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C Luderschmidt

Publications and source records attributed to C Luderschmidt.

At least 19 recordsLinked to original sources
PubMed1998

Immunological characterization of heterochromatin protein p25beta autoantibodies and relationship with centromere autoantibodies and pulmonary fibrosis in systemic scleroderma.

Anticentromere antibodies (ACA) are immunological markers for the subset of systemic scleroderma with the symptoms calcinosis cutis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia (CREST). In Western blotting, some ACA-positive sera also recognize a doublet of 23 kDa (p23) and 25 kDa (p25) in addition to centromere protein antigens A (17 kDa), B (80 kDa), and C (140 kDa). Two forms of p25 have been shown to be human homologues of Drosophila heterochromatin-associated protein HP1. One form of p25 (p25beta) which was recently cloned in this laboratory was used to evaluate anti-p25beta antibody response in scleroderma sera. Of 318 scleroderma sera 42 had ACA (13.2%), and 16 of the 42 sera (38%) had anti-p25beta antibodies. On the other hand, 5 of 276 ACA-negative sera (1.8%) showed anti-p25beta antibody response, demonstrating that anti-p25beta antibody is significantly associated with the ACA response (P < 10[-8]). Clinically the anti-p25beta response was significantly associated with the CREST syndrome. Fourteen (36.8%) of 38 CREST patients compared to seven (2.5%) of 280 patients with other forms of scleroderma were anti-p25beta antibody positive (P < 10[-8]). The 14 CREST patients with anti-p25beta antibodies had significantly more interstitial lung disease than those without anti-p25beta antibodies (P < 0.003). There was also a tendency to increased liver involvement. Two dominant autoepitopes in p25beta were determined by Western blotting using p25beta recombinant fragments. In immunofluorescence C-terminal specific antibodies showed staining of heterochromatin, but N-terminal specific antibodies showed no staining. Interestingly, the majority of sera reacted preferentially with one or the other of the two dominant autoepitopes.

Autoantibodies↗
PubMed1997

Heterochromatin protein HP1Hsbeta (p25beta) and its localization with centromeres in mitosis.

Some autoimmune sera containing anticentromere autoantibodies also recognize a doublet of Mr 23 000 (p23) and 25 000 (p25) in addition to CENP (centromere protein)-A (Mr 19 000), -B (Mr 80 000), and -C (Mr 140 000). A p25 antigen (HP1(Hsalpha)) has been shown to be a human homolog of Drosophila HP1 (heterochromatin protein 1). We have isolated a cDNA clone encoding another form of p25 (HP1(Hsbeta ) or p25beta) from a lambdaZap HepG2 library using human autoimmune serum. The deduced amino acid sequence of the clone contained a conserved chromodomain (chromatin modifier domain) in the N-terminal region and a heterochromatin binding domain in the C-terminal region. In immunofluorescence experiments, only affinity purified antibodies reactive with the C-terminal (amino acids 70-185) domain showed nucleoplasmic and heterochromatin staining, whereas N-terminal (amino acids 1-115) specific antibodies were nonreactive. In metaphase chromosome spreads, the C-terminal domain antibody was also localized to the centromeric regions of chromosomes. Association with centromeres was most prominent at anaphase and changed to a more generalized association with whole chromosomes in telophase. The cooccurrence of autoantibodies to centromere proteins and HP1 in certain autoimmune diseases might be a reflection of coordinated immune responses to these closely associated sets of proteins.

3T3 Cells↗
PubMed1993

The complement system and systemic sclerosis.

Serum concentrations of the various complement components including the classical and the alternative pathways were determined in 58 control healthy subjects and 80 patients with systemic sclerosis (SSC). The mean concentrations of C1q, C2, C5, C6, C7, C9, and factor B were significantly increased in the SSC patients in comparison to controls, while the increases were not significant for C3 and C8. C4 was an exception in that the mean levels were found to be decreased, with 18 patients having levels < 65% of the mean normal value. Properdin was also found to be decreased, but not significantly. We found a similarity between the pattern of serum complement component concentrations in SSC patients and patients with primary biliary cirrhosis, two disorders frequently associated in the same patients. The significance of complement component patterns in these diseases is discussed.

Complement Activation↗
PubMed1992

Antimitochondrial (pyruvate dehydrogenase) autoantibodies in autoimmune rheumatic diseases.

Anti-pyruvate dehydrogenase (PDH) antibodies were determined in 1451 sera of patients with primary biliary cirrhosis (PBC) and several autoimmune rheumatic conditions by ELISA and immunoblotting. They were detected in sera of 93% of the patients with PBC (179 of 192 patients) in 60 of 277 (22%) patients with Sjogren's syndrome (SjS), 34 of 437 (8%) patients with scleroderma, 33 of 191 patients with SLE (17%), and 5 of 55 (10%) patients with rheumatoid arthritis (RA) but in none of the patients with polymyositis or the antiphospholipid syndrome. The ELISA studies were confirmed by immunoblots showing binding of autoimmune rheumatic sera to the same epitope (74 kd) of mitochondria that the PBC sera reacted with. The identical binding characteristics were also confirmed by protein competition assays with purified PDH. In 4 of 53 patients with SjS who were positive for anti-PDH, high titers as in PBC were detected. The anti-PDH antibodies in Sjogren's patients were associated with deranged liver function tests and extraglandular features but did not correlate with any other non-organ-specific antibody. Follow-up studies confirmed the association of the emergence of anti-PDH antibodies with defects in liver function tests. The antibodies were more prevalent in SLE and RA when they were associated with Sjogren's syndrome (30 and 18.8%, respectively). Among patients with different forms of scleroderma, anti-PDH antibodies were noted in subjects with systemic sclerosis, morphea, and Raynaud's phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Antinuclear↗
PubMed1987

[Co-occurrence of plane and verrucous leukoplakia evolving into an invasive squamous cell carcinoma].

A 40-year old female patient showed extended areas of homogeneous and verrucous leukoplakias on the floor of her mouth. In addition, we found leukoplakia of the speckled type on her right lower alveolar ridge. Histological examination of specimens taken from this region revealed squamous cell carcinoma with invasion into the mandibular bone. Heavy smoking as well as chronic irritation caused by a poorly fitted denture were considered predisposing factors. We carried out radical excision of the carcinoma and the verrucous leukoplakias including partial bone resection. During a follow-up period of two years, we did not observe any recurrences of the carcinoma.

Carcinoma, Squamous Cell↗
PubMed1987

[Neuroendocrine (Merkel cell?) carcinoma of the skin].

A neuroendocrine carcinoma of the skin was diagnosed in one male and four female patients. Their case histories were short (five months on the average). In two patients, we found metastases of the regional lymph nodes already at the first physical examination; another patient died of distant metastases after 15 months. Histopathological examination revealed cells fairly uniform in size. The tumors replaced the dermis and subcutaneous tissue without affecting the epidermis. In all cases, the cells were arranged in solid sheets and compact nests with occasional cords and trabeculae in the periphery. The cells and nuclei usually were round and hyperchromatic, and showed many mitoses. Typically, the neuron-specific enolase was positive in all tumor formations, whereas the protein S 100 marking was always negative. Electron microscopic examination of the tumor cells showed cytoplasmatic, neurosecretory granules, which were confined to the membranes, as well as collections of perinuclear intermediate filaments and intercellular junctions. A reliable diagnosis regarding neuroendocrine carcinoma of the skin should consider histological, immunohistochemical, and ultrastructural techniques. Cutaneous metastases of other neuroendocrine carcinomas have to be ruled out.

Aged↗
PubMed1987

Orientation staining for the demonstration of Mycobacterium leprae in semithin sections.

In Spurr-embedded biopsies for ultrastructural examinations, Mycobacterium leprae hardly differed from the surrounding tissues using the staining technique of Richardson. Also, the usual histological staining methods of Ziehl-Neelsen and Fite did not achieve positive results for the determination of M. leprae. Therefore, we applied the methylene blue-borax and basic fuchsin technique for the demonstration of the bacilli in plastic-embedded tissue of 11 patients suffering from Hansen's disease. In every patient the diagnosis was confirmed by histological examination of skin biopsies. Portions of the biopsies of nine patients were then fixed in glutaraldehyde and osmium tetroxide and embedded according to Spurr. In the other two cases, the material was first fixed in 10% Formalin and embedded in paraffin. After cutting 3-micron sections for routine histological examination, the remaining material was prepared adequately for ultrastructural examination. Using the methylene blue-borax and basic fuchsin technique, the semithin sections of plastic-embedded material presented a considerably more differentiated picture than other comparable methods. M. leprae located in foamy cells or in the tissue stained violet. These findings were corroborated in subsequent electron-microscopic examinations. The semithin sections thus prepared allow, through the clear demonstration of the microorganisms, a precise demarcation of the ultrathin area.

Biopsy↗
PubMed1987

[Intestinal scleroderma: clinical aspects, diagnostic possibilities and therapy].

Progressive Systemic Scleroderma (PSS) is a generalized disease of the connective tissue, caused by vascular changes, an increased collagen synthesis as well as inflammatory and immunological phenomena. Manifest intestinal scleroderma is a rare complication. The connection of internal symptomatology with esophagus attack is of practical importance. The bacterial deconjugation of bile acids is of pathogenetic relevance, regarding the release of an intestinal symptomatology. This results in a direct application of Tetracycline or Metronidazole by parenteral administration. The increase of unconjugated serum bile acids, such as cholic acid and chenodeoxycholic acid, gives a diagnostic indication which can be carried out in special laboratories by means of gas-chromatography.

Bile Acids and Salts↗
PubMed1987

Association of progressive systemic scleroderma to several HLA-B and HLA-DR alleles.

The HLA-A, B, C, and DR loci of 136 patients with progressive systemic scleroderma have been determined. The patients were classified according to the extent of their skin affection and into groups with or without immunologic and inflammatory signs of the disease. The antigens of the A locus did not show any significant deviations in frequency of occurrence. An increase of HLA-B8 and HLA-DR3 was only proved in the male patient group. Furthermore, in the HLA-DR gene locus, an increase in frequency of HLA-DR1, 2, 3, and 5 could be found. However, in the total set of patients, only the correlation of HLA-DR5 with progressive systemic scleroderma reached significance. Patients suffering from the CREST (calcinosis, Raynaud's phenomenon, esophagus, sclerodactyly, and telangiectasia) syndrome showed an increase of HLA-DR1. Patients with inflammatory signs of the scleroderma showed an accumulation of HLA-DR2. Several HLA-linked genes control the susceptibility to scleroderma.

Adult↗
PubMed1987

Relative binding affinity at metribolone androgenic binding sites of various antiandrogenic agents.

Sebaceous glands are androgen sensitive structures with activity reduced by antiandrogens. We characterized the relative binding affinity of cyproterone acetate, 17 alpha-propyl-mesterolone, spironolactone (canrenoic acid), ethisterone and dexamethasone by means of the competitive binding analysis at metribolone (R1881) androgen binding sites. Using the DCC-assay (dextran-coated charcoal absorption) with the Scatchard plot and saturation analysis we quantified R1881 androgen binding sites from sebaceous glands situated in the ventral side of the pinna of the Syrian hamster. As parameters for ligand affinity at these binding sites served the ligand concentration for 50% displacement of 3H-labelled synthetic steroid R1881 in constant concentrations. The in vitro measurements of the used steroids were compared to the biologic sebosuppressive effect in vivo. 17 alpha-Propylmesterolone showed the highest affinity at the androgenic binding site followed by ethisterone, cyproterone acetate and spironolactone. The results, however, do not admit an interpretation about the mode of action of the given substances, which display their biologic activity either after systemic or topic administration. In vivo distribution problems and metabolizing procedures might be due to this discrepancy.

Androgen Antagonists↗
PubMed1986

[Bullous phototoxic contact dermatitis caused by Dictamnus albus. The Bible's "burning bush"?].

A bullous phototoxic reaction occurred in a 27-year-old man working with the plant Dictamnus albus. The skin changes disappeared, leaving behind areas of hyperpigmentation, after treatment with corticoid-containing ointments. Possible causes are 5- and 8-methoxypsoralen, perhaps also photodynamically active alkaloids of the plant, as well as sun-ray exposure and sweating. Dictamnus albus may be the biblical "burning bush". Since the plant becoming ever more popular in German gardens, a phytophototoxic reaction should be considered in the differential diagnosis of the described symptoms.

Administration, Topical↗
PubMed1986

[Osteonecrosis in acne conglobata].

We report on a 17-year-old man suffering from acne conglobata, who developed osteomyelitis with osteonecrosis of the left clavicula after a rash of acne fulminans. The infection spread from a cystic nodule into the adjacent bone.

Acne Vulgaris↗
PubMed1986

[Systemic inflammatory reactions and extracutaneous manifestations of acne vulgaris].

166 patients suffering from acne of different severity were examined with regard to associated systemic manifestations. 74 of the patients showed acne conglobata, 12 acne tetrade, 11 acne fulminans, and 69 acne papulopustulosa. Subjective symptoms like weakness, fever, and arthralgia, as well as unspecific serological inflammatory parameters and internal symptoms were taken into consideration. Acne papulopustulosa was not associated with any internal symptoms. Such extracutaneous reactions were observed, however, in severe forms of acne as in acne tetrade or acne conglobata (41% vs 17%). Acne fulminans revealed musculoskeletal manifestations and severe inflammatory signs in the blood. The high rate of kidney involvement with severe inflammatory types of acne was alarming. Three patients developed on acute glomerulonephritis, which evolved into a chronic form in two patients.

Acne Vulgaris↗
PubMed1986

[Isotretinoin in local treatment of acne and rosacea and animal experiment studies on isotretinoin and arotinoid].

Fifteen patients with acne and 4 with rosacea were treated topically with 0.2% isotretinoin cream twice a day for 16 weeks. Inflammatory lesions responded better (30 +/- 22 versus 15 +/- 12) than non-inflammatory lesions (23 +/- 44 versus 17 +/- 24). Neither the "causal level" (123 +/- 85 versus 130 +/- 66 micrograms/cm2 nor the "replacement sum" (70 +/- 29 versus 77 +/- 30 micrograms/cm2) were changed (lipometer assay). In 150 adult male Syrian hamsters 1-2 drops of isotretinoin in concentrations varying from 0.3% to 0.001% and arotinoid ranging in concentration from 0.3% to 0.00001% in acetone were applied to the left ventral ear or the left flank organ twice a day (5/7 days) for 21 days. In higher concentrations there was a significant reduction in sebaceous gland size. Arotinoid, however, is extremely toxic. Even in concentrations as low as 0.00001% the animals showed severe side-effects within the 1st week.

Acne Vulgaris↗