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K Rothenberger

Publications and source records attributed to K Rothenberger.

At least 19 recordsLinked to original sources
PubMed1999

Human p120ctn catenin: tissue-specific expression of isoforms and molecular interactions with BP180/type XVII collagen.

Catenins, a family of structurally related proteins, are involved in epidermal keratinocyte cell-cell adhesion by interacting through their central Armadillo repeats with the intracellular domains of cadherins, transmembrane components of the adhesion junctions. p120ctn is a catenin expressed in different isoforms due to alternative splicing and multiple translation start sites. BP180 is a collagenous transmembrane protein (type XVII collagen) localized to hemidesmosomal attachment complexes in basal keratinocytes. In this study, we have delineated the molecular interaction between these two proteins utilizing the yeast two-hybrid system, which was confirmed by an in vitro protein-protein interaction assay. Specifically, it was shown that an amino-terminal segment of BP180 (aa. 13-25) contains the information necessary for binding to p120ctn isoforms 1-3, but not to the isoform 4, suggesting that the interacting domain is located immediately upstream from the Armadillo repeats and is encoded by exons 5 and 6, which are subject to alternative splicing only in a minority of transcripts. In addition to epidermal keratinocytes, p120ctn was shown to be expressed in a variety of adult and fetal tissues as well as in a number of human tumors. The expression pattern of various p120ctn transcripts, reflecting alternative splicing of the 5' exons, was strikingly similar between the corresponding adult and fetal tissues, while the expression patterns were discordant between certain tumors and their normal parental tissues, suggesting a functional role for the tissue-specific expression of the p120ctn isoforms. Finally, the tissue-specific expression of BP180 was shown to partially overlap with that of p120ctn, suggesting that the interaction of these two proteins may contribute to the modulation of cell-cell/matrix interactions in such tissues.

Alternative Splicing↗
PubMed1999

Human periplakin: genomic organization in a clonally unstable region of chromosome 16p with an abundance of repetitive sequence elements.

Periplakin, a member of the plakin family of proteins, has been recently characterized by cDNA cloning, and the corresponding gene, PPL, has been mapped to human chromosome 16p13.3 (Aho et al., 1998, Genomics 48: 242-247). Periplakin has also been shown to serve as an autoantigen in a malignancy-associated autoimmune blistering disease, paraneoplastic pemphigus (Mahoney et al., 1998, J. Invest. Dermatol. 111: 308-313). In this study, we have elucidated the intron-exon organization of human PPL and characterized its promoter region. The flanking 5' sequences were rich in G and C ( approximately 80%) and included multiple AP2 sites and a SP1 site, while no canonical TATA or CCAAT sequences were found. The functionality of the upstream sequences (-709 to +135) as a promoter in cultured epidermal keratinocytes was detected by a CAT reporter gene, and a limited region (-382 to +135) showed activity in cultured dermal fibroblasts, attesting to cell-type specificity of the promoter. The genomic organization, including the intron-exon borders, was determined by direct nucleotide sequencing of human genomic P1 clones. Comparative analysis of cDNA and genomic sequences revealed that PPL consists of 22 exons, with the distribution of exons in PPL being consistent with that of other plakin genes: 21 small exons, separated by large introns, encode the amino-terminal globular domain, and 1 large exon encodes the entire rod and the tail domains. Characterization of four P1 clones spanning the PPL locus revealed multiple Alu repeats, 20 of them within 33 kb of the entirely sequenced segments (0.60/kb), in addition to numerous MIR and L1 elements. These repetitive elements could lead to the clonal instability detected throughout the genomic P1 clones and may give rise to the genomic rearrangements possibly underlying the paraneoplastic pemphigus.

Base Sequence↗
PubMed1999

Explanations for the clinical and microscopic localization of lesions in pemphigus foliaceus and vulgaris.

Patients with pemphigus foliaceus (PF) have blisters on skin, but not mucous membranes, whereas patients with pemphigus vulgaris (PV) develop blisters on mucous membranes and/or skin. PF and PV blisters are due to loss of keratinocyte cell-cell adhesion in the superficial and deep epidermis, respectively. PF autoantibodies are directed against desmoglein (Dsg) 1; PV autoantibodies bind Dsg3 or both Dsg3 and Dsg1. In this study, we test the hypothesis that coexpression of Dsg1 and Dsg3 in keratinocytes protects against pathology due to antibody-induced dysfunction of either one alone. Using passive transfer of pemphigus IgG to normal and DSG3(null) neonatal mice, we show that in the areas of epidermis and mucous membrane that coexpress Dsg1 and Dsg3, antibodies against either desmoglein alone do not cause spontaneous blisters, but antibodies against both do. In areas (such as superficial epidermis of normal mice) where Dsg1 without Dsg3 is expressed, anti-Dsg1 antibodies alone can cause blisters. Thus, the anti-desmoglein antibody profiles in pemphigus sera and the normal tissue distributions of Dsg1 and Dsg3 determine the sites of blister formation. These studies suggest that pemphigus autoantibodies inhibit the adhesive function of desmoglein proteins, and demonstrate that either Dsg1 or Dsg3 alone is sufficient to maintain keratinocyte adhesion.

Animals↗
PubMed1998

Desmoglein 3 anchors telogen hair in the follicle.

Little is known about the function of desmosomes in the normal structure and function of hair. Therefore, it was surprising that mice without desmoglein 3 (the autoantigen in pemphigus vulgaris) not only developed mucous membrane and skin lesions like pemphigus patients, but also developed hair loss. Analysis of this phenotype indicated that hair was normal through the first growth phase ('follicular neogenesis'). Around day 20, however, when the hair follicles entered the resting phase of the hair growth cycle (telogen), mice with a targeted disruption of the desmoglein 3 gene (DSG3-/-) lost hair in a wave-like pattern from the head to the tail. Hair then regrew and was lost again in the same pattern with the next synchronous hair cycle. In adults, hair was lost in patches. Gentle hair pulls with adhesive tape showed that anagen (growing) hairs were firmly anchored in DSG3-/- mice, but telogen hairs came out in clumps compared to that of DSG3+/- and +/+ littermates in which telogen hairs were firmly anchored. Histology of bald skin areas in DSG3-/- mice showed cystic telogen hair follicles without hair shafts. Histology of hair follicles in early telogen, just before clinical hair loss occurred, showed loss of cell adhesion (acantholysis) between the cells surrounding the telogen club and the basal layer of the outer root sheath epithelium. Electron microscopy revealed 'half-desmosomes' at the plasma membranes of acantholytic cells. Similar acantholytic histology and ultrastructural findings have been previously reported in skin and mucous membrane lesions of DSG3-/- mice and pemphigus vulgaris patients. Immunoperoxidase staining with an antibody raised against mouse desmoglein 3 showed intense staining on the cell surface of keratinocytes surrounding the telogen hair club in normal mice. Similar staining was seen in human telogen hair with an anti-human desmoglein 3 antibody. Finally, a scalp biopsy from a pemphigus vulgaris patient showed empty telogen hair follicles. These data demonstrate that desmoglein 3 is not only critical for cell adhesion in the deep stratified squamous epithelium, but also for anchoring the telogen hair to the outer root sheath of the follicle and underscore the importance of desmosomes in maintaining the normal structure and function of hair.

Acantholysis↗
PubMed1986

Penile cancer. Aspiration biopsy cytology for staging.

Appropriate management and prognosis of patients with penile carcinoma depends on an accurate knowledge of the regional node status. The usefulness of clinical and radiologic examinations in detecting the nodal spread of the disease is limited by the high rates of false-positive and false-negative results. On the other hand, routine or prophylactic lymphadenectomy is associated with 30% to 50% of the major morbidity and 3% of the mortality rate, so that caution is advisable for its use in patients with disease-free nodes. Even bilateral sentinel lymph node biopsy, as proposed by Cabanas, does not warrant an adequate selection of patients candidates to surgical treatment. The role of aspiration biopsy cytology in the management of penile carcinoma was evaluated in a study of 29 cases from the authors' institutions. Aspiration under fluoroscopic or computed tomographic guidance was performed using a 22-23-gauge Chiba needle. The accuracy of aspiration biopsy cytology in identifying the true stage of the disease was 100%. On histologic control, only one node contained malignant cells that were not detected by aspiration biopsy cytology, but this finding did not alter the stage of the patient. Positive cytology is conclusive of Stage III disease and, in this case, a curative lymphadenectomy may be attempted. Negative aspirations do not warrant the absence of metastatic nodal involvement as can be seen in two patients in this series. In such cases, however, a policy of "wait and watch" may be adopted, with repeated aspiration biopsies or surgical biopsy of the sentinel node area.

Adult↗
PubMed1983

Transurethral laser coagulation for treatment of urinary bladder tumors.

Owing to the biophysical properties involved, the Nd:YAG laser is most suited for coagulation of even inhomogeneous tissue. We determined the optimal laser parameters for therapy of urinary bladder tumors. Deep homogeneous necroses can be obtained without perforation risk of the bladder wall, and the procedure does not cause dangerous damage to the intestinal loops. We have studied animal experiments by close examination and systematic inquiry, and thus we were able to determine sufficient laser parameters in dependence on tissue thickness. Clinical studies verified these results for living human tissue. After some years of clinical use of the Nd:YAG laser we can make the first statistical statements.

Fiber Optic Technology↗
PubMed1983

Controlled bipolar high-frequency coagulation for transurethral application: a new method for the destruction of urinary bladder tumors.

The coagulation of small bladder papillomas or of the resection base after transurethral resection by unipolar high-frequency current has turned out not to be sufficiently radical so far. There is no definite and reproducible correlation between the achieved biological effect. Bipolar high-frequency current produces the desired necrosis in the deeper layers of tissue. When providing the high-frequency generator with a new experimental automatic control equipment, reproducible deep and homogeneous necrosis of the tissue can be achieved without taking a great deal of time. Moreover, adherence of the probe and carbonization are prevented. First, the experiments had been carried out in vitro on livers of cattle and secondly, in vivo on canine livers. By the conventional unipolar high-frequency coagulation a reproducible and homogeneous necrosis cannot be achieved. With the regulated high-frequency coagulation, however, we are able to produce homogeneous tissue necroses up to a depth of 7 mm, the extension of which can definitely be assigned to the adjusted technical parameters. The electrodes do not adhere, since carbonization does not occur because of the automatic control. Premature interruption of the coagulation process, even if the generator is adjusted too high by mistake, can be considered a further advantage of this protective switch. A first clinical experience is reported.

Adult↗
PubMed1982

[Differential diagnosis of testicular neoplasms. Tumorous and clinically tumor-like diseases of the scrotum].

The observation of a case of inguinal omental hernia with marked peritoneal carcinosis treated by operation for suspected testicular tumor leads us to discuss systematically the differential diagnosis of tumors and tumor-like conditions of the scrotal region. In order to analyse the frequency and importance 420 cases of ours were reconsidered. Of these 30 had been admitted to our hospital because of suspicion of tumors of the testis. The diagnosis on admission and after morphological analysis by the pathologist are compared.

Aged↗
PubMed1982

Various effects of the CO2-, the neodymium-YAG-, and the argon-laser irradiation on bladder tissue.

Application of lasers as cutting or coagulation instruments is based on the conversion of light energy into heat in the irradiated tissue. The extent and degree of the thermal action depends on the beam geometry and the energy of the incident light, as well as on the optic and thermal properties of this tissue. The extinction behavior in the tissue differs for the various laser systems employed in medicine. A comparison of the effects on bladder tissue of rats and rabbits is made with Neodymium-YAG laser and the argon and CO2 lasers to demonstrate the advantages of the Neodymium-YAG laser, especially for the therapeutic irradiation of bladder tumors.

Animals↗
PubMed1981

[Comparison of the antibacterial effects of gentamycin, tobramycin, dibekacin and amikacin in urinary germs].

We isolated 491 pathogens of urinary tract infections of our urological in-patients. Sensitivity against gentamycin, tobramycin, dibekacin and amikacin was tested in vitro. Our data were compared with the statements of the medical literature. It should be pointed out the great fraction of grampositive staphylococci. Their sensitivity rate of 40% against the tested aminoglycosides was remarkably small. Enterococci had a sensitivity rate of 70% against gentamycin, tobramycin and dibekacin. Their sensitivity rate against amikacin was only 20% as expected, because enterococci do not belong to the proper antibiotic spectrum. The four aminoglycosides are highly effective against gramnegative organisms with with no appreciable differences.

Amikacin↗