From decimeter-scale elevated ionic conductivity regions in the cloud to lightning initiation.

In this work, we represent the lightning initiation scenario as a sequence of two transitions of discharge activity to progressively larger spatial scales: the first one is from small-scale avalanches to intermediate-scale streamers; and the second one is from streamers to the lightning seed. We postulate the existence of ion production centers in the cloud, whose occurrence is caused by electric field bursts accompanying hydrometeor collisions (or near collisions) in the turbulent thundercloud environment. When a new ion production center is created inside (fully or partially) the residual ion spot left behind by a previously established center, there is a cumulative effect in the increasing of ion concentration. As a result, the essentially non-conducting thundercloud becomes seeded by elevated ion-conductivity regions (EICRs) with spatial extent of 0.1-1 m and a lifetime of 1-10 s. The electric field on the surface of an EICR (due to its conductivity being at least 4 orders of magnitude higher than ambient) is a factor of 3 or more higher than ambient. For a maximum ambient electric field of 100 kV/m typically measured in thunderclouds, such field enhancement is sufficient for initiation of positive streamers and their propagation over distances of the order of decimeters, and this will be happening naturally, without any external agents (e.g., superenergetic cosmic ray particles) or extraordinary in-cloud conditions, such as very high potential differences or very large hydrometeors. Provided that each EICR generates at least one streamer during its lifetime, the streamers will form a 3D network, some parts of which will contain hot channel segments created via the cumulative heating and/or thermal-ionizational instability. These hot channel segments will polarize, interact with each other, and cluster, forming longer conducting structures in the cloud. When the ambient potential difference bridged by such a conducting structure exceeds 3 MV, we assume that the lightning seed, capable of self-sustained bidirectional extension, is formed.

Compound heterozygous deletion of the PROP-1 gene in children with combined pituitary hormone deficiency.

Mutations in the prophet of Pit-1 gene (PROP1) have been shown to be responsible for combined pituitary hormone deficiency (CPHD) with deficiencies of growth hormone (GH), Prolactin (Prl), thyroid-stimulating hormone (TSH) and gonadotropins. We previously reported that homozygosity for a 2bp deletion in exon 2 (296delGA) accounted for CPHD in three patients from two Russian families. Here we report a second mutational hot spot in exon 2. This 2bp 149delGA deletion results in a frame shift that leads to the same serine to stop codon change at codon 109 (S109X). The predicted proteins are each truncated at residue 108 but diverge from the wild type sequence at different points in the homeodomain. Compound heterozygosity for the two mutations (149delGA/296delGA) was detected in 5 of 14 CPHD children from 4 families (36%). This provides the first evidence of heterozygosity for two common deletions as a cause of CPHD in Russian children.

Growth hormone (GH)-releasing effects of synthetic peptide GH-releasing peptide-2 and GH-releasing hormone (1-29NH2) in children with GH insufficiency and idiopathic short stature.

To investigate how growth hormone (GH)-releasing peptide (GHRP) and GH-releasing hormone (GHRH) interact in patients with short stature, we examined the acute effects of GHRH1-29NH2, GHRP-2, and the combination of GHRH1-29NH2 and GHRP-2 on GH release in children with GH insufficiency ([GHI] group A) and idiopathic short stature ([ISS] group B). Ten children with GHI (aged 11.8 +/- 1.1 years; height, -4.2 +/- 0.5 SDS) and five children with ISS (aged 11.1 +/- 1.2 years; height, -3.2 +/- 0.1 SDS) were studied. Intravenous bolus infusions of GHRH1-29NH2 (1 micrograms/kg), GHRP-2(1 microgram/kg), and GHRH plus GHRP-2 (each 1 micrograms/kg), were administered in a randomized order. Because of the variability of GH responses, results were analyzed by a nonparametric statistical method. Patients in group A showed low GH responses to both GHRH1-29NH2 and GHRP-2 stimulation: in only three of 10 and one of nine cases, respectively, were the peak GH levels above 5.0 micrograms/L. GH area under the curve (AUC) 90 minutes after GHRP-2 administration was slightly less than for GHRH1-29NH2 (179 +/- 150 v 214 +/- 68 micrograms/L.min, P = .06). In group B, GH responses to GHRH1-29NH2 and GHRP-2 were approximately of the same magnitude (1,943 +/- 819 v 1,981 +/- 887 micrograms/L.min, P = .9).(ABSTRACT TRUNCATED AT 250 WORDS)

[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.

[Physico-chemical, immunochemical, and biological activity of prolactin from human amniotic fluid]. / Fiziko-khimicheskaia, immunokhimicheskaia i biologicheskaia kharakteristika prolaktina amnioticheskoi zhidkosti cheloveka.

Highly purified preparation of prolactin with molecular mass 23 kDa, which is the main form of the hormone in human amnionic fluid, was isolated from the fluid using gel filtration on Sephadex G-100, chromatography on DEAE-Sepharose, concanavalin A Sepharose, CM-cellulose. Physico-chemical, immunochemical and biological properties of the amnionic prolactin were studied as compared with those of hypophyseal hormone. Properties of the hormonal forms isolated from both these tissues were similar. The glycosylated form of prolactin with molecular mass 25.0 kDa was detected either in amnionic fluid or in hypophysis.

[The alpha subunit of glycoprotein hormones as a biochemical marker of pituitary tumors]. / Al'fa-sub''edinitsa glikoproteinovykh gormonov kak biokhimicheskii marker opukholei gipofiza.

Specific radioimmunoassay was developed for detection free glycoprotein hormone alpha-subunit (AS), by using AS prepared from highly purified human thyroid-stimulating hormone (TSH). The assay showed that the basal content of free serum AS in the majority of 24 females with hormonally pituitary tumors secreting somatotropic hormone (STH, growth hormone), prolactin or either and in 24 females with unfunctioning pituitary tumors was significantly higher the mean one in 12 females matched for the same age who had no endocrine diseases (control). The cultured cells of STH- and P-secreting tumors released excessive quantities of free AS along with STH and P into the medium with low glycoprotein holo-hormone levels. The content of AS changed little in 12 patients with non-functioning pituitary tumors despite the greatly increased serum TSH levels in response to the hypothalamic stimulator thyroid-releasing hormone. The findings suggest that free AS secreted into blood in excess despite hypothalamic control may be regarded as a biochemical marker of pituitary tumors.

[Effect of whale somatotropin and its biologically active fragment on various indicators of carbohydrate metabolism in the rat diaphragm in vitro]. / Issledovanie vliianiia kitovogo somatotropina i ego biologicheski aktivnogo fragmenta na nekotorye parametry uglevodnogo obmena v diafragmal'noi myshtse krys in vitro.

The ability of somatotropin seival and its fragment 77-107, retaining a marked growth-stimulationg activity, to change the intensity of 14C-glucose consumption from the medium and 14C-glucose inclusion into glycogen by in vitro incubated semidiaphragm of hypophysectomized rats was studied. It was detected that somatotropin seival, contacting with the diaphragmatic muscle tissue, provokes "insulin-like" effect. (i.e. stimulates glucose consumption and glycogen synthesis by this tissue), similar to that of the other animal somatotropins studied. Somatotropin fragment 77-107, revealing growth-stimulating activity, is not able to intensify glucose consumption and glycogen synthesis in the muscle tissue, in contrast to the whole hormone, being indicative of dissociation between structural determinants of these effects in hormone molecule.

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.

[Achievements of molecular endocrinology and biochemistry of hormones and new approaches to the study and correction of endocrine disorders]. / Uspekhi molekuliarnoi endokrinologii i biokhimii gormonov i novye podkhody k izucheniiu i korrektsii endokrinnykh narushenii.

Considerable progress in a study of the molecular mechanisms of the hormone biological effect has shown that practically all hormones regulate metabolism in the body by influencing the cell genetic system. These fundamental results served as a basis for a rapid development of a new direction--molecular endocrinology. In recent years effective approaches that make it possible to penetrate the secret of human and animal gene structure have been worked out. The paper is concerned with the results of a study of nucleotide sequences of genes and mRNA of various protein hormones and an analysis of the importance of these developments for present-day endocrinology and biochemistry of hormones.

[Isolation and certain properties of human pituitary prolactin]. / Vydelenie i nekotorye svoistva gipofizarnogo prolaktina cheloveka.

A simple method of isolation of highly purified prolactin from acetonated preparations of anterior hypophysial lobes is described. The new method permits to obtain higher (about 10-fold) yields of the hormone, as compared to those obtained using previously described methods. Prolactin was extracted by acid aqueous acetone and was subsequently purified of extract by fractionation with acetone and NaCl and by isoelectric precipitation. The final stage of the hormone purification involved gel-filtration through Sephadex G-200; prolactin yield was 400 microgram per 1 hypophysis. The lactogenic activity of the hormone is 14 MU/mg; the sequence of N-terminal amino acid residues of prolactin is as follows: NH2-Leu-Pro-Ile-x-Pro-Leu(?)-Gly-Ala-.

[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.

[Effect of pituitary hormones on phosphodiesterase and adenyl cyclase activity of brain tissue in vitro]. / Vliianie gipofizarnykh gormonov na aktivnost' fosfodiésterazy i adenilattsiklazy v tkani mozga in vitro.

Effects of seiwhale somatotropin (STH), its biologically active fragment 77--107, porcine corticotropin (ACTH) and seiwhale prolactin on phosphodiesterase and adenylate cyclase activity of glial cells and synaptosomes isolated from the rat brain cortex were investigated. As compared with control, ACTH increased phosphodiesterase activity of glial cells by 392%, of synaptosomes by 123%, while STH by 49 and 77%, respectively, somatotropin fragment by 455 and 74%, and prolactin by 30 and 37%, respectively. Adenylate cyclase activity was significantly changed only by ACTH and only in synaptosomes (a 50% decrease). STH, its fragment and prolactin virtually failed to alter adenylate cyclase activity. The data obtained indicate that some of pituitary hormones, primarily ACTH and STH, may play the role of neuromodulators in some brain structures by decreasing the cyclic AMP level, by activating phosphodiesterase (STH and ACTH) and inhibiting adenylate cyclase (ACTH in synaptosomes).

[Polymorphism of prolactin in amniotic fluid of women at various times of pregnancy]. / Polimorfizm prolaktina v amniotichekoi zhidkosti zhenshchin v razlichnye sroki beremennosti.

The level and molecular forms of prolactin (PRL) in amniotic fluid of pregnant women were investigated at various time of pregnancy with the help of radioimmunoassay, electrophoresis in polyacrylamide gel and immune blotting technique using poly- and monoclonal antibodies to human hypophyseal prolactin (PRL). Changes in the level of immunoreactive PRL in amniotic fluid had the shape of a Gaussian curve with a maximum at 22-29 weeks. Amniotic PRL was characterized by molecular polymorphism. A conclusion has been made that amniotic fluid PRL in pregnancy presents an independent pool of hormones, unrelated to hypophyseal PRL.

[Possible role of somatotropic hormone in regulating the functional state of glial cells in the central nervous system]. / O vozmozhnoi roli somatotropnogo gormona v reguliatsii funktsional'nogo sostoianiia kletok glii v tsentral'noi nervnoi sisteme.

Experiments were made to study the actions of STH and its fragment capable to stimulate the growth processes on MAO activity and selective binding of catecholamines by alpha- and beta-adrenoreceptors in glial cells of the rat brain cortex. For comparison the effects of STH and its fragment on 3H-PGE1 binding were studied. STH and its fragment were found to produce no influence on MAO activity or specific binding of 3H-PGE1 with glial cells. STH and its fragment (5.10(-9) M) were found to reduce specific binding of 3H-dihydroergocryptine with beta- and alpha-adrenoreceptors of glial cells, respectively. It is suggested that STH and its fragment can modulate the function of glial cells by changing the selective action of catecholamines on subpopulations of adrenergic receptors.

Biochemical nature of high-molecular-weight prolactin of human serum: identification of a prolactin-binding protein.

The biochemical nature of a high-molecular-weight immunoreactive prolactin (HMW-irPRL) prepared by gel filtration of women's sera with predominance of this hormone form was studied. Immunochemical characteristics of HMW-irPRL are different from those of 23 kD prolactin (23 kD-PRL). A protein which specifically and reversibly binds to human [125I]PRL is isolated from the pooled fractions of HMW-irPRL by affinity chromatography on prolactin-Sepharose. According to gel filtration, the binding protein (BP) has molecular weight about 150 kD, and it reversibly binds to protein A immobilized on Sepharose. Analysis of BP by SDS-PAGE resulted in two major protein bands, of 65-70 and approximately 150 kD. Both the bands, when transferred to nitrocellulose, interacted with [125I]protein A. Binding of highly purified human pituitary prolactin to the BP significantly decreased the immunoreactivity of the hormone. The molecular weight of BP and its interaction with protein A and recognition by poly- and monoclonal antibodies against human (but not guinea pig) IgG indicate that BP may be an immunoglobulin. Thus, our data demonstrate that HMW-irPRL is formed by the binding of 23 kD-PRL to a specific serum protein which is probably an anti-prolactin IgG.

[Immunoanalysis of free alpha-subunits of glycoprotein hormones in human blood serum and its relationship with pituitary glycoprotein hormones]. / Immunoanaliz svobodnoi alpha-sub"edinitsy glikoproteinovykh gormonov v syvorotke krovi cheloveka i ee vzaimootnosheniia s glikoproteinovymi gormonami gipofiza.

A radioimmunoassay test system has been designed for measurements of free alpha-subunit (AS) of glycoprotein hormones in human blood serum with a sensitivity of 0.15 ng/ml. This test system revealed the absence of a direct correlation between the levels of free AS and levels of glycoprotein hormones in the blood sera of women with various endocrine profile, this being indicative of the specificity of this test system, on the one hand, and, on the other, confirming the possibility of independent secretion by the pituitary of free AS into the blood. Basal blood serum level of free AS in normal subjects is low: 0.9 ng/ml in women aged 17 to 30. The level of free AS secretion in the blood of many patients with nonfunctioning tumors of the pituitary was found increased, this demonstrating the diagnostic significance of measuring free AS as a marker of such tumors.