Host immune response to cytomegalovirus

To confirm that immediate-early (IE) genes of murine cytomegalovirus (MCMV) give rise to antigens recognized by specific cytolytic T lymphocytes (CTL), a 10.8-kilobase fragment of MCMV DNA which is abundantly transcribed at IE times was transfected into L cells expressing the Ld class I major histocompatibility glycoprotein. The viral genome fragment contains sequences of the three IE transcription units of MCMV: ie1, ie2, and ie3. In the transfected cell lines, only the predominant 2.75-kilobase transcript of ie1 and its translation product pp89 could be detected. The transfectants were analyzed for membrane expression of an IE antigen by employing clone IE1, an IE-specific CTL clone, as the probe. Only cells that expressed both the MCMV IE gene(s) and the Ld gene were recognized by the CTL clone

A nonstructural polypeptide encoded by immediate-early transcription unit 1 of murine cytomegalovirus is recognized by cytolytic T lymphocytes

We have constructed target cells by cotransfection of the MHC gene Ld and fragments of murine cytomegalovirus (MCMV) DNA coding for nonstructural immediate-early (IE) proteins. Transfectants were tested by using CTL clone IE1 with specificity for an IE epitope presented in association with Ld. Data show that clone IE1 recognizes a product of the ie1 transcription unit of MCMV, and that its specificity is shared by approximately 25% of polyclonal IE-specific CTL. The results provide the first definite evidence that expression of a herpes virus IE gene encoding a regulatory protein gives rise to antigen expression detectable by specific CT

The economic pressures for biosimilar drug use in cancer medicine

The main rationale for using biosimilar drugs is for cost saving. The market development for biosimilar drugs will therefore depend on the degree to which cost saving measures are required by nations, medical insurers and individuals and the absolute savings that could be gained by switching from original drugs. This paper is designed to discover the degree to which financial constraints will drive future health spending and to discover if legal or safety issues could impact on any trend. A structured literature search was performed for papers and documents to 27 August 2011. Where multiple sources of data were available on a topic, data from papers and reports by multinational or national bodies were used in preference to data from regions or individual hospitals. Almost all health systems face current significant cost pressures. The twin driver of increasing cancer prevalence as populations age and cancer medicine costs rising faster than inflation places oncology as the most significant single cost problem. For some countries, this is predicted to make medicine unaffordable within a decade. Most developed countries have planned to embrace biosimilar use as a cost-control measure. Biosimilar introduction into the EU has already forced prices down, both the price of biosimilar drugs and competitive price reductions in originator drugs. Compound annual growth rates of use have been predicted at 65.8% per year. Most developed countries have planned to embrace biosimilar use as a major cost-control measure. Only legal blocks and safety concerns are likely to act against this trend. For centralised healthcare systems, and those with a strong tradition of generic medicine use, biosimilar use will clearly rise with predictions of more than 80% of prescriptions of some biologic drugs within 1 year of market entry in the USA. Delaying the implementation of such programmes however risks a real crisis in healthcare delivery for many countries and hospitals that few can now afford

Parents' Adverse Childhood Experiences and Their Children's Behavioral Health Problems.

: media-1vid110.1542/5789654354001PEDS-VA_2018-0023Video Abstract BACKGROUND AND OBJECTIVES: Adverse childhood experiences (ACEs) include stressful and potentially traumatic events associated with higher risk of long-term behavioral problems and chronic illnesses. Whether parents' ACE counts (an index of standard ACEs) confer intergenerational risk to their children's behavioral health is unknown. In this study, we estimate the risk of child behavioral problems as a function of parent ACE counts.MethodsWe obtained retrospective information on 9 ACEs self-reported by parents and parent reports of their children's (1) behavioral problems (using the Behavior Problems Index [BPI]), (2) attention-deficit/hyperactivity disorder diagnosis, and (3) emotional disturbance diagnosis from the 2013 Panel Study of Income Dynamics (PSID) core interview and the linked PSID Childhood Retrospective Circumstances Study and 2014 PSID Child Development Supplement. Multivariate linear and logistic regression models were used to estimate child behavioral health outcomes by parent retrospective ACE count.ResultsChildren of parents with a history of 4 or more ACEs had on average a 2.3-point (95% confidence interval [CI]: 1.3-3.2) higher score on the BPI, 2.1 times (95% CI: 1.1-3.8) higher odds of hyperactivity, and 4.2 times (95% CI: 1.7-10.8) higher odds of an emotional disturbance diagnosis than children of parents with no ACEs. Maternal ACEs revealed a stronger association with child behavior problems than paternal ACEs. Relationships between parents' 9 component ACEs individually and children's BPI scores revealed consistently positive associations. Mediation by parent emotional distress and aggravation were observed.ConclusionsParents with greater exposure to ACEs are more likely to have children with behavioral health problems