The ischemically injured kidney undergoes tubular cell necrosis and apoptosis, accompanied by an interstitial inflammatory cell infiltrate. In this study, we show that iNos-positive proinflammatory ...(M1) macrophages are recruited into the kidney in the first 48 hours after ischemia/reperfusion injury, whereas arginase 1- and mannose receptor-positive, noninflammatory (M2) macrophages predominate at later time points. Furthermore, depletion of macrophages before ischemia/reperfusion diminishes kidney injury, whereas depletion at 3 to 5 days after injury slows tubular cell proliferation and repair. Infusion of Ifnγ-stimulated, bone marrow-derived macrophages into macrophage-depleted mice at the time of kidney reperfusion restored injury to the level seen without macrophage depletion, suggesting that proinflammatory macrophages worsen kidney damage. In contrast, the appearance of macrophages with the M2 phenotype correlated with the proliferative phase of kidney repair. In vitro studies showed that IFNγ-stimulated, proinflammatory macrophages begin to express markers of M2 macrophages when cocultured with renal tubular cells. Moreover, IL-4-stimulated macrophages with an M2 phenotype, but not IFNγ-stimulated proinflammatory macrophages, promoted renal tubular cell proliferation. Finally, tracking fluorescently labeled, IFNγ-stimulated macrophages that were injected after injury showed that inflammatory macrophages can switch to an M2 phenotype in the kidney at the onset of kidney repair. Taken together, these studies show that macrophages undergo a switch from a proinflammatory to a trophic phenotype that supports the transition from tubule injury to tubule repair.
Emerging evidence suggests that the intravenous injection of bone marrow-derived stromal cells (BMSC) improves renal function after acute tubular injury, but the mechanism of this effect is ...controversial. In this article, we confirm that intravenous infusion of male BMSC reduced the severity of cisplatin-induced acute renal failure in adult female mice. This effect was also seen when BMSC (or adipocyte-derived stromal cells (AdSC)), were given by intraperitoneal injection. Infusion of BMSC enhanced tubular cell proliferation after injury and decreased tubular cell apoptosis. Using the Y chromosome as a marker of donor stromal cells, examination of multiple kidney sections at one or four days after cell infusion failed to reveal any examples of stromal cells within the tubules, and only rare examples of stromal cells within the renal interstitium. Furthermore, conditioned media from cultured stromal cells induced migration and proliferation of kidney-derived epithelial cells and significantly diminished cisplatin-induced proximal tubule cell death in vitro. Intraperitoneal administration of this conditioned medium to mice injected with cisplatin diminished tubular cell apoptosis, increased survival, and limited renal injury. Thus, marrow stromal cells protect the kidney from toxic injury by secreting factors that limit apoptosis and enhance proliferation of the endogenous tubular cells, suggesting that transplantation of the cells themselves is not necessary. Identification of the stromal cell-derived protective factors may provide new therapeutic options to explore in humans with acute kidney injury.
Objectives: Renal scintigraphy is widely used to evaluate residual function of a transplanted kidney from the donor. Dynamic computed tomography (CT) imaging can evaluate both kidney morphology and ...regional renal function. The aim of this study was to develop an imaging protocol and a calculation method using dynamic CT for assessing the effective renal plasma flow (ERPF) by model analysis, and to evaluate the validity of the obtained ERPF values.Methods: Preoperative dynamic CT examination with a low radiation dose exposure system was performed for 25 renal transplant donors, and ERPF was calculated from the obtained images (CT-ERPF). To calculate CT-ERPF, we set the region of interest (ROI) in the renal cortex using automatic ROI-setting software developed in our laboratory. We compared the processing time with automatic and manual ROI settings. To evaluate the validity of CT-ERPF, we examined the correlation of age with CT-ERPF and compared with reported ERPF values. We also compared the uptake rates of technetium-99m-dimercaptosuccinic acid and CT-ERPF in terms of the right-to-left ratio.Results: There was good agreement of CT-ERPF assessed using automatic and manual ROIs. CT-ERPF was negatively correlated with age and showed values below the reference ERPF range in 21 cases. The right-to-left ratio of CT-ERPF showed a significant correlation with that of technetium-99m-dimercaptosuccinic acid.Conclusions: Using our method, CT-ERPF was a useful indicator for preoperative evaluation of donor’s renal function.
We report a rare case of a 58-year-old male patient with a gastrocolic fistula (GCF) caused by a benign peptic ulcer who had been referred because of epigastric pain and weight loss. Emergent ...gastrointestinal endoscopy revealed a gastric ulcer at the posterior wall of the stomach. Conservative treatment with a proton pump inhibitor (PPI) was immediately initiated ; however, a second endoscopic examination showed a portion of exposed colonic wall located in the center of an active gastric ulcer on day 4 after the administration of PPI. Endoscopic findings of the penetration site implied that the colonic wall invaginated into the stomach might have functioned as a check valve that prevented the flow of gastric contents into the colon. Supportive parenteral nutrition was preoperatively provided. Resection due to adhesion between the transverse colon and posterior wall of the stomach was performed without gastrectomy and partial colectomy under laparoscopy.
Abstract A method for estimating age based on occlusal wear of the teeth and palatine suture morphology has been widely used. This allows us to estimating age based on macroscopic findings. However, ...even if the living status and jaw growth are taken into consideration, the accuracy of this method is not sufficient. In this case, a marked difference was observed in estimated age between two methods based on the degree of occlusal wear and palatine sutures. To avoid this discrepancy, a number of approaches, including radiography, a comparison of the morphology of teeth using a study model, and data preparation employing dental charts are necessary. Some factors, such as distortion, growth and developmental disorders of the jaw-bone, diet, occlusal relationship, and habits often influence age estimation especially when the dental attrition degree of the tooth is used. When there is a discrepancy in the estimated age, caution should be exercised. There is an individual difference in the status of the synechia. We observed a case that misled us into presuming younger age. It is rare that estimated age is higher than a real age. Age estimation is performed from both sides of dental attrition and palatal suture in this time. This case demonstrated a large discrepancy in age estimation between dental attrition and sutures of the palatine bone.
A 73 year-old man who was diagnosed as hepatocellular carcinoma (HCC) underwent extended right hepatic lobectomy. Four years after the hepatectomy, multiple nodules in bilateral lungs were detected. ...A diagnostic percutaneous biopsy revealed pulmonary metastases from HCC. The patient was treated with oral uracil/tegafur (UFT) first. However, his condition deteriorated because of refractory massive hemoptysis. Therefore, bronchial arterial infusion (BAI) of epirubicin (EPI) was performed twice for a metastatic mass at right pulmonary hilum. In contrast to decreasing trend of tumor burden, improvement of hemoptysis was not observed. The replacement of EPI with fine-powder cisplatin (IAC) finally contributed to complete disappearance of a metastatic mass and his symptom. Additional treatment for another nodule at right azygos lobe was successfully performed as well. The efficacy of BAI for the other metastatic nodules without hypervascular stain by angiography was not certified. BAI could be a useful therapeutic option for symptomatic pulmonary metastases, if the primary lesion is well-controlled.
Two highly related receptor tyrosine kinases, TIE and TEK, comprise a family of endothelial cell-specific kinase. We established monoclonal antibodies against them and performed detailed analyses on ...their expression and function in murine hematopoietic stem cells (HSCs). TIE and TEK were expressed on 23.7% and 33.3% of lineage marker-negative, c-Kit+ and Sca-1+ (Lin− c-Kit+ Sca-1+) HSCs that contain the majority of day-12 colony-forming units-spleen (CFU-S) and long-term reconstituting cells, but not committed progenitor cells. Lin− c-Kit+ Sca-1+ cells were further divided by the expression of TIE and TEK. TIE+ and TEK+ HSCs as well as each negative counterpart contained high proliferative potential colony-forming cells and differentiated into lymphoid and myeloid progenies both in vitro and in vivo. However, day-12 CFU-S were enriched in TIE+ and TEK+ HSCs. Our findings define TIE and TEK as novel stem cell marker antigens that segregate day-12 CFU-S, and provide evidence of novel signaling pathways that are involved in the functional regulation of HSCs at a specific stage of differentiation, particularly of day-12 CFU-S.
Abstract We examined two hit-and-run accidents. In the first case, the victim was a 42-year-old man. Severe lacerations were observed in the front face. Alcohol levels were 2.9 mg/ml in the femoral ...venous blood, and 4.1 mg/ml in the urine. It seemed that the victim was drunk and probably lying on the road and was hit and run over by a vehicle at night. The cause of death was profuse severe bleeding from multiple rib fractures and a crushed liver. Abraded wounds were observed on the back of the head. A tire mark was left on the victim's jacket. Rupture of the right eyeball, crush fracture of the maxilla and contused-lacerated wounds on the lips were observed. In the second case, the victim was a 16-year-old boy. While riding a motorbike, he collided with a truck and fell off. He was run over by the truck dragged 6.6 km, and was found dead under the truck. In the right temporal region, the skull had been rubbed flat and the right cerebral hemisphere was exposed and flattened. Severe abrasions were observed on both shoulders, buttocks and on both backs of the calves. Some abrasions were accompanied blackened necrotic tissue supposed to be caused by heat friction, and were partially worn away. The cause of death was cranial bone crush ; however, hit-and-run accidents vary from case to case. These two cases are entirely different, and the two victims in this report showed severe and characteristic injuries. Our first victim had crush fractures and contused-lacerated wounds, with a tire mark on his jacket. Our second victim had deep abrasions in the right temporal region by dragging. Some of these accumulated injuries to the victim's skin by dragging might have been caused by frictional heat.
TEK, or TIE-2, is a receptor tyrosine kinase (RTK) that is known as a functioning molecule of vascular endothelial cells. TEK comprises a subfamily of RTK with TIE, and these two receptors play ...critical roles in vascular maturation, maintenance of integrity and remodeling. We generated mAb against the extracellular domain of human TEK protein to elucidate its expression pattern in human hematopoietic cells. Flow cytometric analysis of bone marrow cells revealed that TEK was expressed in 27% of CD34+ cells, 20% of c-KIT+ cells and 26% of CD34+CD38- cells, indicating that TEK is expressed in a subset of primitive hematopoietic stem cells (HSC). TEK was also expressed in 20% of CD19+ B lymphocytes but not in other lineage-committed cells. Progenitor assays in methylcellulose culture showed that CD34+TEK+ cells formed significantly less BFU-E and CFU-Mix than CD34+TEK- cells, but there was no difference in the number of CFU-GM between these two populations. Two recently identified TEK ligands, termed Angiopoietin-1 and -2, bound to TEK with similar affinities, and Angiopoietin-1 effectively induced TEK phosphorylation in hematopoietic cells. Angiopoietin-2 also induced a low level of TEK phosphorylation and weakened the phosphorylation induced by Angiopoietin-1, suggestive of an elaborate regulator of the TEK-TEK ligand signaling pathway. Although neither ligands affected the proliferation of TEK-transfected hematopoietic cells or the colony formation of CD34+TEK+ bone marrow cells, both promoted the adhesion of TEK-transfected hematopoietic cells to a collagen matrix or a layer of bone marrow stromal cells. These findings indicate that the TEK-TEK ligand signaling pathway is regulated in a refined manner and is involved in hematopoietic cell-microenvironment interaction.
A 38-year-old Japanese man presenting with liver dysfunction was admitted to our hospital. He had never received a blood transfusion or iron agent treatment. Blood examinations showed elevated ...aminotransferases, serum iron, and serum ferritin. Furthermore, a Berlin blue staining of the liver biopsy specimen was conducted for confirmation, which showed iron deposition in the hepatocytes. Subsequently, we performed genetic analysis for hereditary hemochromatosis based on results, including HFE, HJV, HAMP, TfR2, and SLC40A1 analysis. Genetic analysis revealed a heterozygous mutation (c.1206c>M) in TfR2. Therefore, we diagnosed him with type 3 hereditary hemochromatosis. Elevated serum ferritin and liver dysfunction were improved by changing lifestyle, in addition to periodic phlebotomy. Hereditary hemochromatosis due to aTfR2 mutation takes the form of an autosomal recessive inheritance. However, although the patient had a heterozygous TfR2 mutation, an unbalanced lifestyle with excess dietary iron intake can also contribute to the onset of hereditary hemochromatosis. Thus, an improved lifestyle and phlebotomy successfully reduce iron overload.
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