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Biomedical subjects

T Schwarz

Publications and source records attributed to T Schwarz.

At least 19 recordsLinked to original sources
PubMed1992

Modulation of intercellular adhesion molecule-1 expression on human melanocytes and melanoma cells: evidence for a regulatory role of IL-6, IL-7, TNF beta, and UVB light.

Intercellular adhesion molecule-1 (ICAM-1) is involved in cell-cell interactions of leukocytes and parenchymal cells and thus plays an important role in immunologic and inflammatory reactions. The expression of ICAM-1 that is found on many different cells such as melanocytes and melanoma cells is induced by various cytokines, including interferon-gamma (IFN gamma), interleukin (IL)-1 and tumor necrosis factor alpha (TNF alpha). Because expression of ICAM-1 in melanoma was found to correlate with increased risk of metastasis, the regulation of ICAM-1 expression on human melanocytes and melanoma cells was investigated. Foreskin-derived melanocytes and melanoma cell lines (A375, G361) were incubated with different cytokines and ICAM-1 expression was evaluated by fluorescence-activated cell sorter. IFN gamma, IL-1, IL-7, TNF alpha, and TNF beta significantly upregulated ICAM-1 expression in a dose-dependent manner. Most interestingly, the cytokine IL-6, which does not influence adhesion-molecule expression on other cells, significantly upregulated melanocyte and melanoma cell ICAM-1 expression. This effect was dose dependent and could be blocked by an IL-6 antibody. Irradiation with ultraviolet (UVB) light did not influence constitutive ICAM-1 expression on melanoma cells and melanocytes, but suppressed cytokine-induced ICAM-1 expression when cells were harvested 16 h after irradiation. These findings were further confirmed by Northern blot analysis, showing a marked accumulation of ICAM-1 mRNA after cytokine treatment, which was reduced by irradiation with UVB light. However, when UVB-exposed melanoma cells were cultured for at least 48 h induction of ICAM-1 expression was observed. These data indicate that, similar to other cells, ICAM-1 expression on melanoma cells and melanocytes is regulated by cytokines and that UVB light affects ICAM-1 expression on melanocytic cells in a biphasic manner.

Cell Adhesion Molecules↗
PubMed1991

Limited proteolysis of the beta 2-dimer of tryptophan synthase yields an enzymatically active derivative that binds alpha-subunits.

Proteolytic modification of tryptophan synthase holo-beta 2-subunit from Escherichia coli at the C-terminal side of E-296 leads to an active species (E-296-nicked holo-beta 2) capable of interacting with alpha-subunits. Although this heterologous subunit interaction is rather weak, it induces an increase in catalytic efficiency in E-296-nicked holo-beta 2 by a factor of about 150. Correspondingly, enzymatic activity of alpha-subunits is enhanced 180-fold. This is in striking contrast to the findings from earlier reports which demonstrated that proteolytic derivatives modified at other positions in the "hinge region" embedded in the C-domain of the beta 2-subunit (K-272, R-275, and K-283) are enzymatically inactive and cannot associate with alpha-subunits. The equilibrium binding curve for the cofactor pyridoxal 5'-phosphate to E-296-nicked apo-beta 2 is hyperbolic (i.e., noncooperative), yielding an apparent microscopic dissociation constant, Kd, of 5 x 10(-6) M. This value closely resembles the low-affinity dissociation constant of cooperative cofactor binding to the native beta 2-subunit, indicating that the conformational interactions between structural domains in the modified beta-protein seem to be disturbed considerably.

Amino Acid Sequence↗
PubMed1991

Therapeutic use of cytokines in dermatology.

Cytokines are glycoproteins produced by many different cells. Via binding to specific receptors on target cells they regulate the activation, differentiation, and proliferation of immune and nonimmune cells. After injury keratinocytes synthesize and release cytokines such as interleukins, colony stimulating factors, and growth factors. In addition, a network of interacting cytokines appears to be crucial to maintain proper balance. Dysregulation may contribute to certain diseases, particularly those of infectious and autoimmune origin. Therefore many of these mediators appear to be promising candidates to treat infectious and malignant diseases. This article briefly discusses the most important cytokines. Newly developed regimens with cytokines to treat cutaneous disorders will be reviewed.

Cytokines↗
PubMed1991

Regulation of epidermal cell interleukin-6 production by UV light and corticosteroids.

Epidermal cells (EC) are well known as a source of cytokines, including interleukin (IL)-6. In the present study, we investigated whether ultraviolet (UV) light and corticosteroids (CS) affect IL-6 production by normal (HNK) or malignant (KB) human keratinocytes. Supernatants derived from UVB (100 J/m2)- but not from UVA (100-1500 kJ/m2)-exposed EC (HNK and KB) contained significantly increased levels of IL-6 activity. This was also confirmed by Western blot analysis, resulting in specific bands at 23 kD and 27 kD. Northern blot analysis revealed an enhanced IL-6 mRNA expression after UVB exposure. Addition of hydrocortisone, prednisolone, or dexamethasone immediately after UVB irradiation significantly blocked UVB or IL-1-induced IL-6 mRNA expression and production by EC. The suppressive effect was observed at doses in the physiologic (10(-7)-10(-9) M) as well as pharmacologic (10(-5)-10(-7) M) range. In contrast, the nonactive steroid prednisone did not affect EC IL-6 mRNA expression. These findings indicate that increased IL-6 production by EC after UVB irradiation may mediate local and systemic inflammatory reactions following extensive sun exposure. Thus, the therapeutic effect of corticosteroids observed in various inflammatory diseases may be partly due to their downregulating capacity of IL-6 production.

Adrenal Cortex Hormones↗
PubMed1991

Increased IL-6 production by monocytes and keratinocytes in patients with psoriasis.

Interleukin-6 (IL-6) is a multifunctional inflammatory cytokine that is produced by monocytes and keratinocytes upon stimulation. Because psoriasis is a skin disease characterized by a hyperproliferative activity of keratinocytes and an inflammatory infiltrate, in the present study IL-6 production of monocytes and keratinocytes of patients with psoriasis was investigated. Peripheral blood mononuclear cells (PBMC) derived from psoriatics, atopics, and healthy controls were incubated for 24 h and, subsequently, supernatant IL-6 activity was measured using an IL-6-dependent hybridoma cell line (B9). Compared to controls and atopics, PBMC of psoriatics produced significantly increased amounts of biologically active IL-6. These findings were also confirmed by Western blot analysis using a specific antiserum directed against IL-6. Moreover, when the sera of the same patients were tested for IL-6 activity, sera of psoriatics contained significantly elevated amounts of circulating IL-6 in comparison to samples from atopics and healthy controls. In contrast to normal or uninvolved skin, keratinocytes in psoriatic lesions were remarkably positive for IL-6 as detected by immunohistochemistry and in situ hybridization. In addition, IL-6 also was found to induce its own synthesis and release by monocytes. These findings indicate that keratinocytes and monocytes in psoriasis are activated to produce increased amounts of IL-6, which may be one of the mediators involved in the regulation of both local and systemic inflammatory reactions occurring in skin diseases such as psoriasis.

Adult↗
PubMed1991

[Preliminary studies of the content of lead, cadmium and arsenic in feed, cattle and food of animal origin from different production regions of Saxony].

The modern industrial and agricultural production provides many contact points for the food animals with several toxic substances. After their ingestion by the way of feed or water they may endanger the human health as residues or environmental contaminants in food of animal origin. Currently meat, milk and eggs produced on farms in the new federal states of Germany are considered to be dangerous with respect to their xenobiotic burden by numerous consumers. The own trials have been made to give first information about lead, cadmium and arsenic concentrations in feedstuffs, meat and milk from different dairy farms in Saxonia. No serious problems could be detected referring to the metal contents in roughage, grain and crops. Only a few feed samples reached eg. exceeded the permissible upper limits for arsenic and cadmium. But none of the examined feedstuffs contained inadmissible lead concentration. Milk and muscle produced in a metal polluted and not polluted areas were very low in cadmium, lead and arsenic. Total different is the situation in the cases of liver and kidney. Both organs of cows held on farms near a smelter were rich in cadmium and lead. The cadmium concentration in liver and kidney often and the lead concentration sometimes exceeded the permissible upper limits for food. In this context cadmium in kidney of older cows seems to be a problem in general. The results of the own examinations give no information about differences in the mean metal burden of feed and food between new and old federal states of Germany.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMed1991

[Drug reaction to amoxicillin simulating toxic pustuloderma].

Noninfectious pustular reactions can be observed in association with a variety of dermatoses. Thus, precise knowledge of these is important for the differential diagnosis. Toxic pustuloderma (TP) has been described as a clinical entity and is characterenized by the sudden onset of intense erythemas followed by sterile pustulation, primarily located in the flexural areas and groins. Most frequently TP is induced by drugs, in particular by betalactam antibiotics. In this paper, a typical case of TP caused by the combination of amoxicillin and clavulanic acid will be described, and clinical features, pathogenesis and differential diagnosis will be discussed.

Amoxicillin↗
PubMed1991

[Successful use of isotretinoin in type Zumbusch generalized pustular psoriasis following recovered etretinate-induced hepatitis].

Administration of etretinate in a 29-year-old female patient suffering from severe pustular psoriasis caused a dramatic increase in liver enzymes. Liver biopsy revealed changes characteristic for drug-induced hepatitis. After normalization of liver parameters following withdrawal of etretinate, isotretinoin was administered during a severe pustular relapse. In contrast to etretinate, isotretinoin was well tolerated and resulted in a good therapeutic response. Thus, isotretinoin can be considered as an effective and safe therapeutic alternative for pustular psoriasis even after the occurrence of etretinate-induced hepatitis.

Adult↗
PubMed1990

Human keratinocytes are a source for tumor necrosis factor alpha: evidence for synthesis and release upon stimulation with endotoxin or ultraviolet light.

Tumor necrosis factor alpha (TNF-alpha), in addition to being cytotoxic for certain tumor cells, has turned out as a multifunctional cytokine that is involved in the regulation of immunity and inflammation. Since human keratinocytes have been demonstrated to be a potent source of various cytokines, it was investigated whether epidermal cells synthesize and release TNF-alpha. Supernatants derived from normal human keratinocytes (HNK) and human epidermoid carcinoma cell lines (KB, A431) were tested both in a TNF-alpha-specific ELISA and a bioassay. In supernatants of untreated epidermal cells, no or minimal TNF-alpha activity was found, while after stimulation with lipopolysaccharide (LPS) or ultraviolet (UV) light, significant amounts were detected. Western blot analysis using an antibody directed against human TNF-alpha revealed a molecular mass of 17 kD for keratinocyte-derived TNF-alpha. These biological and biochemical data were also confirmed by Northern blot analysis revealing mRNA specific for TNF-alpha in LPS- or ultraviolet B (UVB)-treated HNK and KB cells. In addition, increased TNF-alpha levels were detected in the serum obtained from human volunteers 12 and 24 h after a single total body UVB exposure, which caused a severe sunburn reaction. These findings indicate that keratinocytes upon stimulation are able to synthesize and release TNF-alpha, which may gain access to the circulation. Thus, TNF-alpha in concert with other epidermal cell-derived cytokines may mediate local and systemic inflammatory reactions during host defense against injurious events caused by microbial agents or UV irradiation.

Blotting, Northern↗
PubMed1990

Cross-linking Fc receptors on monocytes triggers IL-6 production. Role in anti-CD3-induced T cell activation.

IL-6 is a multifunctional cytokine which is produced by a variety of cells. Therefore it was examined whether anti-CD3-induced T cell activation was associated with the induction of functionally relevant IL-6 in human monocyte accessory cells. Significantly increased amounts of IL-6 were detected in supernatants of anti-CD3-treated PBMC. Stimulation of FACS-sorted greater than 98% pure monocyte accessory cells, but not of highly purified T cells with anti-CD3, resulted in an increased IL-6 production. Furthermore, anti-CD3 significantly enhanced IL-6 mRNA expression in monocyte accessory cells. IL-6 production was not limited to anti-CD3, inasmuch as equivalent IL-6 stimulation could be achieved with a mouse IgG2a isotype control antibody. In contrast to solid phase-bound mouse IgG2a, the soluble form of this antibody failed to induce IL-6 secretion indicating a requirement for Fc gamma RI receptor cross-linking. Moreover, this property may be specific for the Fc gamma RI receptor inasmuch as mouse IgG1 antibodies binding to the Fc gamma RII receptor did not significantly enhance IL-6 production. The role of IL-6 being an additional signal in T cell activation was confirmed by the finding that an anti-IL-6 antiserum was able to suppress anti-CD3-induced T cell activation. These data indicate that binding of anti-CD3 to Fc gamma RI may generate an activation signal towards the monocyte accessory cell leading to the production and secretion of monocyte IL-6, which in turn augments T cell activation, and also may be relevant to a variety of antibody-mediated immune responses against viral and bacterial infections.

Antigen-Presenting Cells↗
PubMed1990

[A simple test for the monitoring of plasma anti-XA activity of patients following subcutaneous administration of enoxaparin].

Since low molecular weight heparin is used for the prevention of thromboembolism, the coagulation laboratories are in need of a simple, reliable and practicable test for factor Xa inhibition in order to monitor the effect of low molecular heparin in plasma. Effects of subcutaneous administration of 20 mg or 40 mg enoxaparin were studied in blood samples drawn from 20 patients before and 1, 2, 3, 4, 6, 12 and 24 hours after injection. Thrombin time, aPTT, Heptest and the anti-Xa activity (amidolytic assay) were measured. Subcutaneous administration of 20 mg or 40 mg enoxaparin was followed by a barely significant (p less than 0.05) rise in aPTT (only at the higher dosage) and thrombin time four hours after injection. Heptest and amidolytic assay (S-2222) correlated well and significant (p less than 0.01) increases, with maximum values 4 hours after injection, were seen after administration of 20 mg as well as of 40 mg enoxaparin. Higher mean values were achieved after injection of 40 mg than 20 mg enoxaparin. We believe the Heptest to be a quick and easily performed test, giving results which agree well with those of the amidolytic anti-Xa activity reference method.

Aged↗
PubMed1990

Ultraviolet light induces increased circulating interleukin-6 in humans.

Although the clinical effects of acute exposure to ultraviolet (UV) light--such as cutaneous inflammation, malaise, somnolence, chills and fever--have been appreciated many years, the underlying mechanisms mediating these effects are poorly understood. Interleukin-6 (IL-6) is a potent cytokine with a wide variety of biologic activities, including induction of fever and acute phase response. Because IL-6 is produced by keratinocytes in vivo and in vitro and because the release is enhanced by UV light, the present study was performed to investigate the effect of a single UV dose eliciting moderate to severe sunburn reaction on the production of IL-6 in vivo. Therefore, plasma of UV-treated human subjects was evaluated for IL-6 activity by testing its capacity to induce the proliferation of an IL-6-dependent hybridoma cell line (B9). In contrast to plasma samples obtained before UV exposure, post-UV-specimens contained significant levels of IL-6 peaking at 12 h after UV irradiation. Plasma IL-6 activity was neutralized by an antiserum directed against recombinant human IL-6, and upon HPLC gel filtration exhibited a molecular weight of around 20 kD. Moreover, plasma IL-6 levels correlated remarkably with fever course followed by an increase of acute phase proteins such as C-reactive protein. These data indicate that IL-6, which is released by keratinocytes following UV exposure, may gain access to the circulation and via its pyrogenic as well as acute phase-inducing effect may function as an important mediator of systemic sunburn reaction.

Adult↗
PubMed1990

Evidence for an epidermal cytokine network.

Cytokines are (glyco)proteins that are synthesized and secreted by various cells, which bind to specific receptors on target cells and which regulate activation, proliferation, and differentiation of immune as well as non-immune cells. Keratinocytes upon injury release interleukin (IL)-1, IL-6, IL-8, colony-stimulating factors, and tumor-necrosis factor, as well as growth and suppressor factors. There is also strong evidence for a network of interacting cytokines, which has been only partially characterized so far, maintaining a proper balance. However, excessive or insufficient production of these mediators may contribute to certain disease states, particularly those with infectious and autoimmune genesis. Therefore the understanding of cytokine interactions may be helpful in elucidating the pathomechanisms of such diseases. Moreover, certain cytokines, as well as their analogues and antagonists, may prove to be of therapeutic value.

Colony-Stimulating Factors↗
PubMed1990

Epidermal cell-contra-interleukin 1 inhibits human accessory cell function by specifically blocking interleukin 1 activity.

Ultraviolet B (UVB) radiation (280-320 nm) is capable of suppressing selected cell mediated immune responses by inhibiting the function of antigen presenting/accessory cells. Human keratinocytes and carcinoma cell lines (A431) upon UVB radiation or treatment with PMA secrete a suppressor factor, which blocks IL 1 activity (hEC-contra-IL 1). Therefore, the capacity of this UVB-inducible cytokine to modulate human accessory cell function was tested. Human peripheral blood mononuclear cells were stimulated with the mitogenic anti-CD3 monoclonal antibody OKT3 and thymidine incorporation into proliferating T-cells was measured as an index for monocyte accessory cell activity. Addition of hEC-contra-IL 1 which was purified by HPLC chromatography partially decreased OKT3 induced T-cell proliferation in a dose dependent manner. Human EC-contra-IL 1, however, failed to inhibit blastogenesis when T-cells depleted of accessory cells were stimulated in an accessory cell independent fashion via OKT3 attached to the bottom of microtiter plates. Recombinant human (rh) IL 1, but not rhIL 6 was able to reconstitute hEC-contra-IL 1 suppressed blastogenesis in a dose dependent manner. Furthermore, the combined addition of h-EC-contra-IL 1 and an antibody against rhIL 6 to cultures resulted in an additive inhibitory effect which could not be observed when hEC-contra-IL 1 was added together with a monoclonal antibody against rhIL 1 alpha/beta. These studies indicate that hEC-contra-IL 1 is capable of suppressing human accessory cell function by specifically blocking IL 1 activity. This property of hEC-contra-IL 1 points to a novel mechanism by which UVB radiation may modulate human accessory cell function in an indirect manner.

Animals↗
PubMed1990

Successful intrauterine treatment of fetal hydrops caused by parvovirus B19 infection.

The infection with parvovirus B19 during pregnancy causes in 1/3 of the cases an aplastic crisis in the fetus and consecutively generalized fetal hydrops as a result of severe anemia. Some cases of fetal hydrops and intrauterine death are reported. In our two cases, the fetal therapy by intrauterine intravasal transfusion was successful and the children developed normal. The techniques and indications for fetal blood sampling and the method of intrauterine intravasal transfusion are explained.

Adult↗