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T Luger

Publications and source records attributed to T Luger.

At least 19 recordsLinked to original sources
PubMed1996

Expression of a glycoprotein of the carcinoembryonic antigen family in normal and neoplastic sebaceous glands. Limited role of carcinoembryonic antigen as a sweat gland marker.

BACKGROUND: Carcinoembryonic antigen (CEA) is a well-known marker for sweat gland differentiation in adnexal neoplasms. OBJECTIVE: The aim of this study was to examine the expression of glycoproteins of the CEA family, that is, CEA-180, nonspecific cross-reacting antigens (NCAs), and biliary glycoprotein (BGP), in sebaceous glands and in neoplasms with sebaceous differentiation. METHODS: Normal adult and fetal skin, hyperplasias, hamartomas, and neoplasms with sebaceous or follicular differentiation were stained immunohistochemically with a panel of polyclonal and monoclonal antibodies highly specific for CEA-180, NCAs, and BGP. Double immunostaining was performed to correlate the CEA expression with that of epithelial membrane antigen (EMA), a glycoprotein consistently found in differentiating sebocytes. RESULTS: Whereas sweat glands coexpressed CEA, NCAs, BGP, and EMA, sebaceous glands were exclusively labeled with the antibodies recognizing BGP or EMA. Staining of the sebaceous glands was restricted to mature sebocytes, sparing immature cells. At the ultrastructural level immunoreactivity for BGP and EMA was demonstrable in the golgi area, in small vesicles, and along the cell membranes. During fetal development BGP was not found until the sebaceous glands matured. The expression of BGP and EMA was highly conserved in reactive, hamartomatous, and neoplastic proliferations of adnexal structures with sebaceous differentiation. CONCLUSION: The expression of BGP, a CEA glycoprotein, in differentiating sebocytes accounts for the reactivity of many anti-CEA antibodies with sebaceous glands and thus disqualifies the CEA family as a monospecific marker for sweat gland differentiation.

Adolescent↗
PubMed1995

Normolipemic papular xanthomatosis in erythrodermic atopic dermatitis.

We describe papular xanthomatosis that progressively developed in a patient with long-standing erythrodermic atopic dermatitis and normal lipid metabolism and without an associated systemic disease. Light microscopy showed a lobulated aggregate of sometimes foamy histiocytes. Ultrastructurally, these histiocytes contained lipid inclusions and lacked features of Langerhans or epithelioid cells. Other granulomatous skin diseases such as tuberculosis, sarcoidosis, or foreign body granuloma were excluded by histologic study, polarizing microscopic examination, electron microscopy, and microbiologic investigations. Nevertheless, these xanthomas showed an antigen expression pattern similar to that found in noninfectious granulomas (CD1a-, MS-1-, CD11c+, MRP-8/-14+, 25F9+, RM 3/1+/-, CD36(+), indicating that normolipemic papular xanthomatosis may be reactive process and should not be included among the true cutaneous non-Langerhans cell histiocytoses.

Adolescent↗
PubMed1995

Chronic urticaria, arthralgia, raised erythrocyte sedimentation rate and IgG paraproteinaemia: a variant of Schnitzler's syndrome?

Schnitzler's syndrome is a distinct disease entity characterized by the association of chronic urticaria, intermittent fever, arthralgia, elevated erythrocyte sedimentation rate and IgM macroglobulinaemia. We report a patient with the same symptoms, but a monoclonal IgG instead of IgM gammopathy. Histological examination of the urticarial lesions showed signs of mild leucocytoclastic vasculitis. Except for the different class of the monoclonal immunoglobulin, the clinical symptoms, laboratory findings and histology in this patient were identical with those in classical Schnitzler's syndrome. IgG and IgM paraproteins may be equivalent with regard to the putative pathophysiology of the disease process in Schnitzler's syndrome. We therefore suggest that the spectrum of Schnitzler's syndrome is expanded to include patients with chronic urticaria and monoclonal IgG gammopathy, as a closely related variant.

Arthralgia↗
PubMed1994

Neuropeptides are potent modulators of human in vitro immunoglobulin E synthesis.

We determined the effect of adrenocorticotropin hormone (ACTH) on the regulation of IgE synthesis. Depending on the concentration, ACTH enhanced or inhibited IgE synthesis in a culture system where IgE synthesis was induced with interleukin-4 (IL-4) and anti-CD40 monoclonal antibody in peripheral blood mononuclear cells. Similar effects on IgE synthesis were observed by adding ACTH-related peptides, e.g. corticotropin-releasing factor (CRF), the inducer of ACTH, or alpha-melanocyte stimulating hormone (alpha-MSH), a cleavage product of ACTH. However, ACTH had no effect on IgG or IgM synthesis in this culture system. ACTH did not act directly on either B or T cells as there was no influence on IgE synthesis in a system using purified B cells alone or co-cultured with T cells. The effect of ACTH on IgE synthesis was mediated by accessory cells. This was shown by priming purified CD14-positive monocytes with ACTH and reconstitution experiments. Therefore, these findings suggest that ACTH and the related peptides CRF and alpha-MSH can influence the microenvironment modulating an IL-4 and anti-CD40 monoclonal antibody driven class switching to IgE via accessory cells.

Adrenocorticotropic Hormone↗
PubMed1994

A unique non-Langerhans cell histiocytosis with some features of generalized eruptive histiocytoma.

A symmetric eruption of hundreds of coalescent small red macules and a few slightly elevated papules sparing the flexures was observed in a 73-year-old man. Light microscopic examination showed loose aggregates of small and large histiocytic cells. Electron microscopy showed an absence of Langerhans cell granules and lipid droplets. Features shared with generalized eruptive histiocytoma were the symmetry of the eruption sparing the flexures, the blue-red coloration, and the absence of lipid-containing foam cells and multinucleated giant cells. However, the primary occurrence of macules rather than papules or nodules, the tendency of the macules to coalesce, and the dimorphic histiocytoid infiltrate are not found in generalized eruptive histiocytoma. Nevertheless, immunohistochemistry confirmed that this unique condition is a form of MS-1+ cutaneous non-Langerhans cell histiocytosis.

Aged↗
PubMed1994

Long-term administration of pancuronium and pipecuronium in the intensive care unit.

This study was performed to determine the optimum dose of pancuronium (n = 30) and pipecuronium (n = 30) under continuous sedation and analgesia in the intensive care unit (ICU). This was an open clinical investigation in 60 critically ill patients with head injury, multiple trauma (in some complicated with sepsis and multi-organ failure), requiring neuromuscular block for ventilation for at least 48 h. Emphasis was placed on the neuromuscular monitoring with a peripheral nerve stimulator and adequate sedation and analgesia. Satisfactory block was achieved in all cases with an average dose of 3 mg/h with either compound. None of the patients experienced prolonged paralysis, muscle weakness, or other neuromuscular dysfunctions in the postventilatory period. We suggest that adequate use of sedative hypnotics and opioids plus neuromuscular monitoring allowed us to optimize the dose of muscle relaxants according to the need of individual patients.

Adolescent↗
PubMed1993

Human mast cells produce IL-8.

Recruitment of neutrophils is a common feature in diseases that are associated with mast cell activation. The mechanisms that mediate neutrophil activation are not well understood. IL-8 is a recently described potent chemotactic factor that might be pathogenetically involved in this process. We therefore studied the human mast cell line HMCI and human skin mast cells for their ability to produce IL-8 using various stimuli. IL-8-mRNA was expressed in a stimulus- and time-dependent fashion as detected by Northern blot analysis with an IL-8-specific cDNA probe. The molecular mass of HMCI-derived IL-8 was determined to be about 8 kDa by immunoblot analysis. Immunoreactive and biologically active IL-8 protein was measured in the cell culture supernatants of HMCI cells by an ELISA and a chemotaxis assay, respectively. On immunoelectron microscopy of stimulated skin mast cells, IL-8 was found along cytoplasmatic membranes and in intracellular granules. Our data indicate that mast cells may contribute to neutrophil recruitment by secretion of IL-8.

Calcimycin↗
PubMed1993

Immunohistochemical comparison of cutaneous histiocytoses and related skin disorders: diagnostic and histogenetic relevance of MS-1 high molecular weight protein expression.

Twenty-nine cases of Langerhans cell histiocytosis (LCH), non-Langerhans cell histiocytoses (N-LCH), non-infectious granulomas, and fibroblast-related lesions were examined with a panel of monoclonal and polyclonal antibodies on freshly frozen tissue sections to characterize the macrophage phenotype of N-LCH syndromes. MS-1 high molecular weight extracellular protein, specific for sinusoidal endothelial cells and dendritic perivascular macrophages in normal human organs, was expressed by N-LCH cells but was not found in LCH cells, epithelioid cells in sarcoidosis, or palisading histiocytes in granuloma annulare. The subcellular location of MS-1 protein, i.e., cytoplasmic vs. peripheral/extracellular, allowed discrimination of small and large (foamy or multinucleated) N-LCH cells. MS-1-positive cells, which were found intermingled in cellular dermatofibromas but not in fibrous dermatofibromas, differed from MS-1-positive N-LCH cells by their dendritic morphology, and thus rather resembled their normal dermal counterparts. A preserved functional relationship of these two MS-1-positive cell types was indicated by the fact that N-LCH and cellular dermatofibromas were the only lesions found to be highly vascularized. As expected, CD1a showed high specificity for LCH, while CD34 was predominantly expressed by fibroblast-related lesions; in cellular dermatofibromas, CD34 and MS-1 expression partially overlapped. The other antigens tested showed non-specific or overlapping patterns of expression. In conclusion, assessment of MS-1 protein expression (in addition to assessment of CD1a and CD34) promises to be of diagnostic value in the discrimination of N-LCH from related skin disorders, and it may indicate a common differentiative pathway for most N-LCH disease entities.

Antibodies, Monoclonal↗
PubMed1992

Interleukin-6 expression by fibroblasts grown in three-dimensional gel cultures.

We investigated the expression and biological activity of interleukin-6 (IL-6) by human fibroblasts cultured as monolayers and within three-dimensional type I collagen lattices. In the course of contracting the gel to a dense tissue-like structure, the cells upregulated their levels of IL-6 mRNA as well as IL-6 biological activity. While there was little mRNA and protein activity (6,500 U/ml) in monolayer cultures, fibroblasts in the 3D system showed a 13-fold increase in IL-6 mRNA on day 3. IL-6 protein was increased 6-fold (38,000 U/ml) on day 4. Stimulation of fibroblast cultures with IL-1 alpha resulted in enhanced IL-6 production in both systems, but the fibroblasts embedded into the 3D network continued to exhibit higher levels.

Blotting, Northern↗
PubMed1991

IL-6 augments Fc IgE receptor (Fc epsilon RII/CD23) expression on human monoblastic/monocytic cell lines U937, THP-1, and Mono-Mac-6 but not on blood monocytes. Regulatory effects of IL-4 and IFN-gamma.

Human monoblastic/monocytic leukemia cell lines U937, THP-1, Mono-Mac-6, and blood monocytes were incubated with various concentrations of human rIL-6 and other cytokines and analyzed for their capacity to bind several anti-Fc epsilon RII/CD23 mAb. A marked and dose-dependent increase in the percentage of CD23+ cells, as well as in the mean channel fluorescence intensity, as demonstrated by FACS analysis, was noted after 8- to 72-h incubation of U937 cells with 1 to 1000 U/ml of human rIL-6. Furthermore, rIL-4 synergized with rIL-6 and rIFN-tau in augmenting the Fc epsilon RII expression on U937 cells, whereas rIFN-tau and rIL-6 showed rather additive effects. The enhancement of CD23 expression on IL-6-treated U937 cells was blocked by anti-IL-6 antibodies. Northern blot analysis, employing cDNA probes for Fc epsilon RII, showed that U937 cells contain Fc epsilon RII-specific mRNA. The level of Fc epsilon RII-encoding mRNA was evidently increased by treatment of U937 cells with human rIL-6, rIL-4, or with rIL-6 + rIL-4. The expression of CD23 on THP-1 and Mono-Mac-6 cells was increased slightly by rIL-6 and markedly by rIL-4, rIFN-tau, or a mixture of them. Approximately 14% of blood monocytes, isolated from apparently healthy donors, constitutively possess Fc epsilon RII. In contrast to the cell lines, the Fc epsilon RII density and the percentage of blood monocytes bearing Fc epsilon RII was not augmented by IL-6. Furthermore, rIL-6, and more evidently rIFN-tau, down-regulate rIL-4-driven Fc epsilon RII expression on monocytes but not on monocytic cell lines. Our findings point to differences in the capability of mononuclear phagocytes to respond to cytokine treatment, which may be differentiation dependent, and suggest separate regulatory pathways.

Antigens, CD↗
PubMed1990

Cytokine modulation of keratinocyte cytokines.

There is increasing evidence that epidermal cytokines may have an important role in mediating inflammatory and immune responses in the skin. A number of cell types in the epidermis are capable of secreting cytokines including keratinocytes, Langerhans cells, melanocytic cells, and even Merkle cells. Keratinocytes are the major source of cytokines in the epidermis and have been reported to secrete IL-1, IL-3, IL-6, IL-8, CSF, TNF alpha, TGF alpha, TGF beta, and PDGF. Normally these cytokines are not actively secreted by keratinocytes; however, a number of agents are capable of mediating keratinocyte cytokine production, including cytokines themselves. We examined the effect of a number of cytokines on keratinocyte IL-1, IL-6, GM-CSF, and PDGF production. It was found that these keratinocyte cytokines are all modulated by one or more cytokines, including several that keratinocytes themselves secrete. These effects appear to be mediated by high-affinity cytokine receptors on keratinocytes. We are only beginning to understand the molecular mechanisms underlying the production, regulation, and precise role of keratinocyte cytokines in normal and diseased skin; however, recent studies suggest that cytokines secreted by epidermal cells and lymphoid cells may be important modulators of keratinocyte cytokine production.

Animals↗
PubMed1988

Defective intralesional interferon-gamma activity in patients with lepromatous leprosy.

Cryostat sections of full-thickness skin biopsies from 21 patients along the whole spectrum of leprosy were subjected to immunohistological examination with special regard to defective lymphokine production. There was an inverse relationship between intra-lesional IL-1 reactivity and IL-2R expression, in that the latter was markedly observed in tuberculoid lesions. Whenever epithelioid cell containing granulomas were present in paucibacillary forms, significant reactivity within the central phagocytic cells with the monoclonal antibody directed against interferon-gamma was detectable. The keratinocytes covering tuberculoid lesions abundantly expressed class II alloantigens (HLA-DR antigens), indicating high intra-lesional interferon-gamma activity. In contrast, multibacillary forms revealed significant anti-IL-1 reactivity within the cellular infiltrate. IL-2R bearing cells were virtually absent as was anti-HLA-DR reactivity of the keratinocytes, underlining a defective intra-lesional interferon-gamma activity.

Epidermal Cells↗
PubMed1987

Gamma interferon inhibits basal and interleukin 1-induced prostaglandin production and bone resorption in neonatal mouse calvaria.

Production of the osteolytic arachidonic acid metabolites, prostaglandin (PG) E2, PGI2 and PGF2 alpha, by neonatal mouse calvariae was quantitated by gas chromatography/mass spectrometry. Mouse recombinant interleukin 1 (rIL-1) raised medium levels of PGE2 and PGI2 (measured as 6-keto-PGF1 alpha) in the dose range tested (1.0-10.0 U/ml culture medium), while an effect on PGF2 was only observed at 10 U/ml. Bone resorption in response to rIL-1 reached a plateau at 3.0 U/ml. Mouse recombinant gamma-interferon (rIFN-gamma) between 100-500 U/ml suppressed basal PG synthesis and spontaneous resorption of cultured bone. In addition, IFN-gamma at 100 U/ml prevented stimulation of PG synthesis by 3.0 U/ml rIL-1 and thereby reduced the bone resorbing activity of the cytokine by at least 60%. 5 X 10(-7) M indomethacin was equally effective in suppression of PG synthesis and bone resorption. The present study provides evidence that IFN-gamma inhibits PG synthesis and consequently resorption of cultured bone.

Animals↗
PubMed1985

Human epidermal cells synthesize HLA-DR alloantigens in vitro upon stimulation with gamma-interferon.

Under certain pathologic conditions, human keratinocytes synthesize and express HLA-DR antigens. Assuming that soluble mediators might be responsible for this phenomenon, differentiating, primarily DR-keratinocytes were grown in the presence or absence of mixed leukocyte culture supernatants and tested for Ia antigen expression. After 6 days of culture, keratinocytes displayed surface-bound HLA-DR alpha/beta complexes when exposed to mixed leukocyte culture supernatants but not when cultured in media alone. These HLA-DR moieties on keratinocytes result from active biosynthesis as evidenced by the demonstration of the intracytoplasmic HLA-DR gamma (invariant) chain within these cells. In view of reports that interferon-gamma promotes Ia-production in a variety of cell types, we reasoned that this lymphokine might be responsible for the Ia-inducing property of mixed lymphocyte culture supernatants. Indeed, recombinant interferon-gamma, but not interferon-alpha or interleukin-2, proved to be a potent stimulator of Ia expression by keratinocytes. The further finding that this event can be prevented by the addition of a monoclonal anti-interferon-gamma antibody strongly suggests that this cytokine is directly responsible for HLA-DR production by keratinocytes. The interferon-gamma-induced acquisition of HLA-DR antigens by primarily DR-keratinocytes may provide a useful tool to study the role of these alloantigens in T-cell activation and may also add to our understanding of mechanisms operative in epidermal cell-T-cell interactions.

Antibodies, Monoclonal↗
PubMed1982

Human tear lysozyme. A comparison of electro-immunodiffusion, radial immunodiffusion and a spectrophotometric assay.

In 116 persons (67 men and 49 woman) the tear fluid of both eyes was collected using paper discs and once more after topical anaesthesia. After weighing the discs and eluting the tear fluid, the lysozyme content was measured using two immunological methods [radial immunodiffusion (RID) and rocket immuno-electrophoresis (RIE)] and a spectrophotometric assay. Standard curves were established with purified human lysozyme and egg-white lysozyme. In addition, albumin was determined in all the samples by rocket immuno-electrophoresis. All lysozyme assays showed a high degree of correlation, the spectrophotometric technique giving significantly lower values (compared with RID and RIE) when human lysozyme was used for standardization. The lysozyme content of the tears did not correlate with the fluid uptake in the discs, but showed a significant decrease with age, which was abolished by topical anaesthesia. In contrast, albumin levels were dependent upon the weight and independent of the age of the patient. It is suggested that the determination of albumin as a "reference protein' might help in comparing the results of different tear sampling techniques used by various groups, which induce variable amounts of reflex tearing.

Adolescent↗
PubMed1982

[Polyamine levels in blood and plasma of patients with malignant melanoma].

The polyamines putrescine, cadaverine, spermidine, spermine, and the amine histamine in whole blood and plasma of 42 patients with malignant melanoma were analysed after cold acid extraction and ion-exchange chromatography by fluorescence detection. Depending on the degree of tumor spreading the patients were grouped into 5 subpopulations; results were statistically compared with the values obtained from a normal population. The mean values of polyamine concentrations in the patient groups were generally not distinguishable from the mean values of the controls. Solely the mean of the spermidine values of postoperative patients with or without medical therapy and the spermine mean value for postoperative patients in tumor stage I and III were elevated. Cadaverine was never detected. The individual frequency of elevated polyamine levels in the plasma of single patients and variable, depending on patient subpopulation and polyamine under consideration. Spermidine was most frequently elevated (44%) in patients of tumor stage I under immunetherapy. We conclude that due to the low frequency of polyamine elevations to be found in plasma of melanoma patients by our method no diagnostic or prognostic significance and only limited importance for monitoring patients under therapy can be claimed for.

Adult↗