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Biomedical subjects

J Ring

Publications and source records attributed to J Ring.

At least 325 records · Page 18Linked to original sources

Cytokine-mediated effects of peripheral blood mononuclear cells from patients with atopic eczema on keratinocytes (HaCaT) in a new coculture system.

Interactions between keratinocytes and mononuclear cells via cytokines and adhesion molecules are thought to play a crucial part in inflammatory skin diseases. The cytokine-mediated effects of peripheral blood mononuclear cells (PBMC) from patients with atopic eczema (AE) and healthy individuals on keratinocytes (HaCaT) were investigated in vitro. A new coculture model (Transwell system) which consists of a lower and an upper compartment, which are separated by a polycarbonate-treated membrane, was established. 3[H]thymidine incorporation of keratinocytes and lymphocytes, as well as IL-6, IL-8 and IFN-gamma synthesis, were measured. Keratinocyte proliferation was significantly enhanced in the presence of PBMC from patients with AE. In contrast, PBMC from normal donors did not enhance HaCaT cell proliferation when they were cocultured. Lymphocytes from patients with AE showed a significantly enhanced proliferation after coculture with keratinocytes. However, PBMC from normal donors did not proliferate in the presence of HaCaT cells. Keratinocyte supernatants incubated with PBMC from either atopic or normal volunteers induced a suppression of lymphocyte 3[H]thymidine incorporation. In supernatants from cocultures of PBMC from patients with AE and keratinocytes, significantly enhanced amounts of IL-6 and IL-8, compared with normal donor's lymphocytes and HaCaT cells, were measured. No differences in IFN gamma production were observed. When PBMC were cultured without HaCaT cells, supernatants contained equal levels of IL-6, IL-8 and IFN-gamma in normal donors and in patients with AE. Interestingly, HaCaT cells spontaneously secrete measurable amounts of IL-6, IL-8 and IFN-gamma. Blocking experiments with neutralizing antibodies against these interleukins showed a complete inhibition of keratinocyte proliferation when PBMC from normal donors were used whereas the proliferative potency of PBMC supernatants from patients with AE on keratinocytes remained. Our data indicate that (i) PBMC from patients with AE stimulate keratinocyte proliferation via soluble factor(s) that are different from IL-6, IL-8 and IFN-gamma; (ii) probably, HaCaT cells spontaneously produce lymphocyte/monocyte inhibitory soluble factors and IL-6, IL-8 as well as IFN-gamma; and (iii) secretion and/or activity of keratinocyte-derived inhibitory mediators is regulated via cytokines of PBMC infiltrating inflammatory skin.

Antibodies, Monoclonal↗

Decreased monocyte interleukin-1 beta production in atopic eczema.

It has been suggested that in atopic eczema (AE) a reduced lymphocyte response to T-cell mitogens in vitro is secondary to altered production of cytokines or inflammatory mediators. We investigated, in parallel, the mitogen-induced T-cell proliferation, monocyte interleukin-1 beta (IL-1 beta) production, and prostaglandin E2 (PGE2) production of monocytes and of peripheral blood mononuclear cells (PBMC) in AE patients and non-atopic controls. After stimulation with concanavalin A (Con A) PBMC of AE patients showed a significantly reduced proliferative response compared with the controls. The monocyte production of IL-1 beta after stimulation with lipopolysaccharide (LPS) was significantly decreased in AE. No differences between AE patients and controls were observed with regard to the PGE2 production of PBMC after stimulation with Con A or the monocyte release of PGE2 after LPS stimulation. Because IL-1 plays a central role in the activation of T-cell proliferation, the decreased monocyte IL-1 beta production may provide a plausible explanation for the reduced mitogen response of T cells in AE.

Adolescent↗

Acanthosis nigricans: a marker for hyperinsulinemia.

A 12-year-old girl developed acanthosis nigricans due to increased levels of serum insulin. Hyperinsulinemia has been recognized as the underlying cause in most cases of acanthosis nigricans. In this paper we outline a typical clinical case with special regard to the proposed pathogenesis.

Acanthosis Nigricans↗

Origin of angiotensin in human leukocytes.

The capability of human leukocytes to synthesize angiotensin peptides was studied. Leukocytes which were prepared from heparinized blood by sedimentation in dextran were incubated for 0, 1, 2, 4, 6, 8, and 24 h at 37 degrees C with the 3H-labeled amino acid isoleucine. At the various time points the washed cells were extracted with 0.1 M acetic acid. The extracts contained radioactive material which eluted from a Bio Sil TSK 125 gel filtration column in the low-molecular-weight range with the same retention time as synthetic angiotensin I (ANG I) or angiotensin II (ANG II). The extracted radioactive material also bound to anti-ANG I and anti-ANG II antibodies. However, excess of unlabeled synthetic ANG I or ANG II failed to displace the bound radioactivity. Rechromatography of the radioactive material which eluted in the low molecular weight fractions of the gel filtration column could be characterized as non-incorporated 3H-isoleucine on a reversed phase C18 column with an acetonitrile gradient. These findings demonstrate the lack of an angiotensin-generating pathway in human leukocytes. Further studies are necessary to determine the origin of angiotensin peptides in human leukocytes.

Adult↗

Elevated serum levels of soluble adhesion molecules ICAM-1 and ELAM-1 in patients with severe atopic eczema and influence of UVA1 treatment.

BACKGROUND: ICAM-1 is known to be strongly expressed on keratinocytes in lesional atopic eczema correlating with the degree of inflammation. ELAM-1 was found to be expressed on dermal vascular endothelium in lesional atopic eczematous skin. OBJECTIVE: The present study was performed to investigate whether elevated serum levels of soluble forms of these molecules are detectable in patients with severe atopic eczema and whether these parameters could be useful markers for disease activity. METHODS: Serum levels of soluble ICAM-1 (sICAM-1) and ELAM-1 (sELAM-1) were measured by ELISA in 18 patients with severe atopic eczema before and after UVA1 therapy. RESULTS: Before onset of treatment, serum sICAM-1 (565 +/- 99 ng/ml) and sELAM-1 (89.7 +/- 29.9 ng/ml) levels were significantly (p < 0.001) elevated compared to 22 healthy control persons (296 +/- 46 and 48.8 +/- 22.7 ng/ml). After achievement of significant clinical improvement after 3 weeks of UVA1 therapy, there was neither a decrease in serum sICAM-1 nor in sELAM-1 levels. The posttherapeutic serum sICAM-1 and sELAM-1 values remained elevated (p < 0.001) above the normal range. CONCLUSION: Based on these data we suggest that (1) serum sICAM-1 and sELAM-1 are elevated in patients with severe atopic eczema, (2) sICAM-1 does not decrease together with reduction of ICAM-1-positive keratinocytes in atopic eczema following clinical improvement and might therefore be mainly of a different origin, i.e. leukocytes/endothelial cells, and that (3) sICAM-1 and sELAM-1 seem not to be suitable markers of actual disease activity in severe atopic eczema.

Adult↗

Pityrosporum ovale extracts increase interleukin-4, interleukin-10 and IgE synthesis in patients with atopic eczema.

Evidence for a possible role of the lipophilic yeast Pityrosporum ovale in the pathophysiology of atopic eczema has been found both in laboratory and therapeutical studies. Positive type I prick test reactions to P. ovale correlate with the intensity of eczematous skin lesions in the head and neck regions of patients with atopic eczema. Furthermore, antifungal treatment has been shown to be helpful in atopic eczema. In the present study the effect of P. ovale on IgE synthesis and cytokine production (IL-2, IFN gamma, IL-4, IL-10) was investigated in patients with atopic eczema, in vitro. Eight patients with atopic eczema were studied; of these, 5 patients had specific IgE antibodies against P. ovale, as determined by fluoroimmunoassay (RAST). The control group consisted of 5 healthy non-atopic, P. ovale IgE-antibody-negative volunteers. Freshly isolated peripheral blood mononuclear cells (PBMC) were incubated in the presence of different antigen concentrations (0.01, 0.1, 1.0, 10 micrograms/l x 10(6) cells) of P. ovale. IgE contents in the cell culture supematants were significantly elevated in RAST(+) patients with atopic eczema (p < 0.05), compared with RAST(-) atopic eczema patients and healthy volunteers. Coincubation of P. ovale-stimulated PBMC with IL-4 (50 U/l/ 1 x 10(6) cells) resulted in a significantly higher IgE synthesis only in the RAST(+) atopic eczema patients. Additionally, incubation of PBMC from RAST(+) patients with atopic eczema led to an elevated synthesis of the TH2 related cytokines IL-4 and IL-10. Within the atopic eczema group, two subgroups differed markedly in their response to P. ovale antigen stimulation with a good correlation to the presence of specific IgE in serum and in vitro IL-4 and IL-10 production. The data support the assumption that P. ovale antigens might play a role in skin inflammation in at least a subgroup of patients with atopic eczema characterized by the presence of specific IgE antibodies to P. ovale.

Adult↗

Low dose versus medium dose UV-A1 treatment in severe atopic eczema.

Twenty-two patients with severe atopic eczema were included in a therapy study with UV-A1 (wavelengths > 340 nm) treatment. The patients were divided into two dose groups, each consisting of 11 patients. One group received 10 J/cm2 and the other 50 J/cm2 five times a week for 3 consecutive weeks. No topical or systemical steroids or antihistamines were allowed. Using the SCORAD index as a measure of disease activity before onset of therapy and after 10 and 15 treatments, we observed a significant improvement in both dose groups after 15 treatments (10 J/cm2: p < 0.05, 50 J/cm2: p < 0.005). After 10 treatments only the improvement in the 50 J/cm2 group was significant (p < 0.005); the difference between the two dose groups was significant (p < 0.05). The clinical efficacy of treatment was reflected neither by a decrease of serum IgE nor by a decrease of elevated serum levels of soluble adhesion molecules sICAM-1 and sELAM-1 in the two dose groups. In contrast, a marked but not significant decrease of serum ECP could be observed in the 50 J/cm2 group only. We conclude from these and other published data that although 10 J/cm2 UV-A1 has a limited effect on patients with severe atopic eczema, higher doses are of higher efficiency in the treatment of this condition.

Adult↗

[Food-induced anaphylaxis in latex allergy].

Contact uticaria and anaphylactic reactions to latex-containing rubber products are being recognized with increasing frequency in all kinds of medical disciplines. Recently a number of reports have been published describing anaphylactic reactions to food items in patients with latex allergy. The cases of three patients who developed anaphylactic reactions to both latex and food items are presented, and the importance of the association of latex and cross-reactivity with food items is stressed. The food items that led to anaphylactic reactions were banana and avocado; banana, avocado and buckwheat; and banana, avocado and tomato. The cross-reactivity of latex to buckwheat and tomato has not been reported before.

Adult↗

Contamination of heparin by histamine: measurement and characterization by high-performance liquid chromatography and radioimmunoassay.

Plasma samples which were collected in the presence of heparin contained 12.83 +/- 0.34 ng/ml histamine-immunoreactive material (n = 10). In contrast, histamine-immunoreactive material in plasma samples which were collected in the presence of EDTA/phenanthroline contained 0.32 +/- 0.01 ng/ml (n = 10). Histamine-immunoreactive material was found as a contaminant in three different heparin formulations with unrelated batch numbers. The concentrations of the histamine-like material were 32.82, 81.93, and 280.23 ng/ml, respectively. Octadecasilyl-silica (ODS) cartridges were used to purify histamine from other constituents in the heparin preparations. The histamine-immunoreactive material in the three preparations could be characterized as histamine with cation-exchange high-performance liquid chromatography (HPLC) on a TSK SP-5 PW column with NaH2PO4, pH5.0, as a mobile phase and gradient elution. For the accurate measurement of histamine in plasma samples with heparin as an anticoagulant, one should be aware of a possible contamination of heparin formulations by histamine.

Chromatography, High Pressure Liquid↗

Human leukocytes contain angiotensin I, angiotensin II and angiotensin metabolites.

Angiotensin I (ANG I) and angiotensin II (ANG II) were measured radioimmunologically in human leukocytes extracted with a mixture of acetone, 1N HCl and water (40:1:10 vol). The analytical recoveries of 125I-ANG I and 125I-ANG II, which were added prior to extraction, were 92.00 +/- 3.10 and 99.19 +/- 0.91% (mean +/- SEM; n = 12). The concentration of ANG I- and ANG II-like material in leukocytes from healthy volunteers was 32.04 +/- 3.64 and 13.05 +/- 1.26 fmol/mg protein (n = 24). The immunoreactive material could be characterized on HPLC as Ile5-ANG I, Ile5-ANG II and angiotensin metabolites such as Ile4-ANG III, Ile3-ANG II hexapeptide, Ile2-ANG II pentapeptide and Ile1-ANG II tetrapeptide. From the ANG I-immunoreactive material determined in the extracts, 26% could be characterized on HPLC as Ile5-ANG I. The ANG II-immunoreactive material present in the extracts could be separated on HPLC into 44% Ile5-ANG II, 14% Ile4-ANG III, 7% Ile3-ANG II hexapeptide, 4% Ile2-ANG II pentapeptide and 8% Ile1-ANG II tetrapeptide. Patients with a history of anaphylactic reactions to bee or wasp venom showed significantly reduced ANG II concentrations in their leukocytes as compared to controls (6.76 +/- 0.76 fmol ANG II/mg protein, n = 22, vs. 13.05 +/- 1.26 fmol ANG II/mg protein, n = 24; p < 0.05). A significant correlation between the severity of clinical symptoms and the ANG II levels was found for grade I and II reactions (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Increased urinary excretion of angiotensin during anaphylactoid reactions.

Immunoreactive angiotensin I (ANG I) and angiotensin II (ANG II) were measured in human urine, after purification on octadecasilyl-silica cartridges. The total daily excretion of ANG I and II in healthy volunteers was 292.2 +/- 62.5 and 12.2 +/- 2.5 pmol/24 h (mean +/- SEM; n = 14). No differences in the concentrations of ANG I or II were detected between females and males. Although lower levels of ANG I and II were found during the nighttime, no clear-cut circadian rhythm in the excretion of the peptides was found. ANG II was not degraded in acidified urine which shows the effective inhibition of ANG-II-degrading enzymes. Oral provocation tests (OPT) in patients with a history of anaphylactoid reactions (AR) to drugs, foods and food additives were associated with elevated ANG I and II concentrations when symptoms of anaphylaxis occurred. The excretion of ANG I increased by a factor of 7.8 +/- 2.4 and the excretion of ANG II by a factor of 6.1 +/- 1.6 (mean +/- SEM; n = 15). In patients with negative OPT and no clinical symptoms of anaphylaxis, the levels of ANG I and II remained unchanged (n = 26). It is concluded that angiotensin peptides play a role during the events of AR. The peptides may be considered as counteracting factors which stabilize cardiovascular functions.

Adolescent↗

Histamine, tryptase, norepinephrine, angiotensinogen, angiotensin-converting enzyme, angiotensin I and II in plasma of patients with hymenoptera venom anaphylaxis.

Markers of immediate-type hypersensitivity such as histamine and tryptase were measured in the plasma of nonallergic volunteers and patients with a history of hymenoptera venom anaphylaxis. No significant differences in histamine or tryptase were found between patients and controls. Norepinephrine, an important compound involved in the control of cardiovascular functions and blood pressure, was the same in patients and nonallergic volunteers. In addition, components of the renin-angiotensin system were determined. Patients with hymenoptera venom anaphylaxis showed significantly lower plasma angiotensinogen concentrations as compared to healthy nonallergic controls (p < 0.007), whereas plasma ACE activity was the same. Likewise, the plasma levels of angiotensin I and angiotensin II were significantly reduced in patients as compared to controls (p < 0.04 and p < 0.003, respectively). These findings suggest that the renin-angiotensin system may play an important role as a counteracting factor in hymenoptera venom anaphylaxis.

Adult↗