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Biomedical subjects

C G Larsen

Publications and source records attributed to C G Larsen.

At least 55 records · Page 3Linked to original sources
PubMed1991

Soluble IL2 receptor serum levels and epidermal cytokines in mycosis fungoides and related disorders.

We examined the immune activation in 20 patients with mycosis fungoides, 6 patients with erythrodermia of unknown origin (Pré-Sézary's syndrome), 5 with lymphomatoid papulosis, 4 with parapsoriasis, 2 with Sézary's syndrome, and 2 with actinic reticuloid, by measuring soluble interleukin-2 receptor levels in serum. In Mycosis fungoides we observed normal levels in 3 patients (less than 500 units/ml), between 500 and 1000 units/ml in 9 patients, and greater than 1000 units/ml in 5 patients. Four of these 5 patients died within one year after this observation, as did 2 patients with Pré-Sézary and Sézary's syndrome, respectively, who had a similarly large increase in sIL2R. Although sIL2R is not a specific parameter for cutaneous T-cell lymphoma, a value above 1000 units/ml is correlated with clinical disease activity and is a serious prognostic parameter. We also studied cytokine activity in epidermal homogenates from 9 patients with Mycosis fungoides and one patient with Sézary's syndrome. We observed interleukin-1-like activity within the normal range for healthy skin. However, we also observed in the same epidermal homogenates a T-lymphocyte chemotactic activity in patients with stage II, but not in stage I. The nature of this activity is not yet fully elucidated, but it may be an important biological factor for the epidermal T-cell accumulation in this disorder.

Aged↗
PubMed1990

Monocyte chemotactic and activating factor gene expression induced in endothelial cells by IL-1 and tumor necrosis factor.

Inflammation, thrombosis, and immunity involve close interactions between leukocytes and vascular endothelium. Endothelial cells represent both targets and producers of lymphokines. Our study was designed to define the capacity of human endothelial cells (HEC) to produce a novel, recently purified, and molecularly cloned monocyte chemotactic and activating factor. This factor has been identified in the culture supernatants of tumor cell lines (tumor-derived chemotactic factor (TDCF)) as well as activated monocytes and fibroblasts (monocyte chemotactic and activating protein, MCAF, or monocyte chemoattractant protein-1, MCP-1). IL-1 induced high levels of production of chemotactic activity for monocytes in culture supernatants of HEC. IL-1-treated HEC expressed high levels of MCAF/MCP-1/TDCF mRNA transcripts, as assessed by Northern blot analysis. TNF and LPS, unlike IL-6, also induced MCAF/MCP-1/TDCF gene expression. Nuclear run off experiments revealed that IL-1-activated transcription of the MCAF/MCP-1/TDCF gene. The production of MCAF/MCP-1/TDCF may represent one of the mechanisms whereby endothelial cells, exposed to inflammatory signals, participate in the regulation of leukocyte extravasation. Production of this cytokine by vascular cells may in particular be relevant under conditions of selective extravasation and activation of mononuclear phagocytes.

Biological Factors↗
PubMed1990

Detection of interleukin 8 biological activity in synovial fluids from patients with rheumatoid arthritis and production of interleukin 8 mRNA by isolated synovial cells.

The presence of neutrophils in the synovial joint of patients with rheumatoid arthritis (RA) is thought to be due to the activity of chemotactic factors released by activated cells in the joint. We have shown in this report, for the first time, the abundance of one such factor, interleukin 8 (IL 8), in the synovial fluid of patients both with RA and other non-RA joint diseases, and the spontaneous production of IL 8 mRNA by RA synovial cells in culture. There was no correlation between the levels of chemotactic activity and IL 8 protein, suggesting that other factors with similar neutrophil chemotactic activity are also present in the synovial fluid exudate. In support of this concept neither the level of chemotactic activity nor IL 8 protein levels correlated with neutrophil or leukocyte infiltration, indicating that the mechanism of migration into the inflammatory environment of the joint is complex. Such migration is likely to be due to a number of chemotactic signals in addition to IL 8, which may either synergize with, or inhibit, the action of IL 8.

Adult↗
PubMed1989

Production of monocyte chemotactic and activating factor (MCAF) by human dermal fibroblasts in response to interleukin 1 or tumor necrosis factor.

Normal human dermal fibroblasts rapidly expressed (less than 30 min.) considerable mRNA for monocyte chemotactic and activating factor (MCAF) and released high levels of biological activity in response to interleukin 1 (IL 1) or tumor necrosis factor (TNF). In contrast, cultured normal human keratinocytes did not express MCAF mRNA when stimulated with IL 1 or TNF. These results suggest the important role of dermal fibroblasts, the predominant cells in dermal connective tissue, in the recruitment of monocytes during inflammation. This is the first report of the induction of MCAF by IL 1 or TNF in any cell type.

Cells, Cultured↗
PubMed1989

Purification and characterization of a novel monocyte chemotactic and activating factor produced by a human myelomonocytic cell line.

A novel basic heparin-binding monocyte chemotactic factor (MCF) was purified to homogeneity from the conditioned media of human myelomonocytic cell line THP-1 based on its in vitro monocyte chemotactic activity. The purified MCF was homogenous and estimated to be 15 kD on SDS-PAGE. Purified MCF stimulated normal human monocytes to be growth inhibitory in vitro at 2-3 d for several human tumor cell lines. This represents the first report of the identification and purification of a chemoattractant cytokine that also activates monocytes but is distinct from interferons and other known cytokines.

Cell Line↗
PubMed1989

The neutrophil-activating protein (NAP-1) is also chemotactic for T lymphocytes.

T lymphocyte chemotactic factor (TCF) was purified to homogeneity from the conditioned media of phytohemagglutinin-stimulated human blood mononuclear leukocytes by a sequence of chromatography procedures. The amino-terminal amino acid sequence of the purified TCF showed identity with neutrophil-activating protein (NAP-1). Both TCF and recombinant NAP-1 (rNAP-1) were chemotactic for neutrophils and T lymphocytes in vitro supporting the identity of TCF with NAP-1. Injection of rNAP-1 into lymphatic drainage areas of lymph nodes in Fisher rats caused accelerated emigration of only lymphocytes in high endothelial venules. Intradermal injection of rNAP-1 caused dose-dependent accumulation of neutrophils and lymphocytes.

Animals↗
PubMed1989

Cloning and sequencing of the cDNA for human monocyte chemotactic and activating factor (MCAF).

cDNA clones having a nucleotide sequence encoding a human monocyte chemotactic and activating factor (MCAF) were isolated and sequenced. The amino acid sequence deduced from the nucleotide sequence reveals the primary structure of the MCAF precursor to be composed of a putative signal peptide sequence of 23 amino acid residues and a mature MCAF sequence of 76 amino acid residues. The amino acid sequence of MCAF showed 25-55% homology with other members of an inducible cytokine family, including macrophage inflammatory protein and some putative polypeptide mediators known as JE, LD78, RANTES and TCA-3. This suggests that MCAF is a member of family of factors involved in immune and inflammatory responses.

Amino Acid Sequence↗
PubMed1989

Production and characterization of recombinant human neutrophil chemotactic factor.

A putative mature human neutrophil chemotactic factor (NCF) corresponding to the C-terminal 72 amino acids of its precursor was directly produced in Escherichia coli by recombinant DNA technology. Human NCF was present in both the soluble and insoluble protein fractions of the homogenate of host cells, and it was partially purified as a water-soluble polypeptide from both fractions, separately. The partially purified NCF preparation was highly purified to an endotoxin-free homogeneous polypeptide by means of CM-Sepharose CL-6B column chromatography and gel filtration on Toyopearl HW-55. No difference between the human NCF preparations purified from both starting materials could be found concerning purity, primary structure, solubility, molecular weight, and chemotactic activity for human neutrophils. The amino acid sequence of recombinant human NCF was identical to the sequence deduced from the cDNA sequence. A methionine residue due to the translation initiation codon was removed. Recombinant human NCF was found to be biologically active and to exhibit chemotactic activity for human neutrophils in vitro and cause a neutrophil infiltration in vivo in mice.

Amino Acid Sequence↗
PubMed1989

The immunology of contact dermatitis. A review with special reference to the pathophysiology of eczema.

This review summarizes current knowledge of the pathophysiological events which lie behind the development of contact dermatitis. The clinical distinction between allergic and irritant eczema is discussed. New observations are evaluated on our understanding of how allergic and irritant eczema may in many respects be similar, evolving through common physiological pathways of immune inflammation.

Dermatitis, Contact↗
PubMed1989

Production of interleukin-8 by human dermal fibroblasts and keratinocytes in response to interleukin-1 or tumour necrosis factor.

Cultured normal human fibroblasts were stimulated to produce neutrophil-activating protein/interleukin-8 (IL-8) in response to IL-1 alpha (0.1-1000 U/ml) or tumour necrosis factor (TNF) alpha (0.1-1000 U/ml). Induction of mRNA for IL-8 in fibroblasts was rapid (within 30 min) and maximal responses were obtained with either 100 U/ml IL-1 alpha or 100 U/ml TNF alpha. Expression of mRNA for IL-8 was accompanied by the production of high levels of neutrophil chemotactic activity. IL-1 alpha (1000 U/ml), but not TNF alpha, induced mRNA for IL-8 in cultured normal human keratinocytes. The relevance of production of IL-8 by these cell types was evaluated further by comparing the local inflammatory effects of IL-1 alpha, TNF alpha and IL-8. Intradermal injection of either recombinant IL-8, IL-1 alpha or TNF alpha lead to a similar in vivo effect, i.e. dose-dependent accumulation of lymphocytes and polymorphonuclear leucocytes at sites of injection. The in vivo attraction of neutrophils and lymphocytes to the site of injection by TNF or IL-1 (which is not chemotactic for neutrophils or lymphocytes in vitro), may be partly mediated by locally produced IL-8. Thus, IL-8 may be a vital participant in the cascade of interacting cytokines that is induced by tissue injury and immunologically induced inflammation.

Cells, Cultured↗
PubMed1988

Epidermis and lymphocyte interactions during a tuberculin skin reaction. I. Increased ETAF/IL-1 like activity, expression of tissue antigens and mixed skin lymphocyte reactivity.

Forty-one persons were tested for tuberculin skin reactivity. Epidermal cells (ECs) were isolated from the tuberculin reaction and from a contra lateral, non injected skin area. We found a significant increase of epidermal thymocyte activating factor (ETAF) in epidermis overlying a positive tuberculin reaction together with an increase of OKT6 and class II (HLA-DR) positive cells. Allogeneic lymphocytes proliferated significantly more when mixed with ECs from a positive tuberculin skin test. Injection of tuberculin per se or a negative reaction did not induce similar changes. The described model seems useful for functional studies of ECs and lymphocytes in patients with contact dermatitis.

Adult↗
PubMed1988

Epidermal lymphocyte chemotactic factor specifically attracts OKT4-positive lymphocytes.

Epidermal lymphocyte chemotactic factor (ELCF) from skin overlying a positive tuberculin reaction was compared with the chemoattractants leukotriene B4 (LTB4), N-formyl-methionyl-leukyl-phenylalanine (FMLP), and complement split product C5a (C5a). The chemotactic assay used is a modified Boyden chamber technique. The lymphocytes were subsets of T lymphocytes from healthy young individuals first separated by flotation of E rosettes on Isopaque Ficoll followed by incubation of T cells with anti-CD4 and anti-CD8 monoclonal antibodies and further separation using fluorescence-activated cell sorting. ELCF specifically attracted OKT4+ lymphocytes, while LTB4, FMLP, and C5a induced significant migration in both OKT4+ and OKT8+ lymphocytes without any clear difference between the various chemoattractants or cell populations. We found no blocking of the chemotactic capacity of ELCF when we added antibodies towards IL-1 alpha and IL-1 beta to the chemotactic assay. Further recombinant IL-1 alpha and Il-1 beta did not induce any chemotactic response. Our observation may be of significance in explaining the predominance of OKT4+ cells in allergic contact dermatitis and certain other skin diseases.

CD4-Positive T-Lymphocytes↗
PubMed1988

Epidermis and lymphocyte interactions during an allergic patch test reaction. Increased activity of ETAF/IL-1, epidermal derived lymphocyte chemotactic factor and mixed skin lymphocyte reactivity in persons with type IV allergy.

Recently, we have found an increased activity of epidermal-derived thymocyte-activating factor (ETAF/IL-1) and epidermal lymphocyte chemotactic factor (ELCF) in epidermis overlying a positive tuberculin skin reaction. In the present study, we investigated 20 patients with confirmed or suspected allergic contact dermatitis by using the suction blister technique before and during patch testing. The ETAF/IL-1 was found in epidermis before patch testing. Its presence increased 2.8-fold in epidermis overlying a positive patch test compared with pretesting values. This increase was statistically significant. Interestingly, nontested skin also showed a significant increase of ETAF/IL-1, which was 1.9-fold higher than pretest values. The ETAF/IL-1 activity in patch test areas was significantly correlated with the clinical response. ELCF is not present in epidermis from noneczematous persons. We observed a significant content of ELCF in three of seven patients with eczema prior to patch testing. After patch testing, all patients showed ELCF in epidermis. Nontested skin showed a 1.5-fold higher content of ELCF compared with pretest values, and in the test area ELCF was 1.8-fold higher. The increases were statistically significant. We performed mixed skin lymphocyte reactions in seven patients using epidermal cells from the patch test area. All patients with a positive patch test had an increased mixed skin lymphocyte reactivity compared with epidermis coming from a negative reaction.

Adult↗
PubMed1988

Pharmacokinetics of etretin and etretinate during long-term treatment of psoriasis patients.

The aromatic retinoic acid derivative etretin has recently been introduced in the treatment of severe psoriasis and other dyskeratoses. Hitherto, the use of the carboxylic acid ester analogue, etretinate, has been hampered by an extremely long elimination half-life of up to 120 days for this drug. Seven patients of either sex from whom we recently reported single-dose pharmacokinetics have been studied after 1 and 3 months multiple dose administration of the drugs. Four were given etretin and three etretinate. Etretin, both as drug and as metabolite, was absorbed faster than etretinate as judged from t-lag, tm and t 1/2 ka. Etretin as drug was eliminated faster than the metabolite etretin, t 1/2 beta 2.39 +/- 1.16 days compared to 6.51 +/- 2.06 days. In patients receiving etretinate the terminal disposition or elimination half-lives for cisetretin (t 1/2 lambda 3 15.9 +/- 9.9 days) were longer than for the metabolite etretin and exhibit a pronounced interindividual variation from 4.25 to 22.8 days. Similarly, cis-etretin accumulated very marked in comparison to the metabolite etretin of the drug etretinate. Assuming 40% systemic availability for both drugs, the central compartment of distribution constituted about 12-32% in case of etretin and about 0.8-3.6% in case of etretinate of the calculated apparent total volume of distribution at steady state, which showed mean values of 3.5 and 39.6 1.kg.-1, respectively, presumably reflecting the higher lipophilic nature of the latter compound.

Acitretin↗
PubMed1988

Preparation of human epidermal tissue for functional immune studies.

A trypsinization technique was optimized for preparation of human epidermal single-cell suspensions from suction blisters. The conditions which provided the highest epidermal cell yield and viability was Sigma trypsin 0.25% (Type II, crude; cat. no. T8128). The incubation time should be 45 min at 37 degrees C with continuous shaking of the epidermal tissue. The use of suction blisters was evaluated for in vivo determination of epidermal thymocyte activating factor (ETAF/Il-1). Trypsinization of epidermis diminished ETAF/Il-1 activity. Dialysis of epidermal homogenates improves determination of ETAF/Il-1-like activity due to removal of low-weight inhibitors. Determination of ETAF/Il-1-like activity in homogenates of suction blisters constitutes a reliable model with acceptable reproducibility.

Cell Separation↗
PubMed1987

Single dose pharmacokinetics of etretin and etretinate in psoriatic patients.

Etretin, an aromatic retinoic acid derivative, has recently been introduced as a possible substitute for etretinate in the treatment of severe psoriasis and other dyskeratoses. A total of nine patients with psoriasis of either sex in the age range 23-76 years was investigated after single dose oral drug administration, six were given 40 mg of etretin and three 40 mg of etretinate. A newly developed reversed-phase HPLC method was applied for simultaneous determination of etretin and etretinate in plasma. In patients receiving etretinate, the lag-time i.e. the time elapsing until appearance of first-order drug absorption was 1.24 +/- 0.27 for the parent drug and 0.69 hrs +/- 0.16 (mean value +/- S.D.) for its metabolite, etretin. Absorption half-times were 0.86 +/- 0.04 and 0.55 hrs +/- 0.09, respectively. The patients receiving etretin showed a lag-time of 0.42 hrs +/- 0.23 and an absorption half-time of 0.33 hrs +/- 0.28. This suggests that a fraction of etretinate is rapidly hydrolysed to etretin during the absorption process. The mean half-times of the distributory phases of disposition for etretinate and etretin were about 1 and 1.3 hrs and the apparent terminal half-lives were 6.57 +/- 2.09 and 5.52 hrs +/- 1.76, respectively. Assuming 40% systemic availability for both drugs the mean apparent volumes of distributions were calculated to be 1.50 +/- 0.46 and 1.31 l X kg-1 +/- 0.53 and mean plasma clearances were 177.8 +/- 105.8 and 175.9 ml X kg-1 X hr-1 +/- 81.4 for etretinate and etretin, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acitretin↗