BK polyomavirus interstitial nephritis in a renal allograft recipient

Human polyomavirus (PV) interstitial nephritis has recently been recognized as a cause of severe renal allograft dysfunction. It occurs in immunosuppressed patients after reactivation of the latent virus PV type BK (BK virus) in the renal epithelium. BK disease is defined as a morphologically manifest renal infection with cytopathic signs accompanied by varying degrees of interstitial inflammatory cell infiltrates and functional impairment. It is also identified by the presence of cells containing viral inclusion bodies (decoy cells) in the urine. The authors report a case of BK PV interstitial nephritis in a 36-year-old renal allograft recipient. Under light microscopy the chief diagnostic indicator was detection of intranuclear viral inclusions, which were found exclusively in tubular epithelial cells. Cells with viral changes were often enlarged with nuclear atypia and chromatin basophilia. Widespread interstitial plasma cell infiltrates associated with tubulitis were present. Intranuclear paracrystalline arrays of virus particles 35-38 nm in diameter were present as characteristic ultrastructural indicators. Urine samples revealed decoy cells with ground-glass-type intranuclear inclusions positive for BK virus by electron microcopy.     

Background nonselective cationic current and the resting membrane potential in rabbit aorta endothelial cells

The ion channel conductances that regulate the membrane potential was investigated by using a perforated patch-clamp technique in rabbit aorta endothelial cells (RAECs). The whole-cell current/voltage (I-V) relation showed a slight outward rectification under physiological ionic conditions. The resting membrane potential was -23.3 +/- 1.1 mV (mean +/- SEM, n = 19). The slope conductances at the potentials of -80 and 50 mV were 31.0 +/- 4.0 and 62.8 +/- 7.1 pS pF(-1), respectively (n = 15). Changes in the extracellular and intracellular Cl(-) concentrations did not affect the reversal potential on I-V curves. The background nonselective cationic (NSC) current was isolated after the K(+) current was suppressed. The relative permeabilities calculated from the changes in reversal potentials using the constant-field theory were P(K):P(Cs):P(Na):P(Li) = 1:0.87:0.40:0.27 and P(Cs):P(Ca) = 1:0.21. Increases in the external Ca(2+) decreased the background NSC current in a dose-dependent manner. The concentration for half block by Ca(2+) was 1.1 +/- 0.3 mM (n = 7). Through the continuous recording of the membrane potential in a current-clamp mode, it was found that the background NSC conductance is the major determinant of resting membrane potential. Taken together, it could be concluded that the background NSC channels function as the major determinant for the resting membrane potential and can be responsible for the background Ca(2+) entry pathway in freshly isolated RAECs.     

Sustained release of ascorbate-2-phosphate and dexamethasone from porous PLGA scaffolds for bone tissue engineering using mesenchymal stem cells

The purpose of this research was to develop porous poly(D,L-lactide-co-glycolide) (PLGA) scaffolds from which ascorbate-2-phosphate (AsAP) and dexamethasone (Dex) are continuously released for a month for osteogenesis of mesenchymal stem cells for bone tissue engineering. Porous PLGA matrices containing AsAP and Dex were prepared by solvent casting/particulate leaching method. In vitro release and water uptake studies were performed in Dulbecco's phosphate buffered saline at 37 degrees C and 15 rpm. Drug loading and release rates were determined by high performance liquid chromatography. Release studies of Dex and AsAP showed that, after an initial burst release lasting 4 and 9 days, respectively, release rates followed zero order kinetics with high correlation coefficients at least until 35 days. Incorporation of AsAP into the scaffolds increased the release rates of Dex and AsAP, and the scaffold water uptake. When mesenchymal stem cells (MSCs) were cultured in the AsAP and Dex containing scaffolds in vitro, the amount of mineralization was significantly higher than in control scaffolds. In conclusion, AsAP and Dex were incorporated into porous PLGA scaffolds and continuously released over a month and osteogenesis of MSCs was increased by culture in these scaffolds.     

Cell death in retinoblastoma: electron microscopic, immunohistochemical, and DNA fragmentation studies

Apparent cell loss by apoptosis occurs in carcinomatous tissue. To investigate cell death in retinoblastoma (Rb), ultrastructural examination, ApopTag staining, electrophoresis to detect apoptotic DNA fragmentation, and flow cytometric studies were performed. Immunostaining for the oncogenic products bcl-2 and p53 was also carried out. Relationships between the proliferation fraction (PF), apoptotic index (AI), and the distribution of bcl-2 and p53 were investigated according to the degree of histologic differentiation of Rb. Ultrastructurally, two patterns of cell death were seen. Necrotic cells exhibited vacuolation of cytoplasmic organelles with a marked lytic change in the karyoplasm and cytoplasm. In contrast, apoptotic cells were characterized by crescentic margination of chromatin, condensation of karyoplasm and cytoplasm, and fragmentation of the nucleus. Differentiated Rb had a low AI value (< 1%), whereas undifferentiated Rb had a high AI value (> 8%). The PF of undifferentiated RB (31%) was significantly higher than that of differentiated RB (14%). Analysis of DNA fragmentation using 3'-end labeling with terminal transferase indicated that undifferentiated Rb has increased DNA cleavage. The distribution of apoptotic bodies within Rb was inversely correlated with the expression of bcl-2. A majority of tumor cells of differentiated Rb were negative for p53, whereas 20-40% of tumor cells of undifferentiated Rb showed a positive reaction for p53. These findings suggest that the degree of susceptibility to apoptosis is closely related to PF, is inversely related to the degree of differentiation of Rb, and is protected by oncogene bcl-2.     

An explanation of renal hemodynamics in acute renal failure based on sequential CT in patients with Korean hemorrhagic fever

The pattern of renal enhancement and washout of contrast medium was observed on sequential follow-up CT in 12 patients with Korean hemorrhagic fever, in which acute renal failure is one of the most important clinical features. Renal contrast enhancement and contrast medium washout were delayed longer in patients with severe oliguric renal failure. The delayed washout peaked at 4-5 days and did not return to normal until 8-9 days in the patients with severe oliguria; in the patients without severe oliguria the times were 1-2 days and 3-4 days, respectively. A characteristic "cart-wheel" pattern was observed during the washout stage in patients without severe oliguria. This "cart-wheel" pattern of washout is thought to result from relief of vasoconstriction and repair of tubular function. Multifocal "wedge-shaped" nonenhanced areas of the kidney, seen on the 2 week follow-up postcontrast CT, are thought to be ischemic zones due to persistent vasoconstriction. On the 6 week follow-up postcontrast CT in one patient, scarring of the kidney was detected in the same area that did not enhance on the 2 week CT. This scarring is thought to be a result of permanent vasoconstriction.     

Waning Antibody Responses in Asymptomatic and Symptomatic SARS-CoV-2 Infection

We investigated the kinetics of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies in 7 asymptomatic persons and 11 patients with pneumonia. The geometric mean titer of neutralizing antibodies declined from 219.4 at 2 months to 143.7 at 5 months after infection, indicating a waning antibody response.     

Clinical Significance of De Novo Malignancy After Liver Transplant: A Single-Center Study

BackgroundSeveral studies have reported that solid organ transplant recipients have a high risk for malignant tumors because the suppressed immune system fails in preventing malignant transformations. De novo malignancy after transplantation is the most common cause of death in the late period after liver transplant (LT). This study investigated the clinical significance of de novo malignancy after LT, and it is the largest study based in Korea to report long-term follow-up results associated with de novo malignancy after LT.MethodsData of 1793 adults who underwent LT in Seoul National University Hospital were retrospectively collected, and medical charts and data from the Ministry of Public Administration and Security were reviewed to examine the causes of death and de novo malignancy status. The Fisher exact test and Kaplan-Meier survival analysis were used to analyze the data.ResultsOf the 1793 recipients, 27 died of de novo malignancies. Of 875 hepatocellular carcinoma (HCC) patients, 12 died, and of 918 non-HCC patients, 15 died. De novo malignancy was the main cause of death at 5 years after LT but was not in the initial 5 years. In Korea the most common cancers that developed after LT were gastric cancer (21.4%) and lymphoma (14.3%). De novo HCC in non-HCC cases was found in 2 patients.ConclusionDe novo malignancy is a key factor affecting long-term survival after LT. Therefore, regular screening and education are important for improving long-term survival and quality of life in these patients after LT.     

The influence of preoperative carbohydrate loading on postoperative outcomes in bariatric surgery patients: a randomized,controlled trial

BackgroundPreoperative carbohydrate loading is a component of Enhanced Recovery After Surgery (ERAS) protocols, but there is limited literature in bariatric surgery patients.ObjectivesThe objective of this study was to characterize the impact of preoperative carbohydrate loading on postoperative bariatric surgery outcomes.SettingUniversity Hospital.MethodsPatients undergoing a primary minimally invasive Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) between 2018 and 2020 were randomized to standard management or intervention. Standard management patients were nothing by mouth (NPO) after midnight prior to surgery. Intervention patients consumed 2 carbohydrate drinks: 1 the night before and another 3 hours prior to surgery. Primary outcomes analyzed included postoperative nausea and vomiting (PONV), length of stay, and overall complications.ResultsIn total, 134 patients were analyzed: 64 intervention (47.8%) and 70 (52.2%) standard. In the end, 7% and 15% of patients were lost to follow-up at 6-weeks and 3-months, respectively. There was no statistically significant difference in length of stay (2.0 ± 1.2 vs 2.1 ± .9 d; P = .65) or postoperative outcomes between the 2 groups. There were no episodes of aspiration among the intervention group. Among RYGB patients, intervention patients had a shorter duration of nausea compared with standard patients. There was no significant difference in glycemic control among patients with and without diabetes.ConclusionsPreoperative carbohydrate drinks can be administered to bariatric surgery patients without significant risks. Carbohydrate loading preoperatively can decrease the duration of PONV in RYGB patients. Carbohydrate drinks can be safely included in bariatric ERAS protocols for patients with and without diabetes, although the benefits remain unknown.     

GAG-augmented polysaccharide hydrogel: a novel biocompatible and biodegradable material to support chondrogenesis

The quality of articular cartilage engineered using a cell-polymer construct depends, in part, on the chemical composition of the biomaterial and whether that biomaterial can support the chondrocytic phenotype. Acknowledging the supportive influence of tissue-specific matrix molecules on the chondrocytic phenotype, we have combined chondroitin sulfate-A (CSA) and chitosan, a glycosaminoglycan (GAG) analog, to develop a novel biomaterial to support chondrogenesis. Chitosan is a polycationic repeating monosaccharide of beta-1,4-linked glucosamine monomers with randomly located N-acetyl glucosamine units. Chitosan may be combined with the polyanionic CSA such that ionic crosslinking results in hydrogel formation. Bovine primary articular chondrocytes, when seeded onto a thin layer of CSA-chitosan, form discrete, focal adhesions to the material and maintain many characteristics of the differentiated chondrocytic phenotype, including round morphology, limited mitosis, collagen type II, and proteoglycan production. Our findings suggest CSA-chitosan may be well suited as a carrier material for the transplant of autologous chondrocytes or as a scaffold for the tissue engineering of cartilage-like tissue.