In-depth cross-validation of human and mouse CD4-specific minibodies for noninvasive PET imaging of CD4 cells and response prediction to cancer immunotherapy.

Increasing evidence emphasizes the pivotal role of CD4 T cells in orchestrating cancer immunity. Noninvasive imaging of the temporal dynamics of CD4 T cells and their distribution patterns might provide novel insights into their effector and regulator cell functions during cancer immunotherapy (CIT). We conducted a comparative analysis of Zr-labeled anti-mouse (m) and anti-human (h) CD4-targeting minibodies (Mbs) for positron emission tomography (PET)/magnetic resonance imaging (MRI) of CD4 T cells in human xenografts, syngeneic tumor-bearing wild-type (WT), and human CD4 knock-in (hCD4-KI) mouse models.

Evaluating the immunologically "cold" tumor microenvironment after treatment with immune checkpoint inhibitors utilizing PET imaging of CD4 + and CD8 + T cells in breast cancer mouse models.

Background: Immune-positron emission tomography (PET) imaging with tracers that target CD8 and granzyme B has shown promise in predicting the therapeutic response following immune checkpoint blockade (ICB) in immunologically "hot" tumors. However, immune dynamics in the low T-cell infiltrating "cold" tumor immune microenvironment during ICB remain poorly understood. This study uses molecular imaging to evaluate changes in CD4 + T cells and CD8 + T cells during ICB in breast cancer models and examines biomarkers of response.

Electrostatic properties of human germlines and biodistribution of small biologics.

Off-target biodistribution of biologics bears important toxicological consequences. Antibody fragments intended for use as vectors of cytotoxic payloads (e.g.

Adeno-Associated Virus Type 9-Mediated Gene Therapy of Choline Acetyltransferase-Deficient Mice.

The enzyme choline acetyltransferase (ChAT) synthesizes acetylcholine from acetyl-CoA and choline at the neuromuscular junction and at the nerve terminals of cholinergic neurons. Mutations in the ChAT gene () result in a presynaptic congenital myasthenic syndrome (CMS) that often associates with life-threatening episodes of apnea. Knockout mice for die at birth.

[Enteric microbiocenotic modifiers and ways of enhancing their efficacy].

Efficient recovery of enteric microbiocenosis is one of the central problems not only in gastroenterology, but also in a number of related areas. This problem becomes particularly pressing after antibiotic treatment. The combined modifiers of enteric microbiocenosis are most effective among other symbiotic drugs.

[Computer-assisted 3-D reconstruction of biological objects using serial sections].

In this review, the literature data on the major directions and problems of experimental technology of "3-D Histology", based on the analysis of serial sections, are discussed. The main attention is drawn to the principle problem: achievement of realness (accuracy) of generated 3-D models, i. e.

[Computer volume reconstruction of the anatomical structure of the brain].

The possibility of constructing three-dimensional computer models of the brain and intrabrain structures on the basis of stereotaxic atlases for calculating the geometry of structures and modeling stereotaxic operations was considered. A special program (Contour-1) was developed on the basis of the Kristiansen-Zedenberg's and Ganapatchi-Denechi algorithms with the use of the OpenGL library. Some problems were revealed, which do not allow one to construct three-dimensional models of the geometry of intrabrain structures (breaks between the sections of the brain, insufficient accuracy of the alignment of the images of sections relative one another, etc.

[Influence of prostatilen on smooth muscle organs functional activity in surgical patients (clinical and experimental study)].

The action of prostatilen on contractile activity of smooth muscles of isolated line slices of urine bladder of Wistar rats (myography) and arterial vessels of cat kidneys (resistography) was studied. On the basis of clinical cases effectiveness of prostatilen was analysed as a treatment restorting urine bladder function in acute reflex urinary retention after operations in the area of rectal sphincter, as well as in treatment of patients with chronic prostatitis. It is shown, that prostatilen produces contractile action on smooth muscles of renal blood vessels in cats and urine bladder walls in rats and it raises contractile activity of smooth muscles of human urine bladder.

[Hereditary pemphigus: the problems of classification, diagnosis and prevention].

Basic principles of present-day classification of hereditary epidermolysis bullosa are outlined, and morphologic grounds for distinguishing common, borderline, and dystrophic e. bullosa are validated. Potentialities of prenatal diagnosis of grave forms of e.

[Hallopeau-Siemens' congenital epidermolysis bullosa dystrophica].

Examination of apparently intact skin of patients with generalized Hallopeau-Siemens' dystrophic epidermolysis bullosa has shown that this condition may be diagnosed histologically only in case of manifest changes. If there are no apparent changes, examination of ultrathin sections of the skin should be used. Further studies are necessary to define the diagnostic and prognostic values of the detected changes for prenatal diagnosis.

[The prenatal diagnosis of Herlitz's borderline epidermolysis bullosa letalis].

Methods of morphologic prenatal diagnosis permit optimizing the medicogenetic prognosis thus preventing the birth of patients with severe incurable forms of congenital bullous epidermolysis and preserve normal pregnancy in risk-group females. Studies on the estimation of the prognostic and prophylactic value of methods for the prenatal diagnosis of congenital dermatoses are necessary.

[Acicular ichthyosis (the Curth-Macklin type)].

It is suggested that the double-nucleus phenomenon in the epidermis in type Curth-Macklin [correction of Kurt-McLean] acicular ichthyosis is due to cytokinesis-controlling gene mutation. Other hereditary dermatoses associated with needle-like hyperkeratosis appear to be a heterogenic group not necessarily involving the formation of double-nuclear cells. The essence of double-nucleus phenomenon and morphogenesis of acicular ichthyosis are disputable at present.

[Prenatal diagnosis of several hereditary skin diseases].

Twenty-two control women and 5 women at risk for delivering a baby with Brocq's ichthyosiform erythroderma or fatal epidermolysis bullosa were investigated in order to make prenatal diagnosis of inherited fetal skin diseases. Fetal skin abnormalities were detected in 3 of the 5 high-risk patients, and their pregnancies were terminated. There was a spontaneous abortion with a normal fetus in 1 case.

[The toxicologic characteristics of a new SAKAP-based benzyl benzoate ointment].

The formula of a new stable 20% benzylbenzoate emulsion is presented, so are the results of studies on its toxicity, local irritating and sensitizing effects in guinea pigs. For comparison, the same characteristics of currently used 20% water-soap benzylbenzoate emulsion and of the new ointment base, SAKAP (acryl copolymer), have been examined. Both the ointment and its base have proved to be safe.

[Effect of adrenaline and noradrenaline on the vascular antiaggregation activity in cats].

The anti-aggregation ability of vessels from different circulatory zones was studied under the influence of adrenaline and noradrenaline. Dissimilarity of the basal antiaggregation activity of the vessel wall of various circulatory zones was revealed. The complex character of influence of catecholamines on the anti-aggregation ability of the vessel wall was revealed, the final result of which depends greatly on the initial anti-aggregation activity of the vessel wall.

[Ultrastructural changes in the skin of patients with Fabry's angiokeratoma].

The skin of a patient with Fabry's diffuse angiokeratoma accompanied by a severe decrease of leucocyte alpha-galactosidase (0,7-1,2 nmol/mg protein/h) was studied by a method of semithin and ultrathin sections. Cytoplasmic inclusions having lamellar structure in the form of alternating electron-dense and light strips with a period about 6 nm were found in the endotheliocytes of dilated vessels, lymphoid cells, neutrophil leucocytes, axons and leucocytes of nerve trunks. The presence of these specific inclusions together with the decrease of leucocytic alpha-galactosidase allows the differential diagnosis with other types of angiokeratomas and some skin angiomas.