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T Herlin

Publications and source records attributed to T Herlin.

At least 37 records · Page 2Linked to original sources
PubMed1994

[Behçet syndrome].

Behçet's syndrome (BS) was first described in 1937 as the triad of recurrent oral and genital ulcerations and iritis. BS is a systemic, inflammatory disease of unknown etiology characterized by multiorgan vasculitis. The long-term prognosis is often good, but the disease may lead to blindness and serious neurological sequelae. The broad clinical spectrum of the disease and the lack of pathognomonic lesions make the diagnosis difficult, especially in children. We report a case of BS in a child, and based on a review of the literature we describe the present diagnostic criteria, new immunological aspects, clinical course, and current therapy of the disease.

Adolescent↗
PubMed1994

Chronic arthritis in a boy with 18q- syndrome.

We describe a boy with a terminal deletion of the long arm of chromosome 18 and chronic arthritis involving both knees, one ankle and the temporomandibular joints. In contrast to the majority of patients with 18q- syndrome he has only slight mental disability. His serum IgA is normal.

Abnormalities, Multiple↗
PubMed1993

Basophil histamine release induced by anti-IgE and concanavalin A. Relation to the total plasma IgE content.

The plant lectin concanavalin A (Con A) has been shown to induce basophil histamine release by an IgE-receptor-dependent process resembling that of anti-IgE-antibodies. In this study, the concentration-response for basophil histamine release from washed blood cells was analyzed in a population of blood samples from adults with a total plasma IgE content ranging from < 5 kU/l to > 18,000 kU/l (n = 108), as well as 148 cord blood samples. The concentration-response-curves for anti-IgE in all adult blood samples were similar, despite the large variation in total plasma IgE--only the cord blood samples showed a decreased sensitivity. In contrast, the optimal concentration of Con A was inversely related to plasma IgE, and this relation was most pronounced in the adult blood samples. It is proposed that IgE-receptor-mediated histamine release may be dependent not only on the number of stimulatory, dimeric cross-links formed between IgE-receptors, but also on the molecular structure of the cross-linking agent.

Adult↗
PubMed1993

Modulation of eicosanoid formation by lesional skin of psoriasis: an ex vivo skin model.

The purpose of the present study was to develop an ex vivo skin model to determine the capacity of lesional skin of psoriasis to form leukotriene B4 and other eicosanoids. Keratomed skin samples were incubated in the presence of the calcium ionophore A23187 and arachidonic acid for 45 min at 37 degrees C. After extraction of lipids, eicosanoids were determined by quantitative reversed-phase high-performance liquid chromatography in combination with specific radioimmunoassays. We found that stimulation of skin samples with A23187 and arachidonic acid increased the amount of leukotriene B4 4.0-fold. The 12-lipoxygenase product, 12-hydroxy-eicosatetraenoic acid, and the 15-lipoxygenase product, 15-hydroxy-eicosatetraenoic acid, were both increased 2.7-fold. The cyclooxygenase product, prostaglandin E2, was increased 8.0-fold. Similar incubations using psoriatic scales did not result in formation of eicosanoids. Incubations with the 5-lipoxygenase inhibitor RS43179 inhibited the formation of leukotriene B4 and prostaglandin E2 without significantly affecting the formation of 12-hydroxy-eicosatetraenoic acid and 15-hydroxy-eicosatetraenoic acid. These results reveal that lesional psoriatic skin ex vivo has the enzymatic capacity to increase the levels of eicosanoids. This provides an ex vivo skin model to determine whether putative lipoxygenase inhibitors are able to modulate the formation of eicosanoids in psoriatic skin.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1992

[Clinical use of intravenous immunoglobulin IgG].

Intravenous human immunoglobulins (IVIG) are valuable in the treatment of several immunodeficiency and autoimmune diseases. The classic, well-known indications are primary hypogammaglobulinaemic conditions, immune thrombocytopenia and Kawasaki's syndrome. IVIG's content of specific antibodies toward a series of known, pathogenic microorganisms has led to the treatment of a number of infectious conditions and IVIG has a documented effect on AIDS in children, prophylactically in cases with potentially life-threatening CMV infections in certain types of transplants and prophylactically in hypogammaglobulinaemic patients with the most common variety of leukaemia, chronic lymphocytic leukaemia. Immunotherapy with IVIG in diseases of autoimmune character such as acute and chronic demyelinating neuropathy has recently shown promising results and encouraging reports have been published in the treatment of severe, steroid-dependent asthma, juvenile chronic arthritis and systemic vasculitis and dermatomyositis where IVIG possibly has a favourable immunomodulating effect on the patient's immune response. Future treatment will probably consist of polyvalent immunoglobulins as well as monoclonal or recombinant monovalent antibodies.

Autoimmune Diseases↗
PubMed1992

Hyperosmolarity selectively enhances IgE-receptor-mediated histamine release from human basophils.

Increased osmotic pressure has been reported to cause non-cytotoxic histamine release (HR) from human basophils, as well as a potentiation of HR induced by anti-IgE. In this study, the effects of hyperosmolar Na-K-acetate (300-600 mOsm/kg H2O) on HR was studied in washed human blood cells from newborns, adult volunteers and patients with severe atopic dermatitis. These three patient groups represented 3 very distinct populations with respect to total plasma IgE content, medians were less than 0.2 IU/ml, 20.5 IU/ml and 2508 IU/ml; respectively. Increasing osmolarity to 500 mOsm/kg H2O caused little HR in the absence of other stimuli, whereas at 600 mOsm/kg H2O a significant increase in spontaneous HR was seen. The HR induced by anti-IgE and Concanavalin A, acting through the IgE-receptor, was increased approximately twofold at 500 mOsm/kg H2O. Responses were highly correlated to results at 300 mOsm/kg H2O. The use of 600 mOsm/kg H2O buffers caused a further increase in most, but not all blood samples. The potentiation of IgE-receptor-mediated HR when using hyperosmolar media was clearly independent of plasma IgE contents, and did not change the concentration-response to anti-IgE. In contrast, HR induced by the IgE-receptor-independent stimuli, Formyl-met-leu-phe and calcium ionophore A 23187, were not enhanced at all by increased osmotic pressure. We conclude, that hyperosomolar media selectively enhance IgE-receptor-mediated HR. The use of hyperosmolar media may therefore be beneficial in a diagnostic application of washed blood HR assays used in allergy diagnosis.

Acetates↗
PubMed1990

Proliferation of adherent synovial fluid cell cultures is modified by eicosanoids.

Synovial fluid cells obtained from a carrageenan-induced chronic arthritis in the juvenile dog knee were allowed to adhere and proliferate in culture flasks. After twelve days secondary cultures were made and either 10(-8)M leukotriene B4 (LTB4), 25 microM 15-hydroxy-eicosatetraenoic acid (15-HETE), or both, were added and the cells were cultured for another 6 days. LTB4 is generated via the 5-lipoxygenase pathway of arachidonic acid metabolism and stimulates a number of phagocyte functions. Compared to control cells LTB4 increased proliferation in 9 out of 10 cell cultures (p less than 0.05). The 15-lipoxygenase product, 15-HETE, is not proinflammatory and is an endogenous inhibitor of 5-lipoxygenase. Addition of 15-HETE decreased proliferation of cell cultures by 23% (p less than 0.01). It is speculated that LTB4 in addition to its effect on phagocytes may play a role in synovial hyperproliferation observed in arthritis.

Animals↗
PubMed1990

Histamine release from cord blood basophils.

The histamine release (HR) after challenge with anti-IgE, concanavalin A, N-formyl-met-leu-phe and the calcium ionophore A23187 from 97 cord blood samples was determined by a microfiber-based assay. Maximum HR with anti-IgE showed great inter-individual variation (median: 20.5; range: 1-104 ng/ml blood), but was not significantly different from the results obtained in identically treated blood samples from 50 adults (median: 23; range: 1-93 ng/ml blood). Both the maximum HR and the sensitivity to anti-IgE were dependent on total plasma IgE content. Blood samples with plasma IgE greater than or equal to 0.5 IU/ml (n = 15) had significantly higher maximum HR than those with plasma IgE less than 0.5 IU/ml (n = 82; median: 32 vs. 18 ng/ml blood; p less than 0.01). Passive sensitization with IgE-rich atopic plasma increased the maximum HR with anti-IgE only in samples with a plasma IgE content of less than 0.5 IU/ml, although sensitivity to anti-IgE was universally increased. Preincubation with pharmacologic agents modulating the IgE-mediated HR produced effects generally similar to previous findings in adult blood. However, the effects of inhibiting the cyclooxygenase pathway in cord blood differed from our observations in adult blood, and may represent a maturational phenomenon. The family history of allergy was obtained by a questionnaire, and clinical observations were gathered from patient records. None of these parameters were found to influence HR with any secretagogue. However, HR stimulated by the calcium ionophore A 23187 was found to be highly dependent on the storage time of the EDTA-anticoagulated blood samples, which should be carefully controlled.

Basophils↗
PubMed1990

Hepatosplenic candidiasis in children with cancer. Three cases in leukemic children and a literature review.

Three children with acute leukemia presented with prolonged fever and neutropenia after cytostatic therapy, which was followed by abdominal pain, hepatomegaly, and hepatic dysfunction with raised serum alkaline phosphatase. Abdominal CT scan and ultrasound demonstrated multiple small lesions compatible with the hepatosplenic candidiasis syndrome. Liver biopsies showed microabscesses with a granulomatous appearance, but evidence of yeasts and pseudohyphae was present in 1 case only. Cultures were negative. Treatment with amphotericin B and 5-fluorocytosine was successful in two children. At autopsy, one child had signs of active infection. We reviewed the literature on 27 children with hepatosplenic candidiasis. Abdominal symptomatology and prolonged fever, despite antibiotic therapy, in a patient with previous or present neutropenia after cytotoxic exposure, should lead to a careful evaluation, including noninvasive imaging studies, open liver biopsy, and prompt aggressive antifungal treatment, the response to which requires close follow-up.

Adolescent↗
PubMed1990

Synovitis reduced by inhibition of leukotriene B4. Carrageenan-induced gonarthritis studied in dogs.

The pathophysiologic significance of leukotriene B4 (LTB4) in arthritis was studied in dogs by unilateral intraarticular deposition of 15-hydroxy-eicosatetraenoic acid (15-HETE), an endogenous inhibitor of the formation and the effects of LTB4, in bilateral carrageenan-induced gonarthritis. LTB4 in synovial fluid was selectively inhibited in 15-HETE treated joints, the formation of prostaglandin E2 (PGE2) being largely unaffected. The clinical symptoms, intraarticular pressure, and extractable synovial fluid volume were reduced in treated joints. No effect could be discerned regarding blood flow in the synovial membrane, capsule, or juxta-articular bone as measured by tracer microspheres; and no effect on bone metabolism was found as judged by 99mTc-diphosphonate uptake. Thus, inhibition of LTB4 reduces joint exudation, but does not seem to interfere with changes in juxta-articular hemodynamics or bone metabolism following synovial inflammation.

Animals↗
PubMed1989

[Histiocytosis syndrome in children].

The recommended classification of the histiocytosis syndromes in children is as follows: 1. Langerhans' cell histiocytoses. 2. histiocytoses of mononuclear phagocytes. 3. neoplastic histiocytoses. The previous term, histiocytosis X, including eosinophilic granuloma of bone, the Hand-Schüller-Christian syndrome and Letterer-Siwe's disease, is now more correctly called Langerhans' cell histiocytosis (LCH) since the infiltrating cell in histiocytosis X both histologically and immunophenotypically is identified as the Langerhans' cell. Local and generalized LCH differmarkedly with respect to treatment and outcome. It is therefore necessary to perform an extensive investigation at the time of the initial evaluation of the patient. The most common mononuclear phagocytic syndromes are the familial erythrophagocytic lymphohistiocytosis and infection-associated or reactive hemophagocytic syndromes. The pathognomonic cell in familial erythrophagocytic lymphohistiocytosis is possibly a hybrid phenotype sharing characteristics of the two main types the mononuclear phagocyte system - i.e. the Langerhans' cells and phagocytic macrophages. Malignant histiocytosis is rarely seen in children and is a form of the Ki-1 positive anaplastic cell lymphoma.

Child↗
PubMed1989

Effect of auranofin on eicosanoids and protein kinase C in human neutrophils.

Auranofin (AF), a lipophilic chrysotherapeutic agent, was investigated for its effect on the formation of lipoxygenase products and the activity of protein kinase C in human neutrophils. We have previously shown that inhibition of LTB4 formation by 5-lipoxygenase (5-LO) inhibitors is intimately associated with a marked increased in 15-HETE in excess of arachidonic acid. The calcium- and phospholipid-dependent protein kinase, protein kinase C, is activated in FMLP- and A23187-stimulated neutrophils, is hypothesized to stimulate superoxide generation, and plays an essential role in eicosanoid production. AF dose-dependently inhibited the generation of leukotriene B4(LTB4) in FMLP-stimulated neutrophils, the ID50 was approximately 4.5 micrograms/ml. Unlike known 5-LO inhibitors, AF did not enhance the production of 15-HETE. In neutrophils stimulated with the calcium ionophore, A23187, AF did not inhibit the generation of LTB4 nor did AF change the 15-HETE levels. AF inhibited superoxide generation in FMLP-stimulated neutrophils dose-dependently, but did not change the activation of protein kinase C in the cells. We therefore conclude, that AF inhibition of LTB4 production in neutrophils is different from 5-lipoxygenase inhibitors and is elicited at a step distal to protein kinase C activation.

Auranofin↗
PubMed1989

15-Hydroxy-eicosatetraenoic acid (15-HETE) inhibits carrageenan-induced experimental arthritis and reduces synovial fluid leukotriene B4 (LTB4).

15-Hydroxy-eicosatetraenoic acid (15-HETE), a product of arachidonic acid, has no proinflammatory capacity, but can inhibit the formation and the chemotactic response of neutrophils to leukotriene B4 (LTB4), a potent mediator of inflammation. The purpose of the present study was to determine whether intraarticular administration of 15-HETE in carrageenan-induced acute arthritis might decrease the levels of LTB4 in synovial fluid and modify the arthritis. A bilateral acute knee joint arthritis was established in 7 dogs by intraarticular injections of carrageenan every third day. To the right joints, 15-HETE was administered both concomitantly with the carrageenan injections and continuously via an osmotic pump. In samples of synovial fluid obtained on day 0, 3 and 10 PGE2 and LTB4 were determined using reversed phase high performance liquid chromatography combined with radioimmunoassays and neutrophil chemokinesis. In the presence of 15-HETE the clinical severity of arthritis was significantly reduced and the volume of synovial effusate was decreased on an average by 42%. Furthermore, the relative number of neutrophils in histological sections of synovial tissue was decreased by 58%. Intraarticular caragheenan injections induced LTB4 formation, and maximum levels were obtained on day 3 (279.2 +/- 148.2 pg/joint). PGE2 was also present on day 3, but maximum levels were detected on day 10 (9.5 +/- 4.8 ng/joint). In joints injected with both carragheenan and 15-HETE the levels of LTB4 on days 3 and 10 were inhibited by 90% and 83%, respectively. For PGE2 a small but insignificant decrease was found on both day 3 and on day 10. These results show that LTB4 may be an important mediator of acute arthritis induced by carragheenan in dogs, and that intraarticular administration of 15-HETE can modify this arthritis by inhibiting LTB4 formation.

Animals↗
PubMed1989

Eicosanoids in skin of patients with atopic dermatitis: prostaglandin E2 and leukotriene B4 are present in biologically active concentrations.

The biochemical events leading to atopic dermatitis (AD) are unknown. Certain eicosanoids derived from arachidonic acid are potent mediators of skin inflammation and modulators of certain T-lymphocyte activities. The purpose of the present study was to determine whether eicosanoids are present in biologically active concentrations in the skin of adult patients with AD. The levels of the cyclooxygenase product, prostaglandin E2 (PGE2) and the lipoxygenase products, leukotriene B4 (LTB4), 12- and 15-hydroxyeicosatetraenoic acid were determined in biopsy specimens obtained by keratome from lesional, perilesional, and clinically unaffected skin of patients with AD. Methods for identification of eicosanoids included reversed-phase high-performance liquid chromatography combined with radioimmunoassays. Eicosanoid levels were at the same level in normal skin and in uninvolved skin of AD. Compared with uninvolved skin, both lesional and perilesional skin contained markedly elevated concentrations of PGE2 and LTB4: PGE2, 97.2 +/- 15.6 ng/gm of lesional skin and 128.3 +/- 27.2 ng/gm of perilesional skin; LTB4, 5.2 +/- 1.6 ng/gm of lesional skin and 3.2 +/- 0.6 ng/gm of perilesional skin. Compared with uninvolved skin, the levels of 12- and 15-hydroxyeicosatetraenoic acid were elevated sevenfold and elevenfold, respectively, in lesional skin, but did not reach biologically active concentrations. The results demonstrate that the inflammatory mediators PGE2 and LTB4 are present in lesional skin of atopic subjects in biologically active concentrations. Because these mediators are able to induce cutaneous inflammation and to modulate cellular immunity, they may be involved in the biochemical processes leading to AD.

Adolescent↗
PubMed1989

Eicosanoids in acute and chronic psoriatic lesions: leukotriene B4, but not 12-hydroxy-eicosatetraenoic acid, is present in biologically active amounts in acute guttate lesions.

The biochemical changes underlying the clinical manifestations of psoriasis are unknown. Certain chemotactic eicosanoids derived from arachidonic acid metabolism have been suggested to play important roles in psoriasis, because of their presence in lesional psoriatic skin and their ability to elicit skin inflammation and to stimulate epidermal proliferation. The purpose of the present study was to elucidate which eicosanoids might be involved in the early phases of the inflammatory processes of psoriasis. Eicosanoids were analyzed in scale and in lesional skin without scale both in acute guttate and chronic plaque psoriatic lesions. Methods for identification of eicosanoids included reversed-phase high-performance liquid chromatography combined with radioimmunoassay. Leukotriene B4 was present in both acute guttate and chronic plaque skin lesions in biologically active amounts (acute guttate lesions: 18.7 +/- 7.1 ng/g wet tissue in scale and 3.2 +/- 1.5 ng/g wet tissue in lesional skin without scale; chronic plaque lesions: 33.1 +/- 9.7 ng/g wet tissue in scale and 5.3 +/- 2.0 ng/g wet tissue in lesional skin without scale). 12- and 15-hydroxy-eicosatetraenoic acid (HETE) reached biologically active concentrations only in scale of chronic plaque lesions (1,512 +/- 282 and 1,441 +/- 411 ng/g wet tissue, respectively). The level of prostaglandin E2 in chronic plaque lesions was similar to the level in normal skin, while the level in acute guttate lesions was increased twofold (71.0 +/- 14.8 ng/g wet tissue). These results demonstrate that leukotriene B4, but not 12-HETE, is present in acute guttate psoriatic skin lesions in concentrations able to exert biologic effects. Leukotriene B4 may therefore participate in inflammatory changes of acute psoriasis.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1988

In vivo decline of methotrexate and methotrexate polyglutamates in age-fractionated erythrocytes.

Methotrexate (MTX) accumulates in erythrocytes (ery) during weekly MTX administration, and the ery-MTX concentration reaches a steady state after 4-6 weeks. In order to study MTX accumulation and metabolism to polyglutamate derivatives in different age populations of red blood cells, we took erythrocytes from 12 children with ALL who were receiving maintenance treatment with MTX and 6-MP and separated them according to age on a discontinuous Percoll gradient. When the erythrocytes of these children were separated according to specific gravity a normal distribution was obtained. Age fractionation was confirmed by the exponential decline of the erythrocyte aspartate aminotransferase (ery-ASAT) and by the reticulocyte counts. The ery-MTX declined with increasing red blood cell age in an exponential manner no different from the decline of the ery-ASAT. The youngest population of red blood cells contained 2.3-5.9 (mean 3.8) times more MTX than the oldest population. By linear regression analysis the t1/2 of the ery-MTX was 19-79 days (mean 37 days). The ery-MTX t1/2 seemed to be directly related to the amount of MTX which had been metabolized to MTX-glu3-5. The decline of the ery-MTX was predominantly due to selective disappearance of MTX-glu1+2, whereas MTX-glu3-5 changed to a much lesser extent with advancing red blood cell age. The present investigation showed that steady-state ery-MTX concentration was determined by (1) the amount of MTX added to the circulation by the reticulocytes, (2) the in vivo loss predominantly of MTX with low numbers of glutamyl derivatives from erythrocytes, and (3) the loss of MTX from destroyed red blood cells. The observed in vivo disappearance of MTX from erythrocytes offers a possible explanation of the observation that the ery-MTX steady state was reached after 4-6 weeks of unaltered weekly MTX treatment.

Antineoplastic Combined Chemotherapy Protocols↗