The association between renal elasticity evaluated by Real-time tissue elastography and renal fibrosis

Clinical and Experimental Nephrology - The progression of chronic kidney disease (CKD) depends on the extent of fibrosis in the kidneys; however, a renal biopsy is necessary to evaluate the...     

Complement inhibition for prevention of antibody-mediated rejection in immunologically high-risk heart allograft recipients

Allosensitization represents a major barrier to heart transplantation (HTx). We assessed the efficacy and safety of complement inhibition at transplant in highly sensitized heart transplant recipients. We performed a single-center, single-arm, open-label trial (NCT02013037). Patients with panel reactive antibodies (PRA) ≥70% and pre–formed donor-specific antibodies (DSA) were eligible. In addition to standard of care, patients received nine infusions of eculizumab during the first 2 months posttransplant. The primary composite endpoint was antibody-mediated rejection (AMR) ≥pAMR2 and/or left ventricular dysfunction during the first year. Secondary endpoints included hemodynamic compromise, allograft rejection, and patient survival. Twenty patients were included. Median cPRA and mean fluorescence intensity of immunodominant DSA were 95% (90%–97%) and 6250 (5000–10 000), respectively. Retrospective B cell and T cell flow crossmatches were positive in 14 and 11 patients, respectively. The primary endpoint occurred in four patients (20%). Survival at 1 year was 90% with no deaths resulting from AMR. In a prespecified analysis comparing treated patients to matched control patients, we observed a dramatic reduction in the risk of biopsy-proven AMR in patients treated with eculizumab (HR = 0.36, 95% CI = 0.14–0.95, p = .032). Our findings support the prophylactic use of complement inhibition for heart transplantation at high immunological risk. ClinincalTrials.gov, NCT02013037.     

Analysis of acute-phase toxicities of intensity-modulated proton therapy using a model-based approach in pharyngeal cancer patients

Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% for mucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.     

Determination of diquat in biological materials by electron spin resonance spectroscopy

Summary An electron spin resonance (ESR) method already in use for the quantitative analysis of paraquat was applied to the analysis of diquat in blood, serum, urine, tissue homogenates and several drinks without purification of the samples. The diquat radical produced with ascorbic acid at alkaline pH was much more stable than that produced with the commonly used sodium dithionite. Radical decay in solutions covered with n-hexane was less than 5% after 60 min over a wide range of ascorbic acid concentrations. In 0.2N NaOH solution 85% of the radicals was present even after 24h. The limit of detection was 0.3 g/ml and the required amount of sample was 0.1 ml. When both diquat and paraquat were present in a sample the diquat was first extracted with 1-butanol prior to the ESR measurement, because both species were converted to the radicals.     

Effect of a lysyl hydroxylase inhibitor,minoxidil, on ultrastructure and behavior of cultured rabbit subconjunctival fibroblasts

Background: Minoxidil is an inhibitor of lysyl hydroxylase, an enzyme involved in collagen production, and decreases collagen production in vitro. We investigated the in vitro effects of minoxidil on behavior such as proliferation and migration of rabbit subconjunctival fibroblasts (SCFs). The ultrastructural effect of the drug on SCFs was also examined. Methods: Proliferation of SCFs and closure of the defect produced in monolayer cultures in the presence or absence of minoxidil was studied. The ultrastructure of SCFs treated with minoxidil was also examined. Results: Minoxidil inhibited SCF proliferation and the closure of the defect produced in monolayer cell sheets. Ultrastructural observations revealed extensive areas of irregularly dilated endoplasmic reticulum in cells treated with minoxidil, indicating the accumulation of protein, probably underhydroxylated collagen precursors, in the cisternae of endoplasmic reticulum. Conclusions: The results indicated that minoxidil attenuated cellular activities of SCFs such as proliferation and migration in vitro. The exact mechanism of the inhibitory effects of minoxidil on these cellular activities is unknown. The findings suggest that the drug might help to prevent bleb scarring after glaucoma filtering surgery.     

Role of reactive oxygen in phospholipase A2 activation by ischemia/reperfusion of the rat kidney

Purpose. To investigate the role of phospholipase A₂ (PLA₂) in reperfusion injury of the kidney in an in vivo animal model, renal mitochondrial PLA₂ activity was measured under three different conditions. Methods. Male Wistar rats (n = 72) anesthetized with pentobarbital underwent renal ischemia surgically for 45 min and were reperfused for the indicated time (renal ischemia/reperfusion). Treatments included reperfusion for various predetermined periods (phase 1), exposure to hyperbaric oxygen (phase 2), and administration of reactive oxygen species (ROS) scavenger (phase 3). Thereafter, each kidney was harvested, and mitochondrial PLA₂ activity was measured by a radioisotope technique. Results. Ischemia/reperfusion resulted in time-related PLA₂ activation in the renal mitochondria up to 48 h of reperfusion after renal ischemia. Renal mitochondrial PLA₂ activity was further augmented by hyperbaric oxygen exposure prior to reperfusion, whereas administration of the ROS scavengers suppressed mitochondrial PLA₂ activity. Conclusion. These data suggest that ROS may play an important role in the in vivo activation of PLA₂ associated with renal ischemia/reperfusion. Received for publication on July 6, 1998; accepted on November 30, 1998     

Pulmonary small cell carcinoma associated with sarcoid reactions: Report of a case

A 45-year-old male was admitted to our hospital for investigation of a nodular shadow in segment 5 of the right lung on a chest computed tomogram. A right middle lobectomy with mediastinal lymph node dissection was performed under a diagnosis of lung cancer, and histologic examination confirmed small cell carcinoma. There were sarcoid reactions in the resected lymph nodes and the lung parenchyma, but no signs of systemic sarcoidosis were evident. Sarcoid reactions are rarely observed in the regional lymph nodes draining malignant tumors. Moreover, while they are most common in squamous cell carcinoma of the lung, they extremely rare in small cell carcinoma. To our knowledge, this is only the third report of this unusual entity in the English and Japanese literature.     

Proliferation of intrahepatic bile-duct epithelium in biliary atresia

Proliferating cell nuclear antigen (PCNA) and transforming growth factor (TGF) are considered as markers of cell proliferation. The expression of PCNA and TGF was evaluated immunohistochemically using anti-PCNA antibody and TGF in 31 patients with biliary atresia (BA) (15 jaundice-free and 16 with persistent jaundice) and 6 control infants. The labeling indices (LI) for PCNA- and TGF-positive bile-duct epithelium in BA were 14.1±14.0% and 51.4±33.7%, respectively, which was significantly higher than in the controls (P <0.01). In BA, the number of PCNA-immunoreactive cells was higher in the peripheral bile ductules than in the central bile ducts of the portal tract (P <0.01). LI was not related to patient age at the time of hepatic portoenterostomy in two groups divided at the age of 60 days. Patients in the persistent jaundice group had greater expression of PCNA and TGF (21.7±16.0% and 76.9±20.7%, respectively) compared to those in the jaundice-free group (6.0±2.7% and 24.3±20.9%, P <0.001). PCNA and TGF expression in the bile-duct epithelium of the portal tract was closely related to prognosis in BA patients, and thus could be useful as a prognostic marker.     

Neurovascular developmental interaction: a specific form of vascular maldevelopment in the malformed brain

The process of the development of the intracranial vessels was studied by means of immunohistochemical analysis of factor VIII in normal and exencephalic chick fetuses. The results revealed that the development of blood vessels in exencephalic brain was far advanced beyond the norm, with intense immunoreactivity to factor VIII on postincubation day 16 exceeding that on day 21 in normal controls. Compared with results regarding the direction of the overgrowth in the neuronal maturation process in the previous study using the chick exencephaly model, the findings of overmatured blood vessels were compatible with NSE- and somatostatin-positive elements that appeared especially in the overgrowth foci. The results of the present study suggested the pathogenic development of the area cerebrovasculosa in the neural placode as a phenomenon consequent upon hypervascularization in response to neuronal overgrowth, as seen in human cases of exencephaly or anencephaly. We emphasize the significance of this specific phenomenon in the development of the fetal central nervous system, namely neurovascular developmental interaction.     

Immunolocalization of prolyl 4-hydroxylase in fibroblasts cultured from Tenon's capsule of humans

Background: The excessive accumulation of extracellular matrix (ECM) with the repopulation of fibroblasts may lead to an unsuccessful outcome of glaucoma filtering surgery. We examined the immunolocalization of ECM components and prolyl 4-hydroxylase, an enzyme involved in collagen biosynthesis, in cultured Tenon's capsule fibroblasts (TCFs) of humans to evaluate the production of ECM in the cells. Methods: We used light microscopy to evaluate the immunolocalization of prolyl 4-hydroxylase and ECM components, collagen types I, III, and IV, cellular fibronectin, and laminin in TCFs. Ultrastructural localization of the enzyme was also evaluated by electron microscopy. Results: Immunoreactivity with monoclonal antibodies against the and subunits of the enzyme or with the polyclonal antibody against it was detected in the cytoplasm of the cells in a fine granular pattern, indicating its localization in the indoplasmic reticulum (ER). Immunoreactivity for the enzyme was detected in the cisternae of the ER on electron microscopy. Types I and III collagen reactivities were also observed in the cytoplasm in a fine granular pattern. T reactivity was present diffusely on the cell surface. The distribution of laminin reactivity in the cytoplasm resembled that of types I and III collagen. Cellular fibronectin reactivity was observed in the ECM in a reticular pattern. Conclusion: Prolyl 4-hydroxylase was located in the cisternae of the ER. TCFs produced a variety of ECM components in vitro. The results provide insight into the fibrotic process during scar formation at the site of a bleb following filtering surgery.