Mice treated with anti-CD4 monoclonal antibody accept fully allogeneic thyroid grafts but reject second-donor-type thyroid grafts in maintenance phase.
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Publications and source records attributed to K Hamano.
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Permanent hypoparathyroidism is one of the most difficult of all endocrine disorders to treat medically. To examine the possibility that xenotransplantation can be used to treat hypoparathyroidism, human parathyroid tissues were transplanted into mice. Human parathyroid tissue was taken from specimens excised from patients with hyperparathyroidism. Fresh human parathyroid tissue was implanted under kidney capsule of CBA (H2k) mice. Some mice were treated intraperitoneally with depleting anti-CD4 monoclonal antibody (mAb, YTA 3.1, 100 microg/dose, days -1. 0. 1, 2, 3, and 5). Mice were killed 30 days after transplantation. Survival of parathyroid grafts was examined microscopically and human parathyroid hormone in serum was measured by ELISA. All parathyroid grafts survived under kidney capsule and human parathyroid hormone was strongly detected in serum (621 +/- 576 pg/mL) when recipients were treated with short-course treatment of anti-CD4 mAb. Conversely, no parathyroid tissue was seen microscopically in any recipient mice without anti-CD4 mAb treatment. Human parathyroid hormone was undetectable by ELISA in naive mice and mice transplanted with human parathyroid tissue without short-course treatment of anti-CD4 mAb. Xenogeneic human parathyroid tissue survived and functioned in mice treated with short-course treatment of anti-CD4 mAb.
BACKGROUND: Endocrine allografts are an option for the treatment of endocrine failure. METHODS: One lobe of the thyroid was transplanted under the kidney capsule. RESULTS: C57BL/10 (H2(b)) thyroids were rejected in naive CBA (H2(k)) mice within 14 days after transplantation. When mice were treated with anti-CD4 monoclonal antibodies (mAb), all grafts survived for more than 60 days. The first grafts still survived after second C57BL/10 or Balb/c (H2(d)) thyroid grafts that were transplanted into the same recipients were rejected acutely, which suggests that the primary grafts were modified under anti-CD4 mAb treatment. To confirm this hypothesis, C57BL/10 thyroid grafts from anti-CD4 mAb-treated mice were retransplanted. All grafts survived in naive mice; this correlated with the overexpression of heme oxygenase-1 (HO-1) in the grafts. Next, an inhibitor of HO-1 (zinc protoporphyrin) or control compound (copper protoporphyrin) was injected intraperitoneally after transplantation of C57BL/10 thyroid grafts into the primary CBA recipients that had been treated with anti-CD4 mAb. The grafts in mice that had been treated with zinc protoporphyrin, but not copper protoporphyrin, were rejected when retransplanted to naive recipients. CONCLUSIONS: Overexpression of HO-1 correlated with the protection of fully allogeneic thyroid grafts from rejection when retransplanted into naive recipients.
Species identification is the basis of Biology and has been carried out based on phenotype. Although some genes, such as that for 16S rRNA, have been used for species confirmation, identification of species based only on genotype has never been done before, although recent whole genome sequencing studies have demonstrated it to be possible in principle. However, it is evidently unrealistic for routine experiments of species identification. This paper clarifies that a very limited amount of information derived from a genome sequence is sufficient for identifying the species. It also proves that Genome Profiling [Nishigaki, K., Amano, N., and Takasawa, T. (1991) Chem. Lett. 1097-1100], TGGE analysis of random PCR products, can not only fulfill such requirements, but also serve as a universal method to analyze species. Thus, this compact technology can be used in many fields of biology, especially in microbe-related disciplines such as microbial ecology and epidemiology where exact knowledge about all members of a population is essential but previously difficult to obtain. This is the first demonstration that genotype-based identification of species is possible using a simple and uniform protocol for all organisms.
BACKGROUND: It is well known that coronary arteriosclerosis after heart transplantation is concentric and rich in smooth muscle cells (SMCs); however, the role played by rejection in the intimal thickening caused by SMCs in coronary arteriosclerosis remains unclear. In this study, we examined the process of intimal hyperplasia caused by SMCs and evaluated the relationship between the differentiation state of SMCs and local inflammation caused by rejection. METHODS: Lewis rat hearts were heterotopically transplanted into F344 rats (allotransplantation group) or other Lewis rats (isotransplantation group). Cyclosporin A (5 mg/kg/day) was injected intramuscularly for 20 days after transplantation in both groups. The transplanted hearts were examined immunohistochemically using several monoclonal antibodies; namely, HHF-35, CGA7, vimentin, alpha-actin, HIS36, R73 and proliferating cell nuclear antigen (PCNA). To evaluate the degree of local immunological response caused by rejection, the anti-PCNA antibody was used. To reveal the subtypes of proliferating cells in the thickened intima, HIS36 and R73 antibodies were used. RESULTS: In the allotransplantation group, SMCs in the media began to undergo a phenotypic change toward a poorly differentiated state 30 days after transplantation. Intimal hyperplasia was observed 60 days after transplantation, the thickened intima being composed mainly of dedifferentiated SMCs with abundant PCNA(+), most of which were macrophages and T cells. The state of differentiation of SMCs in the thickened intima 90 days after transplantation varied from a dedifferentiated to a highly differentiated state. These changes were strongly correlated with the expression of PCNA. CONCLUSION: The expression of PCNA was strongly correlated with the differentiation state of SMCs. Thus, local inflammation caused by rejection may play an important role in the initiation of phenotypic change in SMCs.
Arborcandins A, B, C, D, E and F, which possess potent 1,3-beta-glucan synthase inhibitory activity, were isolated from the culture broth of a filamentous fungus, strain SANK 17397. Arborcandins are novel cyclic peptides, that are structurally different from known glucan synthase inhibitors such as echinocandins. The 1,3-beta-glucan synthases of Candida albicans and Aspergillus fumigatus were inhibited by arborcandins with IC50 ranging from 0.012 to 3 microg/ml. The apparent Ki value of arborcandin C for C. albicans and A. fumigatus were 0.12 microM and 0.016 microM, respectively. The inhibition against these two 1,3-beta-glucan synthases by arborcandin C was noncompetitive. These compounds exhibited potent fungicidal activity against Candida spp. with MIC ranging from 0.25 to 8 microg/ml. The growth of A. fumigatus was suppressed by arborcandins with concentrations ranging from 0.063 to 4 microg/ml.
Quinolactacins A (1), B (2) and C (3), novel quinolone antibiotics have been found from the cultured broth of a fungal strain isolated from the larvae of the mulberry pyralid Margaronia pyloalis Welker). The fungal strain, EPF-6 was identified as Penicillium sp. from its morphological characteristics. Quinolactacins were obtained from the culture medium by solvent extraction and chromatographic purification. Compound 1 showed inhibitory activity against tumor necrosis factor (TNF) production induced by murine peritoneal macrophages and macrophage-like J774.1 cells stimulated with lipopolysaccharide (LPS).
This clinical study was conducted to determine whether the serum BNP level after open heart surgery reflects myocardial protection. The levels of BNP and CPK-MB were measured before and after 12 hours of cardiopulmonary bypass, then 1, 3, and 6 days after open heart surgery, and the relationship between the maximum levels of BNP and the CPK-MB after open heart surgery was examined. The patients were divided into two groups according to whether or not the maximum CPK MB was more than 100 IU/l after open heart surgery. A significant relationship between the maximum BNP and the maximum CPK-MB after open heart surgery was observed (p = 0.013). Moreover, the BNP was significantly increased in the group of patients with a maximum CPK-MB > or = 100 IU/l, compared to that in those with a maximum CPK-MB < 100 IU/l, 12 hours 1 day, and 6 days after open heart surgery (p < 0.01). These findings indicate that the serum level of BNP after open heart surgery can reflect myocardial protection.
This clinical study was conducted to determine whether apoptosis is contributed to the occurrence of aortic dissection. The subjects comprised 11 patients who underwent Stanford type A aortic dissection and 4 autopsy cases, being the control group. The occurrence of apoptosis was determined by the TUNEL assay using an aortic wall specimen, and the distribution of macrophages and h-MMP-9 was examined by immunohistological staining. Apoptotic cells were observed in the aortic specimens for all of the 11 patients who underwent Standford type A aortic dissection, but not in any of the 4 autopsy cases. Moreover, apoptotic cells were present in large numbers on the surface of the false lumen strongly in 8 patients who underwent surgery within 1 month after aortic dissection, but not in 3 who underwent treatment after than 1 month. Those phenomena were also observed in the immunohistological staining of CD 68 and h-MMP-9. These findings indicate that apoptosis could be contributed to the occurrence of aortic dissection.
The aim of this study was to investigate the clinical characteristics of children who showed sensitization to any type of seafood and to classify the 10 seafood allergens based on IgE reactivities by a cluster analysis. In children with bronchial asthma (BA) and/or atopic dermatitis (AD), we defined the 'seafood' group as 23 patients having any type of seafood specific IgE antibody (CAP system). We analyzed the clinical features, the serum total IgE and each allergen specific IgE level. In addition, ten seafood allergens were also classified by a cluster analysis. Three patients revealed immediate hypersensitivity to some seafood. The frequency of patients with AD and the total IgE in the seafood group were high and the patients in this group were tend to be sensitized to multiple allergens. Seafood allergens were classified into 4 groups, 1) salmon, sardine, horse mackerel and mackerel, 2) cod and tuna, 3) octopus and squid, and 4) crab and shrimp, by a cluster analysis. These findings corresponded to the biological classification and the classification by the reported common allergens among various types of seafood. Based on our findings, this classification is therefore considered to be useful when selecting allergens to screen for sensitization to seafood.
Recent progress in cardiovascular surgery has promoted less non-invasive surgery. We reoperated in a forty-two year old female for aortic valve regurgitation using the J-sternotomy approach and experienced good results. The patient was operated on with AVR 12 years after her first cardiac operation. Chest computed tomography revealed an adhesion between the anterior chest wall and the right ventricle. We made a sternal incision from the sternal notch down to the fourth right intercostal space (J-sternotomy). Ascending aorta was cannulated in the conventional manner. A conventional Two-stage cannula was placed in the auricle of the right atrium. A venting tube was also cannulated through the right upper pulmonary vein. J-sternotomy and minimal adhesionectomy made for a good operative field to establish cardiopulmonary bypass and to perform aortic valve re-operation.
The results of surgical treatment for a ruptured type B aortic dissection remain far from satisfactory. It is believed that additional perfusion from the right axillary artery might be more beneficial than perfusion from only the femoral artery during surgery for a ruptured thoracic aneurysm. The right axillary perfusion is more likely to perfuse the vital organs proximal to the ruptured area, and thus avoid retrograde emboli. In addition, if the open proximal method is performed, then the right axillary perfusion is able to facilitate the evacuation of air from the aortic lumen. We present herein the case of a patient in whom a ruptured type B acute aortic dissection was successfully treated by applying right axillary perfusion through a left thoracotomy.
The usefulness of phosphorus-31 nuclear magnetic resonance spectroscopy (31P NMRS) for detecting heart graft rejection after transplantation has been investigated by several researchers, and it has thus been demonstrated to be a valid technique for detecting acute myocardial rejection. In this study, we investigated the value of 31P NMRS to assess chronic cardiac allograft rejection. Lewis rat hearts were transplanted into the femoral region of F-344 rat recipients which were treated with cyclosporine, 5mg/kg body weight, by a daily intramuscular injection for 30 days beginning on the day of transplantation. The control isografts employed Lewis donors and recipients not given cyclosporine. The ratios of phosphocreatine (PCr) to inorganic phosphate (Pi), beta-adenosine triphosphate (beta-ATP) to Pi, and PCr to beta-ATP were monitored using surface coil 31P NMRS. 31P NMRS was performed 3, 30, and 60 days after transplantation, and the degree of the rejection and arteriosclerosis of the coronary arteries were then assessed histologically. The PCr:Pi and beta-ATP:Pi ratios for the allografts demonstrated a significant decrease on postoperative day (POD) 60 from that on POD 30 (PCr:Pi, P < 0.001; beta-ATP:Pi, P < 0.01). Although a significant difference existed between the isografts and allografts on POD 60 (PCr: Pi, P < 0.01; beta-ATP:P, P < 0.01), no significant difference was found in the PCr:beta-ATP ratio between the allografts and the isografts. On POD 60, the allografts showed significant graft rejection and arteriosclerotic changes in the coronary arteries. These findings therefore demonstrated the effectiveness of 31P NMRS for detecting chronic graft rejection in a rat model.
This study was conducted to examine whether mixed lymphocyte culture (MLC) could be used as a predictor of the efficacy of anti-CD4 monoclonal antibody (MAb) immunosuppression in vivo in a mouse model. C57BL/10 or BALB/c hearts were transplanted into C3H.He recipients. Anti-CD4 MAb administration prolonged graft survival, but there was a clear difference between the two donor-recipient combinations studied, the median survival time (MST) being >100 days in the C57BL/10 --> C3H group, and 17 days in the BALB/c --> C3H group. Anti-CD8 MAb prolonged the survival of C57BL/10 hearts slightly to a MST of 22 days, but the BALB/c hearts were rejected at control rates. Combining anti-CD4 and anti-CD8 antibody therapy prolonged the survival of C57BL/10 hearts indefinitely, but had little effect on the survival of BALB/c grafts, achieving an MST of only 24 days. Next, MLCs were performed in the presence and absence of the MAbs and compared with the graft survival data. The inhibition rates in the MLC, being the C3H lymph node cell responder, correlated well with graft survival. When three kinds of C3H responder cells, namely lymph node (LN) cells, T cells, and CD4+ cells, were examined to determine which was the most suitable for predicting graft survival, the MLC results showed that the responses of LN cells correlated most closely with graft outcome. In conclusion, MLC using LN cells as the responder is a useful tool for predicting allograft survival induced by anti-CD4 MAb therapy.
A 69-year-old woman was referred to our hospital for investigation of an abnormality detected by a chest roentgenogram, and was subsequently found to have an ascending aortic aneurysm. She had not suffered any symptoms such as headache or polymyalgia rheumatica. Aneurysmectomy and reconstruction of the ascending aorta was performed using cardiopulmonary bypass, and pathological examination of the aneurysmal wall revealed giant cell arteritis (GCA). Preoperatively, she had not suffered any temporal pain, and no signs of inflammation were detected serologically. GCA is a rare cause of aortic aneurysm in the Japanese population, and a brief review of the literature on this unusual entity is presented following this case report.