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Biomedical subjects

M Blaszczyk

Publications and source records attributed to M Blaszczyk.

At least 19 recordsLinked to original sources

Coexistence of scleromyositis associated with PM-Scl antibody and myasthenia.

Myasthenia gravis coexists in about 15% of the cases with other autoimmune diseases. Association with polymyositis or dermatomyositis is very rare, although myasthenic reaction is not infrequent in typical polymyositis and myopathic changes may occur in cases of myasthenia. This is the first case of coexistence of myasthenia and scleromyositis, associated with PM-Scl antibody as an immune marker. The patient was found to have persistent thymus. Myasthenia preceded scleromyositis for 9 yr, was at periods asymptomatic, and recurred simultaneously with development of scleromyositis. Scleromyositis should be added to the list of autoimmune disorders coexistent with myasthenia.

Autoantibodies

Atrophoderma Pasini-Pierini is a primary atrophic abortive morphea.

BACKGROUND: There are divergent opinions whether atrophoderma Pasini-Pierini (APP) is a nosologic entity or a primary atrophic morphea. OBJECTIVE: Since usually single cases are reported without a long-term follow-up the present study was performed in order to elucidate the natural history of the disorder. METHODS: We followed a large series of 139 patients, 91 adults and 48 children, for 4-30 years (mean over 10 years). RESULTS: APP was found to be 6 times more frequent in females and not uncommon in children (10% of our series of localized scleroderma). At some time during the follow-up period, indurations appeared in the central parts of the lesions in 17% of the patients, and in 22% they coexisted with morphea plaques outside the atrophies. The histological pattern was similar to morphea at the stage of atrophy. No case developed full-blown morphea. CONCLUSION: APP appears to be an abortive morphea, in which the indurations failed to develop. The differentiation from morphea is of practical importance because of different management and prognosis.

Adult

Preliminary, dermatologic first step criteria for lupus erythematosus and second step criteria for systemic lupus erythematosus.

BACKGROUND: Comparisons of cases of systemic lupus erythematosus (SLE) with cases of rheumatoid arthritis and other rheumatologic disorders affords the basis of the 1982 revised criteria of the American Rheumatism Association (ARA) for classifying SLE cases. We address three questions: Do comparisons of LE cases with non-LE cases that have suggestive skin lesions yield criteria for use in dermatology clinics for primary classification of cases with photo distributions of skin lesions? Do comparisons of SLE with cutaneous LE cases yield the same or similar criteria to the revised ARA criteria for SLE? How should subacute cutaneous LE cases be evaluated for signs of significant systemic involvement? METHODS: Discriminant analyses on 168 cases with skin lesions suggestive of LE were performed using data based on the ARA criteria for SLE and study factors for cutaneous LE suggested by the European Academy of Dermatology and Venereology. RESULTS: These yielded two sets of criteria: (1) The 11 preliminary, dermatologic first step criteria (10 plus 1 for discoid lesions and histology) serve to classify cases as LE or non-LE. (2) The 11 preliminary, dermatologic second step criteria classify LE cases as cutaneous LE or systemic LE. Interestingly, 5 of 11 of these second step criteria differ from the 11 ARA criteria for systemic LE. These second step criteria afford a useful means of distinguishing between subacute cutaneous LE cases with or without significant systemic involvement. CONCLUSIONS: The study factors included in both the first and the second step criteria fall into three groups, notably clinical criteria, laboratory criteria, and "added study factors." The latter factors distinguish between the groups compared (LE vs. non-LE and cutaneous vs. systemic LE) but not as well as the study factors included as "criteria."

Humans

Adhesion of peripheral blood mononuclear cells to vascular endothelium in patients with systemic sclerosis (scleroderma).

OBJECTIVE: Perivascular infiltrates in skin, subcutaneous tissue, and internal organs are a characteristic feature of early systemic sclerosis (SSc). We studied the first step of migration of peripheral blood mononuclear cells (PBMC) through the vessel wall to the extravascular space, i.e., adhesion of PBMC to endothelial cells (EC), in patients with various forms of SSc (limited scleroderma, diffuse scleroderma, and the transitional form). METHODS: Radioisotope-labeled patient PBMC were coincubated with umbilical cord EC in vitro, and the percentage adhesion was measured. RESULTS: Adhesion of PBMC to EC was markedly decreased, while adhesion of isolated active rosette-forming cells (ARFC) was significantly increased, in SSc patients compared with healthy controls. Decreased adhesion of PBMC to EC was found to correlate with a diminished percentage of ARFC in the peripheral blood. Preincubation of PBMC from healthy donors with interleukin-2 (IL-2) enhanced their adhesion to EC, while preincubation of PBMC from SSc patients with this cytokine resulted in a decrease in adhesion in 10 of 14 individuals. IL-1, interferon-gamma, and transforming growth factor beta had no significant effect on adhesion of SSc patient PBMC to EC. Differences in adhesion of PBMC to EC among the SSc subgroups were not significant. CONCLUSION: Our findings suggest that in SSc, activation of subpopulations of PBMC leads to their enhanced adhesion to vascular endothelium in vivo and to migration of these cells to the extravascular space, resulting in the elimination from the peripheral blood of those PBMC with high ability to adhere to EC.

Adult

Echogenic rings--an ultrasound sign of early nephrocalcinosis.

Echogenic rings in the periphery of renal pyramids were seen in the kidneys of six patients. This appearance is described and is correlated with abdominal radiography or computed tomography (CT) scans, serum calcium levels and, in one patient, autopsy. The findings suggest that echogenic rings are one of the earliest signs of nephrocalcinosis even in the absence of plain radiographic changes.

Adult

Studies on criteria of the European Academy of Dermatology and Venerology for the classification of cutaneous lupus erythematosus. I. Selection of clinical groups and study factors.

A group of 140 cases of various forms of lupus erythematosus (LE) were examined for 24 variables, including the 11 criteria of the American Rheumatism Association (ARA) for the classification of systemic lupus erythematosus (SLE), and 13 additional criteria suggested by the European Academy of Dermatology and Venerology (EADV) for studies of cutaneous LE with or without systemic involvement. The EADV study factors included skin histopathology and immunopathology, complement and IgG levels, and other laboratory tests, as well as selected clinical findings, most notably the papulosquamous and/or annular lesions that characterize subacute cutaneous LE (SCLE). The patients examined included 50 SLE, 35 SCLE, 30 discoid LE (DLE), 25 disseminated DLE (DDLE), and 17 polymorphous light eruption (PMLE) cases. Preliminary analyses of the data reveal the following: (1) The SCLE cases differed significantly from SLE, DLE, and DDLE in 10 of 11 ARA criteria (all but photosensitivity). (2) The frequencies of positive findings in SCLE also differed significantly for 11 of 13 EADV study factors. (3) While no significant differences appeared in the frequency of photosensitivity between the five study groups, photo-testing revealed significant increases in the frequency of persistence of the photo reactions for 10 days and their Koebnerization in the SCLE cases. (4) The presence of SS-A (Ro)/SS-B (La) antibodies had some predictive value for the appearance of systemic involvement in SCLE, as seen by the increased frequencies of five or more ARA criteria, although highly significant differences from SLE occurred in the absence of renal involvement and lower frequency of ANA and LE band test.(ABSTRACT TRUNCATED AT 250 WORDS)

Dermatology

Antikinetochore and antitopoisomerase I antibodies in systemic scleroderma: comparative study using immunoblotted recombinant antigens, immunofluorescence, and double immunodiffusion.

In 135 patients with systemic scleroderma, we compared three different methods to determine antinuclear autoantibody (ANA) specificity: indirect immunofluorescence, double immunodiffusion, and, employing recombinant antigens, immunoblotting using both marker autoantigens of this disease. A characteristic Scl-70 antibody pattern was found on HEp-2 cells in 83.8% of the patients, double immunodiffusion was positive for the Scl-70 antibodies in 81.9%, and immunoblot with the recombinant topoisomerase I (Topo I) was positive in 71% of the patients. For the centromere autoantibodies we found a high concordance between the anticentromere antibody (ACA) pattern on HEp-2 cells (27 patients positive) and the detection of recombinant kinetochore in immunoblotting (26 patients positive). The three testing techniques gave comparable results, except that the Topo I recombinant antigen used in immunoblotting reacted strongly with fewer than expected of the known Scl-70-positive sera. However, a method using recombinant antigens expressing all epitopes (rather than one of the epitopes of Topo I) will undoubtedly become the method of choice for detecting antibodies in systemic scleroderma. Using the immunoblotting technique with the recombinant antigens we detected in four patients antibodies against both Topo I and kinetochore. More severe symptoms of systemic scleroderma were found in patients who had both antibodies. The combined presence of both marker autoantibodies is therefore not as rare as previously reported and may predict severe disease.

Adolescent

[The fibrillarin (Scl-34) autoantibody in systemic scleroderma].

Reexamination of ANA positive sera with nucleolare fluorescence staining on HEp-2 cells and hamster liver imprints revealed 3 sera with an uniform characteristic pattern. It is characterized by: 1. Strong clumpy fluorescence of nucleoli in the interphase. 2. Missing nucleoplasma staining (pure nucleolar). 3. Characteristic granular staining of the cytoplasma from the condensed chromosoma in mitosis. 4. Additive fluorescence of a nucleolus-like body. 5. Extremely high antibody titers. 6. Negative immunodiffusion. This nucleolar staining pattern was described by Bernstein et al. as a clumpy nucleolar pattern. It is produced through an antibody to the dense fibrillar component of the nucleolus (fibrillarin). This antigen is a protein of the U3 RNP with a molecular weight 34 kDa. Clinically is the fibrillarin antibody highly specific for systemic scleroderma especially with diffuse skin involvement. We found it in 1% of scleroderma patients. Its pathogenetic importance is not known.

Antibodies, Antinuclear

Immunopathologic findings in systemic sclerosis patients: clinical and immunopathologic relationships.

Direct immunofluorescence (DIF) of the skin biopsy specimens was performed in 62 patients with systemic scleroderma: 26 cases of acrosclerosis (group 1), 26 cases of diffuse scleroderma (group 2) and ten cases of transitional form acrosclerosis-diffuse scleroderma (group 3). If epidermal nuclear fluorescence and lupus band test (LBT) were considered, the results were positive in 15.3% in group 1, 42.3% in group 2, and 10% in group 3. LBT was positive in 13.5% of the cases in groups 1 and 2 and negative in group 3. The immunoglobulin deposits at the dermoepidermal consisted mainly of IgM or a combination of IgG and IgM. There was no correlation between the LBT and antinuclear antibodies as detected by indirect immunofluorescence (IIF) or double immunodiffusion (DID).

Adult

Characteristic nucleolar-reticular immunofluorescence staining pattern on touch prints of hamster liver: a marker for Scl-70 antibody.

Sera from 48 patients with systemic sclerosis (SSc) and from 62 patients with other connective tissue diseases were studied for nuclear staining patterns by indirect immunofluorescence (IIF) using touch prints of hamster liver, HEp-2 and cryostat sections of monkey esophagus as substrates. Immunodiffusion studies performed in all cases disclosed Scl-70 antibody in 36 SSc patients. The IIF pattern of Scl-70 antibody is characterized by diffuse granular and nucleolar staining on HEp-2, a combined nucleolar and diffuse reticular staining on imprints of hamster liver and large speckled (nucleolar) fluorescence on cryostat sections of monkey esophagus. Touch prints of hamster liver revealed a partially nucleolar fluorescence as a dominant sign of the combined staining. Hamster liver substrate which is easily available might replace the expensive HEp-2 cells for detecting Scl-70 antibody.

Animals

[The Scl-70 antibody and its clinical significance].

In the review of the literature on the Scl-70 antigen, methods of detection of the Scl-70 antibody, the correlation between its presence and the clinical, genetic and immunological parameters are presented. It is emphasized that the Scl-70 antibody which is regarded as a marker of diffuse scleroderma, may have a prognostic significance. In indirect immunofluorescence on HEp-2 cells the Scl-70 antibody gives a characteristic pattern described as diffuse fine speckles with dotted nucleolus. A somewhat different but distinct staining pattern on hamster liver described by the authors was found to be characteristic of that antibody. The fluorescence associated with Scl-70 antibody is designated as nucleolar-reticular mixed staining with nucleolus predominating. It is suggested that hamster liver substrate which is easily available may replace the expensive HEp-2 cells for detecting Scl-70 antibody.

Antibodies, Antinuclear

[The PM-Scl (polymyositis-scleroderma) autoantibody and its nucleolar fluorescence pattern].

By indirect immunofluorescence studies of antinuclear antibodies on hamster liver imprints as a substrate performed to determine the nuclear staining pattern of sera from patients with connective tissue diseases 10 sera showed a distinct homogeneous nucleolar staining pattern associated with weaker speckled or homogeneous nucleoplasmic fluorescence. In all 10 cases the antibodies revealed the PM-Scl specificity in immunodiffusion. Clinically 9 patients had an acrosclerosis, in 56% overlapped with symptoms of polymyositis. Only one patient had a diffuse scleroderma. The homogeneous nucleolar immunofluorescence pattern of PM-Scl should be distinguished from mixed nucleolar and diffuse reticular nucleoplasmic pattern of Scl-70.

Antibodies, Antinuclear

Natural killer cell activity of peripheral blood mononuclear cells from patients with various forms of systemic scleroderma.

Peripheral blood mononuclear cells from 63 patients with systemic scleroderma, including incipient or prodromal acrosclerosis, and from 20 healthy individuals were tested for natural killer (NK) cell activity and antibody-dependent cell cytotoxicity in a 4 h 51Cr release assay using K562 and L1210 cell lines respectively. In patients with systemic scleroderma natural killer cell activity was significantly decreased compared with the controls. NK cell activity was markedly lowered in patients with diffuse scleroderma and in transitional form acrosclerosis-diffuse scleroderma, and was normal in cases of acrosclerosis and/or CREST syndrome and in cases of prodromal or incipient scleroderma. Antibody-dependent cell cytotoxicity of mononuclear cells from the systemic scleroderma patients was within the normal range. The lowered natural killer cell activity correlated with the severity of systemic scleroderma, in terms of the extent of skin and organ involvement.

Adult

Monoclonal antibody-defined antigens of human prostate cancer cell line PC3.

Over 600 hybridomas were derived from the immunization of mice with live cells and aqueous extracts of the human prostatic carcinoma cell line PC3. A total of 26 hybridomas with restricted reactivities were selected, subcloned and antibodies tested on a variety of tumor and normal cells. Seven monoclonal antibodies showed reactivity for prostate cancer and other tumor cell lines, including breast carcinomas. Three of the antibodies obtained after immunization with live cells reacted with live cells only and three of the four antibodies obtained after immunization with cell extract reacted with cell extracts and spent culture media. The fourth antibody in the latter group was reactive only in the immunoperoxidase staining assay. Antibody PrS5 recognized a 90,000 molecular weight molecule from 125I-surface-labeled cells in immunoprecipitation analysis. Antibodies PrE3 and PrD8 detected a nonacid glycolipid pentasaccharide from PC3 cells and meconium, and a glycoprotein of 115,000 molecular weight from 125I-surface-labeled red blood cells. The similar patterns of reactivity in RIAs and antigen analysis suggest that antibodies PrE3 and PrD8 recognize the same molecule. The results emphasize the usefulness of immunohistochemistry in the testing of monoclonal antibodies and the impact of the form in which the antigen is presented on the resultant antibody specificity.

Animals

Scl 70 antibody--a specific marker of systemic sclerosis.

Scl 70 antibodies were tested for in 107 patients with systemic sclerosis: 68 with acrosclerosis and 39 with diffuse scleroderma. Anticentromere antibodies (ACA) and other antinuclear antibodies (ANA) were tested for by indirect immunofluorescence on HEp-2 cells. Positive results for Scl 70 antibodies were obtained in 77% of cases of diffuse scleroderma and 44% of acrosclerosis. ACA and Scl 70 antibodies were found to be mutually exclusive. If acrosclerosis cases positive for anticentromere antibodies are excluded, the percentage of acrosclerosis cases positive for Scl 70 was 63%. ACA were found to be a marker of a benign, abortive subset of acrosclerosis with almost no cutaneous involvement (CREST), whereas Scl 70 did not discriminate between acrosclerosis and diffuse scleroderma. On HEp-2 cells Scl 70 positive sera gave a characteristic, fine speckled, almost homogeneous nuclear staining pattern.

Antibodies, Antinuclear

[Plasmapheresis in the treatment of pemphigus].

The results of small-volume plasmapheresis were favorable in cases of severe pemphigus vulgaris and foliaceus if applied simultaneously together with corticosteroids and cyclophosphamide, both on lowered doses. The patients went into long-lasting remission. A special indication for this therapy are cases that do not allow the application of large doses of prednison because of severe side-effects of steroids. The effect of plasmapheresis does not appear to depend on the removal large quantity of antibodies. Small-volume plasmapheresis as a supplementary therapy of the combined treatment with steroids and immuno-suppressors showed better effects than large-volume plasmapheresis.

Adult

Selection of monoclonal antibodies detecting serodiagnostic human tumor markers.

Monoclonal antibodies (MAbs) were selected for specific binding to spent media of cultured tumor cells. Out of more than 12,000 hybridomas screened, 19 were selected in preliminary inhibition assays for secretion of MAbs which detected antigens in cancer patients' sera. Antibody CO 29.11, which was studied in detail, bound to an antigen shed and expressed by adenocarcinoma cells of colon, stomach, pancreas and urinary bladder. CO 29.11 bound to purified sialylated Lewis a (Lea) antigen but to a different epitope and with a higher binding affinity than the MAb CA 19-9. CO 29.11 but not CA 19-9 bound weakly to unsialylated Lea antigen. In double-determinant radioimmunoassay with sera of patients with colorectal carcinoma, CO 29.11 was found to be a more sensitive marker than CA 19-9 for the detection in serum of sialylated Lea antigen.

Antibodies, Monoclonal