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Biomedical subjects

M Handa

Publications and source records attributed to M Handa.

At least 145 records · Page 8Linked to original sources
PubMed1994

[Lung transplantation from non-heart-beating donor following brain death in canine model].

Candidates for pulmonary transplantation have been limited because of extreme susceptibility to lung infections and pulmonary edema in the brain-dead donor. To ameliorate the donor shortage, two possibilities for expanding the donor source have been presented, i.e. xenotransplantation and transplantation from cardiac-dead donors. The present study was conducted to evaluate the possibility of lung transplantation from a non-heart-beating donor following brain death, using a canine model. Six mongrel dogs were put into a state of brain death by elevating intracranial pressure with a balloon catheter. Following the intravenous administration of methylprednisolone and heparin used for 6-hour management following brain death mechanical ventilation was discontinued leading to cardiac arrest with in a few minutes. Excision of the left lung was scheduled for twenty minutes after cardiac arrest, followed by washing out the pulmonary vasculature with cold Ep4 solution, and orthotopic transplantation into the recipient animal. Immunosuppression was achieved with methylprednisolone and azathioprine. A right pulmonary arterial occlusion test (RPAO) was performed to assess graft function immediately and 7 days postoperatively. All but one animal survived and three animals had an uneventful postoperative course, with the transplants alone according to immediate and 7 day postoperative, respectively, RPAO results. These outcomes indicate the possible feasibility of lung transplantation from non-heart-beating donors following brain death.

Animals↗
PubMed1994

[A nutritional and immunological investigation of patients with tuberculosis].

In recent years, the rate of decrease of the number of new patients with tuberculosis has slowed down. The aging of the Japanese population partially accounts for the increase in the number of patients with tuberculosis. The disease is often transmitted from these aged patients to those who were uninfected. Since it is well-known that a poor nutritional condition lowers the immunological resistance to tuberculosis, we used Onodera's PNI (Prognostic Nutritional Index; 10 x serum albumin concentration + 0.005 x peripheral lymphocyte count) as a parameter to check the nutritional condition and immunological deficiency in patients suffering from tuberculosis. We examined a total of 451 patients with tuberculosis who were admitted to our hospital from 1987 to 1991. The PNI value decreased with age and was low in patients with extensive lesions on chest X-ray as well as in those with complications, PNI was also low in patients showing negative tuberculin skin reaction, and increased with the intensification of the positive reaction. In patients showing negative conversion of bacilli during treatment, PNI value on admission increased significantly immediately before discharge. Patients with percent ideal body weight (IBW, calculated by the Broca's method modified by Katsura) on admission less than 90% accounted for 48.6% of all patients. There was a positive correlation between PNI and an obesity index (P < 0.01, r = 0.24). After admission, in patients showing negative conversion of bacilli, there was a positive correlation between the increase in PNI and the gain of body weight (P < 0.01, r = 0.30).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[A case of lung cancer combined with ocular myopathy and idiopathic thrombocytopenic purpura which was presumed to be caused by heart catheterization].

A 61-year-old patient was admitted to our hospital because of a chest abnormal shadow. He was suffered from ocular myopathy for more than 4 years. A lab data on the admission showed only a slight thrombocytopenia. After the unilateral pulmonary arterial occlusion test for the preoperative evaluation of thoracotomy, the hemorrhagic tendency was appeared. A detailed examination proved idiopathic thrombocytopenic purpura which was presumed to be caused by the heart catheterization. We employed high-dose intravenous gamma-globulin infusion and concentrated platelet transfusion for 5 days for preventing hemorrhagic complications during the thoracotomy. The partial resection was undergone for the left upper lobe tumor, which was proved as large cell carcinoma. The postoperative hemorrhage was well controlled. We conclude that the high-dose intravenous gamma-globulin infusion and/or concentrated platelets transfusion should be positively employed for the patients with even slight thrombocytopenic purpura.

Carcinoma, Non-Small-Cell Lung↗
PubMed1994

[An experience of suprahyoid release for resection and reconstruction of the lower part of trachea].

An experience of suprahyoid release for resection and reconstruction of the lower part of trachea was reported. 51-year-old woman, complaining of continuous stridor, was diagnosed as tracheal tumor at another hospital and was transferred to our hospital for consecutive examination and surgical treatment. The size of the tumor was about 3 cm in longitudinal diameter and the distance between tracheal carina and lower edge of the tumor was estimated about 2 cm by tomography. At operation, following suprahyoid release in supine position, 6 tracheal rings were resected and reconstructed by end-to-end anastomosis through right posterolateral incision. Patients neck was forced to bend for three weeks and intravenous byperalimentation without oral intake was employed for two weeks to avoid misswallowing and dysphagia postoperatively. Oral intake was started at two weeks after operation and parenteral nutrition was no more necessary at 3 weeks after surgery. Misswallowing and dysphagia were not encountered at all. The tumor was diagnosed as adenoid cystic carcinoma pathologically and residual tumor was demonstrated in submucosal space at the oral margin of the resected specimen as well. She discharged from the hospital uneventfully after postoperative radiotherapy. The recurrence of the tumor has not been observed for 3 years postoperatively. It was confirmed that suprahyoid release is an useful technique and should be ready to introduce in the extensive resection of the trachea because of its little influence on laryngeal function.

Anastomosis, Surgical↗
PubMed1993

Evidence that plasma fibrinogen and platelet membrane GPIIb-IIIa are involved in the adhesion of platelets to an artificial surface exposed to plasma.

We investigated the molecular mechanism(s) by which platelets adhere to an artificial surface exposed to plasma, using polystyrene microtiter plates pretreated with plasma. Washed platelets labelled with 51Cr were incubated with the plates under static conditions. Prostaglandin E1(PGE1) was added to the platelets to prevent platelet-platelet interactions. Adhesion required the presence of a divalent cation such as Mg++ or Ca++. Polyclonal anti-fibrinogen antibody inhibited adhesion by 70%. Polyclonal antibodies against fibronectin, vitronectin, von Willebrand's Factor, and the Fc portion of human IgG, had no effect on adhesion. Platelets adhered normally to a surface pretreated with plasma from a patient with severe von Willebrand's disease. No platelet adhesion occurred when the surface was pretreated with an afibrinogenemic plasma. Monoclonal antibodies against platelet membrane GPIIb-IIIa, potent inhibitors of ADP-induced fibrinogen binding to platelets, completely inhibited adhesion. Monoclonal antibodies against the GPIb alpha subunit and GPIc(VLA alpha 5) showed no inhibitory effects on adhesion. Platelets from a patient with Glanzmann's thrombasthenia (type I) did not adhere to the surface pretreated with normal plasma. These results suggest that plasma fibrinogen adsorbed onto the surface and that platelet membrane glycoprotein(GP)IIb-IIIa were responsible for adhesion in an activation-independent manner.

Adsorption↗
PubMed1993

Transmembrane calcium influx associated with von Willebrand factor binding to GP Ib in the initiation of shear-induced platelet aggregation.

We found that the binding of multimeric vWF to GP Ib under a shear force of 108 dynes/cm2 resulted in the transmembrane flux of Ca2+ ions with a two- to three-fold increase in their intracellular concentration ([Ca2+]i). The blockage of this event, obtained by inhibiting the vWF-GP Ib interaction, suppressed aggregation. In contrast, the blockage of vWF binding to GP IIb-IIIa, as well as the prevention of activation caused by increased intracellular cAMP levels, inhibited aggregation but had no significant effect on [Ca2+]i increase. A monomeric recombinant fragment of vWF containing the GP Ib-binding domain of the molecule (residues 445-733) prevented all effects mediated by multimeric vWF but, by itself, failed to support the increase in [Ca2+]i and aggregation. These results suggest that the binding of multimeric vWF to GP Ib initiates platelets aggregation induced by high shear stress by mediating a transmembrane flux of Ca2+ ions, perhaps through a receptor-dependent calcium channel. The increase in [Ca2+]i may act as an intracellular message and cause the activation of GP IIb-IIIa; the latter receptor then binds vWF and mediates irreversible aggregation.

Biological Transport↗
PubMed1993

Purification and characterization of NADPH-cytochrome P-450 reductase from rat epidermis.

NADPH-cytochrome P-450 oxidoreductase (P-450 red) transfers reducing equivalents from NADPH to cytochrome P-450 (P-450) in the monooxygenase system. Detergent solubilized proteins from the membrane fraction of neonatal rat epidermis were purified by 2',5'-ADP-agarose affinity column chromatography. The purified protein showed an apparent homogeneity on sodium dodecylsulfate-polyacrylamide gel electrophoresis and molecular weight was estimated to be 78 kDa. NADPH-cytochrome c reductase activity increased by 95-fold in the purified enzyme. Epidermal P-450 red in vitro reconstituted benzo(a)pyrene hydroxylase activity in a dose dependent manner with P-450 purified from either rat liver or epidermis. Western blot analysis demonstrated that epidermal P-450 red immunologically cross reacts to liver P-450 red. Immunohistochemical staining showed that the enzyme was predominantly localized in the epidermis. The intensity of immunohistochemical staining of rat skin sections and tissue distribution did not change in the skin treated with beta-naphthoflavone, which results in a substantial increase in P-450 1A1 activity. Quantitative assessment of P-450 red in treated and untreated epidermis also showed no change. These findings indicate that constitutive P-450 red, fully capable of supporting P-450, exists in rat epidermis, and can function in metabolism of endogenous and exogenous compounds.

Animals↗
PubMed1993

Marked thrombocytosis with chromosomal abnormalities in a patient with rheumatoid arthritis.

An 80 year-old Japanese woman with rheumatoid arthritis (RA), complicated with thrombocytosis is described. Mild to moderate thrombocytosis is commonly observed in patients with RA, but she had marked thrombocytosis of over 1000 x 10(3)/mm3 and monosomy 22 with marker chromosome. This case suggests that thrombocytosis unusual with disease activity of RA might occur, and that careful evaluation of the thrombocytosis is required.

Aged↗
PubMed1993

Serious adverse effects induced by simultaneous administration of two nonsteroidal anti-inflammatory drugs.

We have described the case of a 58-year-old woman in whom acute hemolytic anemia, renal failure, and granulocytopenia developed after intake of mefenamic acid and diclofenac. Results of direct and indirect Coombs' tests were negative, but the lymphocyte transformation test was positive for these two nonsteroidal antiinflammatory drugs (NSAIDs). We suggest that the immune complex mechanism could have induced these adverse reactions. Although these drugs are very popular, simultaneous administration should be avoided because serious adverse effects can potentially occur.

Acute Kidney Injury↗
PubMed1993

Soluble P-selectin is present in normal circulation and its plasma level is elevated in patients with thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome.

P-selectin is an integral membrane glycoprotein stored in the secretory granules of platelets and endothelial cells. To determine whether soluble P-selectin may be present in the circulation of healthy humans, we used a sandwich immunoassay to assess citrated plasma from 50 subjects. P-selectin was present in concentrations ranging from 19 to 521 ng/ml (mean +/- SD = 121 +/- 84 ng/ml). The apparent molecular weight of P-selectin immunoisolated from platelet-poor plasma was similar to that of the detergent-soluble form isolated from platelet membrane. Plasma levels of P-selectin were unaffected by the following procedures: (1) drawing of blood in the presence of protease inhibitors; (2) stimulation of platelet-rich plasma with aggregating agents; (3) ultracentrifugation at 100,000 g for 120 min at 4 degrees C or filtration through a 0.22 micron membrane; or (4) preincubation of platelet-poor plasma with immobilized anti-platelet glycoprotein Ib monoclonal antibodies. It appeared that plasma P-selectin did not result from the in vitro activation of platelets, nor was it derived from platelet microparticles. We also found that plasma P-selectin levels were significantly elevated in patients with thrombotic thrombocytopenic purpura (12 patients, 332 +/- 184 ng/ml, P < 0.001) and haemolytic uraemic syndrome (17 patients, 297 +/- 191 ng/ml, P < 0.0001), as compared to the normal levels. Thus, these data should facilitate the study of the pathophysiological significance of circulating P-selectin.

Adult↗
PubMed1993

Low shear stress can initiate von Willebrand factor-dependent platelet aggregation in patients with type IIB and platelet-type von Willebrand disease.

Platelets exposed to shear stress aggregate in the absence of exogenously added agonists, utilizing distinct platelet membrane receptors and ligands depending upon the level of shear stress applied. Using a modified cone and plate type viscometer, we previously demonstrated that, under low shear stress (18 dyn/cm2), aggregation is mediated by platelet membrane glycoprotein (GP) IIb-IIIa and fibrinogen, whereas aggregation induced by high shear stress (108 dyn/cm2) requires the binding of von Willebrand factor (vWF) to both GPIb-IX and GPIIb-IIIa (Ikeda, Y., M. Handa, K. Kawano, T. Kamata, M. Murata, Y. Araki, H. Anbo, Y. Kawai, K. Watanabe, I. Itagaki, et al. 1991. J. Clin. Invest. 87:1234-1240). Here we report that vWF-dependent aggregation occurs under low shear stress in citrated platelet-rich plasma (PRP) from two types of congenital bleeding disorders, platelet-type von Willebrand disease (vWD) and type IIB vWD, in both of which ristocetin-induced aggregation is known to be heightened. Aggregation induced by low shear stress was enhanced in both types of disorders compared to normal controls, and the enhancement was completely abolished by anti-vWF monoclonal antibody NMC-4, which blocks the GPIb-binding site on vWF. Under high shear stress, the extent of maximal aggregation was not different between controls and the patient groups although maximal aggregation was reached much more quickly in the latter. When citrated PRP was exposed to a gradient of shear stress (6 to 108 dyn/cm2 over a 5-min period), vWF-dependent aggregation, as judged from the inhibitory effect of NMC-4, first occurred at 14 dyn/cm2 in platelet-type vWD and at 10-12 dyn/cm2 in type IIB vWD, as compared with more than 81 +/- 20.1 dyn/cm2 in control platelets. These results suggest that an abnormality in either vWF or GPIb-IX triggers the aggregation-inducing interaction of the two molecules under low shear stress, which might explain the intravascular platelet clumping, that presumably underlies the thrombocytopenia observed in these bleeding disorders.

Humans↗
PubMed1993

[Chronic pulmonary mucormycosis diagnosed by bronchoscopy: a case report].

A 56-year-old man with bronchial asthma and diabetes was admitted with massive hemoptysis and thick-walled cavity in the right middle lung field on chest X-ray films. He had been treated with antibiotics for eight months under the diagnosis of lung abscess before his admission. After occlusion of the bronchial arteries with metallic coils, bronchofiberscopy was performed disclosing the obstruction of right B3b. Microscopic examination of bioptic material and bronchial brushing smear taken from right B3b yielded numerous broad, nonseparate hyphae. Right middle and lower lobectomy were performed under a diagnosis of chronic pulmonary mucormycosis. The patient was recovered and discharged on 55 th days after operation.

Biopsy↗
PubMed1993

[Surgical treatment of stage IVa thymoma].

The relationship between prognosis of the disease and the type of surgery were reviewed in 110 cases of thymoma. Surgical procedures were classified into four types: total resection (TR), subtotal resection (SR), partial resection (PR) and exploratory thoracotomy (ET), and the extent of the disease was expressed as stage I through IV based on Masaoka's classification. Ten-year survival rates for stage III and IVa diseases were 5 6.2% in TR, 37.9% in SR and 30.3% in PR. None of the patients in ET survived more than 28 months. Tumor death after surgery was not observed in TR. Two of three patients with stage IVa disease who underwent TR are alive without recurrence of the tumor at 37 months and 6 months after surgery. The pleuropneumonectomy was performed in the former case. One of four patients who underwent SR and one of three patients who underwent PR both with stage IVa disease are alive at 71 and 150 months after surgical intervention, respectively, in spite of the presence of the tumor relapse. In these patients, repeated chemotherapy and radiotherapy were administered following the resection of the primary lesion. In conclusion, it was indicated that the improvement of the survival rate could be obtained by resection the tumor as completely as possible in stage III and IVa thymoma, as long-term survival has been proved to be possible by macroscopically complete removal of the primary site and pleural disseminations followed by combined adjuvant therapy in patient with stage IVa disease.

Adolescent↗
PubMed1992

A monoclonal antibody-based enzyme immunoassay for human GMP-140/P-selectin.

Two hybridoma cell lines producing monoclonal antibodies WGA-1 and PL7-6, reactive only with thrombin-stimulated human platelet have been established. Both these antibodies were investigated for their specific reactivity against GMP-140, based on the amino acid composition analysis of immunopurified antigen and N terminal amino acid sequencing of its protease fragments. A two-site enzyme immunoassay for quantification of human GMP-140 was developed using WGA-1 monoclonal antibody immobilized on 96-well microplates and horseradish peroxidase-labeled PL7-6 monoclonal antibody as detector. The assay was able to measure GMP-140 in serum and plasma with a sensitivity of about 5 ng/ml and a precision better than 10%. This assay will be useful for the detection of GMP-140 derived from platelets or endothelium in biological fluids and tissue extracts.

Amino Acid Sequence↗
PubMed1992

Melorheostosis of the hand: a report of two cases.

Two cases of melorheostosis of the hand are reported. Histopathologic examination confirmed the characteristic x-ray findings and excluded other skeletal dysplasias, such as osteopoikilosis and osteopathia striata.

Adult↗
PubMed1992

Efficacy of oral administration of live herpes simplex virus type 1 as a vaccine.

Mice given herpes simplex virus type 1 (HSV-1) (Miyama +GC strain) intragastrically via a stainless-steel cannula were rendered immune to subsequent lethal intraperitoneal (i.p.) challenge with HSV-1. The orally administered HSV-1 was completely inactivated in the stomach within a few minutes of inoculation. However, systemic immunity was established 14 days after oral inoculation with the virus and retained for up to 6 months. The mechanisms of establishing systemic immunity were investigated by means of adoptive transfer comparisons. When splenic cells from HSV-1-immunized mice were transplanted into nonimmunized mice, all of the recipient mice survived after a lethal i.p. challenge with the virus. Immunity was not established in antithymocyte serum-treated mice or by transfer of serum from immunized to nonimmunized mice. In addition, all HSV-1-immunized mice died after lethal challenge with HSV-2 and influenza virus A. These findings suggest that the immunity was virus specific, with T lymphocytes playing a major role in its establishment. The present study therefore supports the possibility of oral immunization with live HSV-1 as a vaccine.

Administration, Oral↗