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Biomedical subjects

Y Fujimura

Publications and source records attributed to Y Fujimura.

At least 91 records · Page 5Linked to original sources

BASH, a novel signaling molecule preferentially expressed in B cells of the bursa of Fabricius.

The bursa of Fabricius is a gut-associated lymphoid organ that is essential for the generation of a diversified B cell repertoire in the chicken. We describe here a novel gene preferentially expressed in bursal B cells. The gene encodes an 85-kDa protein, designated BASH (B cell adaptor containing SH2 domain), that contains N-terminal acidic domains with SH2 domain-binding phosphotyrosine-based motifs, a proline-rich domain, and a C-terminal SH2 domain. BASH shows a substantial sequence similarity to SLP-76, an adaptor protein functioning in TCR-signal transduction. BASH becomes tyrosine-phosphorylated with the B cell Ag receptor (BCR) cross-link or by coexpression with Syk and Lyn and associates with signaling molecules including Syk and a putative chicken Shc homologue. Overexpression of BASH results in suppression of the NF-AT activation induced by BCR-cross-linking. These findings suggest that BASH is involved in BCR-mediated signal transduction and could play a critical role in B cell development in the bursa.

Adaptor Proteins, Signal Transducing↗

Novel mitochondrial DNA mutation in tRNA(Lys) (8296A-->G) associated with diabetes.

Mutation in the mitochondrial gene at position 3243 was recently identified in a large pedigree of diabetes mellitus and deafness. As the mitochondria play an important role in glucose-stimulated insulin secretion in pancreatic beta-cells, we therefore searched for such mutations to detect a candidate gene for diabetes. We screened 10 diabetic subjects with clinical features suggesting mitochondrial DNA mutations. An adenine to guanine point mutation in tRNA(Lys) in at position 8296 (the 8296 mutation) was newly identified. Subsequently, we screened 1216 diabetic subjects, 44 patients with sensorineural deafness subjects and 300 non-diabetic control subjects for this mutation. We identified the mutation in 11 (0.90%) unrelated diabetic subjects, one (2.3%) patient with deafness and no non-diabetic control subject. Seven of these 12 subjects showed maternal inheritance. Deafness was seen in 7 of 12 probands. Four family pedigrees showed maternal inheritance of diabetes over two or three generations. Subjects carrying the 8296 mutation may develop diabetes and the mutation can explain as high as ca. 1% of the causes of diabetes.

Base Sequence↗

Purification and amino acid sequence of halystase from snake venom of Agkistrodon halys blomhoffii, a serine protease that cleaves specifically fibrinogen and kininogen.

We have isolated a serine protease, halystase, from Agkistrodon halys blomhoffii venom by chromatography on DEAE-Sepharose, heparin-Sepharose and Q-Sepharose columns, and have determined the complete amino acid sequence by Edman degradation and by mass spectral analysis of peptides generated by enzymatic and chemical cleavage. The 238-residue sequence of halystase, containing N-linked carbohydrates (about 13%) at two sites showed significant similarity to other thrombin-like snake venom serine proteases (66-72%), mammalian tissue kallikrein (42%) and thrombin (26%). Halystase contained the tentative catalytic triad of His43, Asp88 and Ser184 common to all serine proteases and Asp178 in the primary substrate-binding site. Although halystase contained an RGD sequence at residues 181-183, it did not inhibit platelet aggregation induced by ADP or collagen. It hydrolyzed most efficiently a tissue-kallikrein substrate, prolylphenylalanylarginyl-4-methyl-coumaryl-7-amide, and released bradykinin from bovine kininogen. Halystase did not coagulate human plasma, but it cleaved the fibrinogen B beta chain at the carboxyl side of Arg42 and cleaved slowly the fibrogen A alpha chain. Fibrinogen thus treated gradually became insensitive to thrombin. The proteolytic activity was inhibited with diisopropyl fluorophosphate, phenylmethylsulfonyl fluoride or leupeptin. These results indicate that halystase is a serine protease structurally similar to coagulating thrombin-like snake venom proteases, but it specifically cleaves fibrinogen at sites different from thrombin without inducing fibrin clotting, and hydrolyzes kininogen to produce bradykinin, resulting in the reduction of blood pressure.

Agkistrodon↗

Magnetic resonance imaging of the spinal cord in cervical ossification of the posterior longitudinal ligament. Can it predict surgical outcome?

STUDY DESIGN: Magnetic resonance imaging findings of an increased signal in the cervical cord in patients undergoing surgery for ossification of the posterior longitudinal ligament were analyzed to determined whether an increased signal on T2-weighted images correlated with a poorer outcome. OBJECTIVES: To clarify whether preoperative magnetic resonance imaging findings of a high signal in the cord constitute a poor prognostic factor. SUMMARY OF BACKGROUND DATA: The importance of a high, T2-weighted, intramedullary signal on preoperative magnetic resonance studies in patients undergoing surgery for ossification of the posterior longitudinal ligament requires further clarification. METHODS: Of 91 patients having cervical surgery for ossification of the posterior longitudinal ligament, 26 had a history of minor trauma. High, T2-weighted signals in the cord were noted in 23 patients who had sustained trauma and in 39 patients who had no history of trauma. Patients were divided into four groups according to the presence or absence of a high cord signal and/or a trauma history. Pre- and postoperative Japanese Orthopaedic Association scores and recovery ratios then were evaluated. RESULTS: The pre- and postoperative Japanese Orthopaedic Association scores and recovery ratios of the patients with a high signal and a trauma history were significantly less than those with no high signal but with a trauma history. Among the patients with no history of trauma, however, there were no significant differences in the pre- and postoperative JOA scores and recovery ratios between the patients with a high signal and those with no high signal. CONCLUSION: A high preoperative cord signal on T2-weighted magnetic resonance images for patients undergoing surgery for ossification of the posterior longitudinal ligament constitutes a poor prognostic factor, when trauma has played a role.

Adult↗

The response of blood flow between the internal thoracic and ileocecal arteries to inotropic agents in a canine model.

The pharmacologic response of coronary artery bypass conduits is of great importance. This study was designed to clarify the response of blood flow between the internal thoracic artery (ITA) and the ileocecal artery (ICA) to inotropic agents. The responses of the ITA and ICA to epinephrine, dopamine, isoproterenol, and dobutamine were examined by collecting free-flowing blood from a canine model. There were no significant differences in the response to inotropic agents between the ITA and the ICA. Epinephrine and dopamine increased the graft flow, whereas isoproterenol and dobutamine decreased the graft flow percentages of the cardiac output. These results suggest that the flow response to inotropic agents is equivalent in canine ITA and ICA grafts.

Animals↗

Recovery after prolonged cross-clamping tepid blood cardioplegia: report of a case.

Despite a prolonged repetitive aortic cross-clamp time of 411 min, a patient who suffered a left ventricular rupture after undergoing mitral valve replacement following mitral valvuloplasty and Maze procedure recovered without any permanent residual left ventricular dysfunction. During the aortic cross-clamping we used tepid blood cardioplegia for myocardial protection. This case report serves to demonstrate the potential of tepid blood cardioplegia as an effective method of myocardial protection.

Aged↗

[Experimental study of coronary artery anastomosis using VCS clips].

The experiment was intended to test the feasibility of VCS clips for coronary anastomosis during minimally invasive direct coronary artery bypass grafting (MIDCAB). Six dogs were anesthetized under endotracheal intubation and were placed on right lateral position. Three 10.5-mm ports were placed on the left lateral chest wall (3rd, 5th and 7th intercostal space) and the left internal thoracic artery (LITA) was dissected completely from its root to bifurcation under thoracoscope. Chest was opened through the left 6th intercostal space. The anastomotic site of LAD was dissected and was then occluded temporally for 5 minutes to obtain ischemic preconditioning. The anastomosis was performed by the following procedure; horizontal mattress sutures of 8-0 polypropylene were placed on heel, toe and the center of both lateral sides. Two VCS clips (8 in total), 0.9-mm in size, were applied between every two sutures. After the measurement of graft flow, the pedicle was transected and an angiography was done. Graft flow was 12-17 ml/min (mean 14.7 +/- 2.1 ml/min) and cineangiogram showed good patency of LITA and no anastomotic stenosis. VCS clips were supposed to have a potential for facilitating port access coronary artery bypass grafting.

Anastomosis, Surgical↗

Arterial reconstruction: justified for patients with intermittent claudication?

The objective of this study was to evaluate the effects of arterial reconstruction in patients with intermittent claudication. A total of 243 patients (305 limbs) underwent lower extremity vascular reconstruction at our institution from 1979 to 1995. They were assessed by physical examination, pulse volume recordings, segmental pressure, Duplex ultrasonography, and intravenous subtraction arteriography to evaluate the effects of arterial reconstruction. Surviving patients (220 limbs) were enrolled for evaluation of outcome during the follow-up period. There were 59 deaths during the follow-up period. The cumulative life-table 5-year patency rates were 90% +/- 3%, 73% +/- 6%, and 74% +/- 10% for aortoiliac, infrainguinal, and aortofemorodistal arterial reconstructions, respectively. Among 129 repairs in the aortoiliac region, Fontaine stages I, II, and III were found in 109 limbs (84.5%), 17 limbs (13.2%), and 2 limbs (1.5%), respectively. There was one (0.7%) minor amputation. There was Fontaine stage I in 50 limbs (76.9%), Fontaine stage II in 14 limbs (21.5%), and Fontaine stage III in 1 limb (1.5%) for repairs in the infrainguinal region. Among the 26 aortofemorodistal repairs, there was Fontaine stage I in 21 limbs (81%) and Fontaine stage II in 5 limbs (19%). There was a statistically significantly higher incidence of Fontaine stage I than Fontaine stage II or III in aortofemoral, infrainguinal, and aortofemorodistal arterial reconstructions (p < 0.0001). Arterial reconstruction for patients at Fontaine stage II offered benefits and improved quality of life at follow-up. Arterial reconstruction for patients at Fontaine stage II offers benefits and improved quality of life at follow-up. It was concluded that the significant improvement in quality of life after arterial reconstruction warrants continued use of the procedure in patients with intermittent claudication.

Adult↗

Increased serum interleukin-8: correlation with poor prognosis in patients with postoperative multiple organ failure.

This study investigated whether cytokines and colony-stimulating factors can predict prognosis in patients with postoperative multiple organ failure (MOF). We evaluated 14 patients with postoperative MOF who underwent operation for cardiovascular disease. Seven patients recovered from MOF (survivors) and seven did not recover and died (nonsurvivors). The white blood cell (WBC) count, granulocyte colony-stimulating factor, monocytic colony-stimulating factor, interleukin-6 (IL-6), and IL-8 were measured on the day the patients were judged to be in MOF and each week thereafter until the patients recovered or died. Survivors and nonsurvivors were equivalent in terms of age, gender, proportion of use of extracorporeal circulation, operation time, volume of blood transfusion, time from operation to the onset of MOF, the MOF score, proportion of bacteremia, duration of MOF, and number of failed organs. The mean duration of MOF was less than 2 weeks in both groups; therefore the measurements were compared on the first day of MOF and 1 week later. No significant differences between the two groups in terms of WBC counts, colony-stimulating factors, and IL-6 levels were noted. However, the serum level of IL-8 was significantly higher in nonsurvivors than in survivors. Patients with a high serum levels of IL-8 at the time of MOF had a poor prognosis.

Aged↗

Multiple regression analysis of the factors influencing the results of expansive open-door laminoplasty for cervical myelopathy due to ossification of the posterior longitudinal ligament.

We conducted a multiple regression analysis on the surgical results (minimum follow-up of 5 years) of 55 patients who underwent expansive open-door laminoplasty (open-door ELAP) for cervical myelopathy due to ossification of the posterior longitudinal ligament (OPLL) in order to determine statistically the impact of factors influencing the results. Duration of myelopathy was found to be a significant factor indicating poor results, while progression of ossification and age at the time of surgery were significant factors indicating deterioration. Three other factors (preoperative severity of myelopathy, degree of spinal canal expansion and changes of the curve indices before and after surgery) did not have a significant influence on the results. To improve the surgical results, it is thus essential to operate on patients as soon as they develop symptoms of myelopathy. There exists a certain limitation in posterior decompression for OPLL including open-door ELAP until prevention of the progression of ossification becomes possible.

Adult↗

Granulocyte elastase release and pulmonary hemodynamics in patients with atrial septal defect.

BACKGROUND: In patients with increased pulmonary artery pressure, the pulmonary vascular endothelium is morphologically and functionally abnormal and may be vulnerable to neutrophil-mediated injury induced by cardiopulmonary bypass (CPB). We investigated the relation between levels of granulocyte elastase (GEL), interleukin-6, or interleukin-8 after CPB and preoperative pulmonary hemodynamics or changes in pulmonary function after the operation. METHODS: We measured plasma levels of GEL, interleukin-6, and interleukin-8 before and after CPB in patients who underwent closure of an atrial septal defect. Preoperative and postoperative respiratory index were evaluated. Preoperative pulmonary hemodynamics were determined within 1 month before the operation. RESULTS: The level of GEL rose significantly after CPB from baseline (164.8 +/- 81.3 versus 819.4 +/- 320.3 microg/L; p < 0.01). Levels of interleukin-6 and interleukin-8 showed no significant changes after CPB. Peak level of GEL was significantly correlated with preoperative systolic pulmonary artery pressure (r = 0.76; p = 0.017), mean pulmonary artery pressure (r = 0.75; p = 0.021) and pulmonary-to-systemic arterial pressure ratio (r = 0.77; p = 0.016), but not with the hemodynamic variables for pulmonary blood flow or pulmonary resistance. Moreover, the value of (postoperative respiratory index - preoperative respiratory index)/preoperative respiratory index was positively correlated with the peak level of GEL (r = 0.72; p = 0.030). CONCLUSIONS: The increase in GEL level after CPB is proportional to the increase in preoperative pulmonary artery pressure, which may cause the accordant pulmonary vascular damage.

Adult↗

Quadriplegia caused by cervical hyperextension injury and intramedullary spinal cord tumour: a case report of autopsy.

A 68-year-old male had neck pain and weakness of the left upper extremity after a fall. MRI showed severe cervical canal stenosis and a high signal intensity of the spinal cord on T2-weighted images extending from the medulla oblongata to the C7 level. Neurological examination showed left hemiparesis, bilateral sensory disturbance and a neurogenic bladder. He underwent expansive laminoplasty 5 weeks later. After the operation his neurological deficit improved and 6 weeks later he left the hospital. However, his neurological conditions became worse (quadriparesis) and he was admitted as an emergency 3 weeks later. Although MRI showed decompression of the spinal cord, the area of high signal intensity on T2-weighted images had extended. Quadriparesis was progressive and he died of dyspnea. Autopsy showed the presence of the intramedullary spinal cord tumor (anaplastic astrocytoma; C1-Th4). We could not detect the intramedullary spinal cord tumour on MRI before surgery because of severe canal stenosis and the history of trauma. The high spinal intensity on T2-weighted images was thought to be oedema or myelomalacia. This case illustrates the difficulty of correctly interpreting MRI in patients with severe canal stenosis.

Aged↗

Cervical curvature in acute whiplash injuries: prospective comparative study with asymptomatic subjects.

The cervical curvature of 488 patients with acute whiplash injury was prospectively studied by comparison with 495 asymptomatic healthy volunteers. Plain radiography of the cervical spine in the neutral position was evaluated qualitatively. No significant difference was noted in frequencies of non-lordotic cervical curvature and local angular kyphosis between acute whiplash injury patients and asymptomatic subjects. No significant association was apparent between clinical symptoms and cervical curvature. These results suggest that non-lordotic cervical curvature and angular kyphosis in acute whiplash injury patients constitute normal variants rather than pathological findings.

Acute Disease↗

The lack of type III collagen in a patient with aneurysms and an aortic dissection.

We analyzed 79 consecutive patients with aneurysms and found a patient who lacked type III collagen. Collagen was extracted from the skin, and the lack of type III collagen was determined by means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Only 1 of the 79 patients was found to lack type III collagen. This patient was a 55-year-old man who had sustained an abdominal aortic aneurysm and aortic dissection. He did not show any of the typical clinical symptoms of Ehlers-Danlos syndrome type IV, such as hyperextensible skin and joints. He had none of the usual risk factors nor any clear family history of the syndrome. Furthermore, his collagen fibrils demonstrated a homogeneous appearance. This case may represent a new form of type III collagen deficiency.

Aortic Dissection↗

Placental ecto-ATP diphosphohydrolase: its structural feature distinct from CD39, localization and inhibition on shear-induced platelet aggregation.

Human placental ecto-ATP diphosphohydrolase (ATPDase), an 82 kDa single-chain glycoprotein, was purified to high specific activity using a specific murine monoclonal antibody MK33 (IgG1-kappa). Structurally, protein-based analysis showed this enzyme to be almost identical to that of CD39 lymphoid cell activation antigen deduced by cDNA sequencing (Maliszewski CR, et al, J Immunol 1994; 153:3574); but differing in the NH2-terminal amino acid sequence, suggesting that placental ecto-ATPDase is most likely an isoform of CD39 generated by alternative splicing of the pre-mRNA. Functionally, placental ecto-ATPDase totally inhibits the secondary platelet aggregation induced by agonists at a final concentration (f.c.) of 1 microgram/ml. The purified enzyme (1 microgram/ml, final), pre-incubated with washed platelets prior to alpha-thrombin stimulation, completely inhibits the activation of platelet glycoprotein (GP) IIb/IIIa, thereby blocking the binding of fibrinogen or von Willebrand factor to platelets. Further, under different shear stresses, the enzyme modulates platelet aggregation differently. Low shear stress-induced platelet aggregation is blocked by this enzyme in a dose-dependent manner and is totally blocked at f.c. 0.5 microgram/ml. Under high shear stress, however, this protein at a f.c. of 0.5 microgram/ml mediates almost complete disaggregation of platelets without affecting the initial aggregation. Using immunohistochemical analysis, this enzyme was observed to be localized at the syncytiotrophoblasts of placental microvilli and the endothelial cells (ECs) of the umbilical vein obtained at full-term normal delivery, but scarcely at the ECs of the umbilical artery.

Adenosine Triphosphatases↗