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Biomedical subjects

G Lemm

Publications and source records attributed to G Lemm.

14 recordsLinked to original sources
PubMed1998

Monitoring of proteinuria in phase I studies in healthy male subjects.

OBJECTIVE: The quantitative measurement of urinary marker proteins may improve the sensitivity of monitoring renal function in healthy male subjects in phase I studies. Little is known about the variability of physiological proteinuria in young, healthy male subjects. Thus, the biological and analytical variability of three marker proteins, i.e. albumin, alpha(1)-microglobulin and N-acetyl-beta-D-glucosaminidase (NAG), were investigated in this population. METHODS: Seven young, healthy male subjects participated in a prospective two-way cross-over study, and 139 in a retrospective study. Albumin and alpha(1)-microglobulin were determined by immunological methods (radial immunodiffusion and/or kinetic nephelometry), and NAG by enzyme activity in a colorimetric assay. RESULTS: The inter-assay precision of NAG, albumin and alpha(1)-microglobulin is good (< 15%) if automated kinetic nephelometry is applied for albumin and alpha(1)-microglobulin determination, but less impressive (< 25%) with radial immunodiffusion. The highest frequency of detectable proteinuria and highest creatinine-adjusted protein levels are found in the second morning urine voided after a night's rest. The intra-individual biological variability of NAG excretion from day to day is low (CV: 15-25%), irrespective of outpatient or inpatient settings. By contrast, albumin and alpha(1)-microglobulin excretion can differ by a factor of 2-3 from day to day, and higher levels are predominantly found in outpatient settings. The reference ranges for young, healthy male subjects are generally lower than published in cross-sectional studies in the total healthy population. CONCLUSION: These findings and established reference ranges for young, healthy male subjects may assist in the evaluation of proteinuria in clinical pharmacological phase I trials.

Acetylglucosaminidase↗
PubMed1996

Lymphotoxin-alpha (TNF-beta) during sepsis.

T cell release of lymphotoxin-alpha (LT-alpha, or TNF-beta) is stimulated by pyrogenic exotoxins of Gram-positive bacteria and mitogens. In contrast to TNF-alpha, it is unknown whether LT-alpha plays any role in the pathogenesis of sepsis and, in particular, the pathogenesis of Gram-positive sepsis. Sera from patients with sepsis were examined for LT-alpha and compared with normal volunteers and pregnant women. LT-alpha was detected in 33% of sepsis sera (mean 608.4 pg/ml SE 306), 16% of normal sera (mean 167 pg/ml SE 87) and 23% of sera from pregnant women (mean 714 pg/ml SE 191). These differences were not significant and there were no differences within sepsis sera when grouped by the type of causative organism, or disease severity. LT-alpha detected by immunoassay in serum was not bioactive, in contrast to that produced in cell culture. Recombinant soluble TNF receptors (rSTNFR) neutralized the bioactivity of recombinant LT-alpha at rSTNFR concentrations which did not interfere with immunoreactivity and which are known to prevail in vivo. Hence, LT-alpha is unlikely to have a critical role in the pathogenesis of sepsis. Much of the potential bioactivity of this lymphokine may be abrogated by TNFR in serum.

Animals↗
PubMed1990

[Interleukin-1 in the pathogenesis of chronic polyarthritis].

The cytokine interleukin-1 plays an important role in the production and modulation of the immune response in rheumatoid arthritis. It is produced by macrophages of the inflamed synovial tissue and induces the autocrine production of interleukin-1, amplifies the T-cell dependent immune response and has potent effects on inflammatory reactions of many non-lymphoid cell-systems. By means of a sensitive and specific ELISA interleukin(Il)-1 beta was measured in the peripheral blood and synovial fluid of patients with rheumatoid arthritis in comparison to controls in significantly increased levels (medium values: 280 pg/ml and 325 pg/ml versus less than 20 pg/ml). The Il-1 beta concentrations in the peripheral blood and in the synovial fluid were well correlated, but there was no correlation to other inflammation parameters like erythrocyte sedimentation rate or C-reactive protein, however, a good correlation to the nephelometrically measured rheumatoid factor (r = 0.71). In twelve hour cultures of adherent cells significantly increased spontaneous intracellular Il-1 beta-production was determined in synovial fluid macrophage cultures of rheumatoid arthritis patients compared to peripheral blood monocyte cultures of controls (median values 91.0 ng/10(6) cells versus 31.5 ng/10(6) cells). The secretion into the culture supernatant has to be stimulated by additional lipopolysaccharide. Interferon-gamma inhibits the spontaneous intracellular Il-1 beta-production of synovial fluid macrophages from rheumatoid arthritis patients. These findings may be of importance for the effect of the interferon-gamma therapy in the treatment of rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1989

Spontaneous and LPS-stimulated production of intracellular IL-1 beta by synovial macrophages in rheumatoid arthritis is inhibited by IFN-gamma.

In the peripheral blood (PB) as well as the synovial fluid (SF) of rheumatoid arthritis (RA) patients significantly elevated levels of interleukin 1 beta (IL-1 beta) were determined compared to controls by means of a sensitive and specific ELISA (median values: 280 pg/ml and 325 pg/ml vs. less than 20 pg/ml). In 12-h cell cultures of adherent cells, significantly increased spontaneous intracellular IL-1 beta production was determined in SF macrophage (SFM phi) cultures of RA patients compared to PB monocyte (PBMo) cultures of controls (median values: 91.0 ng/10(6) cells vs. 31.5 ng/10(6) cells). However, secretion must be elicited by additional stimulation with lipopolysaccharide (LPS). Interferon-gamma (IFN-gamma) significantly inhibited the spontaneous intracellular IL-1 beta production in SFM phi 12-h cultures of RA patients.

Arthritis, Rheumatoid↗
PubMed1988

Interleukin-2 secretion by synovial fluid lymphocytes in rheumatoid arthritis.

Interleukin-2 (IL-2) receptor bearing cells and soluble IL-2, measured in a bioassay with IL-2 dependent human T-cell blasts, were recognized in synovial fluid, but not in the peripheral blood of patients with rheumatoid arthritis (RA). After stimulation in vitro with appropriate concentrations of the mitogen concanavalin A (Con-A), comparable proportions of IL-2 receptor (IL-2R) bearing cells were seen in cultures of synovial fluid lymphocytes (SFL) and in cultures of peripheral blood lymphocytes (PBL). On the other hand, higher levels of secreted IL-2 were found in SFL cultures compared to corresponding PBL cultures of RA patients and normal donors. Specificity of the IL-2 bioassay was confirmed by blocking the T-cell blast proliferation (induced by SFL culture supernatants), by 83 +/- 4%, after addition of a monoclonal anti-IL-2R antibody. Despite the high levels of soluble IL-2, only a weak proliferative response was observed in the corresponding SFL cultures.

Adult↗
PubMed1988

An ELISA for IgA, IgG and IgM-RF measurement. I. Parameters of the assay.

A simple and rapid solid phase ELISA for the stepless determination of IgA, IgG and IgM-RF was developed. The ELISA works with Fc parts of human IgG as antigen. Specificity, validity and precision were tested. RF complex dissociation by urea and separation by gel filtration was performed in several samples to obtain information of the transfer of non-RF-IgG by pentameric IgM-RF. The RF-ELISA may give better information on the significance of RF of the three Ig classes in the clinical course of RA.

Calibration↗
PubMed1988

An ELISA for IgA-IgG and IgM-RF measurement. II. RF in several disease and control groups and under gold therapy in RA.

The before introduced solid phase ELISA was employed for the RF determination in the sera of RA patients and controls. The threshold values for positive results (calculated as the 95% distribution percentile of healthy donors) were 8, 3, and 3 U/ml for IgA, IgG, and IgM-RF, respectively. The results confirm the validity of the assay with clear negative results in several negative control groups (healthy donors, patients of the oto-, rhino-, laryngeal ambulance, diabetes mellitus, degenerative arthropathies; n = 111, median IgA, IgG and IgM-RF values of less than or equal to 2, less than or equal to 2 and less than or equal to 1 U/ml, respectively; 25-75% distribution percentiles within the median value) and positive results in the positive control group (seropositive RA; n = 20, median IgA, IgG and IgM-RF values of 324, 479 and 170 U/ml, respectively). 16/24 patients with so-called seronegative RA (negative Latex Fixation Test or Waaler Rose Test) had positive results in the ELISA, two of them had rheumatoid nodules clinically. The IgG-RF activity in the ELISA appears to be a good parameter for the course control of RA under gold therapy. 10 RA patients with clinical improvement of disease (declining ESR, CRP, joint index) after six months of gold therapy (= 0.6 g total gold amount) had a decline of total RF activity of 70% in median, whereas 10 patients with no clear effect on disease activity had only a decline of 20% in median.

Arthritis, Rheumatoid↗
PubMed1986

Evidence for enhanced interleukin 2 (IL-2) secretion and IL-2 receptor presentation by synovial fluid lymphocytes in rheumatoid arthritis.

Synovial fluid lymphocytes (SFL) and peripheral blood lymphocytes (PBL) from patients with rheumatoid arthritis (RA) and reactive oligoarthritis were investigated for activated T cells (Ia+SIg-), IL-2 receptor bearing cells (Tac+) and IL-2 production in vivo and in vitro. In contrast to negative results with blood, the synovial fluid of the arthritic joints contains considerable amounts of IL-2 activity (median: 11.8 mu/ml), elevated proportions of Ia+SIg- activated T cells (median: 12.5%) and of IL-2 receptor bearing cells (median: 2.5%). In vitro, after stimulation with several Concanavalin A (Con A) doses, SFL develop proportions of IL-2 receptor cells comparable to PBL. Furthermore, they produce higher values of IL-2 activity than comparable PBL cultures. The proportions of Ia+SIg- activated T cells increase only moderately after Con A stimulation compared to in vivo data, indicating different activated T cell subsets in the synovial fluid (Ia+SIg-, Tac+). The findings are discussed as an expression of an acute hyperactivation of lymphocytes in an inflamed joint.

Adolescent↗
PubMed1984

[A solid-phase ELISA with specificity for rheumatoid factors of classes IgA, IgG and IgM].

A solid phase ELISA was developed for the simple and rapid determination of rheumatoid factors (RF) of all major immunoglobulin classes. Micro-ELISA-plates were coated with human Fc-fragments and incubated with various dilutions of serum samples as well as with an international RF reference serum. Rheumatoid factors were quantitatively detected by rabbit antibodies (RaHIgA(alpha), RaHIgM(mu), RaHIgG(Fab] conjugated with alkaline phosphatase. The specificity of the ELISA was proved by means of binding inhibition of all rheumatoid factor classes by heat aggregated human IgG. A comparison of the IgM-RF titres of the latex fixation test with the IgM-RF concentration values of the ELISA yielded high correlation (r = .81).

Arthritis, Rheumatoid↗
PubMed1983

Studies on immunoregulatory mechanisms in acute and chronic hepatitis B.

Patients with acute hepatitis B and HBV-induced chronic hepatitis as well as normal control persons participated in the study. Hepatitis patients of both groups have decreased OKT4+/OKT8+T cell ratios due to an percental increase of OKT8+T cells in peripheral blood compared to the data of controls. Lymphocyte cultures of chronic hepatitis patients show reduced DNA synthesis after stimulation by allogeneic non-T cells, PHA, Con A and PWM. PWM-induced immunoglobulin secretion by B cells, determined by means of a reverse haemolytic plaque assay (RHPA) and a solid phase ELISA, showed comparable results in hepatitis B patients and controls. The AMLR, which is thought to reflect an autologous immunoregulatory phenomenon, is slightly impaired in cultures of hepatitis B patients in comparison to controls. Con A-induced suppressor cell activity on T cell reactions is decreased in hepatitis, whereas suppressor cell activity on B cell activation is within the same range as in cultures of controls. It is concluded from these data, that suppressor cell activity on T cell function is impaired in hepatitis B, whereas B cell functions and suppressor cell activity on B cell function are in the normal range. The results with the functional assays and the finding of increased proportions of OKT8+T cells in hepatitis B are considered to reflect properties of different T cell subpopulations, responsible for different immunoregulatory functions.

Acute Disease↗
PubMed1983

Inhibition of lignin formation by L-alpha-aminooxy-beta-phenylpropionic acid, an inhibitor of phenylalanine ammonia-lyase.

Mungbean (Vigna radiata (L.) Wilczek) seedlings grown for 9 days on filter paper soaked with 0.3 to 1 mM L-alpha-aminooxy-beta-phenylpropionic acid (AOPP), a potent inhibitor of L-phenylalanine ammonia-lyase, had a greatly reduced anthocyanin content, and the cell walls of the xylem vessels did not stain with the phloroglucinol/HCl or safranine/astrablue reagents indicating the absence of lignin-like material. Furthermore, vanillin was detectable in nitro-benzene-oxidized lignin preparations only from control seedlings, but not from AOPP-treated seedlings. Scanning electron microscopy of hypocotyl cross sections revealed collapsed xylem vessels in seedlings grown in the presence of AOPP indicating that lignin is required for resistance against the tensile forces in the conducting cells of the xylem. AOPP enhanced the growth of cultured cells of Lonicera prolifera Rehd. while it inhibited the production of extracellular material that gave a positive reaction with phloroglucinol/HCl.

Ammonia-Lyases↗
PubMedDate not supplied

Enumeration of T cell subsets and functional suppressor cell assays in patients with rheumatoid arthritis and HLA-B27-associated arthritis.

Seronegative rheumatoid arthritis (RA) patients have increased proportions of OKT-4+ (helper) T cells and diminished proportions of OKT-8+ (suppressor/cytotoxic) T cells in the peripheral blood. This phenomenon corresponds to diminished inhibition of B cell activation by peripheral blood lymphocytes (PBL). Seropositive RA patients show a broad range of OKT-8+ T cell proportions (9%-45%) in the peripheral blood, resulting in a mean level comparable to that in controls. Inhibition of T cell activation by suppressor cells in peripheral blood is greater in this group than in controls. HLA-B27-positive arthritis patients show no significant differences from controls with respect to markers and functional suppressor cell assays. In the synovial fluid of all patients both OKT-8+ T cell proportions and functional suppressor cell activity are greatly increased.

Arthritis, Rheumatoid↗