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Biomedical subjects

J Knop

Publications and source records attributed to J Knop.

At least 199 records · Page 11Linked to original sources

Thalidomide in the treatment of sixty cases of chronic discoid lupus erythematosus.

The therapeutic effect of thalidomide in chronic discoid lupus erythematosus (CDLE) was studied in sixty patients who were followed up for 2 years. In fifty-four patients (90%) a complete or marked regression of the disease was observed, but when the thalidomide was stopped, thirty out of forty-one (71%) patients relapsed. Patients undergoing a second course of thalidomide treatment again responded well. Nine of the patients in whom the disease recurred after successful treatment with thalidomide and who had been unresponsive to intermittent treatment with antimalarials, showed a good response to a second or third course with thalidomide. Mild side-effects were common and 25% of patients complained of slight to moderate polyneuritic symptoms. Since electroneurological examinations had not been performed before the thalidomide therapy, the frequency of neurological side-effects cannot be accurately calculated but we recommend neurological examinations before and periodically during thalidomide treatment. Thalidomide is a very effective drug in CDLE, but in most cases it exerts its effect only whilst treatment is continued. Its use should be restricted to patients resistant to topical steroids and systemic antimalarials.

Chronic Disease↗

[Biokinetics of osteotropic radiopharmaceuticals in metabolic osteopathy--comparison of 47Ca and 99mTc-methylene-diphosphonate (MDP)].

Plasma clearance and osseous accumulation rates of 99mTc methylene diphosphonate (MDP) in the lumbar spine were measured in 11 patients with osteoporosis (OP), 7 patients with hyperparathyroidism (HPT), 4 patients with osteomalacia (OM) and in 3 patients (N) who were studied to exclude metabolic bone disease. The findings in 19 patients were compared with the results of 47Ca kinetics. The plasma elimination of 99mTc-MDP during the first hour after application was normal in almost all the patients. The 99mTc-MDP accumulation rates in the lumbar spine were raised in patients with HPT and OM (p less than or equal to 0.01) and normal in patients with OP and N (p greater than 0.05). 47Ca kinetics were disturbed in most of the patients with metabolic bone disease, with minimal deviations in OP. The comparison of 99mTc-MDP accumulation rates with the results of 47Ca kinetics revealed significant correlations with exchangeable bone and soft tissue calcium. The correlations with total calcium turnover and calcium accretion were poor. Only half of the patients had equal results of 99mTc-MDP accumulation rates and bone calcium accretion rates. It is concluded that the 99mTc-MDP uptake by bone is an index of bone metabolism presumably of the organic matrix, whereas 47Ca kinetics represent the mineral metabolism of bone.

Adult↗

Chemotactic efficiency of various chemoattractants for polymorphonuclear leukocytes in inflammatory acne vulgaris.

The chemoattractant efficiencies of a Propionibacterium acnes (P. acnes) cell wall preparation, a P. acnes culture supernatant, and a soluble comedonal extract in the presence and absence of autologous serum for polymorphonuclear leukocytes (PMNs) have been compared in the present study. It has been found that all three preparations have no or very little chemotactic activity for PMNs in the absence of serum. In the presence of autologous serum chemotactic factors is generated by all preparations via the alternative complement pathway. The relative efficiencies of the various preparations to induce chemotactic factor by the alternate complement pathway has been evaluated. Based on the bacterial numbers of the original preparations from which the test preparations had been derived the comedonal extract appears to be more efficient in generating chemotactic factor than the other preparations. It is concluded that in vivo generation of chemotactic factors occurs mainly via the alternate complement pathway activated by soluble comedonal factors diffusing through the follicular wall.

Acne Vulgaris↗

Suppression of the elicitation phase of contact allergy by epicutaneous application of alpha-L-fucose.

Local application of alpha-L-fucose on the ear before elicitation of contact allergy to dinitrofluorobenzene (DNFB) in BALB/c mice results in a suppression of the contact allergic response. However, local application of alpha-L-fucose at the sensitization site on the abdominal wall before sensitizing the animals with DNFB had no inhibitory effect on contact allergy. Alpha-L-fucose has been demonstrated to inhibit lymphokine activity in vitro and manifestation of cellular immunity in vivo. Our results suggest that alpha-L-fucose suppresses contact allergy by locally inhibiting the efferent phase of the cellular immune response.

Animals↗

Modulation of suppressor mechanisms in allergic contact dermatitis: 5. Evidence that inhibition of suppressor T lymphocytes by Corynebacterium parvum is mediated by interferon.

Using a contact hypersensitivity model in BALB/c mice we have previously been able to show that Corynebacterium parvum or C. parvum serum (C.p.s.) of mice treated 24 hr before with C. parvum inhibited the suppressor T-lymphocyte (Ts-cell) response induced by epicutaneous antigen overload with 2,4-dinitrofluorobenzene (DNFB) or by i.v. injection of 2,4-dinitrobenzene sulfonic acid (DNBSO3) without inhibition of the T effector cell response (TDH-cell). In the present investigation we further analyzed the factor responsible for Ts-cell inhibition. Treatment of the C.p.s. with sheep-antimouse interferon (IFN) globulin neutralized its Ts-cell inhibitory effect. Intravenous (i.v.) injection of a crude mouse fibroblast IFN (340 U per mouse) 2 hr after i.v. application of a dose of DNBSO3 inducing tolerance had a similar Ts-cell inhibitory effect as observed with C.p.s. Injection of an electrophoretically pure alpha- and beta-IFN preparation (1000 U per mouse) increased contact sensitivity in mice sensitized with an antigen overload and inhibited the induction of Ts-cells by DNBSO3 i.v. This result is highly suggestive that the Ts-cell inhibitory factor in serum of C. parvum-treated mice is IFN and it shows that Ts-cells as compared to TDH-cells are susceptible to the inhibitory effect of highly purified IFN. This finding suggests that IFN may be an important immunoregulatory factor of delayed hypersensitivity not only in contact allergy but also in bacterial and viral defense.

Animals↗

Biokinetics of bone tracers by means of deconvolution analysis--comparison of 99mTc MDP, 99mTc DPD and 99mTc EHDP.

Transfer functions of 99mTc methylene diphosphonate (MDP), 99mTc 2,3-dicarboxypropane-1,1-diphosphonate (DPD) and 99mTc ethane-1-hydroxy-1,1-diphosphonate (EHDP) into bone and extravascular fluid of soft tissues were determined in 5 dogs by deconvolution analysis of the time-course of plasma, soft tissue and bone radioactivity. The transfer rates 5 min after injection--indicating the rapid exchange of the tracer between plasma and the extravascular fluid--decrease in the order MDP greater than EHDP greater than DPD (P less than 0.05). The transfer rates into bone--determined from transfer rates between 30 and 60 min--decreased in a different order, i.e. MDP greater than DPD greater than EHDP (P less than 0.05). The fractional bone uptake of diphosphonates estimated from the ratio of early to late transfer rates was slightly greater for DPD than for MDP and EHDP respectively. The difference between DPD and MDP was not significant (P greater than 0.05). The average bone and soft tissue concentrations of DPD 60 min after injection were greater than that of MDP and EHDP due to different plasma concentrations (DPD greater than EHDP greater than MDP), whereas the bone-to-soft tissue ratios decreased in the sequence MDP greater than DPD greater than EHDP (P less than 0.05).--Our results reveal different biokinetics of MDP, DPD and EHDP explaining variations in osseous and soft tissue uptake suggesting that deconvolution analysis could play an important role in bone scan interpretation.

Animals↗

Determination of acetaldehyde in human blood by a gas chromatographic method with negligible artefactual acetaldehyde formation.

A method is described for determination of acetaldehyde in blood by head space gas chromatography. The method utilizes sodium nitrite-sulfosalicylic acid as an inhibitor of the ethanol oxidizing systems by means of which the interference of ethanol is reduced considerably. The detection limit was 0.4 mumol/l, the recovery 101.5 +/- 5.2% and the coefficient of variation was 7.8% (1.5 mumol/1 acetaldehyde). There was no disappearance of acetaldehyde if the head space vials were kept at -20 degree C for 24 h. In the comparison study with the semicarbazide method our results were 0.7-4.1 mumol/l lower. The values for acetaldehyde in blood after ethanol ingestion (0.5 g/kg) by volunteers were 0.5-1.3 mumol/l.

Acetaldehyde↗

Deconvolution analysis of 99mTc-methylene diphosphonate kinetics in metabolic bone disease.

The kinetics of 99mTc-methylene diphosphonate (MDP) and 47Ca were studied in three patients with osteoporosis, three patients with hyperparathyroidism, and two patients with osteomalacia. The activities of 99mTc-MDP were recorded in the lumbar spine, paravertebral soft tissues, and in venous blood samples for 1 h after injection. The results were submitted to deconvolution analysis to determine regional bone accumulation rates. 47Ca kinetics were analysed by a linear two-compartment model quantitating short-term mineral exchange, exchangeable bone calcium, and calcium accretion. The 99mTc-MDP accumulation rates were small in osteoporosis, greater in hyperparathyroidism, and greatest in osteomalacia. No correlations were obtained between 99mTc-MDP bone accumulation rates and the results of 47Ca kinetics. However, there was a significant relationship between the level of serum alkaline phosphatase and bone accumulation rates (R = 0.71, P less than 0.025). As a result deconvolution analysis of regional 99mTc-MDP kinetics in dynamic bone scans might be useful to quantitate osseous tracer accumulation in metabolic bone disease. The lack of correlation between the results of 99mTc-MDP kinetics and 47Ca kinetics might suggest a preferential binding of 99mTc-MDP to the organic matrix of the bone, as has been suggested by other authors on the basis of experimental and clinical investigations.

Adult↗

Modulation of suppressor mechanism in allergic contact dermatitis. IV. Selective inhibition of suppressor T-lymphocytes by serum obtained from Corynebacterium parvum treated mice.

We have previously shown that Corynebacterium parvum treatment reduced tolerance induced by intravenous injection of 2,4-dinitrobenzene sulfonic acid (DNBSO3) or by sensitizing BALB/c mice with a supraoptimal dose of 2,4-dinitrofluorobenzene (DNFB). Further analysis by transfer experiments revealed that the generation and/or functional expression of suppressor T-lymphocytes (Ts-cells) was inhibited in both tolerance models. Inhibition of Ts-cells was not entirely correlated with suppression of mitogen induced lymphocyte proliferation mediated by C. parvum activated macrophages. In this investigation we studied the effect of serum obtained at various times after C. parvum injection on tolerance and Ts-cells in DNFB contact allergy. Serum obtained 6 and 24 hr, however, not 72 hr after C.parvum injection inhibited Ts-cells, induced by DNBSO3 and tested by transfer to naive recipients, as efficiently as C. parvum itself. The serum had following characteristics: (1) It inhibited the functional expression of Ts in the recipient animal. (2) It inhibited tolerance induction by an epicutaneous supra-optimal dose of DNFB. (3) It did not inhibit the induction and functional expression of T-effector cells of delayed hypersensitivity (TDH-cells) as shown by transfer experiments. (4) The Ts-inhibitory factor was heat resistant (56 degrees C), not destroyed or lost by dialysis against tris-glycine buffer pH 2 and could not be detected in the serum of NMRI-mice injected 24 hr before with C parvum. (5) The C parvum serum did not significantly increase the spleen weight or suppress mitogen-induced spleen lymphocyte proliferation. The nature of this Ts-cells inhibitory factor is unknown, although the results suggest that cortisone or transfer of bacteria are not responsible. Factors mediating selective inhibition of Ts-cells may be of important regulatory function in delayed type hypersensitivity.

Animals↗

Modulation of suppressor mechanisms in allergic contact dermatitis: 2. Inhibition of suppressor T-lymphocytes by Corynebacterium parvum.

Pretreatment of BALB/c mice with Corynebacterium parvum inhibited the induction of tolerance to the contact sensitizing agent 2,4-dinitrofluorobenzene induced by intravenous injection of DNBSO3. The suppressive effect on tolerance induction has further been analyzed by adoptive transfer experiments. Injection of C. parvum intraperitoneally (0.7-2.8 mg/mouse) before injection of the tolergen inhibited the generation of T-suppressor cells as shown by transfer of spleen cells from the tolerized donor to naive recipients. Pretreatment of the recipients of the suppressor T-cells from tolerized animals with C. parvum also inhibited the function of these cells in the recipient animals. Time-kinetic experiments suggested that more than one mechanism appeared to be responsible for the tolerance induced by DNBSO3; C. parvum (probably via activated macrophages) suppressed tolerance which is mediated by T-suppressor lymphocytes. These results suggest that T-suppressor lymphocytes may--similarly as T-helper cells--be modulated by an activated monocytic-phagocytic system.

Adjuvants, Immunologic↗

Modulation of suppressor mechanisms in allergic contact dermatitis: 1. Effect of C. parvum on the induction phase of contact allergy.

The effect of a pretreatment with corynebacterium parvum (C. parvum) on contact allergy in BALB/c mice was studied. Mice sensitized with 50 microliter (supraoptimal dose) 2.4-dinitrofluorobenzene (DNFB, 0.5%) showed a suppressed response as measured by ear swelling after painting the right ear with 0.3% DNFB in comparison to an allergic response obtained with an optimal sensitization dose (15 microliter DNFB 0.5%). By transfer of spleen cells from donors sensitized with a supraoptimal or an optimal dose to recipients either challenged ro sensitized shortly afterwards with DNFB it could be shown that less functionally active immune T-lymphocytes of the delayed hypersensitivity type and significantly more suppressor T-cells were induced in supraoptimally sensitized mice in comparison to the optimally sensitized animals. Intraperitoneal injection of C. parvum (2.8 mg/mouse) one week before sensitization enhanced the contact allergic response in mice sensitized with a supraoptimal dose of DNFB, with little effect on the response in optimally sensitized animals. Further analysis of this enhancement in transfer experiments showed that C, parvum selectively suppressed the generation and/or functional expression of T-suppressor cells and, probably by this mechanism, increased the number of functionally active T-immune lymphocytes. It is proposed that possibly by activation of the immune system C. parvum will suppress suppressor cells in contact allergy and by this mechanism might facilitate sensitization to the contact allergen.

Animals↗