Initial steroid bolus injection promotes vigorous CD8+ alloreactive responses toward early graft acceptance immediately after liver transplantation in humans.

We have found that steroid bolus withdrawal prior to graft reperfusion increased the incidence of acute cellular rejection (ACR). This study aims to clarify how initial steroid bolus (ISB) injection at reperfusion influences the kinetics of CD8(+) alloreactive immune responses immediately after living donor liver transplantation (LDLT). A total of 49 hepatitis C virus (HCV)-infected recipients were classified into 3 groups according to hierarchical clustering by preoperative CD8(+)CD45 isoforms. The naive T cell proportion was considerably higher in Group I than in Groups II and III, whereas Group II recipients had the highest effector memory (EM) T cells and Group III the highest effector T cells. The frequency of ACR was significantly higher in recipients without ISB than in those with ISB. In particular, the ACR rates were the highest in Group II without ISB. Following ISB, the proportion of effector T cells was promptly upregulated within 6 hours after graft reperfusion, simultaneously with the upregulation of CD27(-)CD28(-) subsets, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha and perforin expression, which significantly correlated with increasing interleukin (IL)-12 receptor beta 1 cells. These were then downregulated to below preoperative levels by tacrolimus (Tac) administered at 24 hours. These changes did not occur in the absence of ISB. In Group II without ISB, the downregulation of IL-12Rbeta1(+) cells was the greatest, consistent with the highest rates of ACR and mortality (60%). In conclusion, ISB must be done in place, especially in Group II with preexisting high EM T cells, to enable the development of early allograft acceptance.     

Myocardial 11C-diacylglycerol accumulation and left ventricular remodeling in patients after myocardial infarction.

Left ventricular (LV) remodeling after myocardial infarction (MI) is a maladaptive process that increases the risk of heart failure and death. The myocardial phosphoinositide cycle, which is located downstream from several neurohumoral factors, plays a crucial role in LV remodeling. Our animal studies demonstrated that 1-[1-11C]butyryl-2-palmitoyl-rac-glycerol (11C-DAG) can be used to visualize regions with an activated phosphoinositide cycle. Therefore, we examined whether myocardial 11C-DAG accumulation assessed by PET is relevant to LV enlargement and systolic dysfunction in post-MI patients. METHODS: We performed PET with 11C-DAG in 13 post-anteroseptal MI patients and 4 healthy volunteers. We placed regions of interest on the noninfarcted myocardium and calculated the myocardium-to-left atrial (LA) chamber ratio of 11C-DAG accumulation. RESULTS: The myocardium-to-LA chamber ratio of 11C-DAG was significantly higher in the post-MI patients (mean +/- SD, 1.73 +/- 0.35) compared with that of the healthy volunteers (mean +/- SD, 1.25 +/- 0.13; P < 0.05). In the post-MI patients, the myocardium-to-LA chamber ratio of (11)C-DAG was significantly correlated with the LV end-diastolic volume index (r = 0.79, P < 0.01) and the plasma concentration of brain natriuretic peptide (r = 0.85, P < 0.001) and negatively correlated with the LV ejection fraction (r = -0.69, P < 0.01). CONCLUSION: These findings suggest that the myocardial 11C-DAG accumulation assessed by PET is relevant to LV enlargement, LV systolic dysfunction, and humoral activation in post-MI patients. This new imaging strategy based on intracellular signaling may contribute to the assessment and treatment of post-MI patients.     

Ruptured pediatric posterior cerebral artery aneurysm 9 years after the onset of Kawasaki disease: a case report

CASE REPORT: A 12-year-old boy who had a history of Kawasaki disease 9 years ago experienced a subarachnoid hemorrhage by ruptured right posterior cerebral artery aneurysm. On day 1 operation, as the aneurysm was very fragile and bled easily, two intraoperative ruptures, including a very premature rupture, were encountered. As a result, a left hemiparesis especially severe in the left hand was caused by the right anterior thalamic infarction due to the occlusion of a thalamo-perforating artery arising near the neck of the aneurysm. DISCUSSION: The histopathological examination of the intraoperative excised aneurysmal dome disclosed the thickening of the endothelial inner due to the endothelial hypertrophy and the invasion of inflammatory cells. This finding of the aneurysm was partially mimicking the finding of the coronary artery of the patients with Kawasaki disease. The combination of cerebral aneurysm and Kawasaki disease has never been reported until now, and the etiology of the aneurysm of this patient is unclear.     

Surgical outcomes of partial nephrectomy for renal cell carcinoma: A joint study by the Japanese Society of Renal Cancer

OBJECTIVE: A joint study was undertaken by the Japanese Society of Renal Cancer to investigate the present status of partial nephrectomy in Japan and to speculate about what may be the indications for partial nephrectomy in patients with renal cell carcinoma. METHODS: Data were tabulated for 469 patients from participating medical institutions and various clinical factors were investigated with regard to disease progression (local recurrence and distant metastasis). RESULTS: Disease progression was observed in 21 patients (4.5%). No significant relation to disease progression was observed for sex, laterality, tumor histology, grade and tumor size. Although patients with solitary tumors displayed excellent prognosis irrespective of tumor diameter, patients with multiple tumors displayed a high likelihood of disease progression. Patients older than 77 years old and patients with imperative indication were found to have a poorer prognosis. CONCLUSION: In patients with solitary tumors, partial nephrectomy can be actively performed, even if the patient displays elective indications and the tumor is >4 cm in diameter. In patients displaying multiple tumors with imperative indications, the decision whether to perform partial nephrectomy should be made by the patients and their physicians after considering the impact on curability and the quality of life.     

Self-expandable metallic stent for unresectable malignant strictures in the esophagus and cardia

Objective Self-expandable metallic stent (EMS) placement has been the first choice for dysphagia because of the certainty over its safety, low invasiveness, and immediate efficacy. However, there still remain some problems in relation to the EMS placement site and anticancer therapies before and after EMS placement. Methods: Consecutive 78 patients in whom EMS was placed due to the unresectable malignant stricture in the esophagus or cardia from July 1995 to August 2003 in our department were studied. Results: Gastroesophageal reflux was found in 5 of 8 patients after placement of conventional EMS for the stricture in the gastroesophageal junction. Meanwhile, acid and bile reflux into the esophagus were not detected by pH and bilirubin monitoring, respectively, in 6 patients after placement of the EMS with an anti-reflux mechanism for the stricture in the gastroesophageal junction. The median survival period of all patients after EMS placement was 123 days. The median survival period of 7 patients with radiotherapy only after EMS placement was 138 days and that of 17 patients with radiotherapy before EMS placement was 60 days, which was shorter than that of the former (p<0.05). On the other hand, the median survival period after hospital admission due to dysphagia of these 7 patients was longer than that of 17 patients with radiotherapy only before EMS placement, although, the difference was not significant. Conclusion: EMS with an antireflux mechanism is not commercially available in Japan and approval is urgently required. The indication of radiotherapy associated with EMS placement is to be studied further.     

Extracellular matrix remodeling in oral submucous fibrosis: its stage-specific modes revealed by immunohistochemistry and in situ hybridization

BACKGROUND: Oral submucous fibrosis (OSF) is a chewing habit-related pre-cancerous condition of the oral mucosa affecting predominantly south Asians. It is histopathologically characterized by epithelial atrophy and fibrosis of the subepithelial connective tissue. Fibrosis extends all the way into the muscle layer, leading to difficulty in mouth opening. However, the dynamics of extracellular matrix (ECM) remodeling with OSF progression is largely unknown. METHODS: Forty biopsy specimens of OSF and 10 of normal buccal mucosa were examined for expression/deposition modes of eight ECM molecules by histochemistry, immunohistochemistry, and in situ hybridization. RESULTS: In the early stage of OSF, tenascin, perlecan, fibronectin, collagen type III were characteristically enhanced in the lamina propria and the submucosal layer. In the intermediate stage, the ECM molecules mentioned above and elastin were extensively and irregularly deposited around muscle fibers. In the advanced stage, such ECM depositions decreased and were entirely replaced with collagen type I only. Their gene expression levels varied with progression of fibrosis, but the mRNA signals were confirmed in fibroblasts in the submucosal fibrotic areas. CONCLUSIONS: The results indicate that the ECM remodeling steps in OSF are similar to each phase of usual granulation tissue formation. Restricted mouth opening may be a result of loss of variety of ECM molecules including elastin into the homogeneity of collagen type I replacing muscle fibers.     

Synchronous growth of triple lung cancer

The case of a 75-year-old man with three synchronous carcinomas of the lung (large cell carcinoma, adenocarcinoma, and small cell carcinoma) is reported. This is the eighth well-documented case report in the literature; however, our case is the first to be reported with the newly described histological combination.     

The Effect of Total Blood Exchange with PHP Solution on Cardiac Xenotransplantation

Abstract: Prevention of hyperacute rejection is a difficult and unsolved problem in xenotransplantation. Natural antibodies and complement activation have been known to play an important role in the xenotransplantation between discordant species pairs. In the present study, total blood exchange (TBE) was performed with pyridox-alated-hemoglobin-polyoxyethylene conjugate (PHP) solution (Ajinomoto Co., Inc., Kawasaki, Japan) before cardiac xenotransplantation in order to remove the immunoglobulins and prolong xenograft survival time. Guinea pigs and rats were used as the discordant species combination for donor and recipient. Two groups were established: Group 1, untreated control (n = 8) and Group 2, TBT with PHP solution (n = 8). The exchange blood transfusion was carried out at the rate of 15–20 ml/h utilizing PHP solution using a blood pump. After the blood exchange was processed, hematocrit (Ht) levels dropped to 4 or 5%, and a cardiac xenotransplantation was performed within 24 h. The levels of serum IgA, IgM, and IgG were decreased to less than 25, 25, and 10% of the base line, respectively, after blood exchange. A mean xenograft survival time in Group 2 was prolonged to 472 ± 74 min and to 10.4 ± 1.8 min in Group 1 (p < 0.01). A titer of the anti-guinea pig lymphocytotoxic antibody in rat serum was decreased to almost nil. The data from this study suggest that total blood exchange with PHP solution may be useful in preoperative removal of xenograft antibodies in xenotransplantation.     

Striatal cells containing the Ca2+-binding protein calretinin (protein 10) in ischemia-induced neuronal injury

The present study concerns the vulnerability of striatal interneurons immunopositive for the Ca²⁺-binding protein calretinin to ischemic neuronal injury. An immunohistochemical study was carried out on the striata of rats which had undergone transient middle cerebral artery occlusion. Two weeks after the ischemia, there was a marked reduction in the number of calretinin-positive neurons in the ipsilateral ischemic lesion, although the striatal interneurons positive for parvalbumin, which are a neuronal population distinct from the calretinin-immunoreactive cells in the striatum, were spared in the insulted areas. The present data indicate that the striatal calretinin-positive neurons are less resistant to transient ischemia, suggesting that there may exist vulnerability differences among the striatal interneurons in ischemia-induced neuronal injury.     

Ultrastructural and immunohistochemical study of Ewing's sarcoma and related tumors: Morphological neural markers suggesting neural histogenesis in 32 small round-cell sarcomas

The purpose of this study was to validate the hypothesis of neural histogenesis of Ewing's sarcoma of bone and related tumors by light microscopic, electron microscopic, and immunohistochemical analysis. We studied 32 round-cell sarcomas (19 cases of Ewing's sarcoma of bone, 3 extraskeletal Ewing's sarcomas, 5 peripheral primitive neuroectodermal tumors (PNET) and 5 cases of unclassified small round-cell type of neurogenic sarcoma (NS). Immunoreactivity for MIC2 was observed in all cases of Ewing's sarcoma and PNET, and in 1 cases of NS. Positive immunoreactivity for neural markers (NSE, synaptophysin, S-100) was found frequently in some tumors. Ultrastructurally, some specific features of neural differentiation, such as a fragmented basal lamina and neurosecretory granule-like particles, were found even in typical cases of Ewing's sarcoma of bone, which presented without a rosette arrangement and were almost negative for neural immuno-markers, but positive for MIC2. These ultrastructural neural features were observed less frequently in Ewing's sarcoma of bone than in PNET and NS. However, no significant correlation was demonstrated between the immunoreactivity for neural markers and the ultrastructural and histological neural features. These results support the hypothesis of a neural origin of Ewing's sarcoma and related neoplasms, and suggest that some overlapping entity could persist in PNET and Ewing's sarcoma and that this entity could be seen in histological and immunohistochemical studies of both tumors.