Biomedical subjects

V Schreiber

Publications and source records attributed to V Schreiber.

At least 37 records · Page 2Linked to original sources

PubMed1999

[Endocrinology 1997-1998].

The author presents an account on advances in endocrinology in 1997-1998, starting by mentioning the Nobel prize for physiology and medicine in 1998 and the discovery of nitric oxide as an active substance. Subsequently the author discusses data on "new gerontology", i.e. hormonal aspects of the menopause, andropause, adrenopause and somatopause. Endocrinological contributions to oncology pertain in particular to the discovery of active substances which inhibit neovascularization (endostatins) and some new aspects of the action of antioestrogens and oestrogens. The possible action of hormonal factors in neurodegenerative processes are obvious in ubiquitine, CREB and "heat shock proteins". New types of Ca-channels were detected, in particular "promiscuous" channels, conveying Ca as well as Na, which can be influenced by endogenous ouabain. Subsequently attention is paid to ryanodine receptors and compounds acting as Ca on the sensor for Ca in the parathyroid bodies and inhibition parathormone secretion. The greatest future advances will be achieved obviously in the sphere of oncology, gerontology and hormonal analogues with unforeseen effects.

Calcium Channels↗

PubMed1998

[Endocrinology 1996-1997].

Post-traumatic stress-induced disorders are still the focus of interest and most recently discussions are under way whether stress-induced cortisol excess leads to atrophy of the brain. In investigation on carcinogenesis the first reports were published on the use of antisense-oligonucleotides during inhibition of the development of tumours by a humoral mechanism and on the gene-based neuroendocrine differentiation of the lungs, perhaps associated with the basis for the development of small cell carcinoma. The oncogenic action of superoxides has also humoral mediators. Interest in nitrogen oxide is focused on two areas: inflammations and hypertension. Intraluminal NO concentrations increase in asthma 2-10x, in cystitis 30-100x, in Crohn's disease 20-200x. Humoral mechanisms in asthma offer new drugs--inhibitors of the development or action of leucotrienes. The basal NO production is reduced in "essential" hypertension but it is not known whether it is the cause or consequence. IGF-I increases the formation of NO in the vascular wall and thus perhaps reduces vascular contractility. As far as IGF is concerned, it is obvious that if recombinant preparations will be available, they will be tested in amyotrophic lateral sclerosis, myotonic dystrophy, multiple sclerosis, catabolic conditions, osteoporosis, in renal failure and to promote wound healing. STH may also prove useful in cardiac failure, in particular in cardiac cachexia. That TRH has receptors in the gut is not surprising, it acts, however, even there via TSH. Thrombopoietin is being tested in clinical trials. Neocytolysis is a new phenomenon: when erythropoietin secretion declines new erythrocytes disappear and only old ones remain in the blood stream. Alpha-adducin is a renal tubular protein, regulating the sodium balance.

Hormones↗

PubMed1998

Chromosomal assignment and expression pattern of the murine Lasp-1 gene.

The human Lasp-1 (LIM and SH3 protein) gene was previously identified by differential screening of a breast cancer-derived metastatic lymph node cDNA library. It was located on the q12-q21 region of human chromosome 17 and was shown to be amplified and overexpressed in 12% of breast tumors. Lasp-1 defines a new LIM-protein subfamily, as it associates a C-terminal Src homology 3 (SH3) domain to a N-terminal LIM motif. In this study, the isolation and characterization of the cDNA encoding the mouse Lasp-1 protein are described, and it is shown to be highly conserved with its human counterpart. In addition to the LIM and SH3 domains, both human and mouse Lasp-1 contain an actin-binding domain. The mouse gene was mapped by in situ hybridization to the 11C-11D region of chromosome 11. Northern blot analysis shows that this gene is expressed from 7.5 to 17.5 days post-coitum of mouse embryogenesis and in almost all adult tissues.

Adaptor Proteins, Signal Transducing↗

PubMed1998

The changes of the thyroid function and serum testosterone levels after long-term L-NAME treatment in male rats.

Nitric oxide is a highly reactive gas that is produced by many tissues and exerts a series of physiological and pathophysiological effects. We studied the changes of the serum testosterone, thyroxine and thyrotropin levels, thyroid and anterior pituitary weights and thyroid cGMP concentrations in male Wistar strain rats treated with estradiol benzoate (EB) (1 mg/kg, im twice a week) and nonselective NO-synthase inhibitor L-NAME (N-omega-nitro-L-arginine methyl ester) alone and with combination of these substances. We have found that L-NAME in a dose 100 mg/kg/day but not in a dose 50 mg/kg/day increased the serum thyroxine and testosterone levels and in the case of testosterone in a higher dose partially blocked its drop when administered simultaneously with EB. The serum thyrotropin levels significantly fell after L-NAME and EB treatment. The cGMP thyroid levels changed only slightly in groups treated EB and L-NAME alone and were significantly decreased in group treated with combination of these substances. The nitric oxide thus seems to be an important modulator of thyroid and testicular function. The cGMP activation cascade is not probably involved in the nitric oxide induced changes of thyroid function.

Animals↗

PubMed1998

Estrogenic effect of estradiol-sulfamate on the male rat anterior pituitary.

Estrogen sulfamates (ES) are used for a new treatment strategy to avoid liver-hormone and hormone-liver interactions. ES represent new synthetic steroids having an increased systemic and reduced hepatic estrogenicity when given orally [1,2]. In the present study effects of ES and estradiol-benzoate (EB) on adenohypophyseal (AP) and serum concentrations of prolactin (PRL), luteinizing hormone (LH), and pituitary contents of cAMP and cGMP in the male rat are demonstrated. The weight gain of experimental animals treated by ES, EB or both hormones simultaneously was significantly lower compared to controls. EB but not ES significantly increased the weight of the AP. The amounts of PRL in the AP and serum were significantly increased after EB administration. ES significantly increased only AP content of PRL. EB administered simultaneously with ES exhibited an additive effect on the AP plasma concentrations of PRL. The EB or ES significantly decreased AP and serum concentrations of LH. ES given simultaneously with EB further decreased AP and serum concentrations of LH. After administration of either ES or EB, AP contents of cAMP and cGMP were significantly increased. An additive effect of these estrogens on the cGMP content was found. ES given simultaneously with EB further increased cGMP content in the AP but partially inhibited the effect of EB on the AP cAMP content. The present results demonstrate that the effects of ES on the AP content of PRL, LH, cAMP, and cGMP differ from the effects of EB. Whether this is due to lower levels of estradiol after the administration of ES secondary to its different absorption when compared to EB is unknown. Thus, our data support the concept that the ES has a lesser estrogenic effect on the AP function.

Animals↗

PubMed1998

XRCC1 is specifically associated with poly(ADP-ribose) polymerase and negatively regulates its activity following DNA damage.

Poly(ADP-ribose) polymerase (PARP; EC 2.4.2.30) is a zinc-finger DNA-binding protein that detects and signals DNA strand breaks generated directly or indirectly by genotoxic agents. In response to these breaks, the immediate poly(ADP-ribosyl)ation of nuclear proteins involved in chromatin architecture and DNA metabolism converts DNA damage into intracellular signals that can activate DNA repair programs or cell death options. To have greater insight into the physiological function of this enzyme, we have used the two-hybrid system to find genes encoding proteins putatively interacting with PARP. We have identified a physical association between PARP and the base excision repair (BER) protein XRCC1 (X-ray repair cross-complementing 1) in the Saccharomyces cerevisiae system, which was further confirmed to exist in mammalian cells. XRCC1 interacts with PARP by its central region (amino acids 301 to 402), which contains a BRCT (BRCA1 C terminus) module, a widespread motif in DNA repair and DNA damage-responsive cell cycle checkpoint proteins. Overexpression of XRCC1 in Cos-7 or HeLa cells dramatically decreases PARP activity in vivo, reinforcing the potential protective function of PARP at DNA breaks. Given that XRCC1 is also associated with DNA ligase III via a second BRCT module and with DNA polymerase beta, our results provide strong evidence that PARP is a member of a BER multiprotein complex involved in the detection of DNA interruptions and possibly in the recruitment of XRCC1 and its partners for efficient processing of these breaks in a coordinated manner. The modular organizations of these interactors, associated with small conserved domains, may contribute to increasing the efficiency of the overall pathway.

Adenosine Diphosphate Ribose↗

PubMed1998

[Hormonally active peptides].

The article reviews hormonally active peptides, mechanisms of their biosynthesis and chemical synthesis. Special attention is given to achievements of the Czech school of peptidology. Mechanisms of activity of peptidergic hormones is based mainly on the activation of adenylatcyclase and formation of the "second messenger", cAMP. Other three possible mechanisms are also reviewed. Main groups of peptidergic hormones (neurohypophyseal hormones, hypothalamic regulatory hormones, gastrointestinal hormones, natriuretic peptides, and many others) are described and their therapeutic and diagnostic significance is summarised. Future prospects of peptidology in the clinical praxis are briefly reviewed.

Gastrointestinal Hormones↗

PubMed1998

Independence of estrogen-induced pituitary proliferation on local IGF-I mRNA and EGF mRNA expression. Modifying effects of tamoxifen and terguride.

Pituitary hyperplasia as well as proliferation of the endometrium are typical responses to estrogen administration in rodents. Both insulin-like growth factor-I (IGF-I) and epidermal growth factor (EGF) have been implicated as paracrine mediators and amplifiers of estrogen action in the rodent uterus. The auto/paracrine role of IGF-I, EGF, their receptors and IGF binding proteins in pituitary proliferation has not yet been solved. Here we have used a semi-quantitative reverse transcription polymerase chain reaction (RT PCR) assay to demonstrate the changes in IGF-I mRNA and EGF mRNA abundance in the proliferating male rat pituitary in response to estradiol benzoate (EB; 1 mg/kg b.w. twice weekly i.m. for 3 weeks) and modifying effect of drugs antagonizing the pituitary enlargement - antiestrogen tamoxifen (TAM, 5 mg/kg b.w. daily) and also the dopaminergic agonist terguride (TER, 0.66 mg/kg b.w. daily, routinely used for the treatment of prolactinomas). In three separate experiments, EB induced a 2.2-2.5 fold increase in pituitary weight. The abundance of IGF-I and EGF mRNAs in pituitaries of EB-treated animals did not differ from the controls in two experiments and in the third series with the most marked pituitary hyperplasia mRNAs of both growth factors were even significantly decreased. Antiestrogen TAM administered with EB partially blocked the EB-induced proliferation and significantly stimulated IGF-I mRNA (p=0.003) and EGF mRNA (p=0.023) expression, while EB or TAM alone did not stimulate mRNAs of the studied growth factors. Significant antiproliferative effect of dopaminergic agonist TER on EB-induced pituitary proliferation (p=0.006) was accompanied with decreased IGF-I mRNA (p=0.025), but not EGF mRNA abundance. Our results suggest that the estrogen-induced pituitary proliferation is independent of the local expression of IGF-I and EGF mRNAs.

Animals↗

PubMed1998

Lasp-1, a novel type of actin-binding protein accumulating in cell membrane extensions.

The Lasp-1 gene, which has been localized to the q12-q21 region of human chromosome 17, is amplified and overexpressed in human breast cancers. In addition to the previously reported LIM and SH3 domains of Lasp-1, we report here the identification of an actin-binding domain in the core of the protein. This domain is functional as we demonstrate that Lasp-1 binds actin in vivo and in vitro. In addition, confocal analysis of the Lasp-1 subcellular distribution shows that the protein is colocalized with actin at peripheral cell extensions in individual epithelial cancer cells and in transformed fibroblastic cells. Moreover, Lasp-1 is tyrosine phosphorylated in fibroblast cell lines transformed by a constitutively active form of c-Src (c-SrcY527F). Altogether, our results show that Lasp-1 defines a new type of actin-binding protein and suggest that the protein may play a role in a signaling pathway involved in the organization of the cytoskeleton.

3T3 Cells↗

PubMed1997

[Endocrinology 1995-1996].

In a brief review of advances in endocrinology in the last two years the author discusses above all the vain expectations of a drug against obesity-the adipose tissue hormone leptin. Its elevated blood level in human obesity indicates that its secretion depends on the mass of adipose tissue and it is not certain whether leptin reduces the food intake in humans. Perhaps resistance to leptin is involved. New receptor diseases were revealed: mutation of LH receptors leads in both sexes to hypogonadism. Mutation of the calcium receptor in parathyroid cells leads to familial hypocalciuric hypercalcaemia or autosomal dominant hypocalcaemia. The complex regulation of the tonus of the vascular wall by endothelins is still the object of interest. Aquaporin is a renal protein which mediates the action of vasopressin. In the sphere of stress evidence is emerging on the participation of CRH in brain activity and the possibility to influence autoimmune inflammations and perhaps even AIDS by interference with the CRH-proopiomelanocortin-ACTH-cortisol system.

Endocrine System Diseases↗

PubMed1997

In vivo antiestrogenic activity of mifepristone in the rat.

The aim of this study was to find out whether mifepristone, known mainly as a substance with an antiprogesterone and antiglucocorticoid effect, also has an in vivo antiestrogenic activity on the adenohypophysis of the rat. Male Wistar rats were given chronically either estradiol-benzoate (EB, 1 mg s.c. twice a week) for a period of 12 days, or the non steroidal antiestrogen tamoxifen (1 mg/day/rat), or mifepristone (1 mg/day/rat), or EB together with mifepristone or tamoxifen. The hypertrophic effect of the EB on the weight of the adenohypophysis (AP) was significantly suppressed both by tamoxifen and by mifepristone. Mifepristone and tamoxifen reduced the increased content of PRL in the estrogenized adenohypophysis. Mifepristone but not tamoxifen significantly increased the content of the LH in the adenohypophysis of estrogen treated rats. Mifepristone and tamoxifen suppressed the increased concentration of cyclic nucleotides cAMP and cGMP in the estrogenized adenohypophysis. Mifepristone given alone increased serum levels of corticosterone, but when given together with EB deepened inhibiting effect EB on them. The results of our preliminary study show that mifepristone exerts a weak antiestrogenic activity on the level of hypophysis, however the pharmacology is not identical to tamoxifen.

Animals↗

PubMed1997

Comparison of in vivo long-term treatment of rats by methylene blue with its in vitro effects on thyroid hormone--nuclear receptor complex formation in liver.

The present study was undertaken to investigate both in vitro effects of methylene blue and its long-term in vivo influence on 3,5,3'-L-triiodothyronine nuclear receptor binding characteristics in rat liver. In vitro, methylene blue at 1 nmol/l was found to inhibit (p < 0.05) the 3,5,3'-L-triiodothyronine (T3) specific binding to its cognate nuclear receptors. Methylene blue at 100 nmol/l significantly (p < 0.05) reduced the thyroid hormone receptor (TR) concentration (expressed as the TR maximal binding capacity). The equilibrium association constant (Ka) of that reduced number of TR resulting from 100 nmol/l methylene blue TR treatment was significantly higher (p < 0.05), when compared to samples without methylene blue. Moreover, the T3 was found to dissociate from the TR-T3 complex in the presence of 1 mumol/l methylene blue. In vivo long-term treatment of rats with 0.125%, 0.25% or 0.5% methylene blue for 28 days did not affect either the TR maximal binding capacity (Bmax) or the Ka values in comparison with rats fed a standard laboratory diet. The data based on both in vitro or in vivo experiments suggest that in spite of a direct and quick in vitro effect of methylene blue on liver TR concentration and/or TR-T3 dissociation, a long-term in vivo treatment of rats by three different methylene blue concentrations does not affect the thyroid hormone receptor status (the concentration and the affinity) in the liver.

Animals↗

PubMed1997

AgNORs in estrogen-induced and lisuride- and thyreoidin-inhibited rat anterior pituitary hyperplasia. Computer image analysis and nonautomated AgNOR typing.

OBJECTIVE: A model of estrogen (E)-induced rat anterior pituitary hyperplasia blocked partly by thyroid hormones (estradiol plus thyreoidin [ET]) and nearly completely by lisuride (estradiol plus lisuride [EL]) and thyreoidin plus lisuride combination (estradiol plus thyreoidin plus lisuride [ETL]) was used to test a computer image analysis program, LUCIA, for argyrophilic nucleolar organizer region (AgNOR) evaluation. STUDY DESIGN: Nuclear and AgNOR area were measured in more than 700 cells in each experimental group. The nucleoli were also typed without the automated procedure. RESULTS: Mean nuclear area was significantly higher in E and lower in T. In all groups with blocked hyperplasia (ET, EL, ETL) the mean nuclear area was lower than in T. Mean AgNOR area was significantly higher in E but also, to a lesser extent, in T. The ET combination produced a partly diminished mean AgNOR area as compared to E; a severe reduction was observed in the EL and ETL groups. In nucleolar typing, thyreoidin, lisuride and their combination inhibited the increase in large nucleoli with finely dispersed AgNORs induced by estradiol. CONCLUSION: The LUCIA image analysis program for AgNOR evaluation proved able to monitor the slight changes in AgNORs in thyroid hormones- and lisuride-inhibited, estradiol-induced rat anterior pitutary hyperplasia.

Animals↗

PubMed1997

[The effect of phytogenic brassinosteroid steroidal hormones on transport of 86Rb+ ions into human erythrocytes].

The uptake of 86Rb+ ions by human erythrocytes as the measure of inhibition or stimulation of Na+, K(+)-ATPase by synthetic brassinolides, steroid fytohormonal promotors, was determined. No compound of the 12 tested brassinosteroids exerted higher inhibition of ATPase than digitoxin. A lower but significant inhibition of ion transport by 3 of tested derivatives, and a stimulation by 4 compounds was found. All active compounds were steroids with a 7-membered B-ring with an oxygen atom in the position 7a and with an oxogroup in position 6, i.e. they contained an lactone ring which is characteristic for natural brassinosteroids.

Adenosine Triphosphatases↗

PubMed1997

[Changes in thyroid function in rats after administration of methylene blue and interactions with estrogens and acetylsalicylic acid].

We have studied the thyroxine and triiodothyronine concentrations in male rats--the control, groups treated separately with estradiol benzoate, acetylsalicylic acid and methylene blue and with combinations of these substances. We have found out that the treatment with acetylsalicylic acid significantly lowers the thyroxine and triiodothyronine serum concentrations. The estradiol benzoate as well as methylene blue inhibited the drop in the serum thyroxine level when administered simultaneously with acetylsalicylic acid. The serum triiodothyronine decrease after acetylsalicylic acid treatment was inhibited by methylene blue and estradiol benzoate only in one of our two experiments. The simultaneous treatment with estradiol benzoate, acetylsalicylic acid and methylene blue did not change the triiodothyronine concentration comparing to control group and decreased the thyroxine serum concentration.

Animals↗

PubMed1997

[The effect of an NO-synthase inhibitor, methylene blue, on the function of certain endocrine glands].

Methylene blue is a thiazine dye, which has been used in the clinical medicine as disinfection agent and in treatment of methemoglobinemia. The recent investigations showed that this dye is able to inhibit the activation of guanylate cyclase pathway in the guanylate cyclase or in the NO-synthase level. This paper summarizes the experimentally obtained results concerning the influence of methylene blue on the hypothalamic, hypophyseal, thyroid and testicular function in rats. The possible mechanism of its influence with potential role of nitric oxide in the modulation of regulating pathways in these endocrine glands is discussed.

Animals↗

PubMed1997

The decrease of serum leptin levels in oestrogen-treated male mice.

Adipocyte hormone leptin (OB protein) is considered to be an "adiposity signal" regulating body weight homeostasis and energy balance. We have previously reported that oestrogens (oestradiol-benzoate) significantly decrease the body weight in male rats, increase anterior pituitary and serum levels of the intracellular messenger cAMP, which activates cAMP-dependent protein kinase A, their targets include hormone-sensitive lipase and they influence the brain sympathetic system. The present study tested our hypothesis that oestrogens could influence serum leptin levels in male mice. We found that chronic administration of oestradiol-benzoate significantly attenuated serum levels of leptin, in the dependence on the duration of its administration, and simultaneously decreased body weight. We suppose that oestrogens affect leptin levels interacting with the signal transmission system of cAMP, possibly at the genome level. Our observations that the food consumption of mice with simultaneously decreased body weight and levels of serum leptin support the idea that there exists a satiety factor that counters the effect of low leptin.

Adipocytes↗

PubMed1997

Possible participation of EDRF-NO in the hormonal regulation of bone blood flow in rats.

An increase in bone blood flow (BBF) was observed in rats after castration whereas a decrease in BBF occurred after oestradiol or testosterone. The possible participation of prostaglandins in these changes was demonstrated. The present results show that the endothelium-derived relaxing factor, i. e. nitric oxide (EDRF-NO), might play a role in these hormonal actions on BBF. Until now, almost nothing is known about the possible action of NO on bone circulation. Methylene blue (MB) as a substance blocking EDRF-NO was administered to sham-operated or oophorectomized (OOX) female rats. We determined local blood flow (85Sr-microsphere uptake), cardiac output, blood pressure, heart rate, density of the tibia and ash weight, as well as 24-h incorporation of 45Ca and 3H-proline into the tibia. The administration of MB (0.5% in the food for 4 weeks) significantly lowered both 85Sr-microsphere uptake and blood flow values in the tibia and distal femur of sham-operated and OOX rats. MB lowered cardiac output and blood pressure to the same extent, indicating no change in the vascular resistance. After the administration of MB (0.1% in the food), 85Sr-microsphere uptake decreased significantly in the tibia of OOX females while no significant change was found in soft tissues. Bone density and ash weight were significantly lower in OOX rats and in sham-operated rats after MB treatment. Finally, the 24-h incorporation of both 45Ca and 3H-proline decreased significantly in OOX females after MB administration (0.04% in the food). It can be concluded that 1) MB lowers BBF, suggesting the participation of EDRF-NO in BBF regulation, 2) MB does not influence or may even suppress cardiac output and blood pressure in high dosage, 3) MB lowers 24-hour incorporation of 45Ca and 3H-proline into the tibia of OOX rats, which is in agreement with the circulatory effect, 4) MB lowers bone density and ash weight of the tibia in non-castrated female rats. The effects of MB observed in our experiments partially differ from those of arginine-derived blocking agents. This requires further elucidation.

Animals↗