Epstein-Barr virus infections and DNA hybridization studies in posttransplantation lymphoma and lymphoproliferative lesions: The role of primary infection

Fourteen patients who developed B cell lymphomas or lymphoproliferative lesions after kidney, liver, heart, or heart-lung transplantation in Pittsburgh during 1981-1983 had active infection with Epstein-Barr virus (EBV)of the primary (six patients), reactivated (seven patients), or chronic (one patient) type. In transplant patients without tumors, the incidence of EBV infection was 30% (39 of 128). Only three of these patients had primary infections. Thus the frequency of active infection was significantly higher in patients with tumors, and patients with primary infections were at greater risk of developing tumors. Five of 13 tumors tested contained EBV nuclear antigen (EBNA) and nine of 11 contained EBV genomes detected by DNA-DNA hybridization with BamHI K, BamHI W, or EcoRI B cloned probes. All EBNA-positive tumors, except one, were also positive by hybridization. Only one tumor was negative for both EBNA and EBV DNA. These data suggest that EBV plays an etiologic role in the development of these lesions. © 1985 by The University of Chicago

Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy

Post-transplant lymphomas or other lymphoproliferative lesions, which were usually associated with Epstein-Barr virus infections, developed in 8, 4, 3, and 2 recipients, respectively, of cadaveric kidney, liver, heart, and heart-lung homografts. Reduction or discontinuance of immunosuppression caused regression of the lesions, often without subsequent rejection of the grafts. Chemotherapy and irradiation were not valuable. The findings may influence policies about treating other kinds of post-transplantation neoplasms

Risk factors for the detection of Salmonella in ileocolic lymph nodes in US slaughtered pigs.

Salmonella harborage at slaughter can be viewed as a nsk for human health through contammation of the pork food cham. Better understanding of herd level factors associated with this harborage would be useful to prioritize further study of epidemiology and control of Salmonella in pork production. Ileocolic lymph node samples collected at slaughter from 115 Midwest US sw1ne herds were assayed for Salmonella entenca. A subset of these herds was collected sequentially one or two additional times. Herd characteristics and management factors were assessed by a written survey. Risk factors were screened at the univariate level (p \u3c 0.3), then offered for Inclusion by stepw1se analysis including herd I sample as a random statistical effect. Pigs at increased risk of Salmonella harborage at slaughter included those placed in finisher barns at heaver weights (OR 1.2 per 10 kg Increased we1ght), those from larger herds (OR 2 0 comparing upper quintile to lower quintile of herd size), those from herds that allowed VISitors w1th recent (\u3c8 h) contact with other herds (OR 2.2), or those fed pelleted feeds (OR 2.1 ). Further invest1gat1on of these risk factors and potential biological mechanisms will requ1re further study

Cannabis sativa extracts protect LDL from Cu2+-mediated oxidation

Background: Multiple therapeutic properties have been attributed to Cannabis sativa. However, further research is required to unveil the medicinal potential of Cannabis and the relationship between biological activity and chemical profile. Objectives: The primary objective of this study was to characterize the chemical profile and antioxidant properties of three varieties of Cannabis sativa available in Uruguay during progressive stages of maturation. Methods: Fresh samples of female inflorescences from three stable Cannabis sativa phenotypes, collected at different time points during the end of the flowering period were analyzed. Chemical characterization of chloroform extracts was performed by 1 H-NMR. The antioxidant properties of the Cannabis sativa extracts, and pure cannabinoids, were measured in a Cu2+-induced LDL oxidation assay. Results: The main cannabinoids in the youngest inflorescences were tetrahydrocannabinolic acid (THC-A, 242 ± 62 mg/g) and tetrahydrocannabinol (THC, 7.3 ± 6.5 mg/g). Cannabinoid levels increased more than twice in two of the mature samples. A third sample showed a lower and constant concentration of THC-A and THC (177 ± 25 and 1 ± 1, respectively). The THC-A/THC rich cannabis extracts increased the latency phase of LDL oxidation by a factor of 1.2–3.5 per μg, and slowed down the propagation phase of lipoperoxidation (IC50 1.7–4.6 μg/mL). Hemp, a cannabidiol (CBD, 198 mg/g) and cannabidiolic acid (CBD-A, 92 mg/g) rich variety, also prevented the formation of conjugated dienes during LDL oxidation. In fact, 1 μg of extract was able to stretch the latency phase 3.7 times and also to significantly reduce the steepness of the propagation phase (IC50 of 8 μg/mL). Synthetic THC lengthened the duration of the lag phase by a factor of 21 per μg, while for the propagation phase showed an IC50 ≤ 1 μg/mL. Conversely, THC-A was unable to improve any parameter. Meanwhile, the presence of 1 μg of pure CBD and CBD-A increased the initial latency phase 4.8 and 9.4 times, respectively, but did not have an effect on the propagation phase. Conclusion: Cannabis whole extracts acted on both phases of lipid oxidation in copper challenged LDL. Those effects were just partially related with the content of cannabinoids and partially recapitulated by isolated pure cannabinoids. Our results support the potentially beneficial effects of Cannabis sativa whole extracts on the initial phase of atherosclerosis

Pork producers attitudes, knowledge and production practices that relate to on farm HACCP development

For the HACCP approach to be the basis of pathogen reduction on farms, pork producers will need knowledge about the pathogens and the methods for their control. In the United States, there are no recent broadly based reports in the scientific literature on the knowledge, attitude and opinions of pork producers regarding pork food safety. Several major U.S. production systems have adopted onfarm production practices uniquely designed for their company operations and which are standardized farm-tofarm. However, much of swine production within the U.S. involves independent pork producers interfacing with independent packers. With the introduction of packing plant HACCP plans, the expectation of the packer/processor has of the producer\u27s role in food safety and quality assurance is changing. Producers have a need to understand the HACCP system and the role they have in the pork production chain

Repeated observations on the Salmonella culture status of midwest U.S. herds

Mesenteric lymph nodes were collected from pigs from 115 Midwest U.S. swine herds at slaughter on two occasions separated by 6-9 months. These herds were sampled up to three additional times during a three-year period, with 30 herds sampled five times. Thirty pigs were sampled at each collection. Herds were categorized positive if one or more samples revealed Salmonella spp. While culture status at collection one was associated with the second sampling collection (p \u3c 0.01), the association was only moderate in strength (OR = 2.6). Herds with three consecutive positive tests (9 of 38) were all positive on sample four. Prevalence estimates were weakly or not correlated between samplings. In conclusion, Salmonella culture status of these swine herds was weakly predictive of future culture results. Accurate description of Salmonella status based on bacterial culture appears to require repeated or ongoing testing

The effect of feed withdrawal on the shedding of Salmonella typhimurium by swine

This project was designed to determine if feed withdrawal in conjunction with transportation-related stress caused increased shedding of Salmonella by carrier pigs. In this experiment, 48 pigs were challenged orally with S. typhimurium after weaning and allowed to grow under typical production practices. Antibiotics were not included in feeds. At monthly intervals, fecal and serum samples were collected from each pig. All pigs shed the challenge organism at least once during the experiment. By the sixth month, most pigs were negative for the challenge organism when cultured from feces. When pigs reached market weight (-240 pounds), they were split into 4 groups and subjected to one of the following feed withdrawal protocols: group I had no feed withdrawal, groups 2-4 had feed withdrawn at 6, 12 or 24 hours, respectively. Pigs in each group were transported -225 kilometers (4 hours), returned to the production facility and necropsied. Contents at the ileal-cecal junction were collected and cultured for the test organism. There was a direct correlation between the time of feed withdrawal and the number of pigs with S. typhimurium in intestinal contents. Pigs that had no feed withdrawal had the fewest number of positive pigs, whereas pigs that were off feed for 24 hours had the highest number of positive pigs. Serum samples were assessed using a mixed ELISA to detect antibodies against Salmonella. All pigs had detectable antibodies. Over the various bleedings, most pigs exhibited increases in anti-Salmonella antibodies over time. Some had modest drop-offs at the later times. In about I 0% of pigs, there was no increase or decrease in anti-Salmonella antibodies. In these non-responding pigs, the specific titers were lower than responding pigs, and above background levels. The results from this experiment complement our previous work and demonstrated that feed withdrawal when in conjunction with shipping contributes to shedding of Salmonella by pigs. Most pigs were not shedding the challenge organism just prior to slaughter, yet most (\u3e80%) had persistent infections. This indicates that the detection of infected, asymptomatic carriers using conventional culture methods is difficult and could complicate plans to develop programs to certify Salmonella-free pigs

Prevalence and Predictors of Abnormal Cardiovascular Responses to Exercise Testing Among Individuals With Type 2 Diabetes: The Look AHEAD (Action for Health in Diabetes) study

OBJECTIVE We examined maximal graded exercise test (GXT) results in 5,783 overweight/obese men and women, aged 45–76 years, with type 2 diabetes, who were entering the Look AHEAD (Action for Health in Diabetes) study, to determine the prevalence and correlates of exercise-induced cardiac abnormalities. RESEARCH DESIGN AND METHODS Participants underwent symptom-limited maximal GXTs. Questionnaires and physical examinations were used to determine demographic, anthropometric, metabolic, and health status predictors of abnormal GXT results, which were defined as an ST segment depression ≥1.0 mm, ventricular arrhythmia, angina pectoris, poor postexercise heart rate recovery (<22 bpm reduction 2 min after exercise), or maximal exercise capacity less than 5.0 METs. Systolic blood pressure response to exercise was examined as a continuous variable, without a threshold to define abnormality. RESULTS Exercise-induced abnormalities were present in 1,303 (22.5%) participants, of which 693 (12.0%) consisted of impaired exercise capacity. ST segment depression occurred in 440 (7.6%), abnormal heart rate recovery in 206 (5.0%), angina in 63 (1.1%), and arrhythmia in 41 (0.7%). Of potential predictors, only greater age was associated with increased prevalence of all abnormalities. Other predictors were associated with some, but not all, abnormalities. Systolic blood pressure response decreased with greater age, duration of diabetes, and history of cardiovascular disease. CONCLUSIONS We found a high rate of abnormal GXT results despite careful screening for cardiovascular disease symptoms. In this cohort of overweight and obese individuals with type 2 diabetes, greater age most consistently predicted abnormal GXT. Long-term follow-up of these participants will show whether these abnormalities are clinically significant. Cardiovascular disease (CVD) risk factors improve with exercise in individuals with diabetes (1). Similarly, individuals with diabetes who are physically active or have higher fitness levels have reduced CVD incidence and mortality (2,3). Nevertheless, participation in exercise may involve risks for individuals with diabetes because of their high prevalence of CVD, including silent ischemia, and other comorbid conditions (4). Knowledge about the typical cardiovascular responses to exercise in individuals with type 2 diabetes has come mainly from small clinic-based studies (5) and a few larger studies in the general population (4,6,7). The Look AHEAD (Action for Health in Diabetes) study is a multicenter randomized clinical trial designed to evaluate the long-term effects of an intensive lifestyle intervention program of weight loss and physical activity on morbidity and mortality from CVD in overweight and obese individuals with type 2 diabetes (8). Graded exercise tests (GXTs) with electrocardiographic monitoring were conducted at baseline in 5,783 individuals, providing the largest sample of systematic stress testing ever conducted in individuals with type 2 diabetes. The aims of this analysis are to examine the range of abnormal exercise responses and to examine the degree to which demographic factors, health characteristics, and medication use associate with abnormal exercise responses. Identifying predictors from readily available demographic and clinical data may assist risk stratification before exercise testing or exercise prescription for individuals with diabetes

Lung adenocarcinoma originates from retrovirus infection of proliferating type 2 pneumocytes during pulmonary post-natal development or tissue repair

Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer