaedic Association score, and the surgical results were based on the recovery rate. The upper-level limit of decompression and fusion via the extrapleural approach was T4-5. The recovery rate for the mean postoperative follow-up period of 41 months was 66.7%. An age of 60 years or more, long duration of illness and severe preoperative myelopathy were indicators of a poor prognosis. Two patients suffered from a postoperative transient pulmonary complication due to hemothorax. X-ray examinations revealed good bone union in all the patients. The present study indicates that anterior decompression and fusion via the extrapleural approach is a useful technique which can be used to achieve a high success rate in the surgical treatment of thoracic disc herniation, if intervention is early.

Adult↗