PubMed Health⌕ Search

Biomedical subjects

M Handa

Publications and source records attributed to M Handa.

At least 199 records · Page 11Linked to original sources
PubMed1989

[Diagnosis of rejection using immunologic probe in lung allotransplantation].

We attempted to establish the method of early diagnosis of rejection in lung transplantation using dog, rat and monkey experimental models. Orthotopic left lung allotransplantation was performed in these animals and lymphocytes from peripheral blood (PBL) and/or bronchoalveolar lavage fluid (BALF) were examined as a probe of rejection monitoring. The recipient dog showed a decreased response of PBL to PHA and an increased spontaneous blastogenesis (SB) at the period undergoing rejection which were confirmed by blood samples taken within 2 days before sacrifice of the animal. In rat lung transplantation, 2 groups of animal pair were used; WKA to F344, and WKY to F344. The former recipient rejected the graft within 5 days postoperatively and the latter rejected within 2 weeks after the operation. In both groups parameters for detection of rejection included lymphocyte count, SB and T cell subsets of PBL and BALF lymphocyte. Lymphocyte SB of BALF from lung transplant reflected early stage of rejection and preceded the changes in PBL. This seemed to be useful for early diagnosis of lung allograft rejection. In monkey experiment, BALF lymphocyte from the transplanted lung seemed to well reflect the grade of rejection when compared total cell count and differential cell count with histologic findings of the graft, though the number of this experiment was small.

Animals↗
PubMed1989

[Present status of lung transplantation and heart-lung transplantation].

On the basis of development of the immunosuppressive drugs such as cyclosporine since 1981, many successful cases have been reported on clinical lung and heart-lung transplantations. A principal disease for a single lung transplantation is pulmonary fibrosis. Obstructive lung disease and bilateral pulmonary sepsis such as cystic fibrosis and bronchiectasis are now considered to be done double lung transplantation. On the other hand, heart-lung transplantations have been performed not only on primary pulmonary hypertension and Eisenmenger's syndrome but also on restrictive and/or obstructive lung disease. Today's subjects on lung and heart-lung transplantations are as follows 1) The establishment of preservation method of transplant organs. 2) Development of an appropriate technique of monitoring for the rejected lungs. 3) Assessment and improvement of bronchial anastomotic healing. 4) Investigation of the causal factors on reimplantation response and obliterative bronchitis. Long-term survivals have been reported in both lung and heart-lung transplantation. Therefore, many attempts have been increasingly made in order to obtain the heart beating cadaver donors in Japan. But experimental study on the unsolved problems of transplantation should be continuously carried out for successful clinical lung and heart-lung transplantation.

Graft Rejection↗
PubMed1988

Biochemical studies on lymphoblastoid cells with inherited N-acetyl-glucosamine 1-phosphotransferase deficiency (I-cell disease).

Lymphoblastoid cells transformed by Epstein-Barr virus from peripheral lymphocytes of normal individuals and I-cell disease (ICD) patients were used for the enzymic study of lysosomal hydrolases and N-acetylglucosamine 1-phosphotransferase. ICD lymphoblastoid cells secreted a larger amount of hydrolases into medium than normal cells, although the intracellular hydrolases were not deficient in ICD cells. The stimulating effect of 10 mM ammonium chloride on secretion of hydrolases was found only with normal cells, and not with ICD cells, indicating that the hydrolase molecule bearing mannose 6-phosphate was secreted. The ICD lymphoblastoid cells retained the enzymologic characteristics of both lysosomal hydrolases and N-acetylglucosamine 1-phosphotransferase seen in ICD fibroblasts, which allows us to study the pathophysiology of ICD in cells other than fibroblasts.

Adsorption↗
PubMed1987

Amino acid sequence of the von Willebrand factor-binding domain of platelet membrane glycoprotein Ib.

We report the amino acid sequence of a 299-residue segment from the alpha chain of the human platelet membrane glycoprotein Ib. This includes the complete sequence of the amino-terminal tryptic fragment of 290 residues comprising the von Willebrand factor-binding domain. Two primary sets of overlapping fragments were obtained by cleavage of the S-carboxymethylated protein at methionyl and lysyl bonds following treatment with cyanogen bromide and Achromobacter protease I, respectively. Additional fragments were obtained by treatment of native glycocalicin with trypsin, Staphylococcus aureus V8 protease, and Serratia marcescens protease. Analysis of all these fragments provided data that allowed determination of the continuous sequence corresponding to approximately half of the alpha-chain polypeptide. This region of glycoprotein Ib is largely hydrophobic and contains only two N-linked and one O-linked carbohydrate chains. A hydrophilic region exists between residues 215 and 299, which contains a cluster of 10 negatively charged residues at 269-287. This area is likely to attract positively charged molecules. The hydrophilic, highly glycosylated (at serine and threonine residues) region corresponding to the previously described "macroglycopeptide" and representing the carboxyl-terminal half of the alpha chain is likely to begin at residue 292. The determined sequence of the alpha chain of glycoprotein Ib contains a region (residues 29-193) with seven repeats, which is indicative of gene duplication and is highly homologous to human leucine-rich alpha 2-glycoprotein. This protein sequence agrees completely with that deduced from the cDNA sequence reported by Lopez et al. [Lopez, J.A., Chung, D.W., Fujikawa, K., Hagen, F.S., Papayannopoulou, T. & Roth, G.J. (1987) Proc. Natl. Acad. Sci. USA 84, 5615-5619].

Amino Acid Sequence↗
PubMed1987

Pancreatic lysosomal thiol proteinases and inhibitors in acute pancreatitis induced in rats.

When examining the level of esterolysis and that of cathepsin B or H, a significant positive correlation was found in the rat pancreas with inflammation induced by a closed duodenal loop, whereas there was a significant negative correlation between the activity of cathepsin B or H and that of its endogenous inhibitors. The levels of endogenous inhibitors of cathepsins B and H in rats with a pancreatitis were lower than in the sham-treated group. The endogenous inhibitors of cathepsins B and H were destroyed by incubation with the supernatant fraction obtained from the inflamed pancreas. These observations indicate that the activities of pancreatic cathepsins B and H are closely related to the severity of acute pancreatitis and that lesser levels of thiol proteinase inhibitors in the pancreatitis group than in the sham-treated group are due to destruction of the inhibitors by the enhanced protease activity.

Acute Disease↗
PubMed1987

Histologic assessment of bronchial anastomotic healing in canine lung transplantation.

Postoperative wound healing of the bronchial anastomosis was studied in dogs with autotransplantation (20 dogs, 7 days to 6 years postoperatively) and allotransplantation (62 dogs, 5 to 174 days postoperatively) of the left lung. In the group undergoing lung allotransplantation, the relationship among three histologic parameters was studied: the grade of lung allograft rejection, the degree of changes in the epithelium, and submucous lymphocyte infiltration along the donor bronchus within approximately a 0.5 cm area distal to the anastomosis. In lung autotransplantation, mucosal continuity began to be observed 1 week postoperatively. Mucosal continuity and apparent collagen formation on any bronchial contiguous site were demonstrated in most animals studied more than 3 weeks postoperatively. Bronchial anastomotic healing tended to be slower in lung allotransplantation than in autotransplantation, although a mucosal continuity at the anastomosis was sporadically observed in immunosuppressed dogs surviving more than 3 weeks postoperatively with a lung allograft. There were significant rank correlations among the three histologic parameters, which showed that lung allograft rejection is closely connected with wound healing of the bronchial anastomosis in lung allotransplantation. Meticulous mucosal approximation is most necessary during bronchial anastomotic procedures. Establishment of an exact method for early monitoring of lung allograft rejection is absolutely necessary for lung allotransplantation.

Animals↗
PubMed1987

Results of surgical treatment for thymoma based on 66 patients.

Sixty-six patients with thymoma have undergone surgical treatment since 1965 and have been assessed from the viewpoint of clinical manifestations and prognosis. Thirty-one patients with encapsulated thymoma were treated with total surgical resection alone, and they had no postoperative tumor recurrence. With the exception of one patient who died of respiratory insufficiency on the fourth day after the operation, 34 patients with invasive thymoma were evaluated on the basis of their postoperative prognosis. Fifteen patients with invasive thymoma died from 1 1/2 months to 10 years, 1 month postoperatively; 9 died of local or metastatic tumor and 6 died of other diseases. Associated autoimmune diseases, as well as the invasive tendency of the tumors, apparently affected the prognosis. Ten-year survival rates of the patients who underwent surgical treatment were as follows: 61.6% for the total group, 74.3% for those with encapsulated thymoma, and 49.4% for those with invasive thymoma. In the surgical treatment for invasive thymomas, one should aim to resect the tumor totally, even though adjacent tissues are resected simultaneously. Even for the patient with total resection of invasive tumor, postoperative radiation should be required. Finally, if residual tumor must be left during the operation, postoperative radiation as well as anticancer chemotherapy should be aggressively scheduled, because postoperative distant metastasis may appear in these patients with residual thymoma.

Adolescent↗
PubMed1986

The von Willebrand factor-binding domain of platelet membrane glycoprotein Ib. Characterization by monoclonal antibodies and partial amino acid sequence analysis of proteolytic fragments.

The glycoprotein Ib (GPIb), a two-chain integral platelet membrane protein, acts as a receptor for von Willebrand factor. In order to obtain information on the domain involved in this function, as well as on the structural organization of GPIb, the protein has been purified and submitted to limited proteolysis using three different enzymes. The resulting fragments were topographically oriented by means of partial NH2-terminal sequence analysis and immunological identification using monoclonal antibodies. One of these antibodies (LJ-Ib1) inhibited the von Willebrand factor-GPIb interaction completely, one (LJ-P3) partially, and one (LJ-Ib10) had no inhibitory effect. Three distinct fragments, the 38-kDa fragment produced by Serratia marcescens protease as well as the 45- and 35-kDa fragments produced by trypsin, had the same NH2 terminus as the intact GPIb alpha-chain (apparent molecular mass = 140 kDa). These fragments and the alpha-chain reacted with the inhibitory antibodies. On the other hand, three fragments produced by Staphylococcus aureus V8 protease, one of 92 kDa similar to the previously described "macroglycopeptide" and two others of 52 and 45 kDa, had NH2-terminal sequences different from that of the GPIb alpha-chain and reacted only with the noninhibitor monoclonal antibody LJIb10. Thus, the binding domain for von Willebrand factor resides near the NH2 terminus of the GPIb alpha-chain, whereas the carbohydrate-rich region is part of the innermost portion of GPIb and does not appear to be involved in the von Willebrand factor binding function.

Amino Acid Sequence↗