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Biomedical subjects

A Bernd

Publications and source records attributed to A Bernd.

At least 55 records · Page 3Linked to original sources
PubMed1990

[Antiproliferative activity of a highly purified coal tar preparation in comparison with clobetasol-17-propionate].

Coal tar and glucocorticosteroids are among the preparations used for the treatment of hyperproliferative inflammatory dermatosis. Coal tar generally seems to have a better effect on psoriasis capillitii than betamethasone-17-valerate. This finding is confirmed by investigations with human skin fibroblasts. The coal tar preparation Berniter has a strongly inhibitory effect on cell proliferation. The action of the preparation with tar can be clearly distinguished from the effect of the vehicle. At the ED50 concentration of the substance with tar, the vehicle without tar causes no inhibition. Based on weight equivalents Berniter has a greater inhibitory effect on proliferation of human skin fibroblasts than clobetasol-17-propionate. In the case of both substances protein biosynthesis is only affected at concentrations higher than those needed for the inhibition of proliferation. Berniter and the vehicle without tar have an equally strong effect on protein synthesis. Berniter affects the nucleoside triphosphatase bound to the nuclear membrane, and thus influences the nucleocytoplasmic transport of mRNA. The effect of the vehicle and the preparation containing tar on this parameter are very similar. Berniter has a positive effect on cell mobility. In preconfluent cultures the mobility of the cell is slightly increased and in confluent cultures significantly. Our results show that Berniter inhibits proliferation in cell cultures of human skin fibroblasts to a higher degree than clobetasol-17-propionate. It is to be assumed that neither the inhibition of protein synthesis nor the inhibition of mRNA transport play a causal role in the antiproliferative effect of coal tar. Inhibition of proliferation as a result of general damage to the cell can also be practically ruled out.

Adenosine Triphosphatases↗
PubMed1990

[The effect of hydrocortisone aceponate on proliferation, total protein synthesis and collagen synthesis in human skin fibroblasts in vitro].

Effect of Hydrocortisone Aceponate on Proliferation, Total Protein Synthesis and Collagen Synthesis in Human skin Fibroblasts in vitro. Hydrocortisone aceponate, a new topical hydrocortisone derivative with esterification in positions 17 and 21, inhibits the incorporation of 3H-thymidine in DNA in human skin fibroblasts less strongly than the halogenated glucocorticosteroids betamethasone-17-valerate and clobetasol-17-propionate. Prednicarbate, a prednisolone derivative esterified in positions 17 and 21, possesses antiproliferative properties which are stronger than those of hydrocortisone aceponate, but weaker than those of the halogenated corticosteroids. The glucocorticosteroid effect on total protein and collagen synthesis of skin fibroblasts was determined by measurement of amino acid incorporation. In logarithmically growing cultures, the total protein synthesis rate was stimulated by low corticosteroid concentrations and inhibited by high concentrations. The strongest inhibition was obtained with halogenated glucocorticosteroids. In confluent, non-proliferative cell cultures, all glucocorticosteroids had a stimulating effect on total protein and collagen synthesis. Hydrocortisone aceponate and prednicarbate had a more favourable effect on collagen synthesis than the two halogenated glucocorticosteroid derivatives. According to these results, halogenation and the insertion of double bonds in the steroidal skeleton lead more readily to anti-proliferative effects than esterification in positions 17 and 21.

Cell Division↗
PubMed1990

Uptake kinetics and the effect of minoxidil on human keratinocyte cultures.

The antihypertensive drug minoxidil (Lonolox) is rapidly taken up by human keratinocytes (HaCaT-cells). After 3 h the uptake is half of its maximum. Specific minoxidil receptors could not be found. High minoxidil concentrations (greater than 100 micrograms/ml) inhibited the incorporation of thymidine into DNA (ED50 = 263 micrograms/ml) and the incorporation of amino acids into proteins (ED50 = 251 micrograms/ml). The inhibition was reversible up to a concentration of 400 micrograms/ml. In the presence of 100 micrograms/ml minoxidil, the cell division remained active for a longer period of time and a higher cell density was achieved as opposed to the parallel control group. A prolongation of the proliferative capability of keratinocytes may be partially responsible for the positive effect of minoxidil on hair growth.

Amino Acids↗
PubMed1989

[Alpha-MSH and pregnancy].

In 32 pregnant women, we repeatedly determined the levels of alpha-MSH, melatonin, ACTH and progesterone. In the radioimmunoassay, all of these hormones showed a significant increase from the first to the third trimester. In contrast to progesterone, neither the level of alpha-MSH nor that of melatonin rises significantly until between the 28th and 36th week of pregnancy. The authors suggest that the increasing pigmentation may be due to the rising levels of alpha-MSH, while the preferential hyperpigmentation of sexual areas in additionally mediated by sex hormones.

Adrenocorticotropic Hormone↗
PubMed1989

[Detection of a mitogenic serum factor in psoriasis].

Using human fibroblast cultures in vitro, a study was carried out on the effect of sera from patients with psoriasis and from healthy volunteers on DNA and protein synthesis. Thymidine incorporation was enhanced under the influence of psoriatic sera whereas there was no difference in amino acid incorporation in the control sera. Based on these results, we conclude that systemic psoriasis may be under humoral control.

Adult↗
PubMed1989

[The cytotoxic and antimutagenic effect of dithranol].

The anti-psoriatic compound anthralin (dithranol, cignolin) was determined to exhibit a strong cytostatic activity on HeLa-Köln cells; an ED50 concentration of 1.2 microM was determined for the cells. These growth-inhibition data were confirmed by thymidine-uptake experiments. The drug anthralin was determined to be neither direct a mutagen nor a premutagen in the Ames test using Salmonella typhimurium strain TA 100 (anthralin-concentration = 5 microM). Moreover, this compound was a strong inhibitor of benzo(a)pyrene monooxygenase, an enzyme which causes the metabolic conversion of premutagens to mutagens. These data demonstrate anthralin to be an antipsoriatic compound devoid of mutagenic property in vitro with regard to base-pair substitutions and provided at least with some antimutagenic potential.

Benzopyrene Hydroxylase↗
PubMed1988

[Experimental and clinical demonstration of the antiproliferative effect of a highly purified coal tar fraction in a special gel vehicle].

In this study a combination of clinical and experimental investigations demonstrates the antiproliferative effect of the coal tar-containing preparation Berniter. From a concentration of 70 micrograms/ml onwards (= 0.35 micrograms coal tar/ml) Berniter inhibits DNA synthesis of transformed human keratinocytes in vitro. The growth inhibiting effect is reversible up to the ED50 concentration (257 micrograms Berniter/ml = 1.3 micrograms coal tar/ml). The tar-free vehicle has no identifiable effect on the proliferation of the cells at a concentration of 260 micrograms/ml. However, at higher concentrations (ED50 = 1023 micrograms/ml) the vehicle also inhibits cell growth, this inhibition being irreversible. The effect of Berniter and the tar-free vehicle on amino acid metabolism corresponds with the reduced growth rate. The ED50 concentrations (331 micrograms/ml for Berniter and 1445 micrograms/ml for the tar-free vehicle) are higher than those in the investigation of the proliferation. The clinical trial was performed in two groups of 12 and 11 patients, respectively, suffering from Psoriasis capillitii. After 3 days' topical treatment of both groups with salicylic acid for scaling, one group was treated for 4 weeks with betamethasone-17-valerate (in the following briefly called Bet-17-v), as a commercial lotion. The other group received Bet-17-v initially for 3 days and was then treated for 4 weeks with Berniter. The 4 parameters used for evaluation (erythema, scaling, infiltration and itching) showed a more significant improvement in the Berniter group than in the Bet-17-v group. Subjectively, treatment with Berniter was assessed to be preferable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Antimutagenic potency of the cytotoxic and anti-psoriatic compound anthralin (cignolin).

The anti-psoriatic compound anthralin (cignolin) was determined to exhibit a strong cytostatic activity on HeLa-Köln cells; an ED50 concentration of 1.2 microM are cytotoxic for the cells. These growth-inhibition data were confirmed by thymidine-uptake experiments. The drug anthralin was determined to be neither direct a mutagen nor a premutagen in the Ames test using Salmonella typhimurium strain TA 100 (anthralin-concentration = 5 microM). Moreover, this compound was a strong inhibitor of benzo(a)pyrene monooxygenase, an enzyme which causes the metabolic conversion of premutagens to mutagens. These data demonstrate anthralin to be an anti-psoriatic compound devoid of mutagenic property in vitro with regard to base-pair substitutions and provided at least with some antimutagenic potential.

Anthralin↗
PubMed1987

Superoxide radical-induced loss of nuclear restriction of immature mRNA: a possible cause for ageing.

In eucaryotic cells, immature mRNA is normally restricted to the nucleus, where it is posttranscriptionally processed to mature mRNA. The intranuclear binding site for both the immature and mature mRNA is thought to be the nuclear matrix which serves as a platform for posttranscriptional RNA maturation and transport. The selectivity of nucleocytoplasmic transport for mature mRNA species seems to be due to the selectivity of the ATP-caused release of mature mRNA from the nuclear matrix; the attachment of immature mRNA to the matrix is not altered in the presence of this nucleotide. Here we show that in the presence of superoxide radical anions (O2-), which are very likely one of the causative factors in ageing, the selection mechanism for mature mRNA at the level of nuclear matrix attachment is disturbed. In the presence of a superoxide radical-generating system (xanthine/xanthine oxidase), both the mature ovalbumin mRNA and the immature ovalbumin mRNA precursors were found to be released from the nuclear matrix of hen oviduct cells, in the absence as well as in the presence of ATP. This result was also obtained when whole, isolated nuclei preincubated with xanthine/xanthine oxidase were used. The superoxide radical-caused effect could be partially prevented by co-addition of superoxide dismutase (SOD) which dismutates O2- to H2O2 and O2. On the other hand, in the presence of antibodies against the SOD, the effect of superoxide anions on RNA-matrix attachment was enhanced and its inhibition by SOD was abolished. Our results suggest that cellular ageing may be partially caused by superoxide radical-induced release of immature mRNA from its intranuclear binding site resulting in the appearance of immature messengers in the cytoplasm. This may cause both qualitative and quantitative changes in protein synthesis. Thus, ageing may be associated not only with the expression of genes coding for proteins not characteristic for the proper state of differentiation of a given cell (as suggested by the dysdifferentiative hypothesis of ageing) but also with impaired maturation of the primary gene transcripts due to the interference of superoxide radicals, not sufficiently eliminated by antioxidant mechanisms with age, with RNA-matrix attachment.

Adenosine Triphosphate↗
PubMed1986

Bleomycin enhances the tyrosinase activity of human malignant melanoma cells in culture.

By application of bleomycin fine pigmentations on basal cell layers will appear in irritated parts of the skin. Therefore we investigated the effect of bleomycin on the tyrosinase activity. Bleomycin was determined to exhibit a strong cytostatic activity on human melanoma cells in culture (ED50 concentration = 0.21 microgram/ml) whereas the viability of the cells was not affected. Incubation of pigmented human melanoma cells in the presence of bleomycin containing culture medium (1-100 ng/ml) at 37 degrees C for different periods of time resulted in a marked increase of tyrosinase activity. The level of enzyme activity reached 140% if the controls were set to 100%. Direct addition of bleomycin to the crude cell extract produced no detectable stimulatory effect. There were no significant stimulation if the cells were grown with bleomycin in serum-free culture medium. The serum content influences the activity of tyrosinase in a marked degree. The serum concentration for half-maximal stimulation of tyrosinase was calculated to be 14.2%. Furthermore the inflammatory mediator histamine was found to stimulate tyrosinase in melanoma cells. There were no additional stimulatory effect if cells were incubated in the presence of both histamine and bleomycin. These results suggest that bleomycin is able to enhance tyrosinase activity in intact cell systems. Further a possible role of serum and/or inflammatory factors in the stimulatory process must be considered.

Basidiomycota↗
PubMed1985

Potent antileukemic activity of the novel cytostatic agent avarone and its analogues in vitro and in vivo.

Avarone and avarol are novel cytostatic agents which have potent antileukemic activity both in vitro and in vivo (mice). Cell culture experiments revealed that the cytostatic activity of these two compounds on L5178Y mouse lymphoma cells was 13- to 14-fold higher than that determined for HeLa cells and 40- to 43-fold higher than that for human melanoma cells. Nontumor cells (human fibroblasts and human gingival cells) were highly resistant against the two compounds. The inhibitory potency of avarone on L5178Y cells (50% inhibitory concentration, 0.62 microM) was significantly higher than the avarol activity (50% inhibitory concentration, 0.93 microM). Modification of the molecule at the quinone ring or the double bond in the terpenoid skeleton resulted in a significant loss of activity. In vivo studies with L5178Y cells in the ascites of mice confirmed the strong antileukemic effect determined in vitro. At doses of 10 mg/kg given i.p. once daily for 5 days to mice bearing approximately 10(8) leukemia cells, avarone was found to be curative in about 70% of the mice (20% for avarol). The optimal daily i.p. dose of avarone increased life span over controls by 146% when treatment was begun 1 day after tumor implantation and by 87% when treatment was delayed until day 8. Avarol, although active, was less effective. Based on the determined log10 kill values, avarone can be classified as a highly active and avarol as a markedly active cytostatic agent. The efficacy of the two compounds is also emphasized by the therapeutic index of 11.7 for avarone and of 4.5 for avarol. The two agents were determined not to be either direct mutagens or premutagens in the Ames test.

Animals↗
PubMed1984

The role of protein phosphokinase and protein phosphatase during the nuclear envelope nucleoside triphosphatase reaction.

The activities of nuclear envelope-associated protein phosphokinase and protein phosphatase were determined in nuclear ghosts from liver and oviduct of quails. The protein kinase was found to be inhibited by poly(A) by 75%. During the kinase reaction proteins with molecular weights of 106 000 and 64 000 were phosphorylated. The phosphoprotein phosphatase from liver was stimulated to 190% by poly(A), whereas only a slight enhancing effect by this polymer was determined with the oviduct enzyme (to 125%). Comparative determinations of the nuclear ghost-associated enzyme activities revealed the following values (in nmol Pi/min per 10(8) ghosts); oviduct: phosphokinase, 0.015; phosphatase, 0.004 and nucleoside triphosphatase, 39.4; and liver: phosphokinase, 0.044; phosphatase, 0.012 and nucleoside triphosphatase, 11.7. These data indicate that phosphorylation/dephosphorylation proceeds independently of the nucleoside triphosphatase cycle. This assumption is supported by analytical results revealing that no marked dephosphorylation occurs after poly(A) binding to the nuclear envelope. Moreover, stoichiometrical data showed a nearly 1:1 molar ratio between ATP-binding and phosphorylation of nuclear envelope protein. From these findings a new model for the nucleoside triphosphatase-mediated poly(A)(+)mRNA efflux from nuclei is deducted, proposing phosphokinase and phosphatase only to modulate the affinity of the 'carrier structure' for poly(A) (+)mRNA, but not to constitute the nucleoside triphosphatase.

Animals↗
PubMed1984

Age-dependent changes of nuclear envelope protein phosphokinase and protein phosphatase activities. Significance for altered nucleo-cytoplasmic mRNA translocation during development.

Nuclear envelopes are associated with a protein phosphokinase and a phosphoprotein phosphatase, whose activities are modulated by poly(A) in an opposite manner. The activities of these enzymes were determined in nuclear ghosts from liver and oviduct of quails of different age and of different hormone status. Under optimal conditions, kinase activity was found to increase in immature animals 8-fold in response to diethylstilbestrol; co-administration of progesterone had no marked effect on enzyme activity. After the initial burst, the activity of the enzyme increased only slightly during ageing. Two proteins present in nuclear ghosts of Mr 64 000 and of Mr 106 000 are phosphorylated during the kinase reaction; both the relative and the absolute extents of phosphate incorporation into these proteins alter drastically during ageing or hormone treatment of immature animals. Like the kinase activity, the activity of protein phosphatase increased in immature animals markedly in response to hormone treatment. Thereafter the activity remained constant in liver while in oviducts the phosphatase activity dropped to 30% in both mature and old animals.

Aging↗
PubMed1984

Binding of polyribonucleotides and polydeoxyribonucleotides to bovine brain microtubule protein: age-dependent modulation via phosphorylation of high-molecular-weight microtubule-associated proteins and tau proteins.

Binding of both synthetic poly(A) and naturally occurring poly(A) (+)mRNA as well as DNA to microtubule protein is mediated by microtubule-associated proteins; tubulin itself is not capable of binding these polymers. Bovine brain microtubule protein from immature animals was found to have a significantly lower capacity to bind poly(A) than microtubule protein from old animals. On the other hand, "old" microtubule protein binds DNA more efficiently than "immature" microtubule protein. Microtubule-associated protein 2 [preferred binding site for DNA] and tau proteins [preferred binding site for poly (A)] are specifically phosphorylated by a microtubule-associated, cAMP-dependent protein kinase. It was found that the affinity of microtubule protein for poly(A) is markedly decreased by autophosphorylation of the protein; in the case of DNA, the decrease in affinity was less. Autophosphorylation of "immature" microtubule proteins diminished the binding capacity for poly(A) to a greater extent than do "old" proteins. Scatchard plot analysis revealed that microtubule-protein possesses two different binding sites for poly(A). The corresponding dissociation constants were found to be increased in the phosphorylated system, but phosphorylation does not appear to alter the total number of binding sites. Compared to immature animals, microtubule protein from "old" bovine brains was found to have a reduced number of binding sites for poly(A), whereas the values of the dissociation constants remain unchanged. In contrast to total microtubule protein and homogeneous microtubule-associated protein 2, only one kind of binding site for poly(A) could be detected in homogeneous tau protein. No influence of different RNA or DNA species on microtubule protein-associated cAMP-dependent protein kinase, adenosine triphosphatase and guanosine triphosphatase activities could be detected.

Aging↗
PubMed1984

Effect of dexamethasone on nuclear envelope nucleoside triphosphatase in fibroblasts 3T3 and melanoma cells MMLI.

Glucocorticoids are known to influence DNA and RNA synthesis in skin fibroblasts. In a novel approach to study this effect, we investigated the influence of the hormone analogue dexamethasone on the activity of nuclear envelope-associated nucleoside triphosphatase (NTPase) in intact cell systems (3T3 fibroblasts and MMLI melanoma cells). The NTPase is thought to be responsible for regulation of nucleocytoplasmic transport of mRNA. [3H]Dexamethasone was found to bind to nuclear ghosts at a density comparable with that of nuclear pores in this cellular fraction. Incubation of the cells for 48 h in the presence of different concentrations of dexamethasone resulted in a marked decrease of NTPase activity. Already concentrations as low as 0.1 ng/ml (3T3) or 1 ng/ml (MMLI) reduced the NTPase activity by approximately 50%. These results suggest that nuclear envelope NTPase is a site at which glucocorticoids regulate gene expression.

Animals↗
PubMed1984

Inhibition of nuclear envelope nucleoside triphosphatase-regulated nucleocytoplasmic messenger RNA translocation by 9-beta-D-arabinofuranosyladenine 5'-triphosphate in rodent cells.

Nucleocytoplasmic translocation of polyadenylated messenger RNA is an energy-dependent process which is regulated by a nuclear envelope nucleoside triphosphatase; this enzyme was found to be stimulated by the 3'-terminal polyadenylic acid [poly(A)] tail of messenger RNA (Bernd, A., Schröder, H. C., Zahn, R. K., and Müller, W. E. G. Eur. J. Biochem., 129: 43-49, 1982). RNA efflux from isolated mouse lymphoma (L5178Y) cell nuclei is strongly reduced if 9-beta-D-arabinofuranosyladenine 5'-triphosphate (ara-ATP) is present in the transport medium. Half-maximal inhibition of RNA efflux occurs with 120 microM ara-ATP. Most likely, the inhibitory effect of ara-ATP is caused by inhibition of nuclear envelope nucleoside triphosphatase; this enzyme was found to be highly sensitive to inhibition by this antibiotic. The inhibition type of the nucleoside triphosphatase of rat liver nuclear ghosts is competitive with respect to ATP; the Ki:Km ratio was determined to be 0.27. Besides nucleoside triphosphatase, nuclear envelopes contain a protein phosphokinase modulating the affinity of pore complex laminae to poly(A). This enzyme was also found to be strongly inhibited by ara-ATP in a competitive way with respect to ATP (Ki:Km, 0.056) and could therefore also contribute to the overall inhibition of RNA transport. The polyadenylation of endogenous RNA by poly(A) polymerase(s) in intact rat liver nuclei as well as in nuclear matrices isolated from the same source was found to be markedly suppressed in the presence of ara-ATP. The inhibitions of both poly(A) polymerase activities (contained in whole nuclei or nuclear matrix bound) are of the competitive type with respect to ATP. In in vitro assays, nuclear envelope nucleoside triphosphatase is inhibited by microtubule protein. Of the 2 ATP-dependent enzyme activities associated with microtubule protein (cyclic adenosine 3':5'-monophosphate-dependent protein kinase and adenosine triphosphatase), only the kinase was slightly affected by ara-ATP. Cellular uptake of adenosine 5'-monophosphate and perhaps 9-beta-D-arabinofuranosyladenine 5'-monophosphate (ara-AMP) is facilitated by a cellular membrane-bound 5'-nucleotidase. Our studies revealed that neither cleavage of ara-AMP nor inhibition of the enzyme activity by ara-AMP occurs. 9-beta-D-Arabinofuranosyladenine and ara-AMP represent neither direct mutagens nor premutagens as determined by the Salmonella-mammalian microsome mutagenicity test.

Animals↗
PubMed1983

Modulation of poly(A)(+)mRNA-metabolizing and transporting systems under special consideration of microtubule protein and actin.

At present, three enzymes are known which participate in regulation of polyadenylation and polydeadenylation of eukaryotic mRNA: poly(A) polymerase, endoribonuclease IV and 2',3'-exoribonuclease. Moreover, poly(A)-associated proteins as well as the cytoskeletal proteins actin and tubulin have been found to be involved in poly(A) metabolism of mRNA; their modulation effects on poly(A) metabolizing enzyme systems will be described in greater detail. Nucleo-cytoplasmic transport of poly(A)-containing mRNA is thought to be mediated by nuclear-envelope nucleoside triphosphatase. The stimulation of this enzyme by the poly(A) segment of mRNA and its modulation by microtubule protein are discussed in the second part of this review.

Actins↗