CHEMICAL AND IMMUNOLOGICAL STUDIES ON THE AGENT PRODUCING LEUKOSIS AND SARCOMA OF FOWLS

The activity of the agent producing sarcoma or leukosis in material deposited by high speed centrifugation is the same as that of the original crude extracts. Material sedimentable at high speed containing approximately 10^–5 mg. N produces tumors at the site of injection. Small quantities of material sedimentable at high speed are present in normal chicken sera, and about twice as much in leukemic sera (strain 1). Normal chicken and mouse spleens and all other human and mouse tissues examined contain large amounts of material sedimentable at high speed. Extraction of leukemic blood cells with saline yields little additional virus. The washed cells readily produce leukosis even after irradiation with amounts of x-rays sufficient to destroy the leukemic cells but not the virus. Freezing at –60°C. preserves the activity of the high speed deposits for at least 6 months. Addition of 5 per cent of saturated Na₂SO₄ solution slightly delays deterioration of high speed deposits in the ice box. Most of the agent measured by inoculation of chickens and the fraction sedimentable at high speed measured by its nitrogen content is precipitated by one-third saturation with sodium sulfate.     

Erythematöse,ekzematöse,parenchymatöse Entzündungsprocesse

Ohne Zusammenfassung     

Heart Failure after Laboratory Confirmed Influenza Infection (FLU-HF)

Background:Influenza has been shown to exacerbate heart failure (HF). Importantly, no study to date has examined the relationship between HF hospitalizations (HFH) with laboratory confirmed influenza infections. This study evaluated the association between laboratory confirmed influenza infection and HFH in the two largest hospitals in Saskatchewan, Canada.Methods:We used a retrospective self-controlled case series design to evaluate the association between laboratory-confirmed influenza infection and HFH. We compared the incidence ratio for HFH during the influenza risk interval with the control interval. We defined the influenza risk interval as the seven days after a laboratory confirmed influenza result and the control interval as one year before and after the risk interval.Results:We identified 114 HFH that occurred within one year before and after a positive test result for influenza between April 1, 2010, and April 30, 2018. Of these, 28 (28 admissions per week) occurred during the risk interval and 86 (0.853 admissions per week) occurred during the control interval. The incidence ratio of a HFH during the risk interval as compared with the control interval was 33.53 (95% confidence interval [CI], 21.89 to 51.36). A decline in incidence was observed after day seven; between days 8 to 14 and 14 to 28 incidence ratios was 0.91 (95% CI, 0.13 to 6.52) and 0.91 (95% CI, 0.22 to 3.68) respectively.Conclusion:We have observed a significant association between acute influenza infection and HFH. However, further research with a larger sample size and involving a multicenter setting is warranted.Highlights

• Influenza may contribute and exacerbate heart failure events especially during annual influenza season.
• Early identification of influenza among patients with heart failure, could lead to earlier treatment with antiviral medication, reduce unnecessary antibiotic use, and tail off the morbidity and mortality.
• In this study, despite our efficient study design, our sample size was limited to only the two largest hospitals in the province, possibly excluding a significant population in remote areas.

     

The effect of zinc in vivo and in vitro on the activities of angiotensin converting enzyme and kininase-I in the plasma of rats

Two groups of rats were pair fed, for 18 days, diets containing either 2.6 (Zn deficient) or 100 mg Zn/kg (control diet). Plasma was assayed spectrophotometrically for the activity of kininase-I and angiotensin converting enzyme (ACE) in the presence of varying concentrations of added Zn2+. Zinc deficient rats had only 76% of the activity of both kininase-I and ACE compared with zinc supplemented control rats. There was a significant linear relationship between enzyme activity and concentration of zinc in plasma for both enzymes. When zinc was added to the enzyme incubation mixture for zinc deficient rats, the activity of ACE increased by 73% and that of kininase-I by 33%. This Zn2+-stimulated increase in enzyme activity was negatively correlated with the in vivo concentration of zinc in plasma, and a plateau in enzyme activity was seen at concentrations of plasma zinc that were commensurate with normal zinc status (over 14 mumol/1). The results demonstrate that the activities of both kininase-I and ACE are dependent on the concentration of zinc in vivo and in vitro, and suggest that information concerning the concentration of zinc in plasma and assay solutions be a prerequisite solutions be a prerequisite for the use of these enzymes in the clinical diagnosis of disease states. The results also showed that the activity of ACE and kininase-I in plasma could be used for the biochemical diagnosis of a suboptimal zinc status.     

Antibody levels to parainfluenza,rubella, measles,and influenza a virus in children with polymyositis

The CF and HI antibody titers to rubella and measles viruses, the CF titers to influenza A, and the HI titers to parainfluenza 1, 2, and 3 were carried out on the sera of 20 patients with childhood polymyositis and their matched controls. The titers for measles, parainfluenza 1, and influenza A were slightly higher for patients than for controls. The control group had antibody titers to rubella and parainfluenza 2 and 3 higher than or similar to those of patients. Strong patterns or significant differences for a given virus or virus group were not encountered.     

Rapamycin limits CD4+ T cell proliferation in simian immunodeficiency virus–infected rhesus macaques on antiretroviral therapy

Proliferation of latently infected CD4⁺ T cells with replication-competent proviruses is an important mechanism contributing to HIV persistence during antiretroviral therapy (ART). One approach to targeting this latent cell expansion is to inhibit mTOR, a regulatory kinase involved with cell growth, metabolism, and proliferation. Here, we determined the effects of chronic mTOR inhibition with rapamycin with or without T cell activation in SIV-infected rhesus macaques (RMs) on ART. Rapamycin perturbed the expression of multiple genes and signaling pathways important for cellular proliferation and substantially decreased the frequency of proliferating CD4⁺ memory T cells (TM cells) in blood and tissues. However, levels of cell-associated SIV DNA and SIV RNA were not markedly different between rapamycin-treated RMs and controls during ART. T cell activation with an anti-CD3LALA antibody induced increases in SIV RNA in plasma of RMs on rapamycin, consistent with SIV production. However, upon ART cessation, both rapamycin and CD3LALA–treated and control-treated RMs rebounded in less than 12 days, with no difference in the time to viral rebound or post-ART viral load set points. These results indicate that, while rapamycin can decrease the proliferation of CD4⁺ TM cells, chronic mTOR inhibition alone or in combination with T cell activation was not sufficient to disrupt the stability of the SIV reservoir.     

Rigid and flexible docking studies on PPAR-γ agonists: key interactions for a better antihyperglycemic activity and in silico pharmacodynamic activity versus experimental in vivo activity

We report both automated rigid and flexible ligand docking simulations performed on fifty peroxisome proliferator-activated receptor (PPAR-γ) agonists, namely, glitazones. The binding conformations and binding affinities of these agonists were obtained by the use of the Autodock 4.1 with Lamarckian genetic algorithm (LGA). All the 50 flexible docks are considered as well-docked as all of them were bound to the ligand binding domain of PPAR-γ. The predicted binding affinity values (pKa) were found to have some degree of correlation with their experimental in vivo activity values. The head group hydrogen bond interactions via H323 and H449 histidine residues were found to play a significant role. The results obtained will be valuable in designing newer selective PPAR-γ agonists.     

Initial experience with a self-expanding retrievable stent for recanalization of large vessel occlusions in acute ischemic stroke

Introduction  

Quicker recanalization results in better clinical outcomes in patients with acute ischemic strokes. We describe our experience with the use of a self-expanding, fully retrievable stent in acute intracranial occlusions.