Preclinical Study of Therapeutic Efficacy of a New Russian Radiopharmaceutical 177Lu-DOTA-PSMA.

The therapeutic efficacy of a Russian radiopharmaceutical 177Lu-DOTA-PSMA was studied in vivo using male BALB/c nu/nu (nude) mice with prostate carcinoma 22Rv1 xenografts by tumor growth inhibition criterion. The mean tumor volumes in mice treated with 177Lu-DOTA-PSMA were significantly lower than in animals of the control group. There were no significant differences in the values of tumor growth inhibition between the groups of animals receiving 3.7 or 7.4 MBq of 177Lu-DOTA-PSMA.

Biodistribution of 68Ga-NODA-Aminoglucose in Intact and Tumor-Bearing Mice.

We studied the biodistribution of 68Ga-NODA-aminoglucose (68Ga-NODA-AG) in normal mice and mice with experimental model of colon adenocarcinoma tumor. It was shown that 68Ga-NODA-aminoglucose was retained in the tumor for 3 h after injection and demonstrated high level of accumulation in the tumor. Rapid clearance of radioactivity from other organs was observed. The results suggest that 68Ga-NODA-aminoglucose is a promising agent for tumor visualization by positron emission tomography.

Experimental Study of the Biodistribution of New Bone-Seeking Compounds Based on Phosphonic Acids and Gallium-68.

We investigate biodistribution of gallium-labeled hydroxyethylidenediphosphonic acid (68Ga-HEDP) and diethylenetriaminepentakis(methylenephosphonic acid) (68Ga-DTPMP) in intact Wistar rats. It was shown that 68Ga-DTPMP accumulated mainly in the bone tissue providing high femur/blood and femur/muscle ratios and had high stability in vivo. In contrast, 68Ga-HEDP was characterized by low stability and high uptake of radioactivity in blood throughout the study. So 68Ga-DTPMP can be considered as a new prospective radiotracer in oncology for imaging bone tissue metastasis by positron emission tomography.

[[correlation between macro- and micro-stability C(H)2 domains of human IgG2 and their biological activity. II. Calculation of thermodynamic functions characterizing domains stability].

The thermodynamic parameters of the stabilization of the native structure C(H)2 domains of human myeloma immunoglobulin LOM and SIN second subclass and their firstly obtained hFc fragments were determined using the methods of scanning microcalorimenry. A decrease in the termal stability and energy stability of the native of these domains in the intact proteins correlated in the "phisiological" range of temperatures (20-37 degrees C), mainly, with entropy factor.

[Abdominal cavity adhesions. Some issues of pathogenesis, prophylaxis and treatment].

The abdominal cavity adhesions (ACA) constitute frequent consequence of various abdominal cavity diseases and traumas and frequent cause of the abdominal adhesive disease and its complications. In spite of the known pathogenesis of ACA, the surgeons had failed throughout the decades of years to find out the measures and methods of its prophylaxis. There are several causes of such a situation and the main of them is that ACA in its origin constitutes a philogenetically developed defense biologic reaction of organism. Because of the fact, that an organism constitutes the self-regulated biological system, any external inputs (including the treatment), directed on qualitative or quantitative signs of these reactions, meet systemic counteraction and become annihilated. The forced overcome of such a counteraction may cause the development of severe systemic disorders in organism. The only prophylactic measures against ACA, which were already tested throughout the time, are the tactical and technical methods, promoting the reduction of severity of morphological changes in peritoneum and abdominal organs, thus causing reduction of natural reaction of organism. When the adhesions formation is inevitable it is necessary to apply surgical methods of governing such a process, and omentoparietopexy may constitutes one of such methods.

Measurement of the muon capture rate in hydrogen gas and determination of the proton's pseudoscalar coupling gP.

The rate of nuclear muon capture by the proton has been measured using a new technique based on a time projection chamber operating in ultraclean, deuterium-depleted hydrogen gas, which is key to avoiding uncertainties from muonic molecule formation. The capture rate from the hyperfine singlet ground state of the microp atom was obtained from the difference between the micro(-) disappearance rate in hydrogen and the world average for the micro(+) decay rate, yielding Lambda(S)=725.0+/-17.4 s(-1), from which the induced pseudoscalar coupling of the nucleon, g(P)(q(2)=-0.88m(2)(micro))=7.3+/-1.1, is extracted.

[Associations of hemostasis factors genes with early development of ischemic heart disease and manifestation of myocardial infarction in young age].

AIM: To study polymorphisms of genes of factors of the system of hemostasis in young patients with ischemic heart disease (IHD). MATERIAL: Two groups of patients participated in the study: patients with first manifestation of IHD at the age < or = 50 years (men) or < or = 55 years (women) (n=158), and patients with first IHD manifestation at the age > or = 70 years (n=92). METHODS: We studied polymorphic markers of genes encoding clotting factors V (F5) and VII (F7), subunit IIIa of platelet integrin (ITGB3), beta-chain of fibrinogen (FGB) and tissue plasminogen activator type 1 (PLANH1). RESULTS: After separation of a subgroup of patients with MI without preceding angina we revealed significant differences in distribution of frequencies of genotypes of polymorphic marker C(-426)T of factor V gene: genotype TT was significantly more frequent in young (14.9%) than in old (2%) patients (p=0.008). Multifactorial logistic regression revealed independent association of early IHD with smoking (OR 6.112 [2.567-14.552]; p<0.001) and presence of genotype TT of C(-426)T polymorphic marker of F5 gene (OR=9.410 [1.074-82.459]; p=0.043). CONCLUSION: Thus we obtained data on the presence of independent association between IHD risk and manifestation of MI in young age with genotype TT of polymorphic marker C(-426)T of F5 gene as well as with traditional risk factors of IHD.

Human immunoglobulin light chains lambda form amyloid fibrils and granular aggregates in solution.

Myeloma nephropathy is a disorder characterized by deposition of monoclonal immunoglobulin light chains in the kidneys. The chains deposited form either amyloid fibrils or granular (amorphous) aggregates. Distinct molecular mechanisms leading to the formation of different aggregate types in kidney of patients with multiple myeloma are poorly understood. Here we describe the self-association kinetics of human monoclonal immunoglobulin light chains lambda (GRY) isolated from urine of a patient with multiple myeloma. Under physiological conditions, the isolated light chain exists predominantly in a form of covalent dimer with apparent molecular mass of 50.1 kD. Spectral probe binding, analytical gel filtration, Western blot analysis, and electron microscopy indicate that GRY dimer aggregation occurs via two different pathways producing either amyloid fibrils or amorphous aggregates depending on microenvironment. Incubation of GRY (25 microM) for 4-14 days at 37 degrees C in phosphate buffered saline (PBS), pH 7.0, or in PBS containing urea (0.8 M), pH 6.5, leads to amyloid fibril formation. Under electron microscopy, the fibrils show unbranched thread-like structures, approximately 60-80 x 1000 A in size, which can bind thioflavin T and Congo Red. GRY maintained in acetate buffer, pH 3.5, forms granular aggregates. The structure of GRY oligomers formed during the early stage of amyloid fibril formation (1-4 days) has been examined by means of protein cross-linking with homobifunctional reagents. These oligomers are predominantly trimers and tetramers.

[Helicobacter pylori prevalence among patients with gastroduodenal diseases in Kiev]. / Rasprostranennost' Helicobacter pylori sredi bol'nykh s zabolevaniiami gastroduodenal'noi zony v Kieve.

It is for the first time in Ukraine that a study has been made on the epidemiology of H. pylori infection among patients with disorders of the stomach and duodenum. The diagnosis of the infection was done with the aid of various invasive and noninvasive tests, 13C-urea breathing test, a unique for Ukraine and countries of the Western Europe method of examination included. Ascertained among the above category of patients was wide prevalence of H. pylori, which fact confirms its leading etiological role in disorders of the stomach and duodenum once again.

[The application of laparocentesis and peritoneal lavage and the analysis of hemo-peritoneal volume in the diagnosis of closed abdominal wound]. / Primenenie laparotsenteza i peritoneal'nogo lavazha s opredeleniem ob''ema gemoperitoneuma v diagnostike zakrytoi travmy zhivota.

Laparocentesis and peritoneal lavage--are simple, quick and informative methods widely applied in surgical practice for diagnosis of closed injury of abdominal cavity organs. Modifications of these diagnostic methods, their combination with possibility of hemoperitoneum volume detection, occurring while the internal organs injury, the results of investigation interpretation permit to broaden their possibilities, peculiarly in the absence of other instrumental diagnostic facilities available.

[Effect of immunoglobulin G1 Pro 290 residue on structural and biological characteristics of its SH2 domain]. / Vliianie ostatka Pro290 v immunoglobuline G1 na strukturnye i biologicheskie svoistva ego CH2-domena.

Tryptic hydrolysis of only one of 11 studied Fc fragments of human myeloma immunoglobulins G1 (IgG1) provided an intact CH2 domain in a high yield (up to 40% as opposed to 2-3% for other IgG1s). The only structural difference of this domain was shown to be the substitution of Pro for Lys290. This decreased the capacity of the IgG1 Sem Fc fragment to interact with proteins of the complement system.

[Osmotic homeostasis and radiosensitivity of NKLy lymphosarcoma cells]. / Osmoticheskii gomeostaz i radiochuvstvitel'nost' kletok limfosarkomy NKLy.

In experiments with cells of ascites NKLy lymphoma differing in ploidy and position in the cell cycle, a study was made of the radiosensitivity, osmotic homeostasis peculiarities and thermoradiation changes in potassium content. It was shown that the resistance of osmotic homeostasis of NKLy cells to thermoradiation correlated with their radioresistance and was maximally displayed in cells at the stage of DNA synthesis.

[Possibilities of the use of trypsinogen activation peptide in the pancreatic tissue in the diagnosis of pancreatic necrosis]. / O vozmozhnosti ispol'zovaniia peptida aktivatsii tripsinogena v tkani podzheludochnoi zhelezy v diagnostike pankreonekroza.

The test of peptide of trypsinogen activation (PTA) in various biological media is a principal new diagnostic test for acute pancreatitis. PTA levels in the pancreatic tissue and the plasma of the blood in acute experimental pancreatic necrosis reflects the process of the pathological activation of trypsin in the diseases focus and confirms the source of higher levels of activation peptide in the blood flow. Together with the values of other enzymatic systems of the pancreatic gland the discussed value permits one to make a more precise assessment of the mechanism and stages of autodigestive processes which develop in acute experimental pancreatitis.

Mechanisms of generation of antibody diversity as a cause for natural selection of homoiothermal animals in the process of evolution.

The temperature-dependence of domain interactions in the Fab, Fc, Fb and Fv fragments from human myeloma immunoglobulins (IgG) samples was investigated by scanning microcalorimetry, NMR and difference spectroscopy. The fragments were found to be very sensitive to temperature changes. Lowering the temperature below the physiological value (37 degrees C) considerably decreases the energy of interaction of the variable VH and VL domains, resulting at times in their dissociation. Since the association energies of VH and VL pairs can be affected by the result of somatic recombination and mutation events affecting antibody genes, immunoglobulins can fortuitously acquire the properties of cryoglobulins or cold autoantibodies and induce severe pathological states. It is postulated that this property of immunoglobulins, and by extension, of T-cell antigen receptors might have been one of the causes for the possible natural selection of homoiothermal animals. In these, the high conformational sensitivity of immunoglobulins to temperature change may be important in the mechanisms of induction of secondary functions in immune responses.

Structure of human myeloma IgG3 Kuc.

An electron microscopy study of human myeloma IgG3 Kuc has shown that the hinge region in an intact molecule is in a compact state. The subunits are not fixed rigidly and are very mobile. These data are supported by results of ultracentrifugation and microcalorimetry. Non-extremal denaturating effects (pH 4.0, 20 degrees C or pH 7.8, 65 degrees C) lead to 'unfolding' of the hinge region which has a rod-like shape in electron micrographs.

[Determination of amyloid P component in blood by an immunoenzyme method]. / Opredelenie amiloidnogo P-komponenta v plazme krovi s pomoshch'iu immunofermentnogo metoda.

An ELISA procedure was developed for measuring serum amyloid P-component (SAP). The assay is based on our finding of binding AP to polystyrene microtiter plates. The amount of SAP is determined by concurrent ELISA, wells being sequentially incubated with rabbit anti-AP antiserum and goat anti-rabbit antiserum, conjugated with peroxidase. The limit of sensitivity of the assay is 0.5 micrograms/ml. When applied to the screening of patients plasma, elevation of SAP concentration in patients with rheumatoid arthritis and amyloidosis were found.

[Isolation and characteristics of antibodies against synthetic fragments of oncoproteins. II. Antiserum against the transforming protein pp60src of Rous sarcoma virus]. / Poluchenie i kharakteristika antitel k sinteticheskim fragmentam onkobelkov. II. Antisyvorotka k transformiruiushchemu belku virusa sarkomy kur Rausa pp60src.

To generate the antibodies to the transforming protein of Rous sarcoma virus (RSV) pp60src, rabbits were immunized with the peptide, corresponding to 415-421 sequence of pp60src. These antibodies immunoprecipitate pp60src in RSV-transformed chicken and mammalian cells, and also some proteins (45, 85 and 120 kDa), which could be autophosphorylated in vitro. It was shown that 415-421 sequence of pp60src is not recognized by the antibodies to pp60src from RSV-induced tumour bearing rabbits (TBR serum). In contrast to TBR serum, antibodies, generated against synthetic peptide, corresponding 415-421 sequence of pp60src couldn't be phosphorylated in vitro, when [gamma-32P]ATP is added to the immune complex. The antipeptide antibodies, bound to pp60src did not block phosphorylation of TBR immunoglobulins, added to this immune complex. Hence, 415-421 sequence of pp60src RSV containing the major tyrosine phosphorylation site does not take part in the kinase reaction in vitro.