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Biomedical subjects

H H Peter

Publications and source records attributed to H H Peter.

At least 127 records · Page 7Linked to original sources
PubMed1995

A nitro analogue of staurosporine and other minor metabolites produced by a Streptomyces longisporoflavus strain.

From the staurosporine-producing strain Streptomyces longisporoflavus R-19 various minor metabolites were isolated: They include a new compound with a nitro function in C-4' and other metabolites related to staurosporine. The new structures were elucidated by spectroscopic methods, mainly 1H NMR and 13C NMR and by comparison with TAN-1030A. The new compounds inhibited protein kinase C with IC50 values in the nanomolar range.

Alkaloids↗
PubMed1995

Paeciloquinones A, B, C, D, E and F: new potent inhibitors of protein tyrosine kinases produced by Paecilomyces carneus. I. Taxonomy, fermentation, isolation and biological activity.

Paeciloquinones A to F as well as versiconol have been isolated as inhibitors of protein tyrosine kinase from the culture broth of the fungus Paecilomyces carneus P-177. The novel anthraquinones inhibit epidermal growth factor receptor protein tyrosine kinase in the micromolar range. Two compounds, paeciloquinones A and C, are potent and selective inhibitors of the v-abl protein tyrosine kinase with an IC50 of 0.4 microM. Dependent on the fermentation conditions, partially different sets of paeciloquinones may be produced. An HPLC method allows separation of all major active components.

Animals↗
PubMed1995

Paeciloquinones A, B, C, D, E and F: new potent inhibitors of protein tyrosine kinase produced by Paecilomyces carneus. II. Characterization and structure determination.

Paeciloquinones A to F and versiconol have been isolated as inhibitors of protein tyrosine kinases from the culture broth of the fungus Paecilomyces carneus P-177. The structures of the new anthraquinones were determined by spectroscopic methods, mainly 1H NMR and 13C NMR. The substitution pattern was established by investigation of the respective methylated derivatives.

Anthraquinones↗
PubMed1995

Balmoralmycin, a new angucyclinone, and two related biosynthetic shunt products containing a novel ring system.

A new angucyclinone, named balmoralmycin (1), was isolated as an inhibitor of protein kinase C-alpha (PKC-alpha) from the Streptomyces strain P6417. Chemical screening of extracts of the same strain resulted in the detection of two decaketides with unusual structural features (2 and 3). Both compounds belong to a recently described structural class of secondary metabolites which arises from engineered biosynthesis of a recombinant Streptomyces strain. The isolation of compounds of this class from a wild-type strain has never been reported before.

Anthracyclines↗
PubMed1995

[Defects in the immunoglobulin producing cells in bone marrow of patients with variable immunodeficiency syndrome].

The number of plasma cells, IgG+, IgA1+, IgA2+ and IgM+ cells were determined in bone marrow (BM) biopsies of 12 patients with common variable immunodeficiency syndrome (CVID) and 12 controls without signs of immunodeficiency. Controls had a median of 11 plasma cells/mm2, 76 IgG+, 76 IgA+ and 18 IgM+ cells/mm2 BM, respectively. Compared with the control group, the CVD patients showed a significant reduction of each cell type (p < 0.001). They also demonstrated a close correlation between low numbers of IgG+ and IgA+ cells in the BM and low IgG and IgA serum levels. In general, there was also a good correlation of the IgM+ cells and the respective IgM levels in the serum, except 2 CVID patients with normal IgM serum levels and subnormal numbers of IgM+ cells in the BM. Our results showed that there was an almost complete coincidence between the reduced numbers of Ig-producing cells in the BM and low serum levels of the respective Ig isotype. Thus, immunohistological analysis may be of additional help for the diagnosis of immunodeficiency.

Antibody-Producing Cells↗
PubMed1994

[Unilateral diffuse pulmonary involvement in vasculitis with anti-neutrophil cytoplasmic antibodies and anti-glomerular basement membrane antibodies].

A previously healthy 51-year-old man, hospitalized because of fatigue and joint complaints, was found to have left-sided diffuse pulmonary infiltration and a rapid rise in creatinine concentration. Anti-neutrophil cytoplasmic antibodies (cANCA) and anti-glomerular basement antibodies (anti-GBM) were found in serum. Renal biopsy revealed extracapillary glomerulonephritis with diffuse half-moon formations. Immunohistology showed a diffuse granular pattern for immunoglobulin G, M and complement C3, without linear deposits. Immunosuppressive treatment combined with plasmapheresis brought about rapid clinical improvement and normalization of the lung involvement and renal function, as well as a fall in the cANCA titre. During a follow-up period of 5 years there has been no recurrence of symptoms, although the anti-GBM titre remained strongly positive and the cANCA titre twice rose to abnormal levels.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1994

Overexpression of zinc-finger transcription factor Z-225/Egr-1 in synoviocytes from rheumatoid arthritis patients.

In rheumatoid arthritis (RA) the proliferation of synovial lining cells appears to be one of the initial pathologic changes that contributes to the destruction of articular joints. To understand the pathomechanisms involved in these functional changes, we analyzed the transcriptional regulation of the zinc-finger gene 225 (Z-225/Egr-1), a transcription factor expressed in the immediate early events of cellular activation. We found that Z-225 transcripts were significantly up-regulated in RA synoviocytes. In primary and long term culture Z-225 was spontaneously transcribed at elevated levels. In situ hybridization of zinc-finger probe showed characteristic Z-225 transcripts in RA synovial tissues. Identity of these signals to the Z-225 gene product were confirmed in freshly isolated synovial tissue by enzymatic amplification of cDNA by the PCR technique. Z-225 transcripts were also detected and characterized in a cDNA library established from a RA synovial explant. We therefore conclude that RA synoviocytes spontaneously produce Z-225 gene products at elevated levels. Because early growth response gene Z-225 is involved in the regulation of expression of other genes such as proto-oncogenes c-ras and c-sis, which are also up-regulated in the RA synovium, activation of Z-225 transcription in RA may represent a key event in articular joint destruction.

Arthritis, Rheumatoid↗
PubMed1994

Intravascular lymphoma simulating vasculitis.

The case history of a patient with intravascular lymphoma (IL) is reported. Signs of a systemic illness including fever, muscular weakness, telangiectasias, nephrotic syndrome, and neurologic manifestation suggested vasculitis. Cyclophosphamide treatment produced almost complete remission, but the patient died of respiratory failure 13 months after presentation due to lung involvement. The diagnosis was not revealed until postmortem examination. The differential diagnosis of IL is provided.

Diagnosis, Differential↗
PubMed1994

Anti-neutrophil cytoplasm antibodies (ANCA) in rheumatoid arthritis: relationship to HLA-DR phenotypes, rheumatoid factor, anti-nuclear antibodies and disease severity.

To investigate a possible relationship between the presence of anti-neutrophil cytoplasm antibodies (ANCA), rheumatoid factors (RF), anti-nuclear antibodies (ANA), disease severity and HLA-DR phenotypes, 46 consecutive ANCA+ and 48 ANCA-, clinically well-documented RA patients were studied for RF, ANA and HLA-DR phenotypes. The 46 ANCA+ patients showed predominantly an atypical perinuclear staining pattern (89%). ANCA positivity was associated with higher RF titres (P < 0.005) and advanced functional Steinbrocker grades III/IV (P < 0.015). ANCA+ patients were also more often positive for ANA than ANCA- patients (P < 0.008). There was no correlation between ANCA positivity and certain HLA-DR phenotypes although the frequency of DR4+ (67% vs 52%) and, in particular, of DR4+ blanks (phenotypically homozygous) was increased in ANCA+ as compared to ANCA- patients (20% vs 8%). DR4-DR1-RA patients were twice as frequent in the ANCA- than in the ANCA+ group (22.9% vs 8.7%). Correspondingly, the DR4+DR1- phenotype was increased among ANCA+ RA patients. Regarding functional Steinbrocker grades, the DR4+ phenotypes were slightly but not significantly increased in grades III and IV whereas ANCA positivity was significantly associated with severe functional Steinbrocker grades III/IV (66% ANCA+ vs 39% ANCA-, P < 0.015). ANCA positivity identified a population of RA patients with a long-standing and severe clinical course of the disease. There was no correlation between ANCA positivity and certain HLA-DR phenotypes.

Adult↗
PubMed1994

Monocyte differentiation and accessory function: different effects on the proliferative responses of an autoreactive T cell clone as compared to alloreactive or antigen-specific T cell lines and primary mixed lymphocyte cultures.

An autoreactive T cell clone derived from a patient with reactive arthritis, two alloreactive T cell lines, two antigen-specific T cell lines and allogeneic resting T cells were analyzed for their responses to monocytes and macrophages derived from monocytes by in vitro differentiation. The autoreactive T cell clone strongly proliferated in response to fresh monocytes and to macrophages derived from a 7 day culture, but only poorly to monocytes cultured for 2 days. In contrast, alloreactive and antigen-specific T cell lines proliferated to all stimulatory cells equally well. Finally, primary mixed lymphocyte reactions could be stimulated by both fresh and 2-day cultured monocytes, but not by in vitro derived macrophages. The impaired response of the autoreactive T cell clone to 2-day cultured monocytes could not be attributed to reduced expression of several well-defined surface molecules nor to induction of nonresponsiveness. Neither allogeneic monocytes nor cytokines (IL-1, IL-2, IL-4, IL-6) could correct the defective response of the autoreactive T cell clone. However, preculture of monocytes in the presence of interferon-gamma, IL-1, IL-4 or IL-6 retained their stimulatory capacity. Our interpretation of the selectively impaired response of the autoreactive T cell clone is that it most likely recognizes a differentiation-dependent monocyte/macrophage-specific peptide.

Antigen-Presenting Cells↗
PubMed1994

Characterization of eukaryotic protein L7 as a novel autoantigen which frequently elicits an immune response in patients suffering from systemic autoimmune disease.

Autoantibodies targeted against cellular proteins and nucleic acids are a common feature of autoimmune diseases. In this study, we show that ribosomal protein L7 is a novel autoantigen in patients suffering from systemic lupus erythematosus (SLE) and other connective tissue diseases. From 24 patients diagnosed as having SLE, 18 produce antibodies which precipitate in vitro translated L7 protein. The anti-L7 titer appears to correlate with the active state of the disease. Anti-L7 autoantibodies were also detected in 7 of 13 patients with mixed connective tissue disease (MCTD), 2 of 7 patients with rheumatoid arthritis (RA), 1 of 4 patients with Sjögren's syndrome (SS) and in 1 patient with progressive systemic sclerosis (PSS). Anti-L7 autoantibodies belong to the IgG-class and detect specifically at least two epitopes on the L7 molecule, as shown by immunoprecipitation and immunoblotting. The epitope(s) of the highly conserved C-terminal region are preferentially recognized. Utilizing rabbit anti-L7 serum, autoimmune sera and affinity-purified anti-L7 autoantibodies in immunoblotting, and rabbit and chicken anti-L7 antibodies in indirect immunofluorescence, we detect L7 protein in the nuclei and in the cytoplasm of various cell-lines. Yet unlike most integral structural components of ribosomes, L7 is absent from nucleoli.

Adolescent↗