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Biomedical subjects

Y Fujimura

Publications and source records attributed to Y Fujimura.

At least 109 records · Page 6Linked to original sources

Changes in the morphology and components of the coronary arteries during the progression of coronary arteriosclerosis following cardiac transplantation in rats.

In order to examine the changes in coronary artery morphology following cardiac transplantation, the intimal and medial areas and vascular components were measured 30 and 60 days postoperatively in rats receiving both iso- (n = 5, each time) and allotransplantations (n = 7, each time). Although cyclosporine A was administered intramuscularly (10 mg/kg per day) for 20 days following transplantation, graft rejection progressed gradually in the allotransplanted group. There were no clear changes in the intimal or medial areas following transplantation in the isotransplanted group. The intimal area of the coronary arteries in the allograft group was significantly thicker 30 and 60 days following transplantation, while the medial area of the coronary arteries in this group was significantly thinner than that of the isotransplantation group at these same time points. In the thickened intimal areas in the allotransplantation group, only the density of smooth muscle cells was higher following transplantation. In the thinned medial areas in the allotransplantation group, the densities of the smooth muscle cells and collagen were less than those in the isotransplantation group. These changes suggest that following transplantation, smooth muscle cells proliferate in the intimal areas, while smooth muscle cells and collagen are degraded in the medial areas.

Animals↗

Successful engraftment of unrelated cord blood stem cells for familial erythrophagocytic lymphohistiocytosis. Kinki Cord Blood Bank.

Familial erythrophagocytic lymphohistiocytosis (FEL) is an autosomal recessive disorder that can only be corrected by stem cell transplantation. One of our patients with FEL in second complete remission underwent successful cord blood stem cell transplantation (CBSCT); the donor was an HLA one-locus mismatched and unrelated individual. The conditioning regimen consisted of BU/CY/VP-16. The transfused cell dose was 6.8 x 10(7)/kg, which contained 1.36 x 10(5)/kg of CD34 cells and 3.4 x 10(4)/kg of CFU-GM. After CBSCT, there were no major infectious complications. Acute grade I GVHD was well controlled. Neutrophil counts reached >0.5 x 10(9)/l by day 20 and platelet counts reached >50 x 10(9)/l by day 40. Deficient natural killer activity returned to normal after the transplant. The patient recovered well more than 7 months after receiving CBSCT, without showing evidence of chronic GVHD. We recommend CBSCT for FEL patients who have no HLA-matched siblings or unrelated donors.

Child, Preschool↗

Late postoperative respiratory function in adults after surgical correction of atrial septal defects. Analysis of respiratory dysfunction patterns.

Respiratory function after repair of atrial septal defect (ASD) was analysed in 44 adults (> 40 years), 21 of whom had preoperative respiratory dysfunction, 14 of restrictive type, defined as % vital capacity (% VC) less than 80% of predicted value, 3 with an obstructive pattern, defined as % forced expiratory volume/1 s (% FEV1) less than 70% of predicted value, and 4 patients with a mixed pattern. Increased % VC was found postoperatively in all 14 patients with restrictive respiratory dysfunction, with normal values in 8 out of the 14. Although the three patients with obstructive, and the four with mixed-pattern respiratory dysfunction improved preoperatively in % VC or % FEV1, or both, none had normalized values. We conclude that preoperative restrictive respiratory dysfunction in ASD patients frequently normalizes postoperatively, but not dysfunction of obstructive or mixed restrictive-obstructive type.

Adult↗

Changes of amino acid levels and aspartate distribution in the cervical spinal cord after traumatic spinal cord injury.

To evaluate the role of excitatory amino acids in secondary injury occurring after spinal cord trauma, several experimental studies focusing on the the changes of amino acid levels in the spinal cord have been performed to date. However, because of technical limitations, it has not been possible to correlate the local changes of excitatory amino acids with the total tissue levels of excitatory amino acids. To investigate the connection between the spread of injury and the excitatory amino acids, we assessed, the local changes of aspartate through novel experimental approaches like immunoreactivity via fluorescence microphotometry and histopathology while also analyzing the total tissue levels of amino acids via HPLC. These studies were performed using a model of incomplete cervical spinal cord injury in rats. Through this approach, we found that the levels of excitatory amino acids, such as glutamate and aspartate, began to decrease immediately after injury. No significant decrease was observed in the other amino acids. Similarly, local changes in aspartate in the spinal cord were observed using fluorescence microphotometry. The decrease in the anterior and posterior horns was rapid up to 15 min after injury, but, slowed thereafter, suggesting that a release of excitatory amino acids occurred at the site of primary injury almost immediately following injury. At 15-min post-injury large neurons within the injured cord appeared intact on histopathological analysis demonstrating that the alteration of excitatory amino acids occurs prior to histopathological change. Histopathological change in the white matter occurred more slowly than in the anterior and posterior horns, suggesting the spread of the lesion by secondary damage due to an autoclastic mechanism.

Amino Acids↗

Primary Sjögren's syndrome followed by chronic myelogenous leukemia: a case report with a ten year history.

We describe a female patient with primary Sjögren's syndrome who subsequently developed chronic myelogenous leukemia. The patient received a bone marrow transplant (BMT) from a genotypically HLA-identical brother after pre-transplant preparation with busulfan and cyclophosphamide. Eighteen weeks later, cutaneous and mucosal chronic graft-versus-host disease developed, followed by death 11 months after transplantation. Anti-Ro/SS-A antibodies disappeared within 6 months post-BMT, but antinuclear antibodies remained positive through the post-transplant course.

Adult↗

Correlations among expression of intercellular adhesion molecule 1, cellular infiltration, and coronary arteriosclerosis during chronic rejection using the rat heart transplantation model.

Immunologic mechanisms contribute to the development of coronary arteriosclerosis. In this study the rat heart transplantation model was used to investigate correlations among the expression of intercellular adhesion molecule 1, cellular infiltrate, and coronary arteriosclerosis during chronic rejection. Lewis rats served as heart donors and F-344 rats as recipients. Heart transplantations were performed heterotopically. The recipients were treated with cyclosporin A (5 mg/kg/day) by daily intramuscular injection for 30 days, beginning on the day of transplantation. Rejection grade and the intimal area were measured. The expression of intercellular adhesion molecule 1 and the numbers of infiltrating CD4- and CD8-positive cells and macrophages were examined immunohistochemically. The area of the intima was significantly increased in the allograft group after transplantation. In the allograft group, the level of expression of intercellular adhesion molecule 1 was considerably increased over the same time period. There was increased cellular infiltration in the 60-day group, and many expressed intercellular adhesion molecule 1. The expression of intercellular adhesion molecule 1 in vascular endothelium, infiltrating cells, and the sarcolemmal membrane of myocytes remained constant up to 120 days in the allograft group. In the allograft group, the number of infiltrating CD4- and CD8-positive cells and macrophages increased significantly between 30 and 60 days, and the infiltration of these cells remained constant. Continuous expression of intercellular adhesion molecule 1 induces the infiltration of T cells and macrophages, and the inflammation caused by such cells and their soluble products contributes to the arteriosclerotic process.

Animals↗

MRI of cervical intervertebral discs in asymptomatic subjects.

We studied degenerative changes in the cervical intervertebral discs of 497 asymptomatic subjects by MRI and evaluated disc degeneration by loss of signal intensity, posterior and anterior disc protrusion, narrowing of the disc space and foraminal stenosis. In each subject, five disc levels from C2-C3 to C6-C7 were evaluated. The frequency of all degenerative findings increased linearly with age. Disc degeneration was the most common observation, being present in 17% of discs of men and 12% of those of women in their twenties, and 86% and 89% of discs of both men and women over 60 years of age. We found significant differences in frequency between genders for posterior disc protrusion and foraminal stenosis. The former, with demonstrable compression of the spinal cord, was observed in 7.6% of subjects, mostly over 50 years of age. Our results should be taken into account when interpreting the MRI findings in patients with symptomatic disorders of the cervical spine.

Adolescent↗

Lack of pharmacokinetic interaction between mexiletine and omeprazole.

OBJECTIVE: To investigate the effect of omeprazole on the pharmacokinetics of mexiletine. METHODS: Nine healthy male Japanese volunteers participated in a crossover study. On day 1, the subjects received mexiletine 200 mg. On days 2-7, they received omeprazole 40 mg, and on day 8 they received mexiletine 200 mg and omeprazole 40 mg concomitantly. Serum concentrations of mexiletine were determined just before drug administration and at 1, 2, 3, 4, 6, 8, 12, and 24 hours on day 1 and day 8. RESULTS: No differences in mexiletine concentrations were observed between the two phases of the study. The mean AUCs after administration of mexiletine alone and in combination with omeprazole 40 mg/d were 6.26 and 6.20 ng.h/L, respectively. CONCLUSIONS: These findings suggest that omeprazole does not affect mexiletine metabolism.

Administration, Oral↗

[Minimally invasive cardiac surgery for aortic valve disease].

Recent surgical advances leading to good operative results have contributed to the trend to useminimally invasive approaches, even in cardiac surgery. Smaller incisions are clearly more cosmetically acceptable to patients. When using a minimally invasive approach, it is most important to maintain surgical quality without jeopardizing patients. A good operative visual field leads to good surgical results. In the parasternal approach, we use a retractor to harvest an internal thoracic artery in coronary artery bypass surgery. Retracting the sternum upward allows for a good surgical view and permits the use of an arch cannula rather than femoral cannulation. When reoperating for aortic valve repair, the j-sternotomy approach requires less adhesiolysis compared with the traditional full sternotomy. No special technique is necessary to perform aortic valve surgery using the j-sternotomy approach. However, meticulous attention must be paid to avoiding left ventricular air embolisms to prevent postoperative stroke or neurocognitive deficits, especially when utilizing a minimally invasive approach. Transesophageal echo is useful not only for monitoring cardiac function but also for monitoring the persence of air in the left ventricle and atrium. This paper compare as the degree of invasion of minimally invasive cardiac surgery and the traditional full sternotomy. No differences were found in the occurrence of systemic inflammatory response syndrome between patients undergoing minimally invasive cardiac surgery and the traditional technique. Therefore it is concluded that minimally invasive surgery for patients with aortic valve disease may become the standard approach in the near future.

Aortic Valve↗

[Repair of left ventricular free wall rupture with GRF glue associated with acute myocardial infarction: report of a case].

Histopathological examination of a repair of left ventricular free wall rupture associated with acute myocardial infarction using GRF glue was reported. A 63-year-old male with cardiac rupture due to LMT total occlusion was referred to our ward after unsuccessful PTCA with institution of IABP and PCPS. Left ventricular rupture repair by GRF glue and xenograft pericardial patch with concomitant myocardial revascularization (SVG-LAD, CX) was performed under cardiopulmonary bypass. Hemostasis around the ventricular rupture was easily accomplished. Unfortunately, the patient died at 14 POD because of low output syndrome caused by broad myocardial infarction. At autopsy, rupture site was examined histologically and was revealed that GRF glue made a tight adhesion between patch and myocardium. Neither abnormal inflammatory cells nor giant cells were found. We concluded that GRF glue might be a effective histocompatibly in hemostasis for left ventricular rupture associated with acute myocardial infarction.

Cardiac Surgical Procedures↗

Influence of minor trauma on surgical results in patients with cervical OPLL.

This study was designed to evaluate the relationship between minor trauma and surgical results of cervical ossification of the posterior longitudinal ligament (OPLL), focusing on static compressive and dynamic factors contributing to cord compression plus the type of attendant OPLL. Of the 91 patients treated surgically, 26 had sustained minor trauma (injury group), and the other 65 had no trauma (noninjury group). The pre-/postoperative JOA scores and recovery ratio for the injury group were significantly lower than those for the noninjury group. In the segmental, localized, and mixed types, which had good ranges of motion of the cervical spine, the recovery ratios of the injury group were significantly lower than those of the noninjury group. In the continuous type, which had a poor range of motion and severe spinal cord compression, there was no significant difference in the recovery ratio between the injury and noninjury groups. Thus, dynamic factors may play an important role in neurologic deterioration after minor trauma in patients with segmental, mixed, and localized cervical OPLL.

Adult↗

[Surgery for the treatment of infective endocarditis in the active and inactive stages].

Twenty-eight patients (16 M, 12 F, age 11 approximately 72 yr, mean 52.8 yr) underwent surgery for infective endocarditis. Of the 27 patients, 16 were in the active stage and 11 were in the inactive stage. In patients in the active stage, aortic valve replacement (AVR) was performed in 5, mitral valve replacement (MVR) in 7, AVR + MVR in 1, AVR + MVR + tricuspid valve plasty (TVP) in 1 and other procedures in 2. In patients in the inactive stage, AVR was performed in 3, MVR in 4, AVR + MVR in 2, and other procedures in 2. Causative organisms were detected in 56.3% of the patients in the active stage and 54.5% in the inactive stage. Also in patients in the active stage, infection was not prolonged. No deaths occurred among patients in the inactive stage but five patients (31%) died postoperatively; 4 of the five also died, for had severe heart failure before surgery, three died of multiple organ failure and one died of subarachnoid hemorrhage due to infective aneurysm. We recommend surgery for the treatment of infective endocarditis even in the active stage before emergence of heart failure.

Adolescent↗

Progressive hyperthermia during thoracoscopic procedures in infants and children.

We describe the development of progressive hyperthermia during thoracoscopic procedures in infants and children. Twelve patients (four infants and eight children) underwent closure of a patent ductus arteriosus using the video-assisted technique. A progressive increase in body temperature of more than 2 degrees C occurred in six of the patients during surgery. The increase in body temperature correlated inversely with body weight and directly with duration of surgery (r = -0.76, P = 0.003 and r = 0.68, P = 0.01, respectively). We found that the thoracoscope produces 28.5 joule.min-1 of constant energy in vitro. Our findings show progressive hyperthermia during thoracoscopic procedures, due to energy release from the thoracoscope. This could be a significant complication in infants undergoing prolonged operations.

Age Factors↗

The cDNA cloning and molecular characterization of a snake venom platelet glycoprotein Ib-binding protein, mamushigin, from Agkistrodon halys blomhoffii venom.

The entire cDNA sequences of a novel snake venom platelet glycoprotein (GP) Ib-binding protein (BP) composed of an alpha/beta heterodimeric structure, termed mamushigin, from Agkistrodon halys blomhoffii were determined, that include the leader peptides (21/23 amino acid residues) and mature subunits (136/123 amino acid residues). The mature subunits of mamushigin are 37.5% identical, and showed a high degree of similarity (37.7-67.5% identity) with the respective subunits of group VII C-type lectins (19). The sequences of the leader peptides of the mamusigin subunits showed the highest similarity (alpha-73.9/beta-82.6%) with those of factor IX/X-BP from Trimeresurus flavoviridis, and the cleavage site residue in both proteins was the same Ala(-1). The GPIb-binding specificity of mamushigin is strongly supported by several lines of evidence, but mamushigin can directly aggregate normal platelets, similar to alboaggregin-B (AL-B) (1). This differs from other GPIb-BP's. In mamushigin-treated platelets, serotonin was not released, and flow cytometric analysis using a monoclonal antibody PAC-1 totally excluded platelet GPIIb/IIIa activation. Mamushigin enhanced platelet aggregation at low-shear stress, and this effect totally disappeared in the presence of GPIb-receptor blockers specific for von Willebrand factor binding, but not by GPIIb/IIIa-receptor blockers. At high-shear stress, mamushigin blocked platelet aggregation in a dose-dependent manner, as seen with other GPIb-BP's. This paper, therefore, describes the cDNA cloning and molecular characterization of mamushigin which has a different effect on platelet aggregation under different shear stress.

Agkistrodon↗

Effect of cilostazol on soluble adhesion molecules and platelet-derived microparticles in patients with diabetes.

We evaluated the plasma concentrations of soluble adhesion molecules and platelet-derived microparticles (PMP) in patients with non-insulin dependent diabetes mellitus (NIDDM) and studied the effect of cilostazol on PMP generation. There were differences in the levels of soluble adhesion molecules between NIDDM patients (N = 43) and the control subjects (N = 30) (soluble thrombomodulin: 11.5+/-5.3 vs. 7.0+/-1.2 TU/ml, p<0.0001; soluble vascular cell adhesion molecule-1: 708+/-203 vs. 492+/-113 ng/dl, p<0.0001; soluble intercellular cell adhesion molecules- 1: 274+/-65 vs. 206+/-48 ng/dl, p<0.0001; soluble P-selectin: 194+/-85 vs. 125+/-43 ng/dl, p<0.0001). There were also differences in the levels of PMP and platelet activation markers between NIDDM patients and the controls (PMP: 943+/-504 vs. 488+/-219/10(4) plt, p<0.0001; platelet CD62P: 9.2+/-4.6 vs. 4.4+/-4.3%, p<0.001; platelet CD63: 10.2+/-4.5 vs. 4.5+/-3.3%, p<0.0001; platelet annexin V: 9.1+/-3.9 vs. 5.3+/-3.8%, p<0.001). To study the release of PMP into plasma, a modified cone-and-plate viscometer was used. Increased release of PMP from platelets was observed in diabetic plasma compared to normal plasma under high shear stress conditions (2,672+/-645 vs. 1,498+/-386/10(4) plt, p<0.05). Therefore, one cause of PMP elevation in NIDDM may be high shear stress. The levels of PMP, activated platelets, and soluble adhesion molecules all decreased significantly after treatment with cilostazol. These results suggest that cilostazol may be useful for the inhibition of both PMP-dependent and -independent vascular damage in NIDDM.

Adult↗

Purification and characterization of kaouthiagin, a von Willebrand factor-binding and -cleaving metalloproteinase from Naha kaouthia cobra venom.

A von Willebrand factor (vWF)-binding and -cleaving metalloproteinase, termed "kaouthiagin", was purified from the venom of cobra snake Naja kaouthia. Kaouthiagin is a monomer with a molecular mass of about 46 kDa and 51 kDa under non-reducing and reducing conditions, respectively, and the N-terminal amino acid sequence is homologous to high molecular mass snake venom metalloproteinases. Kaouthiagin bound to vWF in a divalent ion-independent manner, but the reduced kaouthiagin failed to interact with vWF, suggesting that the protein conformation maintained by intrachain-disulfide linkages of the molecule is essential for the binding to vWF. Neither botrocetin nor bitiscetin, vWF-binding modulators from another snake venom, interfered with the binding between kaouthiagin and vWF, but a monoclonal antibody VW92-3 specific to the N-terminal region of vWF (residues 1-910) inhibited the binding. Without affecting platelet GPIb/IX and GPIIb/IIIa, kaouthiagin specifically cleaved vWF between residues Pro-708 and Asp-709 in a divalent ion-dependent manner to diminish the multimeric structure of vWF in plasma, resulting in the loss of ristocetin-induced platelet aggregability and the collagen-binding activity of vWF. These results indicate that kaouthiagin is a unique metalloproteinase which specifically binds to and cleaves vWF at a specific site and that it will be a useful tool for functional dissection of vWF.

Amino Acid Sequence↗

[Relative valve area stenosis after replacement of a Starr-Edwards mitral valve (model 6520) for corrected TGA (S, L, L): report of a case].

The patient was a 38-year-old man who had undergone mitral valve replacement with a Starr-Edwards disc valve (model 6520, 3 M, phi 30 mm, functional valve area: 2.85 cm2) at the age of 15 years for TR combined with corrected TGA. He developed dyspnea on exertion and palpitations at the age of 30 years, and paroxysmal supraventricular tachycardia appeared at the age of 35 years. Cardiac catheterization revealed that the PCWP was 30 mmHg and the TVA was 1.1 cm2, and a diagnosis of stenosis of the prosthetic valve was made. Thus, replacement of the Starr-Edwards disc valve using a BICARBON double leaflet valve (phi 27 mm, functional valve area: 2.85 cm2) was performed. The operative findings of the Starr-Edwards disc valve revealed a normal appearance and no pannus growth. Postoperative echocardiography and cardiac catheterization found that the TVA was 3.7 cm2 and the PCWP was 13 mmHg. The actual valve area of the disc valve sewn on the ventrical, which was anatomically RV construction might have been smaller than the ideal area; however, the double leaflet valve proved efficient in our patient. This case report serves to demonstrate that because of the postoperative difference in measurement between the actual valve area and the prostheticin ball or disc valve, patients undergoing mitral valve replacement must be followed up carefully.

Adult↗

Glycoprotein Ib-von Willebrand factor interactions activate tyrosine kinases in human platelets.

von Willebrand factor (vWF ) in the presence of botrocetin induces p72(syk) activation, assessed as its autophosphorylated level and in vitro kinase assays, the transient association of p72(syk) with p60(c-src), and the translocation of p60(c-src) and p54/58(lyn) to cytoskeletal fractions. Jararaca glycoprotein Ib-binding protein (GPIb-BP), which specifically binds to GPIb, abolished these phenomena, suggesting that they are mediated by the vWF-GPIb interaction. These tyrosine kinase-related events were not inhibited by GRGDS peptide (plus EGTA), indicating that GPIIb/IIIa is not involved in the observed responses. Shc, an adaptor protein, was also tyrosine phosphorylated by the botrocetin-vWF activation. When GPIb was immunoprecipitated with nonfunctional monoclonal antibodies (MoAbs) directed against GPIb, a kinase activity was found to associate with GPIb upon botrocetin-vWF activation. On the other hand, anti-GPIb MoAbs that inhibit the vWF-GPIb interaction did not coprecipitate a kinase activity. Because the recovery of GPIb did not differ significantly, it is suggested that the excessive presence of inhibitory anti-GPIb MoAb dissociated a kinase activity from GPIb. Phosphoamino acid analysis showed that the kinase activity was that of a tyrosine kinase. The identity of the tyrosine kinase and the mode of interaction with the cytoplasmic region of GPIb await to be determined. Our findings suggest that the tyrosine kinase associated with GPIb serves at a most proximal step in the signal transduction pathway involved in the vWF-GPIb-induced platelet activation, which leads to other tyrosine kinase-related intracellular signals.

Blood Platelets↗