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Biomedical subjects

T Luger

Publications and source records attributed to T Luger.

At least 73 records · Page 4Linked to original sources

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↗

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↗

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↗

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↗

[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↗

[Genodermatosis in a pair of brothers: Dowling-Degos, Grover, Darier, Hailey-Hailey or Galli-Galli disease?].

A peculiar polymorphous eruption in two brothers is reported. Histological examination of hyperpigmented macular lesions on the face and neck revealed all diagnostic features of the Dowling-Degos disease. With the electron microscope, singly dispersed melanosomes could be demonstrated in the basal keratinocytes. In biopsies from the erythematosquamous pruriginous lesions in the flexural areas, on the trunk and extremities, acantholysis, formation of lacunae, and some corps ronds were the predominant histological findings. Reduction of desmosomes, separation of desmosomes and tonofilaments, as well as thickened collagen-like tonofilaments could be shown. Not infrequently within a single lesion, all the features compatible with Dowling-Degos, Hailey-Hailey, Darier, and Grover disease were present. Pending further investigations and observation of patients with similar findings we propose with the consent of the patients, the term "Galli-Galli" disease as preliminary designation of this genodermatosis.

Acantholysis↗

Serum lysozyme levels in patients with solid tumors.

Serum lysozyme has been demonstrated to be an indicator for macrophage activity in the tumor-bearing host. Therefore, we investigated lysozyme levels in the sera of 336 untreated tumor patients (121 malignant melanoma, 61 lung cancers, 70 cervical cancers, 49 breast cancers and 35 benign breast tumors, and 36 healthy controls). Patients with malignant melanoma and lung cancer had significantly higher lysozyme levels than the healthy controls. Within the clinical stages in melanoma, there was a decrease of lysozyme in stages II and III in comparison to stage I, but still above that of the control values. Patients with benign breast tumors had normal levels, whereas in breast cancer patients of stages I and II there was a significant reduction in the lysozyme levels. In stages III and IV no differences to the control group could be detected. In patients with cervical cancer (FIGO II and III) serum lysozyme levels were found to be within the normal range. From this study it can not be concluded that serum lysozyme reflects the immunological reactivity of the tumor bearer. Nevertheless, the reduced levels in stages I and II of breast cancer might point to an immunological defect.

Breast Neoplasms↗

[Serum ferritin in patients with malignant melanoma].

In 55 patients with malignant melanoma, in addition to hematologic parameters and blood chemistry, serumferritin was measured by a two-site IRMA-technique using a heterologous antibody system (Behringwerke). Tumor localisation was exactly classified due to a staging system (stage I--III). Elevation of serumferritin values in stage III was highly significant (p less than 0.0005) compared to stage I and II, as well as to normal controls (n = 60). There was no significant correlation between serumferritin and sedimentation rate, erythrocytes or serum iron. Only in stage III we found a significant negative correlation (p less than 0.05) between serumferritin and hemoglobin. Compared to normal controls, patients with stage III showed a significant decrease in serum-iron (p less than 0.01). A significant increase was found concerning serum-copper levels in all patients with melanoma. Though radioimmunometric methods now are not sensitive enough for the determination of tumor-specific isoferritins, serumferritin might be useful in detecting patients with malignant melanoma (stage III).

Copper↗

[The implication of trace metals in household products in the causation of contact dermatitis (author's transl)].

The 6 most common fluid and powder detergent brands in use in Austria were analyzed as to their nickel and chromium content. The analysis was carried out by means of atomic absorption spectroscopy. 1. The above-mentioned metals were found to be present in each of the products analysed. On average, the fluid detergents contained ten times less nickel and chromium than the powders. 2. Repeated investigations revealed a considerable variation in metal ion content in different batches of the same detergent. Thus, presumably the raw products already contain nickel and chromium and it is unlikely that these ions get into the products during the manufacturing process. 3. In the appropriately diluted detergent powder solutions, as recommended by the producer, the content of nickel was found to lie between 0.4 ppm and 0.717 ppm and the chromium content ranged from 0.733 to 0.917 ppm. Since powder detergents also contain complex-producing agents, it can be assumed that these concentrations of metal ions do not suffice for sensitization. In the fluid detergents the nickel and chromium contents were found to be below the safety limit for the elicitation of an excematous reaction.

Allergens↗

[Immuno-chemotherapy in patients with disseminated metastasizing stage III melanoma. Randomized study with methyl-CCNU versus C. parvum plus methyl-CCNU].

34 patients with disseminated malignant melanoma (stage III) were randomized to the following therapy groups: Chemotherapy (MeCCNU, NSC 99441; 200 mg/m2, given orally every 8 weeks), or immuno-chemotherapy (1 mg Corynebacterium parvum i.v., on days 1-4 + MeCCNU 200 mg/m2 on day 8, repeated every 7 weeks). Total therapy response rate was 33%; total and partial remissions were achieved in 26% of the patients receiving chemotherapy, and in 40% under immuno-chemotherapy. Interim life table analysis shows that in the group receiving C. parvum + MeCCNU 50% of the patients survived more than 12 months, whereas in the group with MeCCNU survival of 50% was 6 months. Pretreatment with C. parvum did not only potentiate the therapeutic effect, but also reduce the myelosuppression of MeCCNU.

Bacterial Vaccines↗

Investigations on general immune reactivity in untreated cervical cancer patients.

74 patients with untreated cervical cancer (FIGO II and III) were skintested with a battery of recall antigens, and also sensitised and challenged with DNCB. A significant reduction of reaction to Tuberkulin, Varidase and also to DNCB was found in patients with stage III in comparison to healthy females of the same age group. Significant changes in immunoglobulin levels, increase of IgA and decrease of IgG were observed in the cancer patients. Serum lysozyme values were the same as in the control group.

Carcinoma, Squamous Cell↗

[Suppressive effect of somatostatin on secretin-CCK-PZ-stimulated endocrine and exocrine pancreatic function in man (author's transl)].

With a view toward the therapeutic use of somatostatin in the treatment of acute pancreatitis, a preliminary investigation was conducted with 6 healthy volunteers, in which the suppressive effect of somatostatin on endocrine and exocrine pancreatic function was observed. A 30-minute baseline measurement period was followed by the administration of cyclic somatostatin (100 microgram by i.v. injection plus a 90-minute infusion at a rate of 200 microgram/hr). After the first 45 minutes of this infusion secretion was submaximally stimulated by the infusion of secretin-cholecystokinin-pancreozymin (CCK-PZ) (75 U each), over two hours. No decrease was observed in basal bicarbonate or enzyme concentration under somatostatin administration alone. However, secretion did not show the usual steep rise after the commencement of stimulation. After the somatostatin infusion was stopped, i.e. under secretin-CCK-PZ alone, a significant increase occurred in the values of secretin-induced volume, bicarbonate concentration and total bicarbonate contents of the duodenal aspirate, as well as in CCK-PZ-induced enzyme secretion. The release of insulin, both basal and stimulated, was also significantly decreased by somatostatin.

Adult↗

Treatment of immune-mediated skin diseases: future perspectives.

In recent years there has been an enormous increase in the understanding of the pathogenesis of immune mediated skin diseases which has led to the development and introduction of new therapeutic regimes. Accordingly, non-specific immunomodulating drugs such as cyclosporin A (CyA), rapamycin, leflunomide, mycophenolat mofetil, tacrolimus, pimecrolimus (ASM981) a.o. proved to be beneficial for a variety of skin diseases. Immunomodulators such as tacrolimus, ASM981 and imiquimod also have been developed for topical application. Specific immunomodulating strategies involve humanized antibodies directed against cytokines or cell surface molecules, receptor antagonists, fusion proteins targeting cytokines or receptors and transcription factor inhibitors. Another interesting approach is to target the appropriate T cell-receptor on autoreactive T cells. Transfection with cytokine genes may represent a useful approach to generate immune deviation and, thereby, treat immune mediated diseases. The value of different vaccination strategies are currently investigated. The first promising results have been obtained by targeting the function of antigen-presenting cells such as dendritic cells (DC). Although, the rapid development of research in immune-mediated diseases has led to the development of several new and more effective therapeutic strategies, in most cases cure is still not possible until the genetics of these diseases are revealed which ultimately may result in gene therapy.

Autoimmune Diseases↗

[Transient acantholytic dermatosis (Grover) (author's transl)].

In this report, we wish to demonstrate histological and ultrastructural characteristics of transient acantholytic dermatosis, first described in 1970 by Grover. Papules on the upper part of the body and on the arms and thighs are noted in our two patients. They are small in size (2-4 mm) and encircled by an erythematous border; pruritus and vesicles with serous content are often present. The vesicles are follicular and tend to group. Biological and immunological studies are normal. Histological examination shows acantholysis and intraepidermal vesicles above which is hyperkeratosis with parakeratosis. In the dermis, inflammatory infiltrates are noted. Ultrastructural study reveals rarefaction of desmosomes and widening of intercellular spaces. Fragments of tonofibrils are also noted. Karyolysis is sometimes present. The dermis contains A. Civatte's bodies. It is likely that this recently identified disease is less unfrequent than it appears to be.

Acantholysis↗