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Biomedical subjects

V Schreiber

Publications and source records attributed to V Schreiber.

At least 73 records · Page 4Linked to original sources

Adenohypophyseal ascorbic acid: influences of oestradiol and methylene blue.

The ascorbic acid (AA) concentration in anterior pituitary and blood plasma was measured by the Roe-Kuether method in control rats and rats treated with oestradiol benzoate alone, methylene blue alone and with both oestradiol and methylene blue. We have found that methylene blue alone caused a significant drop in hypophyseal both AA and plasma AA concentrations. Methylene blue treatment prevented the increase in plasma AA concentration in oestradiol benzoate-treated rats.

Animals↗

A eukaryotic expression vector for the study of nuclear localization signals.

We describe a new vector designed to produce beta-galactosidase fusion proteins which can be used to assess subcellular localization of target peptide fragments or proteins in eukaryotic cells. The vector was constructed in such a way as to produce the peptide of interest in fusion via a short linker of proline residues to the N terminus of the reporter protein. Efficiency of the transport machinery is optimized using this particular protein fusion construction. This vector has potential uses for readily testing putative nuclear localization sequences and identifying their crucial amino-acid residues.

Amino Acid Sequence↗

Kin17, a mouse nuclear zinc finger protein that binds preferentially to curved DNA.

Kin17 is a 45 kDa protein encoded by the KIN17 gene located on mouse chromosome 2, band A. The kin17 amino acid sequence predicts two domains, which were shown to be functional: (i) a bipartite nuclear localization signal (NLS) that can drive the protein to the cell nucleus, (ii) a bona fide zinc finger of the C2H2 type. The zinc finger is involved in kin17 binding to double-stranded DNA since a mutant deleted of the zinc finger, kin17 delta 1, showed reduced binding. Single-stranded DNA was bound poorly by kin17. Interestingly, we found that kin17 protein showed preferential binding to curved DNA from either pBR322 or synthetic oligonucleotides. Binding of kin17 to a non-curved DNA segment increased after we had inserted into it a short curved synthetic oligonucleotide. Kin17 delta 2, a mutant deleted of 110 amino acids at the C-terminal end, still exhibited preferential binding to curved DNA and so did kin17 delta 1, suggesting that a domain recognizing curved DNA is located in the protein core.

Amino Acid Sequence↗

[Endocrinology 1992-1993].

In a brief review of advances made in endocrinology during the past two years, focused on steroid hormones, the author discusses findings on mineral corticoid and glucocorticoid receptors and their interaction with hormone responsive elements in nuclei of target cells. The antimicrobial action of some steroid hormones and general characteristics of the cell reaction to stress (proteins of heat shock) are also new findings. In the region of peptide hormones the author mentions findings pertaining to the mechanisms of development of adenohypophyseal adenomas, probably by the action of GHRH. It is assumed that some derivatives of prostaglandins will have an antiviral and anti-tumorous effect. An endogenous ligand for tetra-hydro-cannabinol receptors was isolated. Preventive administration of insulin protects relatives of patients with diabetes mellitus type I from the development of the disease.

Hormones↗

[New findings on endogenous drug receptor ligands].

Since the discovery of endogenous ligands for opiate receptors, endorphins and enkephalins some 30 years have elapsed. The fact that one of the breakdown products of the common precursor (proopiomelanocortin, POMC) ACTH and opioid peptides, i.e. ACTH 1-24 has a saluretic effect (balancing perhaps sodium retention after activation of the adrenal cortex) was not generally accepted yet although MSH as well as some fragments of the ACTH molecule have a natriuretic effect. The endogenous digitalis-like immunoreactive factor, DLF (even ACTH displays some DLF activities) which inhibits NaK-ATPase originates from the adrenals and is probably identical with ouabain, although I have doubts on conclusive evidence. The physiological function of DLF is not known either. Endogenous benzodiazepines ("endozepins") probably play a part in the modulation of cerebral activity: their excess may be associated with a nosological entity, idiopathic recurrent stupor. Nitric oxide, a mediator of vasorelaxing reactions, caused by acetylcholine, has already penetrated into general clinical thinking. There are at least ten diseases where NO plays a part. It is not only an endogenous factor which imitates more perfectly the action of organic nitrates but also a nervous mediator and it shares this function with another gaseous mini-hormone, carbon monoxide (CO). Endogenous ligands of drug receptors comprise also endogenous substances which interreact with receptors for calcium inhibitors (inhibitors of calcium channels). Here are important clinical perspectives not only in cardiology. There are moreover endogenous ligands for receptors for marihuana (tetrahydrocannabinols) in particular a derivative of arachidonic acid anandamide (substance of "inner bliss").(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Structure and function of poly(ADP-ribose) polymerase.

Poly(ADP-ribose) polymerase (PARP) participates in the intricate network of systems developed by the eukaryotic cell to cope with the numerous environmental and endogenous genetoxic agents. Cloning of the PARP gene has allowed the development of genetic and molecular approaches to elucidate the structure and the function of this abundant and highly conserved enzyme. This article summarizes our present knowledge in this field.

Amino Acid Sequence↗

An analog of MIF, alaptide: effect on serum prolactin, dopamine receptors and growth of rat adenohypophysis.

Alaptide is a drug chemically derived from prolyl-leucyl-glycin amide (PLG) which is effective after oral administration. We studied the effect of long term treatment with alaptide and estradiol-benzoate on serum prolactin, growth reactivity and dopamine DA-2 receptors in the anterior pituitary of male rats. Alaptide reduced adenohypophyseal weight when given alone, but only nonsignificantly reduced growth reactivity of the anterior pituitary (AP) raised by estradiol-benzoate (EB). Alaptide significantly decreased the serum level of prolactin but, on the other hand, significantly increased the binding of 3H-spiperone to dopamine DA-2 receptors in AP membrane preparations, without affecting affinity. The administration of alaptide plus EB together resulted in an additional increase of dopamine DA-2 binding sites. We assume that alaptide has a weak dopaminergic activity on the AP of male rats.

Animals↗

Methylene blue inhibition of oestradiol-induced increase of ceruloplasmin serum levels in rats.

The administration of oestrogens increases the hepatic synthesis and plasma level of ceruloplasmin both in man and laboratory animals. Methylene blue, an oxidizing agent and inhibitor of soluble guanylate cyclase, is widely used to block the effects of endothelium-derived relaxing factor (nitric oxide). We describe the inhibitory effect of methylene blue on the increase of ceruloplasmin plasma level in rats during oestradiol treatment.

Animals↗

Methylene blue inhibits the stimulation of bone mass by high doses of estradiol in male rats.

To elucidate the effect of methylene blue on bone metabolism we examined the rats treated with estradiol, with methylene blue alone and with estradiol and methylene blue. The mineral bone mass in the femurs of the animals was measured quantitatively. A significant increase of bone density and bone mineral content was found in the estradiol treated animals compared to animals without estradiol. The rise in bone mineral content after estradiol was inhibited by methylene blue. Methylene blue alone did not affect bone mineral mass. From our work the possibility arose that beside well known effect of estradiol on osteoblast receptors also other mechanism of estrogen action exists which possibly may include the effect of estrogen on cytosolic guanylate cyclase producing cGMP.

Animals↗

Long-term results of uncemented alumina acetabular implants.

We report the clinical and tribological performance of 67 ceramic acetabular prostheses implanted between 1976 and 1979 without bone cement. They articulated with ceramic femoral heads mounted on mental femoral stems. After a mean elapsed period of 144 months, 59 sockets were radiographically stable but two showed early signs and six showed late signs of loosening. Four of the loose sockets have been revised. Histological analysis of the retrieved tissue showed a fibrous membrane around all the implants, with fibrocartilage in some. There was no bone ingrowth, and the fibrous membrane was up to 6 mm thick and infiltrated with lymphocytes, plasma cells, and macrophages. Intra- and extracellular birefringent wear particles were seen. Tribological analysis showed total wear rates in two retrieved alumina-on-alumina joints of 2.6 microns per year in a stable implant and 68 microns in a loose implant. Survival analysis showed a revision rate of 12.4% at 136 months.

Adult↗

[Who is concerned with medical science in Europe?].

On the basis of 34th Meeting of the Standing Committee of the European Medical Research Councils held from 2nd to 3rd June 1994 in Interlaken (Switzerland)--besides the list of EMRC members--a proposal was made for solution of this problem in the Czech Republic that has only been observed in this organization. Government of the Czech Republic, Ministry of Education and Ministry of Health have not yet said anything in response to initiatives submitted by the Czech Medical Research Council.

Czech Republic↗

Epidermal growth factor and prolactin in rat anterior pituitary after chronic treatment with estradiol and triiodothyronine.

Adult male rats were treated for 20 days either with estradiol benzoate (EB; 10 mg/kg twice a week i.m.) or triiodothyronine (T3; approx. 500 micrograms/kg daily mixed to the food) or both and the concentration of epidermal growth factor (EGF) and prolactin (PRL) in the anterior pituitary (AP) was estimated. In a preliminary experiment no difference in EGF content in the AP of male and female rats was found. The administration of EB was followed by highly significant increase in AP weight and a significant decrease in EGF content per mg of the AP, but not per whole AP. The concentration of rPRL was significantly increased in AP and serum of EB treated animals. After T3 treatment the mean concentration of EGF in the AP was slightly elevated as compared with controls. The administration of T3 together with EB prevented the increase of AP weight as observed after EB alone. However, the content of EGF as expressed per mg of the AP was not different from that in control group, though it was elevated when expressed per whole gland.

Administration, Oral↗

Anterior pituitary weight, cAMP, cGMP and prolactin levels after combined treatment with estradiol and methylene blue.

Male rats received estradiol benzoate in a long acting microcrystalline suspension (1 mg/rat i.m., twice a week), methylene blue (MB) 0.5% in the food and the combination of estradiol and MB. After three weeks, MB partially inhibited the growth response of the anterior pituitary to estradiol and it partially inhibited the increase of cAMP content in anterior pituitary. The increase of anterior pituitary cGMP content was not modified by MB, neither the ratio cAMP/cGMP in the anterior pituitary which, however, decreased after estradiol. This decrease was not modified by MB. On the other hand, the prolactin (PRL) increase in the blood after estradiol was inhibited by MB, although the prolactin content in the anterior pituitary was not. Methylene blue alone did not change blood prolactin concentration, but it unexpectedly elevated blood thyroxine levels and this effect was partially inhibited by simultaneous estradiol treatment.

Animals↗

Anterior pituitary weight, cAMP, cGMP and prolactin levels after combined treatment with estradiol and methylene blue.

Male rats received estradiol benzoate in a long acting microcrystalline suspension (1 mg/rat i.m., twice a week), methylene blue (MB) 0.5% in the food and the combination of estradiol and MB. After three weeks, MB partially inhibited the growth response of the anterior pituitary to estradiol and it partially inhibited the increase of cAMP content in anterior pituitary. The increase of anterior pituitary cGMP content was not modified by MB, neither the ratio cAMP/cGMP in the anterior pituitary which, however, decreased after estradiol. This decrease was not modified by MB. On the other hand, the prolactin (PRL) increase in the blood after estradiol was inhibited by MB, although the prolactin content in the anterior pituitary was not. Methylene blue alone did not change blood prolactin concentration, but it unexpectedly elevated blood thyroxine levels and this effect was partially inhibited by simultaneous estradiol treatment.

Animals↗

Endogenous quinidine-like immunoreactivity in the serum of rats with cardiac overload, stress or hyperthyroidism. Rapid communication.

Quinidine-like immunoreactivity (Abbott TDx Quinidine fluorescence polarization immunoassay) was measured in control, sham-operated, abdominal aorta stenotic and hyperthyroid (thyroxine feeding 0.1 mg/rat/day rats. The mean quinidine levels (mumol quinidine/1 serum) were 0.07, 0.14, 0.13 and 0.25, respectively. The elevation in experimental hyperthyroidism was statistically (analysis of variance, Duncan's test) significant. The possibility of the existence of an endogenous antiarrhythmic, immunologically cross-reacting in quinidine immunoassay, is discussed.

Animals↗

[Correlation between urinary excretion of neopterin and levels of thyroid gland hormones in patients with goiter].

The authors assessed in 18 patients with goitre the urinary excretion of neopterin and the blood level of thyroid hormones. They revealed a significant correlation between urinary neopterin excretion and the thyroxine (T4) and triiodothyronine (T3) blood level. This correlation did not apply in female patients treated with large doses of Carbimazol: these patients had a high neopterin excretion, while the thyroid hormone levels were only slightly elevated. This suggests again that Carbimazol has in addition to an antithyroid effect also an immunomodulating action.

Biopterins↗

[EDRF-NO. The endothelium-derived relaxing factor is nitric oxide].

The author reviews findings assembled during the last 20 years on the endothelium-derived relaxing factor (EDRF), and in particular findings assembled the last five years which revealed that EDRF is identical with nitric oxide, NO. The enzyme NO synthetase produces NO from l-arginine with the concurrent formation of citrulline and is present not only in the endothelium of the vascular wall but also in cerebral neurons and other tissues. NO is probably also the effective factor of the vasodilatating action of organic nitrates (nitroglycerol, amyl nitrite, sodium nitroprusside). In recent years these findings are applied also in clinical work. In atherosclerosis of the coronary vessels NO formation is obviously reduced and l-arginine infusion may improve the coronary blood supply in patients with hypercholesterolaemia. Inhalation of NO has been tried in pulmonary hypertension. Antidotes of NO (methylene blue) conversely may prevent hypotension in hepatic failure. Infusion of an antidote of l arginine prevents hypotension in septic shock. This is due to the fact that an excess of NO is formed from macrophages during infections. NO is, however, also mutagenic and there are reports on its participation in the genesis of genetic and neoplastic diseases.

Animals↗

The human poly(ADP-ribose) polymerase nuclear localization signal is a bipartite element functionally separate from DNA binding and catalytic activity.

Poly(ADP-ribose) polymerase (PARP, EC 2.4.2.30) is a zinc finger DNA-binding protein involved in DNA repair processes in eukaryotes. By deletion and extensive site-directed mutagenesis, its DNA-binding domain fused to the N-terminus of beta-galactosidase was shown to contain a nuclear localization signal (NLS) of the form KRK-X(11)-KKKSKK (residues 207-226). In vitro, both the DNA-binding capacity and the polymerizing activity of PARP are independent of the nuclear location function. Each basic cluster is essential but not sufficient on its own for this function, while both motifs together are. Crucial basic amino acids (K207, R208 and K222) in each of these two motifs are required for nuclear homing. The results presented here support the concept that the human PARP NLS is an autonomous functional element and belongs to the class of bipartite NLSs. We show that the linear distance between the two basic clusters is not crucial. Insertional mutation analysis leading to a partial reversion of the cytoplasmic phenotype displayed by the mutant K222I highlights the crucial positioning of this lysine. The structure-function relationship of the second cluster of basic residues is discussed.

Amino Acid Sequence↗