CDw60 glycolipid antigens of human leukocytes: structural characterization and cellular distribution

Monoclonal CDw60 antibodies recognize glycolipid antigens with restricted surface expression on human leukocytes. They allow us to define new functional subpopulations of T lymphocytes and are able to induce costimulatory signals. In this report, we describe the molecular composition of CDw60 glycolipid antigens derived from different human leukocyte subpopulations. The glycolipids were isolated and their structures were identified by immunochemical methods. All molecules containing the CDw60 determinant were found in the disialoganglioside fraction. They were O-acetylated derivatives of the gangliosides II3 (Neu5Ac)2-LacCer (GD3), IV3 (Neu5Ac)2-nLc4Cer (DSPG), and VI3 (Neu5Ac)2- nLc6Cer (DSnHC), respectively. The most common CDw60 glycolipid antigen in human leukocytes was 9-O-acetyl GD3. In a comparison of various cell types, the highest concentration of 9-O-acetyl GD3 on a per cell basis was determined in granulocytes and in blood T lymphocytes, whereas B lymphocytes, thymus cells, and monocytes contained considerably smaller amounts of this molecule. Polar CDw60 antigens such as 9-O-acetyl DSPG and 9-O-acetyl DSnHC were only detected in granulocytes.     

Metabolic fate of fatty acids in type II cells isolated from adult rat lung

The present study is concerned with the metabolic fate of palmitate, oleate and linoleate in isolated rat lung type II cells. The cells readily oxidize the exogenously supplied fatty acids to CO₂ and incorporate them into lipids. The distribution between the pathways of oxidation and esterification is similar for saturated and unsaturated fatty acids. The majority of the fatty acids taken up by the cells is utilized for lipid synthesis. The fatty acids are incorporated preferentially into phospholipids, particularly into phosphatidylcholine. Addition of unsaturated fatty acids decreases the utilization of palmitate by type II cells. The distribution of palmitate between oxidation and esterification is not altered in the presence of unsaturated fatty acids. Addition of carnitine stimulates the fatty acid oxidation and decreases the esterification of fatty acids.     

Chronic hepatitis C infection in patients with end stage renal disease: characterization of liver histology and viral load in patients awaiting renal transplantation

OBJECTIVES: Hepatitis C virus (HCV) is common in patients with end stage renal disease (ESRD) awaiting renal transplantation (RT). However, few data are available on the liver histology and viral titer in these patients relative to patients with HCV and normal renal function. The aims of this study were to assess liver histology, quantitative HCV-RNA titer, and alanine aminotransferase (ALT) levels in patients with ESRD awaiting RT, and to identify clinical predictors of histological progression to advanced bridging fibrosis and/or cirrhosis. METHODS: A total of 50 consecutive patients (mean age 42 yr, 62% male) with ESRD and HCV, who were awaiting RT, underwent liver biopsy. Two HCV populations, one with persistently normal ALT and another with elevated ALT, both with normal renal function, served as controls. HCV-RNA titer was assessed by quantitative PCR. RESULTS: Of the patients with ESRD, 94% had normal ALT. Log HCV RNA titer was significantly higher in patients with ESRD (5.8+/-0.3) than in either normal ALT (5.4+/-0.1) or elevated ALT (5.3+/-0.1) controls (p < 0.05). Knodell Histological Activity Index (HAI) in patients with ESRD was similar to that observed in control patients with normal ALT (4.8+/-0.4 vs 4.9+/-0.4) but significantly less (p < 0.05) than that observed in control patients with elevated ALT (8.4+/-0.5). The percentage of patients with bridging fibrosis or cirrhosis was similar in patients with ESRD and controls with persistently normal ALT (22% vs 13%) but significantly less (p < 0.001) than that observed in control patients with elevated ALT (48%). No significant differences in ALT, HCV-RNA titer, duration on hemodialysis, or time from first possible exposure was observed between ESRD patients with advance fibrosis (n = 11) and those with mild disease (n = 39). CONCLUSIONS: Our data suggest that liver biopsy is necessary to exclude significant liver pathology in patients with HCV and ESRD, and to help define those patients in whom interferon treatment might be helpful.     

Update in Outpatient General Internal Medicine: Practice-Changing Evidence Published in 2020

In a time of rapidly shifting evidence-based medicine, it is challenging to stay informed of research that modifies clinical practice. To enhance knowledge of practice-changing literature, a group of 7 internists reviewed titles and abstracts in 7 internal medicine journals with the highest impact factors and relevance to outpatient general internal medicine. Coronavirus disease-19 research was purposely excluded to highlight practice changes beyond the pandemic. New England Journal of Medicine (NEJM), The Lancet, Annals of Internal Medicine, Journal of the American Medical Association (JAMA), JAMA Internal Medicine, British Medical Journal (BMJ), and Public Library of Science (PLoS) Medicine were reviewed. The following collections of article synopses and databases were also reviewed: American College of Physicians Journal Club, NEJM Journal Watch, BMJ Evidence-Based Medicine, McMaster/DynaMed Evidence Alerts, and Cochrane Reviews. A modified Delphi method was used to gain consensus based on relevance to outpatient internal medicine, impact on practice, and strength of evidence. Clusters of articles pertaining to the same topic were considered together. In total, 7 practice-changing articles were included.     

The presence of an intrahepatic cytotoxic T lymphocyte response is associated with low viral load in patients with chronic hepatitis C virus infection

BACKGROUND/AIMS: The role of cytotoxic T lymphocytes (CTL) in limiting viral replication and producing hepatocellular injury in patients with chronic hepatitis C virus (HCV) infection is controversial. METHODS: Intrahepatic and peripheral blood HCV-specific CTL activity against the entire HCV polyprotein was assessed in 26 patients. CTL responses were assessed after effector lymphocytes were re-stimulated for 6 days in vitro using HCV-vaccinia virus-infected autologous cells expressing HCV antigens. Serum and hepatic viral loads were measured and immunohistochemistry for CD3 and CD8 was performed to localise and enumerate effector cells in liver. RESULTS: A positive CTL response was detected in 39/52 (75%) of assays conducted with intrahepatic mononuclear cells and 21/52 (40%) of peripheral blood assays (P<0.001). The presence of an intrahepatic CTL response was associated with low hepatic viral load (P=0.004). Hepatic lobular infiltration by CD8(+)T cells correlated weakly with serum alanine aminotransferase levels (r=0.42, P=0.04) and no relationship was demonstrated between CTL activity and histological evidence of liver damage. CONCLUSIONS: HCV-specific CTL activity is found more commonly in liver than in blood. An inverse relationship between CTL responses and viral load supports the hypothesis that HCV-specific CTL limit viral replication in patients with chronic HCV infection.     

Phospholipase A2 levels in acute chest syndrome of sickle cell disease

Acute chest syndrome (ACS) is associated with significant morbidity and is the leading cause of death in patients with sickle cell disease (SCD). Recent reports suggest that bone marrow fat embolism can be detected in many cases of severe ACS. Secretory phospholipase A2 (sPLA2) is an important inflammatory mediator and liberates free fatty acids, which are felt to be responsible for the acute lung injury of the fat embolism syndrome. We measured SPLA2 levels in 35 SCD patients during 20 admissions for ACS, 10 admissions for vaso-occlusive crisis, and during 12 clinic visits when patients were at the steady state. Eleven non-SCD patients with pneumonia were also evaluated. To determine if there was a relationship between sPLA2 and the severity of ACS we correlated SPLA2 levels with the clinical course of the patient. In comparison with normal controls (mean = 3.1 +/- 1.1 ng/mL), the non- SCD patients with pneumonia (mean = 68.6 +/- 82.9 ng/mL) and all three SCD patient groups had an elevation of SPLA2 (steady state mean = 10.0 +/- 8.4 ng/mL; vaso-occlusive crisis mean = 23.7 +/- 40.5 ng/mL; ACS mean = 336 +/- 209 ng/mL). In patients with ACS sPLA2 levels were 100- fold greater than normal control values, 35 times greater than values in SCD patients at baseline, and five times greater than non-SCD patients with pneumonia. The degree of SPLA2 elevation in ACS correlated with three different measures of clinical severity and, in patients followed sequentially, the rise in SPLA2 coincided with the onset of ACS. The dramatic elevation of SPLA2 in patients with ACS but not in patients with vaso-occlusive crisis or non-SCD patients with pneumonia and the correlation between levels of SPLA2 and clinical severity suggest a role for SPLA2 in the diagnosis and, perhaps, in the pathophysiology of patients with ACS.     

Thrombospondin mediates the cytoadherence of Plasmodium falciparum- infected red cells to vascular endothelium in shear flow conditions

Cerebral malaria is thought to involve specific attachment of Plasmodium falciparum-infected knobby red cells to venular endothelium. The nature of surface ligands on host endothelial cells that may mediate cytoadherence is poorly understood. We have investigated the effects of soluble thrombospondin, rabbit antiserum raised against thrombospondin, and human immune serum on cytoadherence of parasitized erythrocytes in ex vivo mesocecum vasculature. Preincubation of infected red cells with soluble thrombospondin or human immune serum inhibits binding of infected red cells to rat venular endothelium. Infusion of the microcirculatory preparation with rabbit antithrombospondin antibodies before perfusion of parasitized erythrocytes also resulted in decreased cytoadherence. In addition, incubation of infected cells with human immune sera obtained from malaria patients significantly inhibited the observed cytoadherence. Our results indicate that thrombospondin mediates binding of infected red cells to venular endothelium and may thus be involved in the pathogenesis of cerebral malaria.     

Acute Q fever and brachial neuritis: case report and literature review

Peripheral nervous system complications of Q fever are uncommon. A case of electrophysiologically documented brachial neuritis occurring during acute Coxiella burnetii infection is reported. The relevant literature is reviewed. Received: June 6, 2001 · Revision accepted: July 8, 2002 J. J. Post (corresponding author)     

Risk of Extraesophageal Malignancy in Patients with Adenocarcinoma Arising in Barrett's Esophagus

Objectives : It has been suggested that the presence of Barrett's mucosa is a marker for potential malignancy in other organs. Our objective was to study subjects with adenocarcinoma of the esophagus arising in Barrett's epithelium. Methods : We reviewed the medical records of patients with esophageal adenocarcinoma, with esophageal squamous cell carcinoma, and with no esophageal pathology and recorded the occurrence of extrae-sophageal malignancies and the heavy use of tobacco and alcohol. Results : The prevalence of extraesophageal malignancies was not higher in patients with esophageal adenocarcinoma (15%) than in patients in either control group (14% each). Patients with either type of cancer of the esophagus had higher rates of tobacco and alcohol use than normal controls (tobacco: p = 0.02 and/7 < 0.01 for adenocarcinoma and squamous cell carcinoma, respectively, vs. normal controls; alcohol:/; < 0.01 for each esophageal malignancy vs . normal controls). The rate of tobacco and alcohol use was higher in patients with esophageal squamous cell carcinoma than in those with adenocarcinoma, but only the difference in alcohol consumption was statistically significant ( p < 0.01). Conclusion : Patients with adenocarcinoma of the esophagus are not at higher risk for development of extraesophageal malignancy. This observation applies to both those with and without underlying Barrett's epithelium. Alcohol and tobacco use appear to be related to the malignant transformation of esophageal epithelium.