Induction of unresponsiveness to islet allograft by preoperative donor spleen cell injection and FK 506 treatment.
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Biomedical subjects
Publications and source records attributed to H Wada.
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Phycoerythrin (PE)-labeled murine monoclonal antibodies (MAB) to CD2, CD10, CD19, CD20, and CD33 were used as lineage markers, as were PE-labeled anti-DR MAB and fluorescein isothiocyanate (FITC)-conjugated MAB to CD34. One hundred CD34+Lin+DR+ or CD34+Lin-DR- cells were individually sorted and incubated without adherent cell layer in alpha-medium with or without cytokines such as 100 U/mL recombinant human interleukin-3 (rhIL-3), 100 U/mL rhIL-6, and/or 500 ng/mL mast cell growth factor (MGF). The incubated cells were harvested and cultured in medium containing methylcellulose every 2 weeks. The numbers of colonies from colony-forming units-granulocyte/macrophage (CFU-GM), burst-forming units-erythroid (BFU-E), and mixed colony-forming units (CFU-Mix) were scored on day 14. In the incubation, CD34+Lin-DR- cells from bone marrow and cord blood produced more CFU-GM and BFU-E, and for longer periods, than did CD34+Lin+DR+ cells. In addition, CD34+Lin-DR- from cord blood supplied more CFU-GM and BFU-E than did CD34+Lin-DR- from bone marrow. Although these data demonstrate that MGF, IL-3, and IL-6 synergistically stimulate the production of CFU-GM and BFU-E, this study indicates that CD34+Lin-DR- cells contain more primitive hematopoietic progenitors and that CD34+Lin-DR- cells are unable to maintain their self-renewal capacity in the presence of IL-3, IL-6, and MGF without adherent cell layer.
Primitive platyhelminths, especially Acoel turbellarians, are thought to be key to understanding the origin and evolution of metazoa. In order to infer their phylogenetic position within the phylum Platyhelminths, we determined and compared the complete nucleotide sequence of a region of about 750 base pairs in the central part of an 18S rDNA for ten turbellarians, including two species of the group Acoela, six species of the group Polycladida, and two species of the group Tricladida. The deduced phylogenetic tree suggests that the three groups examined form discrete and separate entities. In addition, the tree suggests an earlier emergence of the Acoel turbellarians than the other platyhelminths. This animal may not be derived by means of secondary reduction from advanced acoelomates but may be nearest to its metazoan ancestors.
Recent studies of molecular phylogeny based upon comparisons of the partial nucleotide sequences of 18 and 28S rRNAs have suggested that the metazoa are polyphyletic, i.e., that diploblasts (poriferans, cnidarians, ctenophores, and placozoans) and triploblasts form two separated monophyletic units. In order to examine this hypothesis, we determined almost the complete sequences of small subunit (18S-like) rDNA for two poriferans and a ctenophore. Phylogenetic comparisons of the sequences, together with those of a cnidarian, triploblasts and other eukaryotes, supported the monophyly of the metazoa. Among the diploblasts, the ctenophore showed some similarities to the poriferans.
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The aim of this study was to investigate the role of glomerular visceral epithelial cell (GEC) antigens in the induction of proteinuria. An antibody (anti-GECIg) was produced by rabbit immunization with membrane extracts prepared from a clonal GEC line, SGE1, from the isolated rat renal glomeruli. A one-shot intraperitoneal injection of anti-GECIg (day 0) induced rapid and severe proteinuria in rats, reaching a peak on day 2 (mean value, 425 mg/24h), then gradually decreased to normal levels by day 10. By direct immunofluorescence, fine granular binding of anti-GECIg along the glomerular capillary walls was observed within 24 h. Electron microscopy and immunoelectron microscopy revealed GEC alterations consisting of extensive retraction of the foot processes, vacuolar changes in the cytoplasm, microvillous transformation of the cell surface, and binding of anti-GECIg to the surface of the foot process, mainly to its soles. Two major components with Mr of 108,000 and 39,000 were identified by immunoblotting assay using SGE1 cell membrane extracts and anti-GECIg. This model of rat nephropathy induced by anti-GECIg hopefully will lead to a greater understanding of the mechanism by which proteinuria is induced and developed.
We have summarized the results of international data from many institutes. In 1983 in Toronto, Canada, Cooper performed that first successful clinical case lung-transplantation. Subsequently, there have been more than 1,500 cases of lung transplantation. One reason for Cooper's success was the use of cyclosporin, the other was the performing of omentopexy. Among the total lung transplant cases, single lung transplant comprised 66%, bilateral sequential lung transplant comprised 26%, and en-blocdouble lung-transplant, (8%). Of the 1,540 recipients, the most common underlying of sease was emphysema (360 cases), followed by fibrosis (289 cases), cystic fibrosis (206 cases), alpha-1 antitripsin deficiency (210 cases) and rare diseases including pulmonary hypertension, lymphagiomyomatosis and sarcoidosis. The survival rate of all patients was 68% at 1 year, and 60% at two years.
We measured the serum and pleural levels of squamous cell carcinoma related antigen (SCC-Ag) in patients with active pulmonary tuberculosis and studied the relationship between SCC-Ag and tuberculosis. Serum levels of SCC-Ag in 63 patients with newly diagnosed untreated tuberculosis were 1.76 +/- 2.16 ng/ml, significantly higher than in 118 healthy controls (0.67 +/- 0.52 ng/ml) or in 11 patients with old tuberculosis (0.92 +/- 0.38 ng/ml; p < 0.01). Pleural effusion levels of SCC-Ag in 41 patients with tuberculosis pleurisy were 4.5 +/- 3.4 ng/ml, significantly higher than in 54 patients with non-malignant, non-tuberculous, pleurisy (2.3 +/- 1.7 ng/ml: p < 0.05). In patients who responded well to anti-tuberculous chemotherapy, serum levels of SCC-Ag decreased to the normal range (1.6 ng/ml) with clinical improvement, while in nonresponders they did not decrease. Isoelectolic focusing electrophoresis showed serum SCC-Ag to be composed of a neutral fraction as a single peak, which was corresponded to that of squamous cell carcinoma of the lung. The tuberculous lesions were stained with anti-SCC-Ag antibody in one case and weak SCC-Ag positive findings were observed in the intercellular spaces of the epidermoid cells in the area without necrosis. These results raise the possibility that SCC-Ag is produced in or released from not only squamous cell carcinoma of the lung but also pulmonary tuberculous lesions.
To determine the endurable radiation dose before bronchial anastomosis, the bronchial circulation of mongrel dogs was assessed after bronchoplastic surgery conducted after various single doses of radiation. Plastic surgery of the right main bronchus was carried out 1 week after cobalt 60 irradiation to the right hilar region. Bronchial blood flow was measured with laser Doppler velocimetry 7, 14, and 30 days after operation. Animals were killed 30 days after operation and the region of the bronchial anastomosis was examined histologically. The animals were divided into five groups: group A (control group without irradiation), group B (8 Gy irradiation), group C (16 Gy), group D (19 Gy), and group E (24 Gy). Wound healing of the anastomosed bronchus was excellent in groups A and B. In group A, bronchial blood flow did not drop below 80% of the preoperative level throughout the postoperative observation period. In group B, bronchial blood flow on day 7 after operation was only 65% of the preoperative level, but blood flow had returned to the preoperative level by day 30. In groups C, D, and E, bronchial blood flow was less than 60% of the preoperative level on day 30. There was a high prevalence of radiation-induced morbidity in the region of anastomosis in groups C, D, and E. Postoperative recovery of bronchial blood flow and wound healing of the anastomosed bronchus were thus delayed in dogs that had received high doses of radiation before operation. We conclude that the safe dose of preoperative radiation in clinically used fractionation is 36 Gy or less (corresponding to a single dose of 16 Gy or less in dogs).
Gastrointestinal toxicities of tegafur (FT) and doxifluridine (DFUR) were compared using mouse intestinal enzymes as the marker. Enzyme activities were decreased during repeated administration of these 5-FU derivatives. When the drugs were administrated once a day, the decrease of enzyme activities were almost equal, but when administrated twice a day. DFUR showed greater decrease. Pharmacokinetical analysis revealed faster catabolism of DFUR than FT. In vitro 5-FU formation by GI extract was much higher from DFUR than FT. These data show a good agreement with the fact that the incidence of diarrhea is much higher in DFUR than FT.
UNLABELLED: Patients (pts) with hilar type early lung cancer from 5 hospitals served as the subjects to assess the complete response rate and toxicity of PDT with Photofrin II (PHE) and excimer dye laser (PDT EDL-1). ENTRY CRITERIA: 1. Histologically proven lung cancer with endoscopically superficial thickening or small protrusion. 2. All lesions that were located proximally from the subsegmental bronchus, were visible to the distal margin of the lesions. 3. N0M0. METHOD: All pts received PHE (2 mg/kg) i.v., 48 hours before PDT. Tumor lesions superficially photoradiated by an excimer dye laser via flexible bronchoscope. RESULTS: From September 1990 to March 1992, 39 pts with 46 carcinomas (CA) were enrolled. Thirty-three pts with 40 CA were evaluable. 1. RESPONSE: Thirty-five in 40 CA showed a complete response (CR) (87.5%, 95% confidence limit: 73.2-95.8%). All 32 cases of CA equal to or less than 1 cm of tumor length were CR, but 3 CA relapsed locally. Thirty-three of 35 CA visible to the distal margin were CR (91.7%, 95% confidence limit: 77.5-98.3%). 2. Toxicity (> WHO grade 2): Three pts (7.7%) had transient dermatitis and sunburn, while another pt (2.6%) had symptoms due to obstructive pneumonitis. CONCLUSIONS: Tumors equal to or less than 1 cm in length and visible to the distal margin are curable by PDT.
A male patient with CML received a BMT from his sister and developed chronic GVHD. The host-origin normal karyotype (46,XY) was identified for the first time in the 60th month after BMT. Detection of Y-chromosome-specific DNA in BM and peripheral blood (PB) showed that all BM samples obtained 6 months from BMT were positive for Y-specific DNA, while PB became positive in the 60th month after BMT. The BCR-ABL mRNA derived from leukemic cells was detected in the 36th month post-BMT, but not in the 60th month or thereafter. Fluorescence in situ hybridization revealed that 1.5% and 0.6% in BM and PB cells were Y-positive in the 70th month post-BMT, respectively. DNA analysis of hematopoietic progenitor colonies revealed 1 of 42 erythroid colonies to be host derived. These results indicate that host-origin hematopoietic cells survive chronic GVHD, while the Ph1 clone was eliminated.
One hundred and four cases of thymomas were treated between 1967 and 1991 at the Chest Disease Institute, Kyoto University. Forty-two cases were clinical stage I, 12 cases were stage II, 42 cases were stage III and 8 cases were stage IV. Nineteen patients had MG, 17 patients had SVC syndrome. Ninety-six cases were surgically resected combined with radiation therapy. Overall survival was 77.9% at 5 years and 62.5% at 10 years. The survival of 62 cases of invasive thymoma was 77.5% at 5 years and 54.8% at 10 years. We've got better prognosis when total or subtotal resection of invasive thymoma could be accomplished, i.e. 88.8% at 5 years and 72.6% at 10 years.
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In April, 1991, a 61-year-old man was admitted to our hospital because of pancytopenia and disseminated intravascular coagulation (DIC). Five years prior to admission he had developed high fever, skin eruption and arthralgia which had been improved by antibiotics, but recurred. Steroid therapy was ineffective for pancytopenia and DIC. Laboratory findings were as follows: RBC count, 274 x 10(4)/microliters; WBC count, 470/microliters; Platelets, 6.4 x 10(4)/microliters; fibrinogen, 153mg/dl; FDP, 67.0 micrograms/ml; FDP-D.Dimer, 13040ng/ml; thrombin-antithrombin complex, > 60.0ng/ml; and plasmin alpha 2-plasmin inhibitor complex, 10.3 micrograms/ml. As we suspected adult onset Still's disease on the basis of clinical course, we treated him with methylprednisolone pulse therapy, which was, however, ineffective. leukocytopenia, thrombocytopenia and DIC improved after cyclosporine treatment. Since cyclosporine is known to be very effective to autoimmune diseases, we speculate that in this patient immunological mechanism may be involve in the pathogenesis of DIC.