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.     

Short-term therapy with anti-ICAM-1 monoclonal antibody induced long-term liver allograft survival in nonhuman primates

Tolerance induction remains challenging following liver transplantation and the long-term use of immunosuppressants, especially calcineurin inhibitors, leads to serious complications. We aimed to test an alternative immunosuppressant, a chimeric anti-ICAM-1 monoclonal antibody, MD-3, for improving the outcomes of liver transplantation. We used a rhesus macaque liver transplantation model and monkeys were divided into three groups: no immunosuppression (n = 2), conventional immunosuppression (n = 4), and MD-3 (n = 5). Without immunosuppression, liver allografts failed within a week by acute rejection. Sixteen-week-long conventional immunosuppression that consisted of prednisolone, tacrolimus, and an mTOR inhibitor prolonged liver allograft survival; however, recipients died of acute T cell–mediated rejection (day 52), chronic rejection (days 62 and 66), or adverse effects of mTOR inhibitor (day 32). In contrast, 12-week-long MD-3 therapy with transient conventional immunosuppression in the MD-3 group significantly prolonged the survival of liver allograft recipients (5, 96, 216, 412, 730 days; p = .0483). MD-3 effectively suppressed intragraft inflammatory cell infiltration, anti-donor T cell responses, and donor-specific antibody with intact anti-cytomegalovirus antibody responses. However, this regimen ended in chronic rejection. In conclusion, short-term therapy with MD-3 markedly improved liver allograft survival to 2 years without maintenance of immunosuppressant. MD-3 is therefore a promising immune-modulating agent for liver transplantation.     

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.     

Nature of the Kanagawa phenomenon of Vibrio parahaemolyticus.

In a study of the Kanagawa phenomenon of Vibrio parahaemolyticus, both Kanagawa-positive and -negative strains were found to produce hemolytic factors that could not be differentiated on Wagatsuma blood agar. The presence of fermentable carbohydrates in media containing high concentrations of NaCl promoted the growth of V. parahaemolyticus and resulted in a marked decrease in medium pH and increased hemolysin production. The Kanagawa hemolysis of test strains differed according to the carbohydrates added. Clearly defined Kanagawa hemolysis was observed in blood agars of high salt content, but the distinction was lost in media containing 3% NaCl. From the results of this study, the Kanagawa hemolysis was interpreted as an expression of quantitative difference in hemolysin production, a conclusion that is clearly demonstrated on special blood agar of high salt content.     

A case of leukemia-associated arthritis--identification of leukemic cells in synovial fluid by light microscopy

One case of arthritis complicating leukemia is described in which leukemic cells were identified in synovial fluid by light microscopy. Although arthritis is a well-known manifestation of leukemia with an incidence of 13.5%, the pathogenesis often is unclear, and the direct demonstration of leukemic cells in synovial fluid has been very uncommon. A 16 year-old male patient was admitted due to left elbow joint pain and swelling. Synovial fluid examination revealed blast cells and this finding has directed to a final diagnosis of acute lymphoblastic leukemia.