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Biomedical subjects

T Pribyl

Publications and source records attributed to T Pribyl.

At least 19 recordsLinked to original sources

DM20 mRNA splice product of the myelin proteolipid protein gene is expressed in the murine heart.

Northern blot analysis of poly A(+) RNA isolated from mouse heart revealed the expression of 3.3 and 2.4 kb mRNAs that hybridized with a cDNA for the mouse proteolipid protein (PLP). In order to examine the relationship of these RNAs to the myelin PLP/DM20 mRNAs, a mouse heart cDNA library was prepared and screened with a mouse PLP cDNA. A cDNA was isolated, sequenced, and found to encode the DM20 variant of PLP. Polymerase chain reaction (PCR) analysis of heart cDNA with three sets of primers confirmed the presence of DM20 mRNA in mouse heart and indicated that it is the major splice product of the PLP gene expressed in that tissue. In situ hybridization localized the expression of the DM20 mRNA to the myocardial cells. Northern blot analysis indicated that expression of the DM20 mRNA is developmentally regulated in the murine heart, increasing significantly in concentration after 12 days postpartum. Northern analysis also revealed the expression of the DM20 mRNA in the hearts of the jimpy and quaking mutants. These results indicate that the PLP gene is expressed in tissues other than brain and support the concept that products of the PLP gene may have some biological role other than as structural components of myelin.

Animals

Molecular analysis of a patient with neurofibromatosis 1 and achondroplasia.

The gene for von Recklinghausen neurofibromatosis (NF1) is on proximal 17q; the location of the gene for achondroplasia (ACH) is unknown. We have begun a molecular analysis of a patient with mental retardation, NF1 and ACH, a clinical presentation suggestive of a contiguous gene syndrome. In addition, this individual has a 47,XYY chromosome constitution. To define a possible chromosome 17 deletion, we investigated the copy number of DNA sequences linked to NF1 with conventional and pulsed-field gel electrophoresis (PFGE). We found no evidence for a deletion on chromosome 17. These results make it unlikely that this patient harbors a single deletion in the NF1 region causing both NF1 and ACH and suggest different mechanisms for the de novo occurrence of 2 autosomal dominant disorders in this individual.

Achondroplasia

Serum amyloid A and P protein genes in familial Mediterranean fever.

Two recent studies have suggested the involvement of serum amyloid A (SAA) and P (APCS) genes in familial Mediterranean fever (MEF). To test the role of SAA and APCS in MEF and MEF-amyloidosis, we studied 17 informative families (15 Armenians, 2 non-Ashkenazi Jews) and 8 MEF patients with amyloidosis using a candidate gene approach. No evidence for any MEF-associated polymorphism was found in any of the 41 Armenian and Jewish MEF patients tested. Our family studies allowed us to rule out tight linkage between SAA and MEF (lod score = -2.16, theta less than or equal to 0.06). For APCS we found that the allele frequency in the MEF-amyloidosis patients was similar to that in 18 unrelated MEF patients without amyloidosis and their 33 healthy parents. Finally, we excluded close genetic linkage between APCS and MEF at 8.5 cM or less (lod score = -2.2).

Alleles

Effect of dopamine-beta-hydroxylase inhibitor (disulfiram) on the response of adenohypophysis, serum ceruloplasmin and hypothalamic ascorbic acid to estradiol treatment.

The administration of tetraethylthiuramdisulfide (disulfiram, Antabus--inhibitor of dopamine-beta-hydroxylase) resulted in an inhibition of the response of anterior pituitary to estradiol (i. e. increase of weight and of binding capacity of anterior pituitary proteins to thyroxine). At the same time there was no inhibition of an increase of ceruloplasmin (polyphenoloxidase) level after estradiol, while a decrease of ascorbic acid in hypothalamus was fully prevented. It was concluded that disulfiram may inhibit dopamine-beta-hydroxylase activity and thus presumably protect the hypothalamic dopamine which further inhibits the response of anterior pituitary to estradiol either directly or through a dopamine dependent growth inhibiting factor.

Animals

The effect of hexose monophosphate shunt inhibitors on adenohypophyseal and ceruloplasmin reactions to oestrogen.

Oestradiol benzoate, as an aqueous microcrystal suspension, was administered i.m. to rats in doses of 1 mg twice a week; it induced adenohypophyseal hyperplasia and an increase of the thyroxine-binding capacity of the adenohypophyseal proteins in vitro and raised the blood ceruloplasmin level. The simultaneous administration of a hexose monophosphate shunt inhibitor--6-aminonicotinamide (200 microgram/rat/day in food) or oxythiamine (8 mg/rat/day in food)--did not modify the reaction of the adenohypophysis; the hexose monophosphate shunt thus probably does not play a significant role in the adenohypophyseal reaction to oestrogens. By themselves, both inhibitors raised the blood ceruloplasmin level and their effect summated with that of oestradiol. The mechanism of action of the inhibitors is not known, but a nonspecific stress effect leading to an increase in the ceruloplasmin level as an "acute phase protein" is considered to be the most likely.

6-Aminonicotinamide

Dopaminergic control of adenohypophyseal growth after oestrogens: negative results with L-DOPA, RO-4-4602, alpha-methyl-DOPA, apomorphine, haloperidol, pyridoxine and cyproheptadine.

Chronic oestrogen treatment augments adenohypophyseal weight and the thyroxine-binding capacity of adenohypophyseal proteins in rats. Since these reactions are both inhibited by ergocornine and ergoline derivatives (as well as by the thyroid hormones, testosterone, anti-oestrogens and antiandrogens), and are potentiation by perphenazine and the dopaminergic neurone blocker Pimozide, the peroral effectiveness of various other substances presumed to act in the region of the dopaminergic or serotoninergic neurones of the hypothalamus was tested. L-DOPA (10 mg/rat/day) did not modify the adenohypophyseal reaction, either alone or combined with the DOPA-decarboxylate inhibitor Ro-4-4602 (1 mg/rat/day). alpha-Methyl-DOPA (10 mg/rat/day), apomorphine (3 mg/rat/day), haloperidol (0.2 mg/rat/day), pyridoxine (20 mg/rat/day) and cyproheptadine (1 mg/rat/day) were likewise ineffective.

Animals

Increase of ceruloplasmin level in blood of rats after ACTH.

The level of ceruloplasmin in plasma was measured as polyphenol oxidase activity in following groups of rats: 1. controls; 2. adrenalectomized; 3. shamadrenalectomized; 4. formalin arthritis; 5. ACTH treated (25 micrograms ACTH daily for 5 days); 6. adrenalectomized and ACTH treated (as in a previous group). The level of ceruloplasmin was markedly increased after formalin arthritis, after ACTH treatment in controls and in adrenalectomized animals.

Adrenal Glands

Serum polyphenol oxidase activity (ceruloplasmin) in conventional laboratory animals and man.

The optimum pH for ceruloplasmin as polyphenol oxidase (EC 1.10.3.2) activity was determined in human serum (pH 5.4) and the serum of conventional laboratory animals--the rat (pH 5.2), mouse (pH 5.2), hamster (pH 5.3), guinea pig (pH 5.4), multimammate mouse (pH 5.2) and rabbit (pH 5.4). Determined at the optimum pH in 0.1M acetate buffer polyphenol oxidase activity fell in the sequence: rat--man--rabbit--mouse--multimammate mouse--hamster--guinea pig. Ceruloplasmin polyphenol oxidase activity was inhibited by 0.1M phosphate buffer in the mouse, rat and multimammate mouse, but not in the other species. It was inhibited by 0.05M citrate and 0.1M phthalate buffer in all the species tested.

Animals

Effect of interaction of oestrogen, testosterone and thyroid hormones on the serum ceruloplasmin level in rats.

Male rats were given oestradiol benzoate (1 mg as an aquaeous microcrystal suspension i.m. twice a week), testosterone isobutyrate (0.5 mg as an aquaeous microcrystal suspension i.m. once a week) and dried thyroid (Thyreoidin SPOFA, 0.2% in food), alone or variously combined. Oestradiol raised adenohypophyseal weight, the binding capacity of the adenohypophyseal proteins for thyroxine and the serum ceruloplasmin level. Testosterone and Thyreoidin inhibited all three of these reactions, but when they were administered together there was no summation of their inhibitory action. The nature of the relationships between the three given proteosynthetic reactions is discussed.

Animals

Interaction of perphenazine and an ergoline derivative on oestrogen-induced adenohypophyseal growth.

Male and female rats were injected twice a week for three weeks with doses of 1 mg oestradiol benzoate (OE), were given perphenazine (P, 2 mg/rat/day) or the ergoline derivative D-6-methyl-8-ergoline-(I)-yl acetic acid amide (Deprenon SPOFA, D, 200 microng/rat/day) in their food or were treated with various combinations of all three factors. OE-induced adenohypophyseal growth was inhibited by D, but the inhibitory effect of D was completely suppressed by P. D also inhibited the OE-induced increase in the thyroxine-binding capacity of the adenohypophyseal proteins, but this inhibition was not suppressed by the simultaneous administration of P. The administration of OE was followed by elevation of the serum ceruloplasmin level, which was not inhibited by P or D, either alone or combined. Ovarian weight rose markedly after D and the increase was inhibited by the simultaneous administration of either OE or P.

Adrenal Glands

Effect of oestrogen and ascorbic acid on the serum ceruloplasmin level in rats.

The administration of long-acting oestrogen (1 mg twice a week for 3 weeks) is followed, in rats, by an increase in the serum ceruloplasmin concentration to about 150% of the control value. The simultaneous administration of ascorbic acid in a dose of 10, 20 or 50 mg/rat/day in food raises the ceruloplasmin concentration to 180-200% of the control value (no significant difference was observed in the effect of the various doses of ascorbic acid). The increase produced by combining ascorbic acid with the oestrogen amounts to 20-30% of the value recorded in animals treated only with oestrogen. The mechanism by which ascorbic acid potentiates the effect of oestrogens on the ceruloplasmin level is not known.

Animals

Antioestrogenic action of the aldosterone antagonist canrenoate K in the rat (adenohypophysis, ceruloplasmin).

In a dose of 7,k mg/rat/day in food, the aldosterone antagonist canrenoate K inhibited the adenohypophyseal reaction (growth, raised thyroxine-binding capacity of the adenohypophyseal proteins in vitro) and the ceruloplasmin reaction (elevation of the serum ceruloplasmin level) to three weeks' intramuscular administration of long-acting oestradiol benzoate in doses of 1 mg twice a week. The effect was similar to that of the antioestrogen clomiphen in a dose of 1.25 mg/rat/day in food. In combined administration of clomiphen and canrenoate K, no summation of their effect was observed. Neither canrenoate nor clomiphen affected the post-oestradiol drop in body weight, but they both potentiated the oestradiol-induced decrease in testicular weight and canrenoate potentiated the effect of oestradiol on uterine weight. It was therefore concluded that the effect of canrenoate is not of a catatoxic nature, i.e. that it is not determined by increased metabolic degradation of oestradiol.

Animals

Chromosomal changes in rat pituitary and bone marrow induced by long-term estogen administration.

Pituitary weight, mitotic index and chromosomes were studied in male rats following a single or repeated dose of estradiol-benzoate for a total period of 210 days. Estrogen-induced pituitary hyperplasy eventually resulted in large pituitary tumors in some animals. The mitotic index increased until day 90, when it diminished, with chromosomes partly replaced by chromatin clusters. Most of the cells of the hyperplastic pituitaries maintained a normal diploid karyotype. However, a limited number of abnormal stem-lines with marker chromosomes appeared at a relatively early stage of the hyperplastic reaction of the pituitary. Later the tumors were characterized by an increase of number of aneuploid cells. In the bone marrow estrogens significantly lowered the mitotic index without any detectable change in chromosomal morphology.

Aneuploidy

Dopaminergic control of adenohypophysial weight and serum ceruloplasmin level in rats.

Twice a week male rats were given injections of 1 mg estradiol benzoate as an aqueous microcrystalline suspension; they were also given 0.1, 0.2 or 0.4 mg Pimozide (a dopamine receptor blocker) daily in their food. Only the maximum Pimozide dose potentiated the effect of estradiol on adenohypophysial weight and on the binding capacity of adenohypophysial proteins for thyroxine in vitro. The estrogen-induced increase in the serum ceruloplasmin level, however, was potentiated significantly by all 3 Pimozide doses.

Animals