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Biomedical subjects

E Fuchs

Publications and source records attributed to E Fuchs.

At least 307 records · Page 17Linked to original sources
PubMed1985

Complete sequence of a gene encoding a human type I keratin: sequences homologous to enhancer elements in the regulatory region of the gene.

We report here the complete nucleotide sequence of a gene encoding the 50-kDa keratin expressed in abundance in human epidermal cells. According to its sequence, this gene has a single transcriptional initiation site and a single polyadenylylation signal. Nuclease S1 mapping of this gene with total human epidermal mRNA confirmed the presence of a single initiation site for the 50-kDa keratin gene. When the regulatory sequences 5' upstream from this gene were examined, three sequences that share significant homology with viral and immunoglobulin enhancer elements were found. In comparison, the sequence of the regulatory region of vimentin, a structurally similar intermediate filament gene, was highly divergent [Quax, W., Egberts, W. V., Hendriks, W., Quax-Jeuken, Y. & Bloemendal, H. (1983) Cell 35, 215-223]. This finding may provide a clue to understanding the molecular mechanisms underlying the widely varying levels of expression of different intermediate filament genes in different tissues.

Base Sequence↗
PubMed1985

Sequence and expression of a human type II mesothelial keratin.

Using mRNA from cultured human mesothelial cells, we constructed bacterial plasmids and lambda phage vectors that contained cDNA sequences specific for the keratins expressed in these cells. A cloned cDNA encoding keratin K7 (55 kD) was identified by positive hybrid selection. Southern Blot analysis indicated that this sequence is represented only once in the human genome, and Northern Blot analysis demonstrated that the gene encoding K7 is expressed in abundance in cultured bronchial and mesothelial cells, but only weakly in cultured epidermal cells and not at all in liver, colon, or exocervical tissue. The predicted amino acid sequence of this keratin has revealed a striking difference between this keratin and the type II keratins expressed in epidermal cells: whereas all of the epidermal type II keratins thus far sequenced have long nonhelical termini rich in glycine and serine, this mesothelial type II keratin has amino and carboxy terminal regions that are unusually short and lack the inexact repeats of glycine and serine residues.

Amino Acid Sequence↗
PubMed1985

Preoptic catecholamine, GABA, and glutamate release in ovariectomized and ovariectomized estrogen-primed rats utilizing a push-pull cannula technique.

The push-pull cannula technique was used to evaluate the role of the medial preoptic/anterior hypothalamic area (MPO) in regulating pituitary luteinizing hormone (LH) and prolactin release. The concentrations of the three catecholamines--dopamine, norepinephrine (NE), epinephrine (E)--and gamma-aminobutyric acid (GABA) and glutamate could be measured in 15-min fractions at which interval blood samples for LH and prolactin determination were also collected. Comparison of neurotransmitter release rates into the MPO were made between ovariectomized and ovariectomized estradiol benzoate treated rats. Release of the neurotransmitters occurred in a pulsatile manner, the release episodes for each transmitter appeared to be independent of the others. No direct correlation between neurotransmitter release episodes and blood LH or prolactin levels could be established. The release of GABA was significantly lower and that of NE and E higher in ovariectomized animals in comparison to estrogen-primed ovariectomized animals under negative feedback conditions. In the afternoon, however, when the estrogen stimulated LH and prolactin release, preoptic GABA release was low, whereas preoptic NE and particularly E release rates were high. Conspicuously high dopamine and NE release episodes were observed in estrogen-primed animals at noon, i.e., prior to the expression of the positive feedback signal. This may reflect a biochemical correlate to the so-called critical period. No consistent differences between ovariectomized and ovariectomized estradiol-17 beta benzoate treated animals were observed for preoptic glutamate release rates. The data show that preoptic GABA release rates show generally an inverse pattern to NE and E release and therefore also to blood LH and prolactin levels. No direct mathematical correlation between any of the neurotransmitter release rates and blood hormone levels could be established.

Animals↗
PubMed1985

Keratin expression in normal esophageal epithelium and squamous cell carcinoma of the esophagus.

The 8-nm keratin filament is a major component of the cytoskeleton of epithelial cells and epithelial-derived cancers (carcinomas). Recently, it has been shown that the pattern of keratins produced by an esophageal epithelial cell undergoes change upon malignant transformation. In order to evaluate the potential importance of these differences in providing improved diagnostic techniques for pathology, we have investigated the consistency of the patterns of keratins expressed in normal esophageal epithelium, squamous cell carcinoma (SQCC) of the esophagus, and cultured esophageal epithelial cells. In six patients, the keratin pattern expressed by SQCC of the esophagus and corresponding normal esophageal epithelium was consistently different as judged by immunoblot analysis of electrophoretically separated protein extracts. Whereas the SQCCs typically expressed major keratins with molecular weights of 58,000, 56,000, 50,000, and 46,000, the normal esophageal epithelium produced two major keratins with molecular weights of 58,000 and 52,000 and a minor keratin with a molecular weight of 56,000. When normal esophageal epithelial cells were grown in tissue culture, their keratin pattern changed, and keratins with molecular weights of 58,000, 56,000, 52,000, 50,000, 46,000, and 40,000 were expressed. Although some minor variations in keratin patterns were seen, the major differences in keratin pattern expressed by normal esophageal epithelial tissue, SQCC of the esophagus, and cultured esophageal cells were consistent and reproducible.

Antibody Specificity↗
PubMed1984

Sex differences in gamma-aminobutyric acid and glutamate concentrations in discrete rat brain nuclei.

gamma-Aminobutyric acid (GABA) and glutamate concentrations were measured in discrete brain nuclei in adult male and female rats. Significant sex differences in GABA and glutamate concentrations were found in the medical preoptic area (MPA) and ventromedial hypothalamic area (VMH) as well as the lateral hypothalamus, habenula and diagonal band for glutamate. Significant differences in GABA and glutamate concentrations were also observed throughout the estrous cycle in several brain areas. These results suggest that these neuronal systems are sexually differentiated as well as involved in the expression of gonadal steroid feedback.

Animals↗
PubMed1984

[Nocturnal cardiac arrhythmias in the sleep apnea syndrome].

A day vs. night comparison of type and frequency of cardiac arrhythmias documented by long-term ECG was done in 30 patients with nocturnal respiratory disorders in the form of the sleep apnoea syndrome. The commonest nocturnal arrhythmia was pronounced sinus arrhythmia during the apnoeic phases with variations of cardiac frequency between 40 and 120/min. Supraventricular and ventricular extrasystoles occurred significantly more frequently during the night than during the day. In three patients bradycardiac arrhythmias presenting as sinoauricular and atrioventricular blockades of the 3rd degree with node or ventricular substitute rhythm were seen during the sleep apnoea which could not be demonstrated during the day. Predominantly nightly occurrence of cardiac arrhythmias should lead to differential diagnostic consideration of the sleep apnoea syndrome.

Adult↗
PubMed1984

[Therapy and therapeutic control of allergic diseases].

Modern allergen-specific therapeutic procedures (antigen elimination, specific hyposensitization) will be resumed in order to give practical advices for the treatment. Indications, contraindications, principles of dosage, combination of allergen extracts for immunotherapy are discussed besides possible side effects. Drug therapy in allergic disease with different chemical agents including specific drug protection therapy will be discussed under respect of indication and combination with immunotherapy. Finally principles of retrospective and prospective criteria for therapeutic success are reviewed in detail including biological methodics.

Allergens↗
PubMed1984

In vivo release of neurotransmitters in the medial basal hypothalamus of the monkey.

In vivo release rates of norepinephrine (NE), epinephrine (E), dopamine (DA), gamma-aminobutyric acid (GABA), glutamate (GLU) and beta-endorphin (beta E) in the medial basal hypothalamus (MBH) of unanaesthetized female macaca fascicularis monkey, and the effects thereon of estrogen (E2) treatment, have been estimated using push-pull perfusion methodology. DA, NE, E, GABA, GLU and beta E were all detectable in 30 min perfusate fractions. No direct correlation between their release rates and those of LH and PRL could be observed. E2 induced an initial decrease, then an increase, in LH and PRL secretion, and concomitant changes in the release patterns of DA, NE, E. GABA and GLU were apparent. This study demonstrates that in vivo push-pull perfusion methodology may be applied to the unanaesthetized monkey, and when combined with venous catheterization for serial blood sampling may prove to be a powerful tool in the investigation of the central molecular events governing neuroendocrine functions.

Animals↗
PubMed1984

Remarkable conservation of structure among intermediate filament genes.

Using a cloned cDNA complementary to a portion of the mRNA for the 50 kd human epidermal keratin, we have screened a human genomic library and have isolated and sequenced the gene encoding this keratin. A comparison of the keratin gene with the very distantly related vimentin gene has enabled us to explore the relation between the evolutionary conservation of structure in intermediate filament (IF) subunits and the conservation of structure in IF genes. Our results reveal that not only the secondary structure of the IF proteins, but also the structural skeleton of their genes, has been maintained throughout evolution. These characteristics have persisted despite considerable flexibility in both protein and nucleic acid sequence. Surprisingly, although the positions of the introns within these two genes are highly conserved, they do not seem to correspond to the boundaries of the structural domains common to all IF subunits.

Amino Acid Sequence↗
PubMed1984

Differences in keratin synthesis between normal epithelial cells and squamous cell carcinomas are mediated by vitamin A.

A number of recent studies have indicated that the expression of keratins is altered upon malignant transformation of human epithelial cells. We have shown that the altered expression of 67-kDa and 40-kDa keratins in established squamous cell carcinoma lines from tongue and epidermis stems largely from a difference in their sensitivity to vitamin A apparently acquired during tumorigenesis. When the vitamin A concentration in the medium is raised, the 40-kDa keratin is produced at increased levels. Conversely, when the amount of vitamin is reduced, the 67-kDa keratin is synthesized and the cells undergo stratification and terminal differentiation. However, even when vitamin A is quantitatively removed from the medium, the maximal degree of differentiation attained by each squamous cell carcinoma cell as judged by the synthesis of 67-kDa keratin was still less than that of the normal keratinocytes. These findings suggest that the altered patterns of keratins observed for some tissues upon malignant transformation arise from a complex mixture of intracellular changes in the differentiative pathway in addition to changes in the responsiveness of cells to extracellular regulators of keratin gene expression.

Animals↗
PubMed1984

Expression of unusually large keratins during terminal differentiation: balance of type I and type II keratins is not disrupted.

When a basal epidermal cell undergoes a commitment to terminally differentiate, it ceases to divide and begins to migrate outward towards the surface of the skin. Dramatic changes in its cytoskeletal architecture take place, accompanied by numerous changes in the expression of keratins, a family of related polypeptides that form 8-nm filaments in these cells. We show here that a shift to the synthesis of unusually large keratins occurs that does not seem to disrupt the ratio of two distinct subfamilies of keratins. Preliminary studies indicate that this differentiation-specific shift may be at the level of transcriptional rather than post-transcriptional regulation. The striking similarities between these large keratins and the type I and type II keratins of basal epidermal cells suggests the important role that both classes of large keratin sequences must play in the assembly of the intermediate filaments within the differentiating keratinocyte.

Cell Differentiation↗
PubMed1984

Involvement of catecholamines and glutamate in GABAergic mechanism regulatory to luteinizing hormone and prolactin secretion.

There is some evidence that a population of estrogen-receptive neurons exists in the preoptic/anterior hypothalamic area which uses gamma-aminobutyric acid (GABA) as neurotransmitter and which is involved in mediating the negative feedback of estrogens on pituitary luteinizing hormone (LH) secretion. These neurons are proposed to be presynaptic inhibitors to norepinephrine (NE) release thereby inhibiting the stimulatory effect of NE on LHRH neurons. Muscimol, a potent GABA agonist, inhibits pituitary LH release in ovariectomized rats after intraventricular injection of 5 nmol. This treatment significantly increased prolactin levels. Catecholamine turnover rates in micropunches of various hypothalamic and mesolimbic structures following intraventricular treatment with muscimol were determined using the method of blocking the activity of tyrosine hydroxylase by alpha-methyl-p-tyrosine. Muscimol did not affect catecholamine, GABA and glutamate concentrations. Turnover rates of NE were significantly reduced in the medial preoptic/anterior hypothalamic area. In this structure as well as in the nucleus accumbens and in the anterior mediobasal hypothalamus turnover rates of dopamine (DA) were also reduced whereas DA turnover in mediocortical amygdalae was increased by muscimol. The selective reduction of NE turnover following muscimol may be explained by a direct or indirect action of the GABA-eric drug on NE axon terminals. The reduced NE and DA turnover in the medial preoptic area may be causally related to reduced serum LH levels whereas the reduced hypothalamic DA turnover may explain increased blood prolactin levels.

Animals↗
PubMed1983

Complementary DNA sequence of a human cytoplasmic actin. Interspecies divergence of 3' non-coding regions.

We have isolated and sequenced a cloned complementary DNA insert complementary to the messenger RNA of a cytoplasmic actin expressed in human epidermal cells. This provides the first cytoplasmic actin complementary DNA sequence for a vertebrate organism. The actin amino acid sequence predicted from this complementary DNA is identical to that of a bovine cytoplasmic actin and shows 98 and 85% homology with a Dictyostelium and a yeast actin, respectively. The complementary DNA sequence indicates that the 3' end of the mRNA contains an unusually long (greater than 400 nucleotides) 3' non-translated region. A comparison of this 3' non-coding region with those of recently determined actin complementary DNA sequences from other species reveals little or no homology among these sequences. Thus, these results indicate that although the actin amino acid sequences are extremely conserved, the non-coding regions of the mRNAs diverge rapidly.

Actins↗
PubMed1983

The cDNA sequence of a Type II cytoskeletal keratin reveals constant and variable structural domains among keratins.

We present the cDNA and amino acid sequences of a cytoskeletal keratin from human epidermis (Mr = 56K) that belongs to one of the two classes of keratins (Type I and Type II) present in all vertebrates. In these two types of keratins the central approximately 300 residue long regions share approximately 30% homology both with one another and with the sequences of other IF proteins. Within this region, all IF proteins are predicted to contain four helical domains demarcated from one another by three regions of beta-turns. The amino and carboxy termini of the Type II keratin are very different from those of microfibrillar keratins and other nonkeratin IF proteins. However, they contain unusual glycine-rich tandem repeats similar to the amino terminus of the Type I keratin. Thus the size heterogeneity among keratins appears to be a result of differences in the length of the terminal ends rather than the structurally conserved central region.

Amino Acid Sequence↗