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Biomedical subjects

E Christophers

Publications and source records attributed to E Christophers.

At least 217 records · Page 12Linked to original sources
PubMed1989

Patient subgroups and the inflammatory pattern in psoriasis.

Despite great numbers of recent studies on immunological parameters in psoriasis, the question whether psoriasis is an immunological disease is still open. Also, it is not clear how the three main abnormalities of this disease, i.e. the association with the human leukocyte antigen system, excessive epidermal new cell production and a unique neutrophilic infiltrate within the diseased epidermis, are linked together. Analysis of large patient cohorts has now shown that two types of non-pustular psoriasis exist: one showing early onset and linkage disequilibrium for human leukocyte antigen Cw6, B13, Bw57, the other type showing late onset associated with Cw2 and B27. The pathological features of increased cell proliferation and neutrophilic inflammation are likely to be regulated by potent peptide mediators some of which are mitogenic and/or proinflammatory. There are two powerful regulatory peptides (C5ades arg and neutrophil activating peptide-1), large amounts of which have now been isolated from psoriatic scale material. Both are able to stimulate other cells to migrate and to produce further signals. The initiating agent still remains an enigma.

Adolescent↗
PubMed1989

[Liberation of human leukocyte elastase by hypertonic saline baths in psoriasis].

Human leukocyte elastase, a proteolytic enzyme of neutrophils, can be determined by a highly sensitive enzymatic assay. Bathing in hypertonic salt solutions allowed considerable amounts of human leukocyte elastase to be eluted from psoriatic lesions. Optimal elution was achieved with sodium chloride concentrations of 1 M and higher. Thirty patients with psoriasis of varying degrees of severity released significantly increased amounts of human leukocyte elastase following a 10-min bath in salt water. During daily treatment with salt water baths and UV-B radiation the elutable amounts of elastase decreased dramatically within a few days, reaching normal levels when the skin had cleared. Determination of human leukocyte elastase in salt water eluates of psoriatic skin seems to be useful for quantification of therapeutic effects. It appears conceivable that human leukocyte elastase plays a role in the psoriatic tissue reaction.

Adult↗
PubMed1988

Recombinant human tumor necrosis factor alpha lacks chemotactic activity for human peripheral blood neutrophils and monocytes.

Preparations of recombinant human tumor necrosis factor alpha (rhuTNF alpha) free of aminoterminal methionine were tested for human neutrophil granulocyte (PMN) and monocyte (MO) chemotactic activity using the Boyden chamber system. Over a wide range of concentrations (10(-7)-10(-15) M) rhuTNF alpha of two different sources failed to elicit chemotactic responses in PMN or MO, whereas strong PMN and MO chemotactic activity could be detected using the tripeptide N-formyl-methionyl-leucyl-phenylalanine (FMLP). In addition, rhuTNF alpha containing 62% aminoterminal methionine failed to induce PMN and MO chemotaxis. It is concluded that rhuTNF alpha may not be a chemotaxin for human PMN and MO in vitro.

Chemotaxis, Leukocyte↗
PubMed1988

Purification and partial biologic characterization of a human lymphocyte-derived peptide with potent neutrophil-stimulating activity.

A novel neutrophil-activating peptide is detected in supernatants from mitogen-stimulated human T lymphocyte preparations. This chemotaxin was purified to apparent homogeneity by sequential Gel G-75 permeation chromatography, wide pore reversed phase (RP-8) HPLC, size exclusion HPLC, and reversed phase (RP-18) HPLC. Additional characterization of this lymphocyte-derived neutrophil-activating peptide (LYNAP) resulted in a single peak upon reversed phase HPLC and size exclusion HPLC. SDS-PAGE under nonreducing conditions revealed a single line at 10 kDa. LYNAP stimulated neutrophil chemotaxis (ED50 of 3 +/- 3 ng/ml), chemokinesis (ED50 of 2 +/- 2 ng/ml), and caused degranulation of cytochalasin B pretreated human neutrophils (ED50 of 20 ng/ml). In purified human monocytes, chemotactic responses to LYNAP at doses up to 100 ng/ml were absent, indicating nonidentity with a lymphocyte-derived monocyte chemotactic factor previously described by other workers. LYNAP shows biochemical and biologic similarities to a recently detected monocyte-derived neutrophil-activating peptide (MONAP). Moreover, desensitization experiments revealed cross-deactivation between LYNAP and MONAP, not, however, between these two chemotactic peptides and other well characterized polymorphonuclear leukocyte chemotaxins, e.g., C5a, FMLP, leukotriene B4, or platelet-activating factor. This finding points toward structure identity or homology of both chemotaxins, MONAP and LYNAP.

Chemical Phenomena↗
PubMed1988

Identification of different charged species of a human monocyte derived neutrophil activating peptide (MONAP).

Lipopolysaccharide-stimulated human monocytes secrete a 10 kD peptide (MONAP) of high neutrophil, not however monocyte or eosinophil stimulating activity. By reversed phase HPLC MONAP could be distinguished from Interleukin 1. Analytic isoelecto-focusing of pure MONAP (single line upon sodiumdodecylsulfate polyacrylamide gel electrophoresis, single peak after RP-18-HPLC), obtained by size exclusion HPLC followed by two different reversed phase HPLC steps revealed charge heterogeneity giving major components with isoelectric points at 4.7, 4.9, 6.4 and 6.9, all of which exhibited chemotactic activity.

Chromatography, High Pressure Liquid↗
PubMed1988

Structure determination of a human lymphocyte derived neutrophil activating peptide (LYNAP).

Phytohemagglutinin or Concanavalin A-stimulated human T-lymphocytes produce a factor (LYNAP) with potent chemotactic and enzyme degranulating activity in peripheral human neutrophils. Sequence analysis of LYNAP established an apparently novel 72 residue polypeptide structure. Examination of protein data bases showed that LYNAP had about 30% sequence homology with recently characterised connective tissue activating proteins produced by platelets. Furthermore, it was subsequently found that the amino acid sequence is largely the same as that predicted from a cDNA clone derived from mRNA elevated in peripheral human leukocytes stimulated by mitogens.

Amino Acid Sequence↗
PubMed1988

Atopic dermatitis: influence of bacterial infections on human monocyte and neutrophil granulocyte functional activities.

In 15 patients with atopic dermatitis (AD) and without concomitant viral or bacterial infections, chemotaxis, superoxide-anion (O2-) generation, and beta-glucuronidase release of purified monocytes (MO) and neutrophils (PMN) were determined. Defined receptor-dependent stimulators (i.e., N-formyl-methionyl-leucyl-phenylalanine, C5a, and leukotriene B4, as well as native and opsonized zymosan particles) were used for phagocyte stimulation. PMN functional activities in response to the stimuli tested were found to be normal in patients with AD and without infections. MO from these patients revealed a slight enhancement of O2- production after stimulation with opsonized zymosan and a small increase of N-formyl-methionyl-leucyl-phenylalanine-induced chemotaxis. Other MO functions tested were within the normal range. However, investigations of MO and PMN functions during the course of concomitant bacterial infections of three patients with AD demonstrated striking alterations of cellular responsiveness. These changes ranged from enhanced to decreased phagocyte functions, depending on the activity of the infectious disorder. Chemotaxis of PMN and MO was depressed around the third day after onset of the infectious disease. In the beginning of infection, there was a decreased O2- generation and beta-glucuronidase release in PMNs. In MOs, both parameters were enhanced. The results of these investigations provide evidence that functional abnormalities of phagocytes observed in patients with AD are sequelae of concomitant skin infections and not signs of an intrinsic defect present in MOs and PMNs.

Adolescent↗
PubMed1988

Plasma lactoferrin reflects neutrophil activation in psoriasis.

We used a biotinylated antibody ELISA technique to measure plasma levels of lactoferrin (LF) and the LF content of peripheral blood PMN in 20 patients with psoriasis, 21 with eczema or other inflammatory skin conditions, 19 patients with malignant skin tumours and 20 healthy control individuals. In psoriasis, plasma LF levels were significantly increased compared with levels in the other skin conditions and in the healthy controls (P less than 0.01). Furthermore, in psoriasis the LF content of circulating PMN was decreased. These findings provide further evidence that in psoriasis systemic activation ('priming') of circulating PMN may take place.

Adult↗
PubMed1988

Modulation of human monocyte functions during acute bacterial infection.

The in vitro functions of highly purified blood monocytes were studied in 11 patients suffering from acute bacterial infections (e.g. erysipelas, appendicitis, abscesses). Chemotaxis, superoxide-anion generation, and beta-glucuronidase release of the patients' monocytes in response to the receptor-dependent stimuli formyl-methionyl-leucyl-phenylalanine (FMLP), complement split product C5a, leukotriene B4 (LTB4), and opsonized zymosan particles were measured. All the patients were examined in a follow-up study during the course of illness. A group of 33 healthy volunteers served as control. The patients revealed a transient decrease in monocyte chemotactic migration in response to all stimuli between days 3 and 5 after onset of clinical symptoms. Superoxide-anion generation from patients' monocytes was found to be enhanced 3 days after impaired chemotaxis. Stimulated release of lysosomal beta-glucuronidase showed a decrease in the first days of the disease. However, spontaneous beta-glucuronidase release was enhanced between days 3 and 7 in the patients' monocytes. Serial measurements of monocyte responsiveness. These results indicate a distinct modulation of monocyte functions during the course of an acute bacterial infection. Changes in monocyte maturity and/or activation under inflammatory conditions may be responsible for these alterations in monocyte function.

Acute Disease↗
PubMed1988

A multicentric study of loratadine, terfenadine and placebo in patients with seasonal allergic rhinitis.

This multicentric study compared 14-day treatment with loratadine (Clarityne) 10 mg once daily, terfenadine 60 mg twice daily and placebo in outpatients with seasonal allergic rhinitis. Of 275 patients enrolled, 256 (87 in the loratadine group, 89 in the terfenadine group and 80 in the placebo group) were evaluable for efficacy and 266 (90, 91 and 85 in respective groups) were evaluable for safety. Investigators graded the severity of 4 nasal and 4 nonnasal signs/symptoms and investigators and patients rated overall disease condition and therapeutic response on treatment days 3, 7 and 14; patients recorded when signs/symptoms of rhinitis were relieved, as well. Hematology and blood chemistry tests were conducted before and after therapy, and patients were questioned throughout the study about possible adverse experiences. At all visits, loratadine and terfenadine were significantly superior to placebo (p less than or equal to 0.004), and the two active medications were statistically comparable, based on mean totals of sign/symptom severity scores and ratings of overall disease condition and therapeutic response. By patients' last valid visit, mean totals of sign/symptoms severity scores improved by 56% and 53% for loratadine and terfenadine groups, respectively, but exacerbated by 5% for the placebo group. Moreover, an excellent or a good therapeutic response was observed in 58/87 (67%) loratadine-treated patients and 58/89 (65%) terfenadine-treated patients, as compared to 13/80 (16%) placebo-treated patients (p less than 0.01). A total of 61/76 (30%) patients in the loratadine group and 57/78 (73%) in the terfenadine group versus 22/71 (31%) in the placebo group experienced relief within the first 3 days of therapy (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Quadrant distribution of dysplastic nevus syndrome.

A 59-year-old man with numerous aggregated pigmented lesions confined to the left upper quadrant of his body is described. The lesions consist of lentigines, common acquired nevi, and dysplastic nevi. In addition, within this quadrant two malignant melanomas at different stages of progression developed from dysplastic nevi. This patient presents a hitherto undescribed quadrant type of dysplastic nevus syndrome. As quadrant syndromes are due to single mutations, our observation strongly supports the concept of an autosomal-dominant trait in dysplastic nevus syndrome.

Arm↗
PubMed1987

Purification and partial biochemical characterization of a human monocyte-derived, neutrophil-activating peptide that lacks interleukin 1 activity.

A novel monocyte-derived neutrophil-activating peptide (MONAP) produced by lipopolysaccharide- and phorbol myristate acetate-stimulated human peripheral blood monocytes was purified by sequential ion exchange-high performance liquid chromatography (HPLC), size exclusion HPLC, and reversed phase HPLC. Biologic activities of the purified cytokine were monitored by either an enzyme release assay or a chemotaxis assay, using peripheral human neutrophils. Purified MONAP was found to be homogeneous, giving a single peak on size-exclusion HPLC, reversed-phase HPLC, as well as a single 10-kDa band on silver-stained polyacrylamide gels. Purified MONAP stimulate human neutrophil chemotaxis at an estimated molarity of 5 x 10(-11) M. Half-maximal enzyme release of cytochalasin B pretreated neutrophils occurred at 2 to 3 x 10(-10) M, whereas superoxide anion production elicited by various concentrations of MONAP was found to be low. Isolated human peripheral monocytes, as well as human eosinophils, showed no chemotactic response to MONAP, indicating neutrophil specificity. MONAP activity was separated from thymocyte-stimulating activity by reversed-phase HPLC, indicating nonidentity with interleukin (IL)-1. This was further supported by heat resistance of MONAP, which is in contrast to the heat sensitivity of IL-1. In addition, IL-1 obtained as a by-product during isolation of MONAP did not stimulate human neutrophil chemotaxis.

Animals↗
PubMed1987

[Torre-Muir syndrome. Sebaceous gland tumors indicate colon carcinoma and other internal malignant tumors].

The Torre-Muir syndrome belongs to a group of hereditory cancers and expresses itself in the occurrence of cutaneous gland tumors and (often multiple) carcinoma of the colon. The syndrome is probably a phenotypical manifestation of the "cancer family" syndrome, in which familial carcinoma of the colon also occurs. A case of Torre-Muir syndrome in a 43-year-old man is described. Because of the dermatological features, the colon carcinoma was diagnosed in time. Family investigations revealed another case of complete Torre-Muir syndrome, as well as a remarkable frequency of colon carcinoma in one family branch. Inheritance is autosomal dominant. The characteristic morphological features of the sebaceous gland neoplasias makes an early, often life-saving, diagnosis possible.

Adult↗
PubMed1987

Contrasting disease patterns in psoriasis and atopic dermatitis.

In this report we investigate the simultaneous occurrence of psoriasis and atopic dermatitis (AD) as well as the association with infectious skin diseases. Among 29,159 patients hospitalized between 1953 and 1983, 8.5% (2,467 patients) were treated for psoriasis, while 1.6% (470 patients) were hospitalized for AD treatment. On the basis of incidence rates for both diseases, 36 patients (0.14%) with both psoriasis and AD were expected to be seen. However, the two conditions were simultaneously present in 2 patients only. Approximately 30% of the AD patients were suffering from either bacterial or viral infection, while this complication occurred in 6.7% of psoriatics. In addition, among 48 patients hospitalized for eczema herpeticatum 39 were atopics and none was psoriatic. The data demonstrate that the occurrence of psoriasis and AD in one and the same patient is quite rare and this may be related to conflicting immune defense patterns. Thus, increased sensitization against foreign protein together with high susceptibility to cutaneous infection present in AD is in contrast to high phagocyte responsiveness in psoriasis, where concurrent infections are rare.

Acute Disease↗
PubMed1987

C5a-specific modulation of phagocyte functions in patients with localized bacterial infections.

Chemotaxis, enzyme release and superoxide-anion (O2-) generation of purified peripheral blood neutrophils (PMN) and monocytes were studied in a total of 87 patients suffering from localized bacterial infections. Shortly after disease onset, single or several PMN functions became non-responsive to the complement split product C5a. Functional activities elicited by the synthetic peptide f-met-leu-phe or leukotriene B4 remained unaltered. C5a-specific impairment lasted one to several days and returned to normal with the subsidence of the disease. C5a elicited release of beta-glucuronidase as well as generation of superoxide-anions was seen more often to be impaired as compared to chemotactic migration. In contrast to PMN, monocytes from the same patients failed to show paralleling C5a-specific functional alterations. There was no correlation between impairment of PMN functions and plasma levels of the complement split-products C3a and C4a as determined by RIA. It is concluded that in acute infectious disease a graded C5a-specific modulation of PMN functions may be present. This phenomenon is transient and not paralleled by functional alterations of monocytes or changes in plasma complement levels.

Bacterial Infections↗
PubMed1987

Synchronization of plasmapheresis and pulse cyclophosphamide therapy in pemphigus vulgaris.

Long-lasting and complete remission was obtained in a 48-year-old patient with refractory pemphigus vulgaris by an experimental treatment protocol that tries to synchronize plasmapheresis with subsequent pulse cyclophosphamide therapy. The rationale of the approach tries to utilize the plasmapheresis-induced increased proliferation of pathogenic cell clones for partial deletion of these clones through application of maximum pulse immunosuppression treatment during the period of assumed maximum proliferation and, thus, maximum vulnerability of the antibody-producing cells. The treatment schedule consisted of initial withdrawal of immunosuppressive drug therapy, repeated large-volume plasmaphereses substituted with immunoglobulin-free albumin solutions, subsequent application of high-dose (36 mg/kg of body weight) cyclophosphamide therapy, and low-dose maintenance immunosuppression for several months. As a result, our patient remained disease free over a follow-up period of 40 months without any further immunosuppressive treatment. Stimulation of postexchange antibody production and subsequent application of high-dose cytotoxic drugs might be a valuable tool in the management of refractory pemphigus vulgaris and, possibly, in the management of other autoantibody-mediated diseases.

Administration, Oral↗