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Biomedical subjects

J Schweizer

Publications and source records attributed to J Schweizer.

At least 55 records · Page 3Linked to original sources
PubMed1996

Dermal cysts of the rhino mouse develop into unopened sebaceous glands.

The rhino mouse (hr(rh)hr(rh)) is a mutant strain characterized by a wrinkled and hairless skin with epidermal utriculi (pseudocomedones) and dermal cysts. The epidermal cysts have been extensively studied. The present work focused on the dermal cysts. By electron microscopy it was found that they appear on day 20 after birth and that they originate from a pool of undifferentiated epithelial cells of the deepest part of the initial follicular unit. Progressively, the number of cells in these islets increased and a central cavity was formed. Peripheral cells differentiated into sebocyte-like cells and outer root sheath cells. Staining with Oil Red O solution indicated accumulation of lipid material in the central cavity. The dermal cysts of the adult rhino mouse were isolated and purified in several steps including enzyme digestion, centrifugation, and separation on Nylex sieves. The integrity of the isolated cysts was confirmed by histology and electron microscopy. Study of their keratin polypeptide pattern by gel electrophoresis indicated that they express the mouse keratins 5, 14, 6 and 17. Neutral lipid analysis of the dermal cyst contents showed that they were mainly composed of cholesterol esters, wax esters, lipid fractions which migrate between triglycerides and cholesterol esters but very small amounts of triglycerides, cholesterol and ceramides. In conclusion, the present results demonstrate that dermal cysts of the rhino mouse have strong similarities with sebaceous glands and outer root sheath cells. These structures can easily be isolated and could therefore serve as a 'closed sebaceous gland' model to study the physiology or differentiation of the sebaceous gland, or the effects of pharmacological agents.

Animals↗
PubMed1996

Comparison of tissue plasminogen activator and urokinase in the local infiltration thrombolysis of peripheral arterial occlusions.

Recanalization of the vascular lumen by means of local fibrinolysis is of major importance in the treatment of peripheral arterial occlusive disease. While urokinase and streptokinase have been extensively used for local fibrinolysis, there have been few studies of infiltration thrombolysis with genetically engineered tissue plasminogen activator (rt-PA). The aim of the investigation reported here was to establish whether there is any difference between urokinase and rt-PA in the short- and long-term outcome of local fibrinolytic therapy. One-hundred twenty patients (70 men, 50 women) with acute or subacute femoral (n = 21), femoropopliteal (n = 33), popliteal (n = 13) or popliteocrural (n = 53) thrombotic occlusions were randomized to local lysis using urokinase or rt-PA, and 6 months later follow-up investigations took place. Recanalization of thrombotically occluded vessels, particularly in the lower leg, was found more frequently, and after treatment of shorter duration, with rt-PA. Large local haematomas occurred in 8% of cases in the urokinase group and 15% in the rt-PA group. No serious haemorrhages were encountered in either group. Six months after treatment, the rt-PA group showed lower rates of Fontaine stage III and IV disease and amputation than the urokinase group, with a higher number of patients in Fontaine stage IIb. This study shows that local lysis with rt-PA yields better results than urokinase, not only in the short term but also 6 months later.

Adult↗
PubMed1996

[Measuring basilar artery blood flow velocity with transcranial Doppler and and transcranial Doppler color ultrasound].

GOAL: The aim of the present study was to clarify, by means of transcranial colour-coded duplex sonography of the basilar artery, whether there are changes in basilar artery blood flow in patients with acute inner ear disturbances and whether the flow in the basilar artery is affected by acoustic stimuli in such patients and in normal, healthy controls. METHOD: Basilar artery blood flow velocity was measured in 52 patients with severe inner ear impairment over a period of two weeks by means of conventional transcranial Doppler sonography and transcranial colour-coded duplex sonography. The same measurements were carried out in 45 healthy control subjects. At the end of the two week period, both patients and controls were exposed to 70-dB noise, with basilar artery flow evaluated before and during exposure. The basilar artery Doppler curves were analysed for systolic flow velocity, end-diastolic flow velocity, resistance index (Pourcelot) and pulsatility index (Gosling). RESULTS: During the first two days of the study, the basilar artery resistance index and pulsatility index were significantly (p < 0.001) higher in patients than in controls. During noise exposure, both patients and controls showed significant (p < 0.01) increases in these indices. CONCLUSION: This study shows that temporary increases in the basilar artery resistance index and pulsatility index are found both in the acute phase of inner ear disease and during exposure to noise.

Acoustic Stimulation↗
PubMed1996

The region coding for the helix termination motif and the adjacent intron 6 of the human type I hair keratin gene hHa2 contains three natural, closely spaced polymorphic sites.

Mutations in distinct sites of epidermal keratins, in particular in the helix initiation and termination regions, cause human genodermatoses due to faulty intermediate filament formation. Extension of this observation to human hereditary hair and nail diseases includes population analyses of human hair keratin genes for natural sequence variations in the corresponding sites. Here we report on a large-scale genotyping of the short helix termination region (HTR) of the human type I cortical hair keratins hHa1, a3-I, and a3-II, and the cuticular hair keratin hHa2. We describe two polymorphic loci, P1 and P2, exclusively in the cuticular hHa2 gene, both creating dimorphic protein variants. P1 is due to a C to T mutation in a CpG element leading to a threonine to methionine substitution; P2 concerns a serine codon AGT that also occurs as an asparagine coding variant AAC. A third polymorphism, P3, is linked with a C to T point mutation located at the very beginning of intron 6. The three polymorphic sites are clustered in a 39-nucleotide sequence of the hHa2 gene. Both allelic frequency calculations in individuals of different races and pedigree studies indicate that the two-allelic hHa2 variants resulting from P1 and P2 occur ubiquitously in a ratio of about 1:1 (P1) and 2:1 (P2) respectively in our survey, and are clearly inherited as Mendelian traits. A genotype carrying both mutations simultaneously on one allele could not be detected in our sampling, and there was no association of a distinct allelic hHa2 variant with the known ethnic form variations of hairs. Sequence comparisons of the HTR of hHa2 with those of other type I hair keratins including the hHa2-ortholog from chimpanzee provide evidence that the P1- and P2-linked mutations must have occurred very early in human evolution and that the two P2-associated codon variants may be the result of two independent point mutations in an ancestral AGC serine codon. These data describe natural polymorphisms in the HTR of a member of the keratin multigene family.

Alleles↗
PubMed1996

Genomic characterization of the human type I cuticular hair keratin hHa2 and identification of an adjacent novel type I hair keratin gene hHa5.

Hair keratins, a subset of the keratin multigene family expressed in hard keratinizing structures, previously have been thought to comprise four members of each subfamily, designated Ha1-4 (type I) and Hb1-4 (type II), which are differentially expressed in the cuticle and cortex of the hair follicle. This report describes the genomic cloning and sequencing of the human type I cuticular hair keratin hHa2, as well as the identification of a previously unknown human type I hair keratin gene. The 12.5-kilobase pair genomic clone ghkI2.12, obtained by hybridization of a human genomic deoxyribonucleic acid library with a 3'-complementary deoxyribonucleic acid probe of hHa2, as well as the partially overlapping 14.4-kilobase pair genomic clone ghkI2.17, isolated using a 5'-fragment of clone ghkI2.12, allowed the characterization of the entire hHa2 gene. The gene displays the same exon/intron structure as two previously characterized type I mouse and sheep hair/wool keratin genes with strict positional conservation of the six introns in the region coding for the central alpha-helix. At the 5'-extremity of clone ghkI2.17, i.e., approximately 8.0 kilobase pairs upstream of the hHa2 gene and oriented in the same transcriptional direction, lies the gene for a hitherto unknown human type I hair keratin. Clone ghkI2.17 contains partial sequence information for this gene beginning with intron 5 and extending to the end of the gene. Screening of a human scalp complementary deoxyribonucleic acid library with a 3'-fragment of the gene yielded a full length complementary deoxyribonucleic acid clone of the new hair keratin, which in continuation of the current nomenclature for hair keratins was termed hHa5. Remarkably, the hHa5 gene, which contains an additional 7th intron in its 3'-noncoding region, is expressed mainly in supramatricial cells and lowermost cortical cells of the hair bulb and thus constitutes a very early component of hair morphogenesis. Our results confirm the type specific clustering of keratin genes and indicate that the human type I hair keratin subfamily contains more members than previously assumed.

Amino Acid Sequence↗
PubMed1996

[Are beta-blockers generally contraindicated in patients with peripheral arterial occlusive disease?].

Ninety patients with chronic ischemic heart disease and stage IIb peripheral arterial occlusive disease were investigated to determine the effect of celiprolol, atenolol and isosorbide dinitrate on peripheral arterial blood flow. Walking distance and the resistance index in the femoral artery were measured before and after 3 months medication and compared with the findings in controls (30 patients with chronic ischemic heart disease and stage IIb peripheral arterial occlusive disease) who received placebo. Patients with peripheral arterial occlusive disease who were treated with atenolol 50 mg/day demonstrated significant decreases in both pain-free and maximal walking distance. In contrast, the walking distances in those given celiprolol 200 mg/day and those who received isosorbide dinitrate 80 mg/day did not differ from the distances in control subjects. The Doppler flow through the femoral artery, as measured by color duplex sonography, showed a significant decrease in resistance index, both in patients given celiprolol and in those given isosorbide dinitrate. In patients treated with atenolol the resistance index rose significantly. The results of this study confirm that the beta-adrenoceptor blocker celiprolol exerts a supplementary vasodilatory action resembling that of nitrates and hence can be used in patients with chronic ischemic heart disease and impaired peripheral arterial perfusion.

Adrenergic beta-Antagonists↗
PubMed1996

[Long-term results after caval filter implantation].

In order to help clarify the long-term results of filter implantation and how best to manage the post-operative care, 92 patients with implanted filters were observed for up to 6 years. The follow-up examinations included detailed interrogation, a clinical investigation, plain abdominal radiography in two planes, contrast-enhanced computed tomography of the vena cava and colour-coded duplex sonography of the vena cava and the veins of the pelvic and legs. In the early phase of the study, two patients who received Günther filters in 1988 experienced dislocation of the filter after 3 months. In the later phase, 85% of those treated with oral anti-coagulants and compression showed patent pelvic veins in areas where, at the time of filter implantation, there had been thrombi with the potential to cause embolism. In 72 cases, the inferior v.cava proved to be patent in the area of the filter.

Aged↗
PubMed1996

[Light-evoked blood flow changes in the posterior cerebral artery].

In 20 healthy volunteers light evoked changes in blood flow of the posterior cerebral artery were studied with color coded Doppler sonography. Doppler flow profiles of the PCA were recorded before, during and after exposition with light. Under the treatment with light the RI decreased in the mean form 0.61 down to 0.50, indicating an increase of flow. After redarking the RI increased again up to a mean of 0.62. The applied test could be a helpful tool to clarify the pathophysiological mechanism in defect seeing.

Adult↗
PubMed1995

A cDNA encoding the human type I hair keratin hHal.

A full-length cDNA of a human type I hair keratin was isolated that encodes a protein of 416 amino acids. Northern blot analysis shows that the mRNA is present in human scalp but not in hairless skin. Based on sequence homology comparisons with the four known mouse type I hair keratins mHal-4 the keratin could be identified as the human hair keratin hHal.

Amino Acid Sequence↗
PubMed1995

Sequence data and chromosomal localization of human type I and type II hair keratin genes.

A cDNA library constructed with poly(A)+ RNA from human scalp was screened with selected fragments of both murine type I and type II hair keratin cDNAs. Two keratin clones, one type I, phKI-2, and one type II, phKII-1, were isolated and sequenced. In Northern blots, cDNA probes containing the 3'-noncoding sequences of the clones specifically hybridized to scalp mRNA species. Based on sequence homology comparisons with the four known murine type I hair keratins mHa1-4, the phKI-2 encoded keratin could be identified as human hair keratin hHa2. Similarly, sequence comparison with the four type II sheep wool keratins K2.9-12 revealed an orthologous relationship between the largest member of the type II wool keratin subfamily, K2.9 (i.e., sHb1) and the phKII-1 encoded human hair keratin (hHb1). The specific 3'-noncoding sequences of hHa2 and hHb1 were also used to isolate genomic fragments for both keratins from human genomic libraries which were than used for fluorescence in situ hybridization to human metaphase chromosomes. The hHa2 gene could be mapped to the long arm of chromosome 17, whereas the hHb1 gene was found on the long arm of chromosome 12. DAPI banding of the chromosomes allowed sublocalization of the hHa2 gene to 17q12-q21 and the hHb1 gene to 12q13, i.e., gene loci that have also been previously determined for human type I and type II epithelial keratins.

Amino Acid Sequence↗
PubMed1995

[Color-coded duplex ultrasound findings and transcranial color duplex ultrasound findings in patients with acute inner ear disorders--a preliminary observation].

A prospective investigation of 98 patients with acute loss of inner ear function showed that such patients display changes in the pulsatility of the basilar artery; however, the differences can be appreciated only by comparison with control sonograms during the course of the disease. Patients with sudden deafness or sudden loss of equilibrium generally showed unremarkable findings on duplex sonography of the cervical portions of vessels supplying the brain.

Acute Disease↗
PubMed1995

[Noise-induced changed in basilar circulation].

In 55 volunteers with good hearing, sound-evoked changes in the blood flow of the basilar artery were studied using colour coded Doppler sonography. After a rest of twenty minutes 2 groups of subjects listened to sound of varying volume using a head phone. In one group (n = 25) the sound volume was 25 dB and in the second group (n = 30) the volume was 65 dB. In both groups significant sound evoked changes of vascular resistance were found, quantified by the RI. In the case of applying soft sound (25 dB) the RI decreased, indicating an increase of volume flow while with louder sound (65 dB) the RI increased, indicating a reduction of flow.

Acoustic Stimulation↗
PubMed1994

Sequence and expression of murine type I hair keratins mHa2 and mHa3.

A cDNA library was constructed with poly(A)+ RNA from mouse tail epidermis which contained all hair follicles of tail skin. The library was subjected to sequential screening procedures aimed at selecting cDNA clones coding for acidic, type I hair keratins. Two clones, pktI-2 and pktI-3, encoded keratins that could be identified as murine type I hair keratins mHa2 and mHa3, respectively, by positive hybridization selection analysis. Sequence comparisons with the known murine type I hair keratins mHa1 (Bertolino et al., J. Invest. Dermatol. 91, 541-546, 1988) and mHa4 (Bertolino et al., J. Invest. Dermatol. 94, 297-303, 1990) revealed a structural heterogeneity within the type I hair keratin subfamily. Three keratins, mHa1, mHa3, and mHa4, are highly related, differing mainly in the penultimate part of their amino and carboxy termini. In contrast, mHa2 is structurally distinct from the three other keratins in both the alpha-helix and, in particular, the non-alpha-helical domains. These findings are confirmed by evolutionary investigations and flexibility calculations which indicate a more flexible nature of the mHa2 amino terminus when compared to the corresponding region of the three other keratins. In situ hybridization experiments with specific 3' fragments of mHa2 and mHa3 show that mHa3 is expressed in cortex cells, whereas mHa2 transcripts are strictly limited to the cuticle of the hair shaft. mHa3 mRNA expression can also be demonstrated in the central unit of the murine lingual filiform papillae, whereas the cuticular keratin mHa2 is not expressed in this body site. These data indicate that the structural heterogeneity within the type I hair keratin subfamily is functionally relevant in the morphogenesis of hard alpha-keratin-expressing tissues.

Amino Acid Sequence↗
PubMed1994

Analysis of a new genetic cross between two East African Trypanosoma brucei clones.

Two clones of East African Trypanosoma brucei, with distinct homozygous isoenzyme patterns for one of three enzymes examined, were cotransmitted through the tsetse fly vector Glossina morsitans centralis. Flies with mature infections were individually fed on mice and the subsequent bloodstream from populations analysed for the presence of hybrid trypanosomes by isoenzyme analysis. Several combinations have previously been detected using this approach (Schweizer, Tait & Jenni, 1988; Sternberg et al. 1989). Four clones were isolated from one of the hybrid-containing populations. They showed a hybrid phenotype, as would be expected for the F1 progeny in a diploid Mendelian system. The analysis of the progeny clones, using two gene probes which detect restriction fragment length polymorphisms between the two parental stocks, showed that alleles had segregated at each locus and given rise to three different non-parental combinations of alleles in the hybrid progeny. Characterization of the hybrid progeny clones by PFGE (pulsed field gradient gel electrophoresis) revealed that all progeny clones were recombinant for the intermediate size chromosomes. From the analysis of the segregation of the larger chromosomes, marked by PGK (phosphoglycerate kinase) and CP (cysteine protease) gene probes, it was inferred that the progeny clones did not result from a direct fusion of diploid cells. Results with the PGK probe fit into a classical system with meiosis and subsequent fusion of the nuclei to form diploid progeny. On the other hand, blots with the CP probe as well as some of the ethidium bromide stained PFGE gels revealed the existence of non-parental size chromosomes in some of the hybrid progeny. This phenomenon was observed previously (Gibson, 1989) and further investigation is required to elucidate the mechanism.

Africa, Eastern↗
PubMed1994

[Diagnosis of iatrogenic vascular injuries with color-coded duplex ultrasound].

Between January 1991 and October 1992, 1052 patients who had previously undergone coronarography were examined for iatrogenic lesions around the catheter entry point. Some 3% of them were found to have local complications in the form of haematomas, aneurysms, and arteriovenous fistulas. At the time of investigation 75% of patients with local complications were on oral anticoagulants. In over half of those who had complications on oral anticoagulants there was no alternative to surgical treatment. Colour duplex sonography has the advantage that it can be repeated as often as possible; thus, in cooperation with the cardiac surgeon, the necessity and urgency of surgical intervention in cardiac risk patients can be assessed on an ongoing basis.

Aneurysm, False↗
PubMed1994

Retinoic acid-induced normal and tumor-associated aberrant expression of the murine keratin K13 gene does not involve a promotor sequence with striking homology to a natural retinoic acid responsive element.

The type I keratin K13, normally restricted to suprabasal cells of internal stratified epithelia, is aberrantly expressed in 7,12-dimethylbenz[a]anthracene (DMBA)-12-O-tetradecanoyl-phorbol-13-acetate-induced murine epidermal tumors and constitutes an early marker of malignant progression. Aberrant K13 expression also occurs in epidermal cell lines derived from DMBA-TPA-induced tumors. As in cultured primary keratinocytes from normal internal stratified epithelia, the in vitro expression of K13 in transformed epidermal cell lines can be induced either by Ca2+ or by retinoic acid (RA). We have found that the promoter of the K13 gene contains a sequence element GGTTCA(N)5TGTTCT, in the following referred to as K13-RARE, that is highly related to the natural retinoic acid responsive element (RARE) of the retinoic acid receptor beta 2 gene. Both elements differ only in the second half-motifs, in which the first and sixth position is occupied by thymidines (K13-RARE) instead of adenines (beta 2-RARE), as well as in their pentameric spacer sequences. Despite this striking homology in the receptor binding domains, we show by transfection of reporter gene constructs of the elements into primary fore-stomach keratinocytes and transformed epidermal cell lines that in both cell systems, unlike beta 2-RARE, the wild-type K13-RARE completely lacks transactivating properties in the presence of RA. A recent hypothesis proposes that aberrant gene expression during tumorigenesis may occur through conversion of inactive response elements with high homology to hormone response elements into functional enhancers by carcinogen-induced point mutations at critical positions (Nawaz et al., Mol. Carcinogen., 7, 76-82, 1993). To investigate whether the aberrantly expressed K13 gene falls into the category of those genes, reporter gene constructs of K13-RARE variants in which either the initial or the terminal thymidine of the second half-motif was replaced by adenine were transfected into epidermal cell lines. Neither mutant exhibited RA-dependent transactivating properties. Strong transactivation could only be achieved by a K13-RARE mutant in which both critical thymidines were substituted by adenines. This type of closely spaced base exchange, unlikely to be created during DMBA initiation of mouse epidermis, was not detectable on sequencing genomic DNA of a squamous cell carcinoma and a transformed epidermal cell line. Instead, in both cases, only the wild-type K13-RARE could be demonstrated. A regulatory role of this RARE-like sequence in the promoter of the murine K13 gene for both normal and aberrant expression of the gene can therefore be excluded.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

SENCAR mouse skin tumors produced by promotion alone have A to G mutations in codon 61 of the c-rasHa gene.

SENCAR mice, developed by selective breeding for high susceptibility to skin carcinogenesis by initiation with 7,12-dimethylbenz[a]anthracene and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA), form squamous papillomas in approximately 20% of animals treated repeatedly with TPA, without chemical initiation. DNA from eight skin tumors produced by a TPA-only protocol and four cell lines derived from these tumors was amplified by polymerase chain reaction and analyzed by discriminative oligonucleotide hybridization using oligomers specific for various c-rasHa gene codon 61 sequences. Five tumors and three cell lines had CAA (wild-type) to CGA mutations. In addition, one tumor had a CAA to CTA mutation, for a total of six of eight tumors having an activating mutation at this codon. Two tumors and one cell line had no codon 61 mutations detectable by this method. Since tumors derived from promotion-only protocols presumably originated from constitutively initiated cells, we examined tumor-free skins of untreated newborn and eight-month-old retired breeders and of 78-88-week-old SENCAR mice of both sexes, which were treated with TPA for 10 weeks starting at age 16-28 weeks and were untreated thereafter. Only the wild-type c-rasHa gene codon 61 sequence was seen, suggesting that the constitutively initiated cell population, if present, is below the limit of detection by this method.

9,10-Dimethyl-1,2-benzanthracene↗