Engineering Chimeric Antigen Receptors.

Chimeric antigen receptors (CARs) are recombinant protein molecules that redirect cytotoxic lymphocytes toward malignant and other target cells. The high feasibility of manufacturing CAR-modified lymphocytes for the therapy of cancer has spurred the development and optimization of new CAR T cells directed against a broad range of target antigens. In this review, we describe the main structural and functional elements constituting a CAR, discuss the roles of these elements in modulating the anti-tumor activity of CAR T cells, and highlight alternative approaches to CAR engineering.

[CAR T-cell therapy: Balance of efficacy and safety].

Early results from clinical trials of autologous chimeric antigen receptor (CAR)-expressing T cells for the therapy of B-cell malignancies have encouraged extending the potency of this therapy to other cancers. However, the success of using CAR T-cells to treat patients with solid tumors has been limited. In this review, we summarize current knowledge on the design and applications of CARs for the targeted therapy of cancer. We describe existing issues that limit the widespread application of CAR T cells and discuss the optimization steps needed to further improve safety and efficacy of this therapeutic platform.

Investigation of the Belousov-Zhabotinsky reaction by thermal lensing.

Thermal lensing is used for monitoring the course of unstirred Belousov-Zhabotinsky reaction (a bromate oscillator) based on malonic acid as an organic substrate in 1.5 M sulfuric acid with a mixture of free Fe(II) and its chelate with 1,10-phenanthroline as a catalyst and a photometric indicator of the reaction process. The dependences of the oscillation period and oscillation lifetime on the component concentrations are found. The sensitivity of thermal lensing in determining reaction components was compared to spectrophotometry and potentiometry by the model determination of bromide ions by its inhibition effect on the reaction kinetics.

[Burkitt's lymphosarcoma in a child with HIV infection]. / Limfosarkoma tipa Berkitta u rebenka s VICh-infektsiei.

A case of Burkitt's lymphosarcoma in an HIV-infected girl aged 4 years is described. The child was infected with HIV and hepatitis B virus in the hospital focus of infection at the age of 1 year 4 months. An attempt to treat lymphosarcoma with large doses of prednisolone and cytostatics (vincristine and cyclophosphamide) produced no effect.

[Children, adolescents and HIV infection]. / Deti, podrostki i VICh-infektsiia.

The analysis of the occurrence of HIV infection in adults, children and adolescents under 18 years of age on the basis of statistical data by February 1, 1997, is presented. The total number HIV-infected persons registered by this date was 6,232; among them 902 (14.5%) were children and adolescents. 267 children were infected in the hospital focus of HIV infection; of these, 80 children (30%) died of AIDS during the period of 1989-1997. In 1992 only 16 adolescents, HIV infected were registered, while in 1995 the number of HIV-infected adolescents was 34, in 1996 their number rose to 144 and in 1997, to 435. The main cause of adolescent infections (80%) was the intravenous injection of narcotic drugs.

[Amplification of the activity of HIV-1 isolates purified from seropositive children after cryopreservation of persistently-infected cells]. / Usilenie aktivnosti izoliatov VICh-1, vydelennykh ot seropozitivnykh detei, posle kriokonservatsii persistentno infitsirovannykh kletok.

HIV-1 strains MC-1974 and MC-1978 were isolated from children infected in hospital. Both children presented with symptoms of HIV infection by the moment the blood samples for virus isolation were collected. In vitro the isolated strains showed weak infective activity and caused no cytopathic effect in sensitive cells. It may be explained by azidothymidine antiviral therapy or by initial immunodeficient status of both children not caused by HIV infection. Virus activity was enhanced in both cultures after reactivation of Jurkat-tat cells persistently infected with MC-1974 and MC-1978 strains after cryopreservation. Viruses isolated from culture fluid effectively infected Jurkat-tat cells. The infection was associated with formation of syncytia, accumulation of viral particles detected by electron microscopy and of intracellular antigens detected by fluorescent antibody technique and by immunoblotting. The results suggest the presence in the body of infected children and in Jurkat-tat-1974 and Jurkat-tat-1978 persistent lines of a viral genome containing all virusspecific genes necessary for productive expression of HIV-1.

[Problem of clinico-roentgenological diagnosis of acute pneumonia in infants in their first few months of life]. / K voprosu o kliniko-rentgenologicheskoi diagnostike ostroi pnevmonii u detei pervykh mesiatsev zhizni.

Studies into the problems of diagnosing pneumonia in children of the first months of life carried out for many years have shown that pneumonia may be referred to the diseases with indefinite diagnostic criteria. In view of this fact the x-raying of the chest should be regarded as a method of varifying the diagnosis of pneumonia. The roentgenographic findings should be estimated bearing in mind the presence or lack of a syndrome such as bronchial obstruction and the epidemiological anamnesis data.

[Priority trends in the realization of complex programs aimed at decreasing infant mortality in the regions of high mortality rate]. / O pervoocherednykh napravleniiakh realizatsii kompleksnykh programm po znizheniiu mladencheskoi smertnosti v regionakh s ee vysokim urovnem.

PIP: Approaches to reducing infant mortality in southern regions of USSR are outlined. Middle Asia and Kazakhstan comprise 16.7% of the USSR population; the birth rate in this region is 34-39/1000, and the birth interval is 2 years (often, 1 year). Infant mortality rate is 25/1000 births; more than 46% of children die during the 1st year of life. In the structure of infant mortality, infections and respiratory diseases are dominant. The peak of infant morality occurs during the summer (July-September). Special surveys indicated an unsatisfactory state of health of pregnant women associated with nutritional deficiency, observance of certain religious customs, and occupational exposure to agricultural chemicals. The adopted program for the regions with high infant mortality consists of the following priority measures: family planning and birth control; improvement of the health of women of child-bearing age; nutrition of pregnant women; breast feeding for mothers with young children; strict adherence to the labor laws for working women; improvement of the social and legislative assistance to a family; improvement of the system of outpatient care facilities for large families; development of a system of emergency care; carrying out social, hygienic and medical measures of control of intestinal and other hospital infections; drastic changes in the methods and style of educational campaign; campaign against harmful customs; development of the system of medical genetic care and prenatal diagnosis; improvement of the training of medical personnel.^ieng