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Biomedical subjects

S Karl

Publications and source records attributed to S Karl.

18 recordsLinked to original sources
PubMed2006

NF-kappaB-independent sensitization of glioblastoma cells for TRAIL-induced apoptosis by proteasome inhibition.

The transcription factor nuclear factor-kappaB (NF-kappaB) is a key regulator of stress-induced transcriptional activation and has been implicated in mediating primary or acquired apoptosis resistance in various cancers. In the present study, we therefore investigated the role of NF-kappaB in regulating apoptosis in malignant glioma, a prototypic tumor refractory to current treatment approaches. Here, we report that constitutive NF-kappaB DNA-binding activity was low or moderate in eight different glioblastoma cell lines compared to Hodgkin's lymphoma cells, known to harbor aberrant constitutive NF-kappaB activity. Specific inhibition of NF-kappaB by overexpression of inhibitor of kappaB (IkappaB)alpha superrepressor did not enhance spontaneous apoptosis of glioblastoma cells. Also, overexpression of IkappaBalpha superrepressor had no significant impact on apoptosis induced by two prototypic classes of apoptotic stimuli, that is, chemotherapeutic drugs or death-inducing ligands such as TNF-related apoptosis inducing ligand (TRAIL), which are known to trigger NF-kappaB activation as part of a cellular stress response. Similarly, inhibition of NF-kappaB by the proteasome inhibitor MG132 did not increase doxorubicin (Doxo)-induced apoptosis of glioblastoma cells, although it prevented DNA binding of NF-kappaB complexes in response to Doxo. Interestingly, proteasome inhibition significantly sensitized glioblastoma cells for TRAIL-induced apoptosis. These findings indicate that the characteristic antiapoptotic function of NF-kappaB reported for many cancers is not a primary feature of glioblastoma and thus, specific NF-kappaB inhibition may not be effective for chemosensitization of glioblastoma. Instead, proteasome inhibitors, which enhanced TRAIL-induced apoptosis in an NF-kappaB-independent manner, may open new perspectives to increase the efficacy of TRAIL-based regimens in glioblastoma, which warrants further investigation.

Active Transport, Cell Nucleus↗
PubMed2006

Y-duplication of the male urethra: use of anterior anorectal wall for posterior urethral lengthening.

We have approached two patients with Y-duplication of the male urethra by a new two-staged technique to provide better results. A strip of anterior anorectal wall in continuity with the posterior urethra was used for posterior urethral lengthening and a tubed pedicled prepucial flap was used to reconstruct the anterior urethra without using the native urethra. This was done under a covering colostomy. After a gap of 6 months to allow for healing of the anorectum and to ensure adequate functioning of the perineal neourethra, second stage reconstruction was done using buried scrotal tube for the mid urethra along with colostomy closure. On follow-up at 8 and 12 months, respectively, both children were well with no stricture or fistula. There was normal anal continence and no stenosis. This technique tackles the problem in Y-duplication of the male urethra of lengthening the posterior urethral channel, which is often difficult to bring to the anterior half of the perineum especially if the opening is high up in the anorectum (case 2).

Child↗
PubMed2000

Isolated congenital nail dysplasia: a new autosomal dominant condition.

OBJECTIVE: Developmental nail abnormalities are extremely heterogeneous, with hereditary isolated conditions being a small and rare subgroup. An unusual congenital nail dysplasia observed in a large South German kindred was characterized clinically to review the question of uniqueness. DESIGN: Case series of affected family members. SETTING: University department of dermatology and houses of patients. PATIENTS: The history and clinical features in 22 affected family members (13 females and 9 males, aged 5 to 74 years) were recorded and documented by photographs. Nail biopsy samples were taken from 2 patients. INTERVENTIONS: None. RESULTS: The pedigree spanning 5 consecutive generations was best compatible with autosomal dominant inheritance with complete penetrance. Nail alterations were mostly present since birth and soon reached an individually variable degree of severity. Affected persons showed longitudinal streaks and thinning of nail plates, mostly of all fingernails and toenails, with some accentuation of the thumbnail and big toenails, poorly developed lunulae, longitudinal angular ridges of individual nail plates occasionally starting proximally from a reddish prominence, platonychia and koilonychia of individual nails often overgrowing the lateral folds, and notches and fissures of the free margins. Histological abnormalities included a prominent granular layer of the nail matrix and epithelial strands and buds extending from the nail bed. There were no associated anomalies. Other nail dystrophies were excluded by differences in clinical and histological features. CONCLUSION: The nail abnormality observed in our family represents a new autosomal dominant disorder for which we propose the term isolated congenital nail dysplasia. Arch Dermatol. 2000;136:1239-1243

Adolescent↗
PubMed2000

Assignment of the gene for a new hereditary nail disorder, isolated congenital nail dysplasia, to chromosome 17p13.

Isolated congenital nail dysplasia is an autosomal dominant disorder recently observed in a large family from southern Germany. The disorder is characterized by longitudinal streaks, thinning, and impaired formation of the nail plates leading to increased vulnerability of the free nail margins. In most cases, all fingernails and toenails are similarly involved with some accentuation of the thumb and great toenails. Histologic changes include hypergranulosis of the nail matrix and epithelial outgrowths from the nail bed. Patients do not show any alterations of hair growth and dentition, no malfunction of sweat glands and sensory organs, and no skeletal abnormalities. Isolated congenital nail dysplasia manifests from the first year of life with variable expressivity. In order to localize chromosomally the gene underlying isolated congenital nail dysplasia, linkage to the known keratin gene cluster regions on chromosomes 12q12 and 17q21 was ruled out first. The analysis of 150 microsatellite markers on various chromosomes mapped the isolated congenital nail dysplasia gene to the 6 cM interval between markers at D17S926 and D17S1528 on chromosome 17p13. Markers at D17S849, D17S 1840, and D17S1529 co-segregated completely with the isolated congenital nail dysplasia locus. The maximum two-point LOD score was found for the marker at D17S 1840 (Zmax = 6.72 at Thetamax = 0.00). The identified region harbors no currently known genes involved in skin or nail abnormalities. Isolated congenital nail dysplasia probably represents a novel isolated defect of nail development. The localization of this gene is, therefore, the first step towards the identification of a new factor in nail formation.

Child↗
PubMed1999

Torted ovarian cyst with lethal bleeding diathesis in an infant.

We report a 9-month-old infant with a torted ovarian cyst who presented with an acute consumptive coagulopathy (CC) with lethal outcome. That ischemic tissue can act as a trigger for a CC is well-known, but we did not find any report of a torted ovarian cyst causing a coagulopathy in the pediatric literature. This potential complication constitutes one more reason for the prompt surgical removal of torted ovarian cysts in infants.

Disseminated Intravascular Coagulation↗
PubMed1999

Pro and contra of specific hyposensitization.

Specific hyposensitization is the practice of administering gradually increasing quantities of a specifically relevant allergen to allergic patients until reaching a maintenance dose or loss of symptoms. The most important hypothesis regarding the mechanism is a switch from a Th 2- into a Th 1 reaction pattern in the T cell regulation. The efficacy of specific hyposensitization has been assessed in controlled studies. Allergen extracts are obtained by extraction of the active constituents from animal or vegetable substances with a suitable menstruum. There is a great assortment of different allergen extracts available, but only standardized extracts should be used. Specific hyposensitization is a causal treatment for patients with IgE-mediated allergies like seasonal or perennial allergic rhino-conjunctivitis, asthma or hymenoptera venom allergy. The principal and most effective route of allergen application is the subcutaneous injection. The risk of side effects, especially life threatening anaphylaxis must be considered and can be minimized by careful allergology practice. Oral/sublingual application of allergen extracts is still discussed controversially. Specific hyposensitization requires the high motivation and cooperation of an informed patient.

Allergens↗
PubMed1998

Paraneoplastic pemphigus treated with dexamethasone/ cyclophosphamide pulse therapy.

Paraneoplastic pemphigus (PNP) is an autoimmune, mucocutaneous bullous disease associated with underlying malignancies. We report a patient with Waldenström's macroglobulinemia who developed clinical, histological and immunopathological features typical of PNP. The patient was treated twice with i.v. dexamethasone and cyclophosphamide pulse therapy (day 1: cyclophosphamide 500 mg i.v.; day 1-3: dexamethasone 100 mg i.v.) at 3-week intervals. Therapy was continued with oral cyclophosphamide (50 mg/d). Two weeks after initiation of treatment, significant improvement of the cutaneous and mucosal lesions was noted. The therapy also had beneficial effects on the macroglobulinemia in terms of a marked reduction of the IgM lambda serum level. Three months after the second pulse, severe stomatitis recurred but the patient rejected any further systemic therapy. The initial response of the usually recalcitrant mucosal and skin lesions of PNP makes dexamethasone/cyclophosphamide pulse therapy an interesting therapeutic option.

Administration, Oral↗
PubMed1996

Evolutionary conservation of microsatellite flanking regions and their use in resolving the phylogeny of cichlid fishes (Pisces: Perciformes).

A phylogeny of the principal lineages of cichlid fishes and two other fish families of the suborder Labroidei was based on phylogenetic information from DNA sequences of the flanking region of a (CA)n microsatellite locus. Microsatellite (CA)n containing clones from a genomic library of an African cichlid fish from Lake Tanganyika, Tropheus moorii, were sequenced and primers for the polymerase chain reaction designed. All primers amplified the homologous microsatellite loci in many more than the source species and one microsatellite flanking locus (TmoM27) was particularly conserved and amplified in several lineages of perciform fishes that diverged more than 80-100 million years ago. Despite the extensive level of evolutionary conservation of this microsatellite flanking region (MFR), this nuclear region contained reliable phylogenetic information in the form of both point and length mutations. A phylogeny of cichlids based on this MFR agrees with other phylogenetic hypotheses based on morphological, mitochondrial, and anonymous nuclear DNA. Madagascan and Indian cichlids are found to be paraphyletic and the most basal group in the family Cichlidae. African and Neotropical cichlids are both monophyletic and sistergroups. Within African lineages, the East African cichlids are most likely to be monophyletic and the West African cichlids are probably paraphyletic and basal to all African species. The focal microsatellite locus contained much variation in (CA)n repeats in African cichlids and in surfperches (up to 64 repeats), but was short (with only 2-4 repeats) and almost invariant in Neotropical cichlids. The design of phylogenetically highly versatile MFR-primers will be of use not only for phylogeny reconstruction among families of perciform fishes, but also for population-level work in the thousands of species belonging to this highly species-rich suborder of fishes.

Animals↗
PubMed1995

Toxicity evaluations of wastewaters in Austria with conventional and cost-effective bioassays.

The acute toxicity of 42 samples of different types of domestic and industrial discharges was assessed with a battery of tests comprising the standard Daphnia magna bioassay and three cost-effective new microbiotests (cyst-based Toxkits): the Rotoxkit F with the freshwater rotifer Brachionus calyciflorus and the Streptoxkit F and Thamnotoxkit F tests with the freshwater fairy shrimps Streptocephalus proboscideus and Thamnocephalus platyurus, respectively. Chemical analyses were performed for conventional water quality parameters such as chemical oxygen demand (COD), biological oxygen demand (BOD5), NO2, NH3, NH4+, O2, and pH. Toxicity of the samples, expressed as German regulatory G-values, was found to vary between 1 and 128. The results of these toxicity tests indicate that the Toxkit bioassays were as sensitive as the D. magna acute test. The crustacean T. platyurus was in 75% of the toxic samples more sensitive than D. magna. Relationships between the chemical composition and the toxicity of the discharges could be established in some cases, but not in others, which confirms the difficulties of extrapolating toxic hazards of complex wastes from (mostly restricted) chemical analyses. This study demonstrates the potential of cost-effective bioassays (such as, e.g., cyst-based Toxkits) as attractive alternatives to (expensive) conventional bioassays for routine monitoring of effluents and wastes.

Animals↗
PubMed1995

[Dermatologic climate therapy--definition, indications and public health necessity].

Dermatological climatotherapy is used in the treatment of chronic and chronically relapsing long-term dermatoses, such as, especially, atopic dermatitis and psoriasis, complementing the dermatological therapies applied at the patient's place of living. It is a classical dermatological in-clinic therapy carried through in specific rough and stimulating climate areas of proven therapeutic benefit, primarily the North Sea climate and certain alpine locations over 1 500 m above sea-level, like especially in the high mountain valley of Davos, Switzerland. Dermatological climatotherapy is a well-tried therapeutic agent which, in comparison to the dermatological therapies applied at home, as a rule has fewer side effects as well as, above all, an additional long-lasting time effect. The latter is of particular importance regarding chronical diseases and cannot be achieved by other therapies. Dermatological climatotherapy, hence, represents an all-entailing therapy form and moreover is the most comprehensive therapy anyway. Dermatological climatotherapy can only be performed in rough and stimulating climate zones with additional special insolation, thermichygric and defined aerosol conditions. On the one hand, the organism is stabilized general by those climatic conditions, and, on the other, the constitutionally damaged skin is affected positively by the direct influence of climate factors. As every climate has its specific overall effect, the therapeutical immediate and long-term effects of a climate have to be proven scientifically by follow-up studies.

Acclimatization↗
PubMed1988

[Hyposensitization with cross-reacting pollen allergens].

Grass-pollen are one of the most common allergens in pollinosis. Rye-pollen are the most important allergens among cereals-pollen in Germany. Between pollen-allergens, the phenomenon of cross-sensitivity is well-known. In the RAST und RAST-Inhibitionstest the cross-sensitivity between grass-pollen and rye-pollen is well documentated. In the clinic the test and challenge with some grass-pollen ist suitable for the diagnosis and planing of therapy. Therefore, it seems, that therapy with grass-pollen should produce the same results as a treatment with grass- and rye-pollen. We treated 35 patients allergic with poaceae-pollen for 3 years in two different ways: One group we treated only with grass-pollen, the other group we treated with grass- and rye-pollen. Under the therapy we controlled the specific IgE and IgG, the nasal challenge-test and the subjective symptoms by diaries and questionnaires. The specific IgE for phleum pratense and rye-pollen decreased, the specific IgG increased in both groups. There were no differences between the two therapy-groups. In the clinical data-subjective and nasal challenge-the therapeutic effect seemed to be better in the group treated with grass- and rye-pollen.

Adult↗