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Biomedical subjects

E Fuchs

Publications and source records attributed to E Fuchs.

At least 325 records · Page 18Linked to original sources
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↗
PubMed1983

Type I and type II keratins have evolved from lower eukaryotes to form the epidermal intermediate filaments in mammalian skin.

We have traced the evolutionary origins of keratin-like sequences to the genomes of lower eukaryotes. The proteins encoded by these genes have evolved to form the intermediate filaments that comprise the backbone of vertebrate skin cells. Two related but distinct types of keratins encoded by two separate multigene subfamilies are expressed in the epidermal keratinocytes of vertebrate species from fish to human. Both at the level of protein and at the level of DNA, these two classes of keratins are coordinately conserved throughout vertebrate evolution, indicating the central role that both types of keratins must play in the assembly and structure of the 8-nm filament.

Animals↗
PubMed1983

Evolution and complexity of the genes encoding the keratins of human epidermal cells.

The keratins are a family of proteins (Mr = 40-70 K) that form 8-nm intermediate filaments in the cytoplasm of most vertebrate epithelial cells. Each epithelial cell expresses its own subset of keratins, which consists of about 2 to 5 polypeptides. In epidermis, the keratins are especially abundant, comprising 30 to 85 percent of the total protein of these cells. Four major keratins (Mr = 46, 50, 56, and 58 K) are expressed in the basal cells, whereas the larger keratins (60-70 K) are found only in differentiating epidermal cells. We have shown that in human epidermis there are multiple mRNAs for the keratins. These RNAs can be grouped into two distinct classes as judged by their ability to hybridize to one of two separate classes of cloned keratin cDNA sequences. Each of these two classes of sequences is encoded by a multigene family of about 10 genes each, and these two families are coordinately conserved throughout vertebrate evolution [21]. Recently, we have determined the DNA sequence of a cloned cDNA insert that is complementary to greater than 90 percent of the coding region for the 50 K keratin and which shares homology with 46 K keratin mRNA [13]. A comparison of the predicted amino acid sequence of this cytoskeletal keratin with partial sequences of keratins of epidermal appendages, e.g., wool, shows that there is a distinct relation with the fibrous keratins of wool, but little or no relation with the matrix keratins. A comparison of the 50 K keratin sequence with the partial sequences known for other intermediate-filament proteins indicates that the keratins may be the most distantly related of this class of 80- to 100-A filamentous proteins. This is in contrast to the actins and tubulins, which are highly conserved components of vertebrate cytoskeletons. The wide flexibility in the amino acid sequence of intermediate filament proteins suggests that these proteins have evolved to meet subtly different requirements in the cytoskeletal architecture.

Amino Acids↗
PubMed1983

The evolution and complexity of the genes encoding the cytoskeletal proteins of human epidermal cells.

In order to explore the differential expression and evolutionary conservation of the genes encoding the cytoskeletal proteins for human epidermal cells, we have constructed a library of bacterial plasmids containing inserts of double-stranded cDNAs complementary to the mRNAs of cultured human epidermal cells. Cloned hybrid plasmids containing 45-95% of the sequences present in keratin, actin, and tubulin mRNAs were isolated and characterized. To identify the cDNAs encoding the four major keratins of human epidermal cells, the clones were initially screened for their ability to hybridize strongly with 32P-labeled cDNA prepared from unfractionated epidermal mRNA (about 30% keratin mRNA). Strongly hybridizing clones were further characterized by positive hybrid selection. Two distinct classes of clones were identified: One class hybridized specifically to the 56 and 58kd keratin mRNAs and one class hybridized specifically to the 46 and 50kd keratin mRNAs. Each class is encoded by a separate multigene family of about 10 genes. The two classes of sequences are conserved throughout vertebrate evolution, indicating the functional importance of each class in filament assembly. Clones containing human cDNA sequences encoding a cytoplasmic actin and alpha-tubulin were selected by hybridization screening using 32P-labeled cloned cDNAs for the mRNAs of beta-actin and alpha-tubulin of embryonic chick brain. The identity of these clones was established by positive hybrid selection and by DNA sequence analysis. Similar to the keratins, the actins and tubulins are also encoded by multigene families which are highly evolutionarily conserved. The availability of cloned cDNAs specific for each of three types of epithelial cytoskeletal proteins allows us to investigate the coordinate expression of their mRNAs during terminal differentiation in human epidermis.

Actins↗
PubMed1982

Corticosteroid, catecholamine and glucose plasma levels in rabbits after repeated exposure to a novel environment or administration of (1-24) ACTH or insulin.

The responsiveness of the adrenal cortex and the sympatho-adrenal-medullary system to stress factors and administration of (1-24) ACTH and insulin was studied in adult rabbits. In comparison to untreated animals, exposure to a novel environment for 10 min followed by artery puncture on 6 consecutive days elicited a moderate increase of corticosteroid (C), norepinephrine (NE) and epinephrine (E) plasma levels. Intramuscular injection of 50 micrograms/kg body weight (1-24) ACTH increased C, NE and E plasma levels. Saline injection resulted in elevated NE levels; C, E and glucose remained unchanged. After injection of 1.0 IU/kg body weight insulin C levels were higher than those found after exposure to a novel environment for 10 min followed by artery puncture; similarly, NE and E increased. In accordance with results obtained in the rat or mouse the sympatho-adrenal-medullary system in the rabbit is stimulated by stress factors such as handling, artery puncture or injection of (1-24) ACTH or insulin. In contrast the adrenal cortex can be stimulated only to a certain extent by these manipulations. An increased activation of adrenal cortex cells occurs only after insulin, a maximum stimulation only after (1-24) ACTH administration.

Adrenal Cortex Hormones↗
PubMed1982

[Occupational allergens as a cause of obstructive lung diseases. Early diagnosis and clinical aspects].

Obstructive diseases of the respiratory tract caused by allergizing substances at the place of work must be classified as occupational diseases, provided certain conditions are fulfilled. The etiopathogenesis and special features of the clinical picture and diagnosis of occupationally conditioned allergic obstruction of the respiratory tract, previously known as bronchial asthma, are discussed. In contrast to "spontaneous" allergy, the occupational cause of the disease is due to often massive exposure to allergens at the place of work and the frequently aggressive potency of several industrial allergens, these being considered the actual "shaping" factors. The need for early diagnosis, as far as possible even at the initial "precursor" stage and during the manifestation of the so-called "equivalents", such as allergic conjunctivitis and rhinitis, is stressed. Treatment directed at removing the causes includes, fundamentally, prophylaxis against exposure (considering the time during which the allergens remain dormant without triggering an allergy); this obviously involves change of occupation or place of work, whereas specific treatment aimed at producing hyposensitization must remain an exception. The possibilities for prevention, chiefly from the medical point of view, are described.

Allergens↗
PubMed1982

The cDNA sequence of a human epidermal keratin: divergence of sequence but conservation of structure among intermediate filament proteins.

We have determined the DNA sequence of a cloned cDNA that is complementary to the mRNA for the 50 kilodalton (kd) human epidermal keratin. This provides the first amino acid sequence for a cytoskeletal keratin. Comparison of this sequence with those of other keratins reveals an evolutionary relationship between the cytoskeletal and the microfibrillar keratins, but shows no homology to matrix or feather keratins. The 50 kd keratin shares 28%-30% homology with partial sequences of other intermediate filament proteins, which suggests that keratins may be the most distantly related members of this class of fibrous proteins. Our computer analyses predict that the 50 kd keratin contains two long alpha-helical domains separated by a cluster of helix-inhibitory residues in the middle of the protein. These findings indicate that despite major sequence divergence among intermediate filament proteins, they retain sequences compatible with secondary structural features that appear to be common to all of them.

Amino Acid Sequence↗
PubMed1981

Regulation of terminal differentiation of cultured human keratinocytes by vitamin A.

Vitamin A is known to exert an important influence on epithelial differentiation. The fetal calf serum supplement of cell-culture medium contains enough of the vitamin to affect the differentiation of cultured keratinocytes derived from epidermis and from other stratified squamous epithelia. The cellular and molecular properties of the cultures are altered when the medium is supplemented with serum from which the vitamin A has been removed by solvent extraction (delipidized serum). Cell motility is reduced, the adhesiveness of cells increases and pattern formation is prevented. In both epidermal and conjunctival keratinocytes, removal of vitamin A leads to the synthesis of a 67 kd keratin characteristic of terminally differentiating epidermis and to much reduced synthesis of the 52 kd and 40 kd keratins typical of conjunctiva. These changes, both cellular and molecular, are reversed by the addition of retinyl acetate to the medium containing delipidized serum. Cell motility and pattern formation are restored, and detachment of the most mature cells from the surface of the stratified epithelium is promoted. Synthesis of the 67 kd keratin is prevented and the synthesis of the 40 and 52 kd keratins is stimulated. The nature of the keratins synthesized is regulated by the concentration of vitamin A, and each cell type adjusts its synthesis differently at a given vitamin concentration.

Cell Aggregation↗