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Biomedical subjects

J Schweizer

Publications and source records attributed to J Schweizer.

At least 91 records · Page 5Linked to original sources
PubMed1991

[Value of color-coded duplex sonography in diagnosis of extracranial vascular changes].

72 patients at the age of 44 to 76 years with transitory ischaemic attacks which happened and for a short time reversible deficits, respectively, were diagnosed both conventionally duplex-sonographically and with the colour-coded duplex sonography under the question of vascular stenotic process in the region of the cervical vessels. After the ultrasound examination within two weeks an angiography was performed. As a result was shown that in 10 patients with an angiogram without pathological findings by means of the colour-coded duplex sonography in 3 cases plaque formations could be proved which could be clearly diagnosed only by colour marking.

Adult↗
PubMed1991

[Experiences with the Günther filter].

In the investigation 17 patients with lung embolism being cared for with a Guenther-filter were post-observed during a period up to two years. Early complications after the implantation of the Guenther-filter did not occur in any case. Late complications after the implantation of the Guenther-filter were dislocations, deformations of the filter and breaks of the spokes. In the result of the post-observation the Guenther-filter application despite its easy handling should be regarded very critically.

Aged↗
PubMed1990

[Results of using EEG and carotid angiography for evaluating cerebrovascular insufficiency].

In the cerebrovascular disease the EEG can give references at localisation, extension and course. The ability of statement is increased by methods of provocation and activation. On 35 patients with cerebrovascular insufficiency can be indicated that there are good correlations between changes on the large cerebral supply vessels and changes of the EEG, in particular in the carotid pressure trial.

Adolescent↗
PubMed1990

[Doppler sonography in the diagnosis of extracranial vascular changes].

On account of cerebrovascular insufficiencies or asymptomatic vascular noises which had taken place 45 patients were examined by means of Doppler sonography and after this by means of angiography. The judgement of the common carotid artery, the internal and external carotid arteries, the vertebral artery, the subclavian artery and the supratrochlear artery were involved into the ultrasound investigation. The sensitivity of the supratrochlear compression test was 50% in the diagnosis of high-degree stenoses and occlusions of the internal carotid artery, whereas the sensitivity of the complete ultrasound investigation way about 80%. The advantages and disadvantages of the ultrasound Doppler sonography investigation are discussed.

Adult↗
PubMed1990

Tissue-specific expression of murine keratin K13 in internal stratified squamous epithelia and its aberrant expression during two-stage mouse skin carcinogenesis is associated with the methylation state of a distinct CpG site in the remote 5'-flanking region of the gene.

Under normal conditions, the expression of the murine type-I keratin K13 is restricted to the suprabasal, differentiating cell layers of internal stratified squamous epithelia that line the oral cavity and the upper digestive tract. It is, however, also expressed aberrantly but constitutively in only the differentiating parts of 7,12-dimethylbenz[alpha]anthracene/12.0-tetradecanoyl-phorbol-13-acetate (DMBA/TPA) induced malignant epidermal tumors of the back skin of mice, whereas its likewise suprabasal expression in papillomas is highly variable [27]. In an approach to unravel regulatory DNA sequence elements involved in the tissue-specific and aberrant K13 expression, the 5'-flanking region of the gene was analyzed with regard to potential methylation sites and DNase hypersensitive regions. We report on the identification of a CpG dinucleotide (designated M1; located about 2.3 kb upstream of the transcriptional start site), whose methylation state correlates with the differential gene activity in various epithelia and tumors. We show that in K13-nonexpressing integumental epidermis the M1 site is methylated in both suprabasal and basal cells. In contrast, internal stratified squamous epithelia (i.e. tongue, esophagus, forestomach) exhibit an unmethylated M1 site not only in their suprabasal. K13-expressing cells, but also in basal cells--in which, however, the keratin is not yet synthesized. The identical situation is encountered in DMBA TPA-induced moderately differentiating epidermal squamous cell carcinomas with compartmentalized K13 expression. In papillomas we observed a striking correlation between the extent of both suprabasally expressed K13 protein and demonstrable DNA copies carrying an unmethylated M1 site. Moreover we found that the sequence region around the M1 site was DNAseI hypersensitive in K13-expressing malignant tumors, but DNaseI insensitive in K13-nonexpressing epithelia and cells. DNAseI hypersensitivity in K13-expressing tissues was, however, independent of an active transcription of the gene in differentiating cells or transcriptional inertia in basal cells. These results strongly suggest that the sequence element around the demethylated M1 site is involved in a multi-level control mechanism mediating the selective expression of the K13 gene in internal squamous epithelia and in DMBA/TPA-induced epidermal tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Characterization of West African Trypanosoma (Trypanozoon) brucei isolates from man and animals using isoenzyme analysis and DNA hybridization.

A total of 18 West African Trypanosoma (Trypanozoon) brucei stocks isolated from man and animals were characterized using isoenzyme analysis with isoelectric focusing (IEF) and DNA hybridization. They were compared with four T. (T.) brucei isolates from East and West Africa that had previously been analysed and well defined. All experiments were carried out with cell lysates of procyclic trypanosomes produced in vitro. The different stocks could be separated into two distinct groups according to their isoenzyme and DNA patterns. The homogeneous group of T. b. gambiense was characterized by zymodeme A and highly specific DNA-banding patterns (type G) always associated with stable human serum resistance. The non-gambiense group (consisting of T.b. rhodesiense and T.b. brucei) was determined by a great variation in these markers. Our results clearly indicate the existence, of T.b. rhodesiense-like parasites in West African patients. Due to their lack of human serum resistance, the four characterized animal isolates can be referred to as T. b. brucei.

Africa, Western↗
PubMed1989

Identification of murine type I keratin 9 (73 kDa) and its immunolocalization in neonatal and adult mouse foot sole epidermis.

The foot sole epidermis of the fore and hind feet of the adult mouse contains an acidic (type I) mRNA-encoded 73-kDa keratin polypeptide which cannot be detected in any other skin site of the mouse integument. Western blot analysis using an antibody specific for the 64-kDa keratin 9 of human and bovine callus-forming epidermis [A. C. Knapp et al. (1986) J. Cell Biol. 103, 657-667] demonstrates that the 73-kDa keratin represents the murine analog of keratin 9 of man and cow. Concomitant investigations in two related rodent species indicate that the size of this keratin varies more among species than that of any other orthologous keratin. Histological examination of adult mouse foot sole skin reveals an extremely thick and undulated epidermis covering the apical portion of the six footpads, whereas the epidermal-dermal junction of the lateral walls of these nodular protuberances as well as that of the remainder of the foot sole skin is essentially flat. If sections of adult foot sole skin are investigated by indirect immunofluorescence with the keratin 9-specific antibody, intense cytoplasmic staining is restricted to the apical rete pegs of the footpad epidermis in which virtually all suprabasal cells express keratin 9. However, we also observed keratin 9-negative cell columns ascending straight above the tips of the dermal papillae and separating the keratin 9-positive rete pegs from each other. At the transition from the strongly undulated apical epidermis to the flat epidermis of the lateral walls of the footpads, keratin 9-positive cells loose their coherence and gradually disappear toward the inter-footpad epidermis. This intimate relationship between the morphogenesis of epidermal ridges and inter-ridges and the expression of keratin 9 is also visible in foot sole epidermis of neonatal mice. Here we observed the appearance of keratin 9-positive suprabasal cells concomitant with the onset of pronounced folding of the apical footpad epidermis by about Day 3 after birth. Our findings confirm the view that the expression of keratin 9 is characteristic of a highly specialized pathway of epidermal differentiation. We propose a hypothesis for keratin expression in skin sites which are subject to pronounced mechanical wear and tear.

Animals↗
PubMed1988

Gene exchange in African trypanosomes: characterisation of a new hybrid genotype.

We describe the isolation of a hybrid Trypanosoma brucei clone following the mixed cyclical transmission of two parental clones through tsetse flies. The characterisation of this clone reveals some new facets of the process of genetic exchange in T. brucei. The inheritance of four isoenzyme loci and restriction fragment polymorphisms at two loci was interpretable in 'mendelian' genetic terms, involving meiosis either before or after the genetic exchange event. However, at a further two isoenzyme loci a deviation from mendelian behaviour was observed. Pulse field gel analysis showed that the hybrid clone possessed a new combination of intermediate size chromosomes. Examination of kinetoplast DNA variants showed uniparental kinetoplast inheritance, and with reference to previous work we conclude that the kinetoplast can be inherited from either parent. The nuclear DNA content of the hybrid clone was measured and found to be identical to the parental nuclear DNA contents. This finding, together with the inheritance of isoenzyme and RFLP markers, is discussed with respect to possible models for genetic exchange.

Animals↗
PubMed1988

Aberrant expression during two-stage mouse skin carcinogenesis of a type I 47-kDa keratin, K13, normally associated with terminal differentiation of internal stratified epithelia.

Specific keratin cDNA probes and monospecific antikeratin antisera were used to analyze mouse epidermis and epidermal tumors for the expression of a type I 47-kDa keratin, K13, normally associated with terminal differentiation of internal stratified epithelia. We demonstrated that this keratin was virtually absent from the entire body epidermis at various stages of development. Also, it was not detected in various forms of acute and chronic epidermal hyperproliferation or in epidermal cells cultured under conditions that favored either cell proliferation or in vitro differentiation. In contrast, K13 was consistently expressed in squamous cell carcinomas of the skin induced by 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate (TPA), whereas papillomas obtained by the same two-stage protocol were distinctly heterogeneous with regard to the expression of this keratin. These findings were true for two different strains of mice (NMRI and Sencar). Papillomas collected from Sencar mice after 12 wk or from NMRI mice after 15 wk of promotion with TPA were either negative for K13 or elicited variable amounts of this keratin. In all cases of positive expression of K13 in tumors, as in normal stratified internal epithelia, both the keratin protein and its mRNA invariably occurred in the differentiating cell compartments. In contrast to what we found in internal stratified epithelia, however, K13 was expressed without its commonly encountered type II 57-kDa partner, K4. Papillomas negative for the K13 protein were also devoid of K13 transcripts. This indicates that the aberrant K13 expression in tumors is regulated at the level of transcription. Our results suggest that K13 may provide a marker for malignant conversion in the mouse two-stage skin carcinogenesis model and may be especially suited for studies of gene expression regulation.

Animals↗
PubMed1988

The intermediate filament system of the keratinizing mouse forestomach epithelium: coexpression of keratins of internal squamous epithelia and of epidermal keratins in differentiating cells.

The internal epithelium of mouse forestomach represents a fully keratinized tissue that has many morphological aspects in common with the integumental epidermis. In the present study we have, therefore, analyzed keratin expression in the total epithelium, in subfractions of basal cells and in living and dead suprabasal cells that were obtained by Percoll density gradient centrifugation of trypsin-dissociated forestomach keratinocytes. The keratin analysis revealed that basal forestomach keratinocytes synthesize the same keratin types as basal epidermal cells (60000, 52,000 and 47,000 daltons), whereas differentiating cells contain both the epidermal suprabasal keratin pair (67,000 and 59,000 daltons) and the suprabasal keratin pair characteristic for other internal squamous epithelia (57,000 and 47,000 daltons). Indirect immunofluorescence using an antibody recognizing the members of the epidermal-type suprabasal keratin pair and in-situ-hybridization experiments using specific cDNA probes for the members of the internal-type keratin pair showed that the two keratin pairs are uniformly coexpressed in living suprabasal forestomach keratinocytes. Furthermore, it could be shown that distinct cells in the basal cell layer acquire the ability to express both the 67,000/59,000 dalton and the 57,000/47,000 dalton keratin pair and that some basal cells apparently lose the ability to synthesize mRNAs for basal keratins.

Animals↗
PubMed1988

The timing and frequency of hybrid formation in African trypanosomes during cyclical transmission.

The frequency of hybrid formation between two Trypanosoma brucei clones during cyclical transmission through Glossina morsitans centralis was analyzed. In two independent experiments, teneral G. m. centralis were infected with an equal mixture of two T. brucei clones showing different homozygous isoenzyme patterns for isocitrate dehydrogenase (ICD; E.C.1.1.1.42) and alkaline phosphatase (AP; E.C. 3.1.3.1). Trypanosomes were cyclically transmitted to mice from 23 infective flies and the subsequent bloodstream-form populations were characterized by isoenzyme electrophoresis. Heterozygous patterns for ICD and AP indicated that hybrid formation occurred in at least 9 of the 23 vectors. There was further evidence that extrusion of hybrid parasites with saliva from a single fly was not necessarily continuous but could alter over time with the occurrence of either or both of the homozygous parental clones.

Alkaline Phosphatase↗
PubMed1987

Three cDNA sequences of mouse type I keratins. Cellular localization of the mRNAs in normal and hyperproliferative tissues.

We have constructed cDNA libraries with poly(A)+ RNA from normal mouse footpad epidermis and from a squamous cell carcinoma of mouse back skin. Both libraries were screened for type I keratin clones. We present sequence data of three keratin cDNA clones which selected mRNAs coding for two 52-kDa proteins (clones pke 52 and pkSCC 52) as well as for a 50-kDa protein (clone pkSCC50). According to their carboxyl-terminal sequences, the two 52-kDa keratin proteins belong to a group of keratins with serine-rich subdomains adjacent to the alpha-helix, whereas the short carboxyl-terminus of the 50-kDa protein lacks a distinct substructure. Sequentially the two 52-kDa keratins are more closely related to each other than to any other mouse type I keratin. However, in situ hybridization with specific subclones reveals a distinctly different pattern of expression in mouse epithelia. Clone pkSCC 52 contains sequence information for a 52-kDa keratin present in basal cells of epidermis and other stratified epithelia, whereas the pke 52 cDNA encodes a keratin which is predominantly expressed in suprabasal cells of nonepidermal tissues. In terms of nucleotide sequence identities, it cannot precisely be decided which of the two mouse 52-kDa proteins is the equivalent of the human epidermal 50-kDa keratin protein (Hanukoglu, I., and Fuchs, E. (1982) Cell 31, 243-252). In the case of the bovine keratin VII, however (Jorcano, J.L., Rieger, M., Franz, J.K., Schiller, D.L., Moll, R., and Franke, W.W. (1984) J. Mol. Biol. 179, 257-281) the sequence identity values speak for an equivalence with the mouse ke 52 keratin. Obviously, in situ hybridization experiments would best be suited to unravel the precise interspecies relationship between the four highly similar keratins. The discriminatory efficacy of this technique is further emphasized by the demonstration that the mRNA for a 50-kDa keratin is present not only in hyperproliferative epithelia, but also in normal cells of hair follicles.

Amino Acid Sequence↗
PubMed1987

Benzoyl peroxide promotes the formation of melanotic tumors in the skin of 7,12-dimethylbenz[a]anthracene-initiated Syrian golden hamsters.

A two-stage carcinogenesis experiment was performed in Syrian golden hamsters using a single intragastric initiation with 10 mg/kg body weight of 7,12-dimethylbenz[a]anthracene (DMBA) and repetitive topical promotion on the back skin with two different doses (80 and 160 mg, respectively) of benzoyl peroxide in 1 ml acetone. Benzoyl peroxide was administered three times per week over a period of 16 months. The treatment with benzoyl peroxide alone leads to both a generalized hyperpigmentation and skin scaling without formation of any tumors. DMBA initiation alone induces a moderate number of melanotic foci and a small number of palpable melanotic tumors. Both lesions are located in the dermis. Papillomas develop in the epithelia of the tongue, esophagus and especially of the forestomach but not, however, on the back skin. The combined treatment with DMBA and both doses of benzoyl peroxide drastically increases the incidence of dermal melanotic foci and at late stages also that of melanotic tumors. Therefore, in addition to its known ability to promote papilloma and carcinoma formation in the back skin of mice, benzoyl peroxide is also able to promote the formation of melanotic tumors in the dermis of hamsters.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1987

Selective suppression of two postnatally acquired 70 kD and 65 kD keratin proteins during continuous treatment of adult mouse tail epidermis with vitamin A.

Using mouse tail epidermis as a model system we have studied the morphologic and biochemical effects of continuous topical treatment with vitamin A acid. Normal tail epidermis shows a regular pattern of parakeratotic scale regions and orthokeratotic interscale regions which arise postnatally from a uniformly orthokeratinizing neonatal epidermis. Daily treatment of tail epidermis with vitamin A acid for 14 days results in the induction of hyperplasia and the orthokeratotic conversion of the scale regions. The degree of these alterations is dose-dependent and maximally brought about by repetitive 30-microgram doses of the vitamin. To correlate morphologic with biochemical alterations, we have analyzed the keratin patterns of normal and vitamin A acid-treated epidermis by one- and two-dimensional gel electrophoresis. The results indicate that repetitive vitamin A treatment leads to the selective suppression of two postnatally acquired 70 kD and 65 kD type II keratin proteins. Again the minimum repetitive dose required for their complete suppression is 30 micrograms vitamin A acid. Kinetic studies reveal an initial lag phase of 6 days of apparent nonresponsiveness, followed by a 5-day period during which the adult pattern is gradually replaced by the neonatal pattern. Repetitive treatment of tail epidermis with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate leads to a strong hyperplasia; however, it strictly maintains the scale parakeratosis. Under these conditions only the 70 kD keratin subunit is suppressed. This indicates that the suppression of the 70 kD keratin is generally linked to the induction of hyperproliferation, whereas the suppression of the scale-associated 65 kD subunit is due to the metaplastic potency of vitamin A. We provide evidence that this vitamin A-specific in vivo effect can be used to determine the biologic activity of synthetic retinoids relative to vitamin A acid.

Animals↗
PubMed1987

An unusual type-II 70-kilodalton keratin protein of mouse epidermis exhibiting postnatal body-site specificity and sensitivity to hyperproliferation.

Keratin extracts from the epidermis of adult mouse ears, footpads, and tail contain large amounts of a 70-kilodalton (kDa) protein which has not been detected in any other body site of the adult mouse or in the epidermis of neonatal mice. Two-dimensional immunoblotting using an antiserum which recognizes both type-I and type-II murine keratins revealed that the 70-kDa protein is indeed a keratin belonging to the type-II subfamily. Its postnatal induction occurs during the first 2 weeks after birth, being first observed in tail epidermis, then in footpad epidermis, and only rather late in ear epidermis. Although in vitro translation experiments with polyA+-RNA from adult tail and footpad epidermis consistently failed to reveal the 70-kDa protein among the translation products, we obtained evidence using a specific cDNA clone that, in vivo, the protein is encoded by a discrete mRNA. This clone, termed pke70, was isolated from a cDNA library of footpad epidermal mRNA. Homology comparisons with a variety of known keratin cDNAs indicated that pke70 contains sequence information for a type-II keratin that is substantially larger than the mouse 67-kDa keratin protein. Northern-blot analysis with a specific 3'-fragment of pke70 demonstrated a single 2.8 +/- 0.1 kb mRNA species exclusively in adult ear, footpad, and tail epidermis. In situ hybridization with the same fragment revealed the presence of the pke70-hybridizing mRNA in both basal and suprabasal cells of ear and footpad epidermis as well as in the orthokeratinizing parts of the tail epidermis; however in the epidermis covering the balls of the feet, labeling was restricted to suprabasal cells at the base of these nodular elevations. Continuous treatment of adult tail or ear epidermis with hyperplasiogenic agents, e.g., vitamin A acid and the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), leads to a gradual disappearance of the 70-kDa protein. We obtained evidence using in situ hybridization that the loss of the 70-kDa keratin is preceded by a specific suppression of the transcription of its putative mRNA in basal cells, whereas initially suprabasal cells are apparently still able to complete their original commitment. The particular properties of the 70-kDa keratin protein, i.e., its topological restriction, its postnatal and time-dependent acquisition, and its pronounced sensitivity to hyperplasiogenic stimuli, make this keratin subunit an especially suitable candidate for studies concerning the regulation of keratin expression and morphogenesis in general, as well as for studies of the factors that control its expression so specifically.

Amino Acid Sequence↗
PubMed1986

Trypanosome hybrids generated in tsetse flies by nuclear fusion.

Genetic exchange may occur between two particular Trypanosoma brucei clones simultaneously transmitted by the same tsetse fly. We report here that this exchange takes place in the fly, through nuclear fusion. The resulting hybrids appear to be sub-tetraploid, some particular DNA sequences from one of the parental stocks being lost before enough cloned hybrid trypanosomes could be harvested for DNA analysis. A further reduction of the DNA content of these hybrids occurs gradually upon growth and yields near diploid value in a major part of the population. This mode of hybrid generation is different from the fusion of haploid gametes, which is thought to occur normally upon inoculation of metacyclic trypanosomes in their mammalian host. In this respect, the sub-tetraploid hybrids appear to undergo meiosis in the fly, generating sub-diploid metacyclic forms, then fusion in the mammalian blood.

Animals↗
PubMed1986

Nonepidermal members of the keratin multigene family: cDNA sequences and in situ localization of the mRNAs.

A keratin set which consists of a type I 47kd and a type II 57kd protein occurs as a major constituent of the keratin patterns of various internal stratified epithelia of the mouse. We have isolated specific cDNA clones of the two complementary keratin subunits from a cDNA library constructed with polyA+RNA of mouse tongue epithelium and present the complete nucleotide and deduced amino acid sequences of the 57kd protein and about 75% of the corresponding data of the 47kd protein. The comparison of the sequence data with those of known epidermal keratin mRNAs coding for the two types of keratin proteins reveals a fundamentally identical and type-specific organization of the mRNAs into both highly conserved and variable domains. In order to avoid cross-reactions with other members of the keratin multigene family, appropriately taylored 35S-labeled cDNA probes comprising the low and non-homologous 3' coding and noncoding domains of the mRNAs were used for in situ hybridization to tissue sections. The localization and distribution of the corresponding transcripts indicates a strongly compartmentalized keratin expression in mouse tongue epithelium.

Amino Acid Sequence↗