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J Heymanns

Publications and source records attributed to J Heymanns.

29 records · Page 2Linked to original sources

Imbalance of CD4+CD45R+ and CD4+CD29+ T helper cell subsets in patients with atopic diseases.

To evaluate the proportion of helper cell subsets we studied 18 children with atopic dermatitis, 30 patients with asthma, 27 healthy age-matched controls aged 1 to 17 years and 11 atopic controls without symptoms related to atopy, aged 9-22 years. Lymphocytes were isolated from heparinized peripheral blood and the proportion of CD4+CD29+ and CD4+CD45R+ cells was determined by double-labelling immunofluorescence. Children with atopic dermatitis yielded a significantly (P less than 0.01) higher proportion of CD4+CD45R+ (median 75%) cells compared with normal controls (median 66.6%), whereas the proportion of CD4+CD29+ cells was significantly (P less than 0.01) lower in patients with atopic dermatitis (median 20.4 versus 29.6%). Interestingly, the percentage of CD4+CD45R+ cells shows an age-dependent decline (r = -0.67, P less than 0.01) in the control group, which is not found in the patient group.

Adolescent↗

A cytofluorometric method to quantify membrane antigens on individual alveolar macrophages.

An immunofluorescence method for assaying membrane-bound antigens on individual alveolar macrophages (AM) collected by bronchoalveolar lavage (BAL) is described. Cells were labelled with FITC-conjugated anti-HLA-DR antibodies in a single (direct) step. Quantification of the fluorescence was performed by computer-assisted cytophotometry. Alveolar macrophages, especially when obtained from cigarette smokers, exhibited an autofluorescence which interfered with the measurement of specific fluorescence. The specific fluorescence was calculated by determination of total fluorescence in the wave-length optimal for FITC and the non-specific fluorescence in a different wavelength during a second measurement. Specificity and reproducibility testing confirmed the reliability of the method.

Analysis of Variance↗

A randomized controlled trial of ciamexon versus placebo in the immunomodulatory treatment of rheumatoid arthritis.

To determine the efficacy of the new immunosuppressive agent ciamexon in patients with rheumatoid arthritis (RA), we conducted a 6-month, prospective, double-blind, placebo-controlled study. The study included 21 outpatients with confirmed RA, who were randomized into 3 treatment groups of 7 patients each. Group 1 received 400 mg/day of ciamexon, group 2 received 100 mg/day of ciamexon, and group 3 received placebo. We investigated the influence of ciamexon on the clinical course, the systemic inflammatory activity, and the lymphocyte subsets in the peripheral blood. Significant, dose-dependent improvement was seen in both the clinical and the biochemical activity indexes at the end of the treatment period (P = 0.02 to P = 0.05). The proportion of activated T lymphocytes was significantly decreased (P = 0.05), and the proportion of CD8-positive lymphocytes was significantly increased (P = 0.03) in patients taking ciamexon. The major adverse effects were hepatotoxicity (2 patients) and rash (2 patients). This study documents the clinical efficacy of ciamexon therapy in RA patients and identifies the agent's potential toxicity.

Adjuvants, Immunologic↗

Flow-cytometric analysis of lymphocyte subsets in patients with advanced periodontitis.

Peripheral blood lymphocytes from 36 patients with advanced periodontitis and from 34 healthy subjects were examined using a panel of monoclonal antibodies and fluorescence flow cytometry. The absolute and relative counts of B-cells, T-cells, T-helper (TH), T-suppressor/cytotoxic (TS) cells, activated T-cells and natural killer cells were assessed and the TH/S ratio was calculated. In the periodontitis patients, the TH/S ratio was 1.56 +/- 0.62 and in the controls 1.35 +/- 0.55. This was not statistically significant. A classification on the basis of sex also did not show significant differences in the TH/S ratio. B-cells and activated T-cells were slightly increased in the periodontitis group. However, all determined lymphocyte subpopulations revealed no significant differences between the groups. These results indicate that local inflammatory reactions and immunoregulatory dysfunction are limited to the periodontium in the patients with advanced periodontitis, with no significant quantitative effects on the peripheral lymphocyte subpopulations.

Adult↗

[Immunomodulating basic therapy of rheumatoid arthritis using ciamexone].

Ciamexone, a 2-cyanoaziridine derivative, had been shown previously in animal studies to inhibit the proliferation of autoreactive lymphocytes dose dependently, without affecting the reaction against foreign antigens. To extend the experimental models of ciamexone's in vitro effects to the clinical level, we performed a pilot study to evaluate the clinical efficacy of ciamexone therapy. We further studied its influence on the systemic inflammatory activity and T-lymphocyte subsets in the peripheral blood of 10 patients with active rheumatoid arthritis (RA). Following 6 months' treatment with ciamexone all patients showed a significant decrease of both the clinical and biochemical scores. Concerning the T-lymphocyte subsets analysis, a relatively decreased rate of the activated T-lymphocytes was observed concurrently. Minor side effects included rash (n = 1), hepatotoxicity (n = 1) and diarrhea (n = 1). The study thus documents the clinical efficacy of ciamexone in patients with RA, but also indicates the agent's potential toxicity.

Adjuvants, Immunologic↗

Tetanus toxin as a marker for small-cell lung cancer cell lines.

Tetanus toxin labeling of human lung cancer cell lines was investigated using direct and indirect immunofluorescence and immunohistochemical staining. Cells of characterized permanent cell lines, eight small-cell lung cancer (SCLC) cell lines of classic subtype, six SCLC cell lines of variant subtype and seven non-small-cell lung cancer (NSCLC) cell lines, were incubated with a saturating concentration of tetanus toxin. For staining, fluorescein-isothiocyanate-(FITC)-conjugated anti-(tetanus toxin) antibodies were used or a mouse monoclonal anti-(fragment C) antibody with subsequent binding of FITC-conjugated anti-(mouse Ig) antibody or peroxidase-anti-peroxidase complex. Only SCLC showed an intense fluorescence/immunoreactivity restricted to the cell membrane. Quantitative analysis of tetanus toxin labeling by flow cytometry revealed the percentage of positive cells to be between 35% and 95% in SCLC without obvious differences between the classic and variant subtypes of SCLC. In NSCLC the percentage of positive cells was lower than 10%. These results demonstrate that SCLC in contrast to NSCLC can be labeled with tetanus toxin, emphasizing the neuroendocrine properties of this tumor, and that tetanus toxin labeling may become a useful diagnostic marker for SCLC cells in cytology.

Animals↗

Peptides and growth factors in small cell lung cancer: production, binding sites, and growth effects.

We investigated the production, binding to cell membranes, and influence on cell proliferation of peptides and growth factors in 4 classic, 5 transitional, and 5 variant SCLC cell lines. Glucagon, neurotensin, and TGF-alpha were present in all cell lines. Bombesin was predominantly found in classic cell lines and insulin in variant cell lines. Neurokinin A, calcitonin, CGRP, GHRF, somatostatin, and CNTF were detectable in some cell lines without prevalence for a particular cell type. We could not detect AVP, growth hormone, neuropeptide Y, substance P, VIP, and NGF. Insulin binding sites were present on 11/14 cell lines, and some cell lines specifically bound bombesin, calcitonin, and EGF. Growth effects were detectable for insulin, GRP-related peptides, tachykinins, and VIP. Using serum-free conditions, insulin and VIP had a growth stimulating effect in liquid culture at nanomolar concentrations. Bombesin and neuromedin B stimulated the clonal growth at a concentration of 3-30 nM. The tachykinins neurokinin A, neurokinin B, physalaemin, and eledoisin inhibited the clonal and mass culture growth with a peak effect in the range of 0.1 to 10 pM. Peptide-induced stimulating and inhibiting effects were within a magnitude of 2-fold. All other peptides and growth factors tested, including ACTH, AVP, calcitonin, glucagon, neurotensin, somatostatin, EGF, CNTF, and NGF did not affect the growth of SCLC. We conclude that the growth of SCLC is partly controlled by such peptides in an autocrine/paracrine fashion.

Amino Acid Sequence↗

Neuroblastoma cells contain a trophic factor sharing biological and molecular properties with ciliary neurotrophic factor.

Ciliary neurotrophic factor (CNTF) is a protein supporting the in vitro survival of a characteristic spectrum of embryonic chicken and rat peripheral neurons. High-speed supernatants of extracts from two neuroblastoma (NB) cell lines--the mouse C 1300 N2a and the human IMR 32--mimic the effects of CNTF on identical target neurons. Promotion of survival is dose-dependent with an ED50 of 80 micrograms (IMR 32) and 140 micrograms (C 1300 N2a) of protein per ml and saturable at plateau values for surviving neurons identical to those achieved with purified CNTF. Small amounts of a CNTF-like material are also detectable in medium conditioned by NB cells. The activity is destroyed by heat and trypsin and not blocked by antibodies to (mouse) nerve growth factor. Unlike the neurite-promoting and neuronal-survival modulating agent laminin, it cannot be depleted on poly(L-alpha-ornithine)-coated plastic surfaces. NB IMR 32 cell extracts were electrophoresed using NaDodSO4/PAGE and transferred to nitrocellulose. Ciliary ganglion neurons seeded on the blotting paper in culture medium lacking CNTF ("cell blot") exclusively survive on two distinct bands with apparent molecular masses of 24 and 48 kDa. Twenty-four kilodaltons is the molecular mass of a CNTF purified from rat sciatic nerve. These results suggest that NB cells may contain a CNTF-like protein and provide further evidence that neurons may store neurotrophic factors. Purified (chicken) CNTF failed to affect proliferation and neurite growth of NB cells. The biological relevance of CNTF for NB cells, therefore, remains to be elucidated.

Animals↗

Comparative studies of mast cells from normal (non-immunized) and actively sensitized dogs.

Morphologically and functionally intact mast cells were isolated from the lung and mesentery of normal or actively sensitized dogs using the pronase or collagenase tissue dissociation methods. The latter method yielded about 6 times as many metachromatically staining cells. Electron microscopic examination revealed the presence of both mast cells and basophils in all samples, independent of the enzyme used for tissue dissociation. The average histamine content of the cells obtained with the pronase method was significantly higher (21.8 +/- 3.1 pg) than after collagenase treatment (16.2 +/- 4.2 pg). There was no appreciable difference in the reactivity to secretory stimulation of the cells obtained by the two methods. The cells isolated from actively sensitized dog tissues showed a significantly higher spontaneous histamine release (12.9 +/- 1.2%) than those from non-sensitized animals (7.8 +/- 1.3%) and responded equally well to challenge with both the antigens ovalbumin and horse serum. In contrast to those from normal animals, the mast cells from actively sensitized dogs released histamine on stimulation with acetylcholine, metacholine or atropine. In addition, the response to the threshold concentration of compound 48/80 (10(-6)) was significantly stronger in the sensitized cells. Small molecular polyvinylpyrrolidone (K25) was effective in mast cells from normal and actively sensitized dogs.

Acetylcholine↗

Palliative treatment of advanced pancreatic carcinoma in community-based oncology group practices.

This study was aimed at evaluating the feasibility, effectiveness, and toxicity of palliative chemotherapy/supportive care in patients with advanced pancreatic cancer being treated on an outpatient basis. A retrospective analysis was performed on 127 consecutive, unselected patients with advanced pancreatic cancer in four community-based oncology group practices. Median age was 63 years and WHO performance status ranged from 0 to 3. Forty-three patients (34%) had locally advanced disease, and 84 patients (66%) had distant metastases; 94 patients (74%) received cytotoxic treatment during the course of their disease, and 33 (26%) received best supportive care only. First-line treatment consisted of gemcitabine (1,000 mg/m2 on days 1, 8, and 15 of a 28-day cycle) in 81 patients (86%), 5-fluorouracil (5-FU) in 8 patients (9%), radiochemotherapy in 4 patients (4%), and radiation therapy only in 1 patient (1%). A total of 1,501 gemcitabine treatments were given during the study period. Toxicity was moderate. Four patients (3%) required hospitalization for treatment-related side effects, and 111 patients (88%) died during the observation period. Symptom control, as measured by reduction of pain medication, was seen in 25% of patients receiving gemcitabine, whereas no reduction in pain medication was seen in the best supportive care group. The median survival of patients receiving cytotoxic treatment (mainly gemcitabine) was 42 weeks, and the median survival of patients receiving best supportive care was 21 weeks. The overall survival rate at 6, 12, 24, and 36 months was 65%, 32%, 14%, and 7%, respectively. Based on these outcomes, it appears that patients with locally advanced and metastatic pancreatic cancer benefit from adequate palliative treatment, including cytotoxic chemotherapy with gemcitabine, and this can be accomplished on an outpatient basis.

Adult↗