Human parathyroid grafts survived and functioned in mice treated with anti-CD4 monoclonal antibody.
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Publications and source records attributed to K Esato.
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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.
The authors report the cases of 2 infants with congenital diaphragmatic hernia (CDH) treated without extracorporeal membrane oxygenation (ECMO) therapy who were discovered to have hearing loss at 1 year of age. Both boys had been diagnosed as having CDH antenatally and were treated with surgery and high-frequency oscillatory (HFO) therapy. The patterns of hearing loss were consistent with sensorineural deafness and believed to be associated with HFO therapy, prolonged mechanical ventilation, and a high pH.
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.
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.
The endovascular stent-graft has been devised for the treatment of thoracic aortic aneurysm (TAA) to reduce complications associated with conventional surgical repair. The present study assessed the usefulness of transesophageal echocardiography (TEE) for intra- and post-operative examinations in patients treated with transluminal endovascular stent-graft repair for TAA. Nine patients with TAA and 2 with chronic type B aortic dissection were studied. Immediately after stent-graft deployment, perigraft leakage was evaluated with both intraoperative TEE and aortography. In 9 of 11 patients, TEE and aortography immediately after stent-graft deployment revealed the same perigraft leakage results. TEE might therefore be useful for evaluating perigraft leakage and thrombus formation after stent-graft repair for TAA and could be an alternative to aortography, especially for patients with renal dysfunction who have the possibility of contrast agent-induced complications.
Mitral annular calcification, a degenerative process usually seen in the elderly or in chronic renal failure, is rarely seen in an extensive form. A 69-year-old man with no history of renal failure, rheumatic fever, or heart disease had mitral valve vegetation and regurgitation, together with extensive mitral annuls and valve calcification, which may or may not have been secondary to the infective endocarditis.
STUDY OBJECTIVES: Dynamic MRI and (133)Xe single-photon emission CT (SPECT) were used to directly evaluate the interaction of regional respiratory mechanics and lung ventilatory function in pulmonary emphysema. METHODS: Respiratory diaphragmatic and chest wall (D/CW) motions were analyzed by sequential MRI of fast-gradient echo pulse sequences during two to three respiratory cycles in 28 patients with pulmonary emphysema, including 9 patients undergoing lung volume reduction surgery (LVRS). The extent of air trapping in the regional lung was quantified by the (133)Xe retention index (RI) on three-dimensional (133)Xe SPECT displays. RESULTS: By contrast to healthy subjects (n = 6) with regular, synchronous D/CW motions, pulmonary emphysema patients showed reduced, irregular, or asynchronous motions in the hemithorax or location with greater (133)Xe retention, with significant decreases in the maximal amplitude of D/CW motions (MADM and MACWM; p < 0.0001 and p < 0.05, respectively). The removal of (133)Xe retention sites by LVRS effectively and regionally improved D/CW motions in nine patients, with significant increases in MADM and MACWM (p < 0.01 and p < 0.001, respectively). In a total of 40 studies of the 28 patients including post-LVRS studies, normalized MADM and MACWM correlated with percent predicted FEV(1) (r = 0.881, p < 0.0001; and r = 0.906, p < 0.0001, respectively), and also with (133)Xe RI in each hemithorax (r = -0.871, p < 0 0.0001; and r = -0.901, p < 0 0.0001, respectively.) CONCLUSIONS: This direct comparison of regional respiratory mechanics with lung ventilation demonstrated a close interaction between these impairments in pulmonary emphysema. The present techniques provide additional sensitivity for evaluating pathophysiologic compromises in pulmonary emphysema, and may also be useful for selecting resection targets for LVRS and for monitoring the effects.
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.
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.