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Biomedical subjects

M Handa

Publications and source records attributed to M Handa.

At least 127 records · Page 7Linked to original sources

Shear stress-induced platelet aggregation in various types of von Willebrand disease.

We here examined the shear stress-induced platelet aggregation (SIPA) in various types of von Willebrand Disease (vWD), using a novel cone-and-plate viscometer recently developed by Ikeda et al. [1]. Under experimental conditions of high shear stress (90-108 dyne/cm2) known to induce von Willebrand factor (vWF)-dependent platelet aggregation in normal individuals, a variety of SIPA patterns, from a normal to total defect, were observed in 6 patients with type I vWD, while SIPA was totally absent in all 7 type IIA patients examined. One patient with Normandy type vWD exhibited a normal SIPA pattern under these experimental conditions. These findings, together with the vWF parameters of each patient, suggested that the presence of higher molecular weight multimers of plasma vWF, as well as an appropriate level of vWF antigen, is essential for SIPA to occur under high shear stress. Interestingly, vWF-dependent SIPA in 3 patients with type IIB vWD was found to be initiated by a low shear stress force, which did not induce such platelet aggregation in normal individuals. This might explain the intravessel platelet clumping that occurs, resulting in the intermittent thrombocytopenia observed in this type of the disease.

Adolescent↗

Spontaneous resolution of transfusion-associated graft-versus-host disease.

BACKGROUND: Transfusion-associated graft-versus-host disease (TA-GVHD) is a serious complication of blood transfusion that is characterized by high fever, a scaly maculopapular erythematous rash, diarrhea, hepatocellular damage with marked elevation of liver function test values, and pancytopenia. It can occur in immunocompetent as well as immunocompromised recipients. The existence of atypical TA-GVHD that resolves spontaneously and does not exhibit all of the manifestations has been suggested, but there has been to date no documented diagnosis of GVHD supported by evidence of engraftment. CASE REPORT: A female patient presented and was diagnosed with acute myelogenous leukemia (AML:M4), and, after unsuccessful combination chemotherapy, she received a transfusion and developed manifestation of TA-GVHD as well as evidence of chimerism. TA-GVHD was proved by demonstrating Y chromosome-specific genes in the skin by polymerase chain reaction. The manifestations of clinical GVHD abated within 4 months. CONCLUSION: Polymerase chain reaction analysis of Y chromosomes in specimens from female patients is useful in the diagnosis of suspected cases of spontaneously resolving TA-GVHD.

Base Sequence↗

Soluble form of P-selectin in plasma is elevated in acute lung injury.

A number of adhesion molecules on neutrophils and the pulmonary capillary endothelium mediate the neutrophil accumulation in the lungs at the onset of adult respiratory distress syndrome or acute lung injury (ALI). P-selectin, located on both vascular endothelial cells and platelets, has been shown to be one of these neutrophil-endothelial cell adhesion molecules. In this study, we measured the soluble form of P-selectin in plasma (PPS) from 19 patients (surviving, 11; deceased, 8) with ALI due to various causes and assessed the clinical significance of this measurement. Twelve healthy subjects and 29 patients with other pulmonary diseases, including idiopathic pulmonary fibrosis (IPF) (n = 8), sarcoidosis (n = 5), pneumonia (n = 8), and sepsis without ALI (n = 8) were also studied for comparison. PPS in patients with ALI (474.5 +/- 366.8 ng/ml, mean +/- SD) were significantly higher than those in control subjects (98.8 +/- 39.7, p < 0.01) and in patients with IPF (210.4 +/- 76.6, p < 0.05), sarcoidosis (135.2 +/- 71.5, p < 0.05), pneumonia (225.3 +/- 81.0, p < 0.05), and sepsis without ALI (271.8 +/- 46.5, p < 0.05). There was no significant difference in PPS levels between seven patients with and 12 patients without multiple organ failure. Lung injury scores correlated significantly with the PPS level (r = 0.605, p < 0.05). PPS levels of deceased patients with ALI (841.0 +/- 252.4) were significantly higher than those of surviving patients with ALI (208.0 +/- 109.2, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Radical prostatectomy in a patient with hemophilia B].

We describe our experience with radical prostatectomy in a patient with hemophilia B. whose factor IX activity was 7% and partial thromboplastin time was 55.9 sec. A total of 43,000 units of factor IX concentrate (PCC) was given perioperatively for 2 weeks. No abnormal hemorrhage was noted. An algorithm for perioperative management of hemophilia B patient is discussed.

Adenocarcinoma↗

[Assessment of nucleolar organizer regions (Ag-NORs) in bronchial dysplasia and roentgenographically occult bronchogenic squamous cell carcinoma].

Mean argyrophil nucleolar organizer regions (Ag-NORs) per nucleus were determined on columnar epithelium, bronchial dysplasia, roentgenographically occult squamous cell carcinoma and squamous cell carcinoma with roentgenographically findings in 76 formalin-fixed, paraffin-embedded resected specimens. 1) Mean Ag-NOR counts per nucleus (mean +/- standard deviation) were 1.67 +/- 0.30 in 10 columnar epitheliums, 2.74 +/- 0.41 in 13 lesions with bronchial dysplasia, 3.75 +/- 0.59 in 57 lesions with roentgenographically occult squamous cell carcinoma and 4.44 +/- 0.51 in 14 lesions with squamous cell carcinoma with roentgenographically findings. There were significant differences between each two groups. 2) In lesions with squamous call carcinoma, mean Ag-NOR counts per nucleus of T2, T3 or T4 tumor were significantly higher than those of T1 tumor. Mean Ag-NOR counts per nucleus of N1 or N2 tumor were significantly higher than those of N0 tumor.

Aged↗

Platelet unresponsiveness to collagen: involvement of glycoprotein Ia-IIa (alpha 2 beta 1 integrin) deficiency associated with a myeloproliferative disorder.

We studied a 66-year-old man with a myeloproliferative disorder who presented with a prolonged bleeding time and marked thrombocytosis (platelet count, 3,890 x 10(9)/l). There was no past history of a bleeding disorder. The patient had normal coagulation data. His platelets completely lacked collagen-induced platelet aggregation and adhesion, but showed normal responses to other agonists. All family members tested showed normal platelet aggregation with collagen. Analysis of 125I surface-labeled platelets by two-dimensional SDS gel electrophoresis disclosed absence of the spot corresponding to platelet membrane GPIa (alpha 2) but no other significant deficiencies of major platelet glycoproteins i.e., GPIb, IIb-IIIa, and IV. Immunoisolation studies of the patient's platelets indicated that neither anti-GPIa nor anti-GPIIa (beta 1) monoclonal antibody (mAb) isolated any surface membrane proteins corresponding to GPIa. GPVI, a putative collagen receptor, was immunoisolated from the platelets. Indirect immunofluorescence study using flow cytometry confirmed that the patient's platelets were totally deficient in surface expression of the GPIa-IIa complex (alpha 2 beta 1 integrin). In contrast, phytohemoagglutinin-activated T-lymphocytes from the patient expressed normal concentrations of this complex. The data suggest that our patient had an acquired deficiency of the platelet GPIa-IIa complex, due to a myeloproliferative disorder, which might account for the absence of responsiveness of his platelet to collagen.

Acute Disease↗

[Neutrophil elastase in postoperative pleural effusion of patients who had undergone pulmonary resections].

We determined whether activity of neutrophil elastase increases in pleural effusion after lobectomy for the neoplasm in the lung. Samples of pleural effusion were obtained 3 and 24 h postoperatively and samples of the peripheral blood were obtained preoperatively, 3 h, 24 h, and 1 w postoperatively, then the neutrophil counts, the levels of neutrophil elastase and alpha 1-antitrypsin by enzyme-linked immunosorbent assay, the activity of neutrophil elastase using succinyl-(L-alanine) 3-p-nitroanilide were measured. We found that the levels of neutrophil elastase increased 170 times greater in pleural effusion than in peripheral blood 3 h after lobectomy. However, the levels of alpha 1-antitrypsin did not increase in pleural effusion. The activity of neutrophil elastase increased to 0.54 +/- 0.1 mumol/min/l in pleural effusion 3 h after lobectomy, however the activity of neutrophil elastase was under the sensitivity level of detection in the peripheral blood after lobectomy. In conclusion, there is an imbalance between the levels of neutrophil elastase and alpha 1-antitrypsin in pleural effusion after lobectomy, the imbalance resulting in the increased activity of neutrophil elastase which probably is relating to tissue injury in the pleural spaces.

Aged↗

[Transport of ions across alveolar epithelial cells in resected human lungs].

Little information is available regarding the effect of ion transport agonists and antagonists on ion transport in the human lung. Therefore, we studied ion transport in lungs resected from patients with lung cancer. A test solution of 45 ml of isosmotic albumin was instilled into one segment of a resected lobe within 10 min of resection. Because protein leaves the air space very slowly, the concentration of alveolar protein over 4 h was used to quantify the volume of alveolar fluid. Ion transport was measured from the changes in ion concentrations and the volume of alveolar fluid. In the basal condition, the net efflux of Na+ and Cl- were 4.66 +/- 0.83 mEq/l/h and 3.52 +/- 0.84 mEq/l/h, respectively. In contrast, the net influx of K+ was 0.44 +/- 0.07 mEq/l/h. Amiloride (10(-5) M), an inhibitor of apical Na+ uptake, ouabain (10(-3) M), an inhibitor of Na(+)-K+ ATPase, and hypothermia (8 degrees C) reduced the efflux of Na+ and Cl-. Ouabain and hypothermia increased the net influx of K+. Terbutaline (10(-3) or 10(-4) M) increased the efflux of Na+ and Cl-, but did not affect the influx of K+. Propranolol (10(-4) M) and amiloride (10(-5) M) inhibited the terbutaline-induced increase in the transport of Na+ and Cl-. Alveolar fluid clearance was closely correlated with Na+ transport and with Cl- transport. However, the values of Na+ transport were greater than those of Cl- transport. These data suggest that Na+ transport is accompanied by Cl- transport and fluid movement out of the alveolar space in resected human lungs.

Adrenergic beta-Agonists↗

[A true aneurysm of the right internal mammary artery, accompanied by diminished grasping power of the right hand].

A 69-year-old man was admitted to our hospital after an abnormal shadow was found on a chest radiograph. The preoperative diagnosis was right subclavian aneurysm. Loss of grip in the right hand developed, and the patient underwent surgery. During surgery, the aneurysm was found to have originated from the right internal mammary artery. The root of the right internal mammary artery was tied and the right subclavian artery, which had been compressed and displaced by the aneurysm, was replaced. A chest radiograph obtained 6 months after surgery showed that the trachea was no longer displaced. However, the gripping force of the right hand had not recovered.

Aged↗

Protein tyrosine phosphorylation in human platelets during shear stress-induced platelet aggregation (SIPA) is regulated by glycoprotein (GP) Ib/IX as well as GP IIb/IIIa and requires intact cytoskeleton and endogenous ADP.

Shear stress-induced platelet aggregation (SIPA) may be essential in thrombus formation in pathologically stenotic arteries. Intracellular events during SIPA are, however, poorly understood. Washed platelets were exposed to shear stress (108 dyne/cm2) in the presence of von Willebrand factor (vWf, 10 micrograms/ml) and 1 mM CaCl2 for various time intervals, and then lyzed in SDS. Platelet proteins were separated by 10% SDS-PAGE and tyrosine phosphorylated proteins were detected by immunoblotting with an anti-phosphotyrosine monoclonal antibody. Increased tyrosine phosphorylation of proteins of 130, 100, 85, 74, 70, 64, 58, and 40 kDa was observed within 30 s after the beginning of exposure of platelets to high shear force and the degree of tyrosine phosphorylation continued to increase up to approximately 2 min after the exposure. A monoclonal antibody (MoAb) against vWf-binding domain of glycoprotein (GP) Ib alpha (GUR83-35), anti-vWf MoAb that inhibits binding of vWf to GPIb alpha (NMC-4), or a MoAb against GP IIb/IIIa complex (AP-2) inhibited SIPA as well as tyrosine phosphorylation of these proteins. Apyrase (an ADP scavenger, 2 U/ml), EDTA (5 mM), or RGDS peptide (200 micrograms/ml) also had inhibitory effects on both SIPA and tyrosine phosphorylation. However, Cytochalasin D (2 microM) or staurosporin (1 microM) did not affect SIPA, while they inhibited SIPA-associated tyrosine phosphorylation of those proteins. SIPA-associated tyrosine phosphorylation is a novel post-aggregatory pathway in signal transduction, which is dependent on the binding of vWf to GP Ib/IX and GP IIb/IIIa, endogenous ADP, and intact cytoskeleton.

Adenosine Diphosphate↗

Alternatively spliced isoform of P-selectin is present in vivo as a soluble molecule.

To demonstrate the presence of a soluble isoform of P-selectin predicted from cDNA sequencing (Johnston, G.I., Bliss, G.A., Newman, P.J., and McEver, R.P. (1990) J. Biol. Chem. 265, 21381-21385), we immunoisolated and compared structurally P-selectin from fresh frozen human plasma with that from washed intact platelets. Plasma P-selectin was reactive with rabbit antiserum to a synthesized peptide (residues 762-774 of mature P-selectin) but was significantly less reactive with antibody to a peptide (residues 747-760). In contrast, platelet P-selectin reacted with both antibodies. S-Pyridylethylated plasma P-selectin was fractionated by reversed phase-high performance liquid chromatography into two major species. From platelets, two virtually identical species were separated. Sequential digestion with Achromobacter protease I and then Staphylococcus V8 protease produced peptides assigned to the tail region of the protein including the putative spliced site. From the more hydrophilic species in both plasma and platelets, a peptide completely lacking the sequence of the putative spliced site was identified. In contrast, the more hydrophobic species yielded a peptide with an intact transmembrane sequence. Hence, these results provide direct evidence that the previously predicted soluble isoform of P-selectin is actually synthesized in vivo and is present as a circulating molecule.

Alternative Splicing↗

Use of the sandwich method with an ultra-high-molecular-weight polyethylene prosthesis and Marlex mesh in sternal reconstruction: report of a case.

A 52-year-old Japanese man with a slow-growing chondroma originating from the sternal bone was referred to our hospital. A subtotal resection of the sternum was performed, hereafter termed the "sandwich method," and an originally designed prosthesis made from ultra-high-molecular-weight polyethylene and Marlex mesh was used for reconstruction. The postoperative course was uneventful without any symptoms due to paradoxical movement of the chest or regional abscess, and no disturbance in the movement of the upper limbs, such as a surgical sequelae, was observed.

Bone Neoplasms↗

Shear-induced platelet aggregation in cerebral ischemia.

BACKGROUND AND PURPOSE: Recent evidence has suggested that shear-induced platelet aggregation is an important mechanism of thrombosis at arterial bifurcations or stenoses. We measured shear-induced platelet aggregation with a new apparatus in patients with cerebral ischemia and also studied correlations with other hemostatic parameters as well as the effect of antiplatelet agents. METHODS: The subjects were 75 patients with cerebral ischemia and 26 control subjects. Platelet aggregation was induced in citrated platelet-rich plasma by a high shear stress (108 dynes/cm2) that was applied by means of a cone-plate streaming chamber based on turbidimetry. We studied the correlation of test results with hemostatic parameters and also the effects of antiplatelet agents. RESULTS: Compared with the control subjects, an increase of shear-induced platelet aggregation was observed in 21 patients with atherothrombotic stroke and 12 with transient ischemic attacks, but not in 11 with cardioembolic stroke or 31 with lacunar stroke. There was no significant correlation of shear-induced platelet aggregation with platelet count, agonist-induced platelet aggregation, fibrinogen level, or beta-thromboglobulin level. The extent of shear-induced aggregation was not correlated with von Willebrand factor antigen levels but was significantly correlated with the amounts of larger von Willebrand factor multimers. Oral aspirin (81 mg/d) did not inhibit shear-induced platelet aggregation, whereas oral ticlopidine (200 mg/d) significantly inhibited it. CONCLUSIONS: These results indicate that shear-induced platelet aggregation is increased in patients with atherothrombotic stroke and transient ischemic attacks, is correlated with the increase of larger von Willebrand factor multimers, and is corrected by ticlopidine but not by low-dose aspirin.

Adult↗

Autologous blood transfusion for pulmonary and mediastinal surgery in 144 patients. The effectiveness of recombinant erythropoietin injection.

Preserved autologous transfusions have been performed for elective pulmonary and mediastinal surgery to prevent the adverse effects of homologous transfusions. Autologous blood was collected preoperatively from 144 patients. The collected blood volume ranged from 400 to 1,600 ml with a mean volume of 544 ml. In four patients with benign diseases, 1,200 to 1,600 ml of blood was collected using 3,000 U of intravenous recombinant human erythropoietin (rh-EPO) administered every other day. One hundred twenty-three of these patients (85 percent) did not require a homologous transfusion. In the 84 patients undergoing either a pneumonectomy, lobectomy, or segmentectomy, 68 (81 percent) avoided homologous blood exposure. A patient with rh-EPO who bled 2,000 g during surgery received an autotransfusion of only 1,400 ml and his postoperative course was uneventful. Preserved autologous blood collected after rh-EPO injections is an effective method for minimizing homologous blood transfusions in pulmonary and mediastinal surgery.

Blood Loss, Surgical↗

Experimental study of lung transplantation from non-heart-beating donor following brain death in canine model of left lung allotransplantation.

Thirty mongrel dogs were divided into 3 groups. Group I was a normal control group (n = 4) without transplantation procedure. Group II was a transplantation control group (n = 5) with left lung allotransplantation from heart-beating donor. Group III consisted of animals (n = 8) which received lung allografts from non-heart-beating donor following brain death. In Group III, brain death was brought about by intracranial hypertension with the inflation of balloon in the subdural space of donor. After 6 hours, the mechanical ventilation was discontinued followed by cardiac arrest. Left lung was excised twenty minutes after the cardiac arrest and was washed out with cold Ep4 solution for subsequent orthotopic allotransplantation. Right pulmonary arterial occlusion test (RPAO) were carried out under right thoracotomy to evaluate graft function immediately and 7 to 14 days after the surgery. PaO2, PAP and CO were measured before and 20 minutes after RPAO. All animals in Group II and 7 of 8 animals in Group III survived more than 7 days after surgery. No significant differences in the value of PaO2, mean PAP and TPVR with RPAO among three groups at each time of assessment, showing the possibility of lung transplantation from non-heart-beating donor followed by brain death.

Anesthesia↗