[VALUE OF THE -2PROPSA INDEX AND THE PROSTATE HEALTH INDEX IN PATIENTS WITH PROSTATE CANCER: REVIEW OF LITERATURE AND DATA OF RUSSIAN PROSPECTIVE STUDY].

The article presents the analysis of the fundamental studies on the -2proPSA and prostate health index (PHI) and the determination of their field of use in patients with prostate cancer (PCa). The main aspects of use of the new markers studied include improvement of detection of prostate cancer, increase of specificity and reduction of the number of unnecessary biopsies, identification of aggressive forms of prostate cancer, as well as determination of the progression of the disease. The results of numerous studies, as well as preliminary data of Russian study on the assessment of new indicators are promising and today allow to recommend the use of the test to determine the values of the -2proPSA and prostate health index (PHI) in routine urological practice.

[Current approaches to laboratory diagnosis of syphilis].

The efficiency of chemiluminescence immunoassay (CIA) used as a treponemal test in the serological diagnosis of syphilis was evaluated, by applying the serum samples of 219 patients screened for syphilitic infection. The efficiency of CIA was evaluated in two steps: (1) comparison of the results of tests using the IMMULITE 2000 Syphilis Screen and LIAISON Syphilis screen reagent kits; (2) that of the results of tests applying the IMMULITE 2000 Syphilis Screen and Recombi Best antipallidum-summary antibodies kits. A 100% correlation was found when comparing the results of tests employing the IMMULITE 2000 Syphilis Screen and DiaSorin LIAISON Syphilis Screen kits (n=66). Comparison of CIA using the IMMULITE 2000 Syphilis Screen kits versus that applying the Recombi Best antipallidum-summary antibodies kits (n=153) revealed 3 discordant samples, which amounted to 1.96% of the number of results. Evaluation of the impact of related microorganisms on the detection of T. pallidum antibodies (n= 140) with the IMMULITE 2000 Syphilis Screen kit indicated no interference or cross-reactivity.

Blood testosterone in rats: correlation of the level of individual anxiety and its impairment after "death threat".

Studies of identical groups of male Wistar rats after preliminary selection to give groups including extreme behavioral types with low and high rankings on the anxiety scale showed that blood testosterone concentrations in intact rats (controls) correlated negatively with anxiety ranking, i.e., minimal hormone concentrations (no greater than 5 nM) corresponded to high levels of anxiety - with a predominance of passive defensive behavioral components on testing. Short-term exposure to a "death threat" situation (sight of a boa attacking and eating two individuals from the group of rats) impaired this correlational relationship in a manner comparable to the sequelae of chronic neuroticization by unavoidable pain stimulation. Impairments were manifest as scatter in measures in low-anxiety animals (3-21 nM). This characteristic, reflecting the multitude of adaptive pathways in the population in threat situations, distinguishes this type of action from neuroticization by unavoidable pain stimulation, which leveled out individual differences and decreased the hormone level.

[Blood testosterone in rats: correlation with individual anxiety and its derangement after the "death threat"].

After preliminary testing on a multiparameter scale, test and experimental groups of Wistar male rats were formed on the principle of identical distribution of individuals with different anxiety levels. A negative Spearman correlation between the testosterone blood concentration and the level of anxiety was observed in intact rats: the minimum hormonal concentrations (lower than 5 nmol/l) were found in rats with high anxiety, whereas the maximum concentrations (up to 16 nmol/l) corresponded to the higher anxiety level (prevalence of passive defense reactions during testing). After a sort-term exposure to life-threatening situation (viewing of a boa's attacking and devouring two victim rats from the test group), the correlation was deranged because of appearance of a scatter in testosterone blood concentration (from 3 to 21 nmol/l) in rats with low anxiety. Neurotization with inescapable pain stimulation also deranged the initial anxiety-testosterone correlation, but, as distinct from the exposure to life-threatening situation, eliminated individual differences in testosterone concentration at its low level. The results suggest the existence of multiple ways of adaptation to life-threatening situations in a rat population.

[Comparison of biological activity of high molecular weight and low molecular weight forms of immunoreactive prolactin from human serum in cultured lymphoma NB2 cells]. / Sravnenie biologicheskoi aktivnosti vysokomolekuliarnoi i nizkomolekuliarnoi form immunoreaktivnogo prolaktina syvorotki krovi cheloveka v kul'ture kletok NB2 limfomy.

In experiments with NB2 rat lymphoma cells culture sensitive to lactogenic hormones the mitogenic activity of high molecular weight (> OOK) immunoreactive prolactin, found in substantial quantities in serum of certain hyperprolactinemic women, as compared to the activity of serum low molecular weight (23K) form, was studied. It was established that the ratio of immunoreactive to biologically active prolactin content in serums in cases of low molecular weight form predominance is close to 1,0 whereas in case of predominant content of high molecular weight form it is substantially higher (1.5-2.3), apparently because of low biological activity of high molecular weight form. Direct comparison of mitogenic effects of equivalent quantities of serum immunoreactive prolactin forms with high and low molecular weight, separated by gel-filtration, confirmed low biological activity of high molecular weight form. Monoclonal antibodies to prolactin completely suppressed mitogenic activity of low molecular weight form and only partially--high molecular weight one. The data obtained indicate that high and low molecular weight forms of human serum immunoreactive prolactin differ in their biochemical and functional characteristics. Therefore their ratio in the circulating blood can substantially affect the clinical manifestations of hyperprolactinemia.

[Comparative study of physico-chemical and biological properties of human somatotropin produced by genetic engineering and isolated from the pituitary gland]. / Sravnitel'noe issledovanie fiziko-khimicheskikh i biologicheskikh svoistv somatotropina cheloveka, poluchennogo gennoinzhenernym metodom i vydelennogo iz gipofizov.

Human somatotropin hormono (STH), produced by means of gene engineering in the complex program "Human growth hormone", managed by the Academy of Sciences of the USSR, Ministry of Medical and Biological Industry of the USSR and Ministry of Public Health of the USSR, was shown to be similar in its physico-chemical properties to the main isoform of highly purified STH, isolated from human hypophysis. As distinct from the hypophyseal STH (STHhyp) containing minor isoforms of the hormone, the preparation of biosynthetic STH (des-Phe1-STH; STHbio) proved to be homogeneous. Studies of biological properties showed that STHbio exhibited high, similar to STHhyp, immunological, growth-stimulating and insulin-like activities as well as it possessed the lipotropic effect in vivo. The lipotropic effect of STHbio in vivo was less prolonged as compared with that of STHhyp, while in vitro it was only slightly expressed in isolated rabbit fat tissue. The effect did not depend on the hormone dose, apparently due to either absence of the hormone modified forms in the STHbio preparation or other hypophyseal contaminating substances responsible for the lipotropic activity. STHbio, similarly to STHhyp, did not stimulate DNA synthesis in blood serum-free culture of human fibroblasts. Studies of STHbio biological properties suggest that multifunctionality of native STHhyp appear to depend on intrinsic specificity of its molecule.

[Use of monoclonal antibodies for immunosorption of growth hormone from human biological tissues and fluids]. / Ispol'zovanie monoklonal'nykh antitel dlia immunosorbtsii gormona rostaiz bioligicheskikh tkanei i zhidkostei cheloveka.

An immunosorbent with high binding capacity was developed using monoclonal antibodies specific to human growth hormone. Potential activity of the sorbent was studied in isolation of growth hormone from biological tissues and fluids. The immunosorbent enabled one to isolate the biologically and immunologically active growth hormone with high purity from the hypophyseal extract using only one step of purification. As shown by affinity chromatography and subsequent electrophoresis in polyacrylamide gel combined with radioimmunoblotting, together with predominant form of growth hormone, also intact and secreted from hypophysis, two-chain form of the hormone arising after proteolysis and large immunoreactive hormone fragments were detected in human circulation. These derivatives of the hormone may be also excreted with urine in unaltered form.

[Hearing function of workers of "noisy" occupations at the Podolsk machinery plant and effectiveness of therapeutic measures]. / Slukhovaia funktsiia u rabochikh "shumovykh" professii Podol'skogo mashinostroitel'nogo zavoda i éfffektivnost' lechebno-ozdorovitel'nykh meropriiatii.

In recent years noise and vibration have become dominant hazards influencing workers' health. A significant share of the resulting disease in covered by occupational deafness. The article demonstrates data of hearing examination among 262 workers exposed to intermittent noise of 95-100 dB A. Slow progress of occupational deafness and bilateral cochlear neuritis with over 15 years of service appeared to be characteristic for the examinees. Helium neon laser applied on mastoid process and general improving treatment appeared to be effective.

Primary structure of seiwhale pituitary somatotropin.

Seiwhale somatotropin has been isolated from seiwhale pituitaries. It was cleaved by cyanogen bromide, trypsin and chymotrypsin. The peptide fragments were separated and purified by gel filtration on Sephadexes, ion exchange chromatography, high voltage electrophoresis and paper chromatography. Amino acid sequences of the isolated peptides were studied by the dansyl-Edman procedure. The data obtained suggested a primary structure of seiwhale somatotropin consisting of 190 amino acid residues and showed a high degree of homology with somatotropins of many other species.

[Hydrophobic peptide possessing growth activity from the trypsin hydrolysate of sperm whale somatotropin]. / Gidrofobnyi peptid iz tripsinovogo gidrolizata somatotropina kashalota, obladaiushchii rostovoi aktivnost'iu.

Hydrophobic 31-member peptide exerting a considerable growth effect in "tibia-test" was extracted in a homogenous state from trypsin hydrolyzate of cachalot somatotropin. Comparison of N-end (1--11) aminoacid succession of peptide content with known somatotropin structure allows a conclusion that the peptide represents the 77th to 107th ingredient of the hormone polipeptide chain. The peptide studied has no analogues among somatotropin ingredients described in the literature capable of retaining the growth effect and having the shortest structure.

[Induction of sensitivity of a fibroblast culture to hypophyseal somatotropin by a thermostable blood serum factor]. / Induktsiia chuvstvitel'nosti kul'tury fibroblastov k gipofizarnomu somatotropinu termostabil'nym faktorom syvorotki krovi.

A study was made of the effects of highly purified preparations of human and bovine pituitary somatotropin on DNA biosynthesis in fibroblast cultures from adults' skin. The intensity of DNA biosynthesis was evaluated from 3H-thymidine incorporation into the cells. It was established that both somatotropin preparations are capable of stimulating DNA synthesis by fibroblasts. However, simultaneous presence in the medium of the thermo- and acid-resistant fractions of rat blood serum is required for the stimulating effect of the hormone to manifest. It was found that the activity of blood serum factor inducing fibroblast sensitivity to somatotropin depends on the pituitary and rises after hypophysectomy.

[Amino acid sequence of seiwhale somatotropin]. / Aminokislotnaia posledovatel'nost' somatotropina seivala.

Thirteen homogenous peptides were isolated from the chymotryptic hydrolysate of seiwhale somatotropin. The amino acid composition and sequence of the chymotryptic peptides were determined. Two large peptides were isolated from the tryptic hydrolysate of the performic acid-oxidized somatotropin. One of them had 20 amino acid residues and contained cysteic acid; the other one consisted of 31 residues and contained tryptophane and numerous leucine residues. The amino acid sequence of tryptic peptides was established after their hydrolysis with chymotrypsin. Based on these and earlier published data a complete amino acid sequence of seiwhale somatotropin comprising 190 amino acid residues was proposed. O comparison of primary structure of somatotropins from 6 different sources revealed the most conservative and variable regions of the hormone polypeptide chain.

The effect of synthetic fragment 31-44 of human growth hormone on glucose uptake by isolated adipose tissue.

Synthetic tetradecapeptide corresponding to amino acid sequence 31-44 of human growth hormone molecule and possessing a lipotropic activity was tested for the ability to stimulate glucose uptake by isolated epididymal fat pads of fed rats. Tetradecapeptide 31-44 (1 microgram/ml), growth hormone (1 microgram/ml) and insulin (50 microU/ml) stimulated in about equal degree the uptake of [U-14C]glucose by adipose tissue. Tissue samples were preliminary incubated for 3-4 hours in the absence of hormones to eliminate the refractoriness to the insulin-like effects of growth hormone. Without preincubation the tissue was refractory to the action of growth hormone and tetradecapeptide 31-44, but was sensitive to insulin. The data obtained together with the findings of Lewis et al., which showed that 20K structural variant of human growth hormone having the deletion of residues 32-46 cannot stimulate glucose uptake and lipolysis in rats, make it possible to suggest that both activities are associated with fragment 31-44.

[Obtaining of monoclonal antibodies to human growth hormone and their characteristics]. / Poluchenie monoklonal'nykh antitel k gormonu rosta cheloveka i ikh kharakteristika.

The aim of present study was to obtain the hybridomas producing monoclonal antibodies against human growth hormone (Mabs hGH), to investigate the properties of the obtained Mabs and the possibility of their application in immunoanalytical systems. Two hybridomas secreting Mabs against hGH and belonging to the IgGI subclass have been obtained. The cross-reactivity of the Mabs with structurally similar to hGH hormones (hGHbio, hPL, hPRL, bGH, bPRL, pPRL) using indirect IFA has been studied. It has been shown that Mabs hGHI and Mabs hGH2 are directed to common specific antigenic determinant i.e. they have the same epitope specificity and don't react with other structurally related hormones, i.-e. this determinant is unique for hGH. The obtained Mabs hGH2 would find application for determination hGH by immunochemical methods in fractions while the hormone isolation from pituitaries and hGH obtained recombinant DNA methodology. The development of immunosorbents on the basis Mabs hGH2 seems to be perspective. Application of this immunosorbent may give possibility to optimize hormone isolation process.

[An electrophoretic analysis of human glycoprotein hormones and their subunits]. / Elektroforeticheskii analiz glikoproteinovykh gormonov cheloveka i ikh sub''edinits.

Stability of heterodimers of human glycoprotein hormones with gonadotropic and thyrotropic activities in sodium dodecylsulfate (SDS) under non-reducing conditions at low temperature permits to resolve the native molecules of these hormones in SDS-PAG and to distinguish from their dissociated subunits by electrophoretical mobility. The analysis of dimers and alpha-, beta-subunits in one polyacrylamide gel allows to detect certain human glycoprotein hormones and to study some of their physico-chemical properties. Using two polyclonal antisera against human LH and FSH by the Western blot immunoassay it was shown that heterodimers as well as alpha and beta subunits after SDS-PAGE retain antigenic activity of native hormones. The method gave possibility to characterize the specificity of the given sera to different glycoprotein hormones.

[New data on the biological activity of pituitary somatotropin fragment 77-107]. / Novye dannye o biologicheskoi aktivnosti fragments 77-107 gipofizarnogo somatotropina.

Some new evidence on the biological activity of somatotropin fragment 77-107 is given. This fragment was prepared from whale somatotropin by tryptic hydrolysis. Beside the previously established ability of the hormone to increase the width of the tibial epiphyseal cartilage in hypophysectomized rats ("tibia" test) two other properties of the fragment indicative of its growth-promoting activity were established. The fragment enhances DNA biosynthesis in cultured human fibroblasts and increases the somatomedin content in blood serum of hypophysectomized rats. However, the fragment unlike the native hormone does not exert any metabolic action on adipose tissue "in vitro", i. e. does not stimulate the nonesterified fatty acid release into the medium. A comparison of the biological activity spectrum of native somatotropin and of its fragment 77-107 suggests that the biochemical information required for the realization of a prolonged growth-promoting effect and a relatively rapid action of the hormone on lipid and carbohydrate metabolism is contained in different parts of the polypeptide chain.

[Monoclonal antibodies to bovine prolactin interacting with human prolactin]. / Monoklonal'nye antitela k prolaktinu krupnogo rogatogo skota, vzaimodeistvuiushchie s prolaktinom cheloveka.

Two stable hybridomas producing antibodies (Mab 1 and Mab 2) to bovine prolactin and belonging to the IgG1 subclass have been prepared. The cross-reactivity of Mab 1 and Mab 2 with some structurally similar pituitary protein (human, pig, whale, rat prolactins, bovine and human somatotropins) using indirect immunoenzymatic assay, was studied. It has been shown that Mab 2 reacts specifically only with bovine prolactin whereas Mab 1 interacts with human prolactin and prolactins of different animals. The specificity of Mab 1 to human prolactin was confirmed by immunoradiodetection assay on nitrocellulose filters. The data obtained give evidence of the existence of at least two different sterically nonoverlapping epitopes: one of them is specific exclusively for bovine prolactin and the other one is common, i.e. extraspecific.

[Hypoinsulinemia, hyperglycemia and circulating antibodies to the islet cells during the development of streptozotocin diabetes in rats]. / Gipoinsulinemiia, giperglikemiia i tsirkuliruiushchie antitela k ostrovkovym kletkam pri razvitii streptozototsinovogo diabeta u krys.

The time course of metabolic parameters and islet cell surface antibodies (ICSA) in low-dose streptozotocin (STZ)-induced diabetes in rats was studied, a total STZ dose being 160 mg/kg body weight. Two-phase diabetes development was observed. Initial mild hypoinsulinemia and hyperglycemia turned to more severe diabetes after day 24 which was preceded by the first ICSA peak at day 13. The second ICSA peak occurred at day 35. The data obtained suggest that in this model of diabetes the toxic STZ effect induces both the diabetic syndrome and humoral autoimmunity to beta-cells, and the latter leads to further impairment of diabetes.