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Biomedical subjects

P Fritsch

Publications and source records attributed to P Fritsch.

At least 19 recordsLinked to original sources

Association between serum-soluble CD8 levels and parameters of immune activation in patients with human immunodeficiency virus infection.

We compared the serum concentrations of soluble CD8 with the immune activation markers neopterin, interferon-gamma, tumour necrosis factor-alpha, soluble CD4, and with CD4+ and CD8+ T-cell counts in patients with human immunodeficiency virus (HIV) infection. The majority of patients had increased concentrations of soluble CD8, interferon-gamma and neopterin, and various significant correlations existed between them. Our results support the view that enhanced soluble CD8 levels indicate activated CD8+ T cells in patients with HIV infection.

Adult

Global degranulation of rat mast cells stimulated with DNP-polystyrene.

Mediator release was studied in rat peritoneal mast cells sensitized with a mouse monoclonal anti-DNP IgE antibody, and stimulated with DNP-ornithine covalently attached to radio-derivatized polystyrene petri dishes. Cells releasing serotonin at maximal rates were investigated by transmission electron microscopy. Generalized exocytosis of granules could be observed, suggesting non-directional release of mediators, and non-compartmentalized action of second messengers in mast cells stimulated with polystyrene-bound DNP. Stimulation of sensitized mast cells by DNP covalently bound to the rigid polystyrene surface is consistent with extrinsic mechanisms proposed for Fc(epsilon)RI receptor action, and suggests that internalization of Fc(epsilon)RI is not needed for triggering cell degranulation.

Animals

Chromosomal, mitochondrial and metabolic alterations in SV40-transformed rabbit chondrocytes.

Karyotype, mitochondrial ultrastructure and several enzymatic activities were studied in two clones, D22 and D27, from SV40-transformed rabbit chondrocytes. Similar chromosome alterations, with recurrent losses and gains were observed at the various passages. Mitochondria were rare, with increase in size and crest alterations. By comparison to non-transformed rabbit chondrocytes, activities of superoxide dismutase 1 and 2 (SOD) and glutathione peroxidase were increased, those of glutathione reductase, glucose-6-phosphate dehydrogenase and glutathione-S-transferase fluctuated according to passages, thymidylate synthase decreased, thymidine kinase and hypoxanthine-phosphoribosyl-transferase increased and the ratio lactate dehydrogenase B/A increased. In most cases, these variations were correlated with the number of chromosomes carrying the genes encoding for corresponding enzymes. These results, compared to those obtained in SV40-transformed human fibroblasts, demonstrate that the two cell types behave differently for detoxication systems against oxygen radicals, in particular for SOD2 activity, and have opposite imbalances of chromosomes carrying the corresponding genes.

Animals

The influence of daily dish-washing with synthetic detergent on human skin.

The effects of regular dish-washing on the stratum corneum barrier function, as determined by transepidermal water loss (TEWL), and objective and subjective skin parameters, were investigated in a 'use test' performed by 18 healthy volunteers. Hands were soaked in a 0.05% solution of a commercial dish-washing product (three times/day, for 15 min, at 37 degrees C) over a period of 3 weeks; one hand was unprotected and the other was protected with a commercial rubber glove. TEWL increased in 13/18 volunteers by more than 25% above baseline on exposed hands within the first 2 weeks of the study. Objective skin signs (erythema, scaling, fissures) and subjective symptoms (itching, dryness, smarting) occurred almost exclusively in subjects with substantial TEWL increases and were most prominent 1-2 weeks following peak TEWL values. There was a highly significant correlation between cumulative relative symptom scores and TEWL changes. TEWL increase and symptom scores were not correlated with a history of inhalant allergy and/or elevated serum IgE levels. Three volunteers, who had shown the highest increase of TEWL values and the most intense clinical reactions to the detergent were subjected to a control experiment in which one hand was soaked in warm tap-water following the same experimental protocol. No significant effects on TEWL values or skin symptoms were observed. We conclude that regular exposure to low concentrations of detergents as used for dish-washing is capable of inducing skin lesions in a substantial proportion of individuals.

Adult

Overview of pulmonary alveolar macrophage renewal in normal rats and during different pathological processes.

We report experimental results on pulmonary alveolar macrophage (PAM) renewal in healthy rats and in rats treated with particles introduced in the lungs. Morphometric studies showed that the lungs of normal rats of the strain used in our study contain 20 x 10(6) PAM, 50 x 10(6) monocytes in alveolar capillaries, and about 3 x 10(5) interstitial macrophages. Pulse labeling with a tritiated thymidine (3HT) gave a labeling index of 0.4% for the monocytes, of which a few could be observed in mitosis within alveolar capillaries. These monocytes are likely to be the PAM precursors. The daily input (greater than 4%) by PAM proliferation exceeds PAM loss by migration to the upper respiratory tract (2.5%). The life span of PAM was measured by sequential counting of lavaged cells after labeling with [125I]iododeoxyuridine instilled intratracheally. The pulmonary lavage procedure used allowed us to recover at least 80% of the whole PAM population. A daily loss of PAM of 8-9% was measured, of which loss by death in the endoalveolar compartment was estimated at 5-6%. During the pathological processes studied, several parameters of PAM renewal were shown to be modified. PAM migration to the upper respiratory tract was frequently inhibited, PAM cytotoxicity was observed, and PAM proliferation increased in some cases and decreased in others. Under most of the pathological conditions investigated, the renewal of endoalveolar macrophages appeared quite different from that in normal rats, and direct blood monocyte migration to the endoalveolar compartment became a major component of PAM renewal.

Administration, Inhalation

Trends in HIV infection among intravenous drug users in Innsbruck, Austria.

The first HIV test among intravenous drug users (IVDUs) at the AIDS clinic and/or the drug dependency clinic of the University of Innsbruck was the basis for the calculation of the proportions of those testing HIV seropositive annually over the period 1985-1990. The numbers testing HIV seropositive at the drug dependency clinic declined drastically, from 72.2% in 1985 to 12.5% in 1990 (chi 2 = 29.62, p less than 0.0001), whereas they rose at the AIDS clinic during this period, from 48.4% to 100% (chi 2 = 5.82, p = 0.016). Overall 132 of the 268 (49.2%) individuals examined tested HIV seropositive. There were 102 individuals of the original 146 seronegative IVDUs who were retested, for an overall incidence rate of HIV seroconversion of 5.8/100 persons-years. Risk of seroconversion was associated with a steady sexual partnership with an HIV seropositive IVDU and with an age of less than or equal to 25 years at study entry (13.1 versus 8.7/100 persons-years). No seroconversions occurred in the subgroup of patients treated by the methadone maintenance treatment program. The cumulative incidence (Kaplan-Meier) rate for HIV seropositivity after 64 months was 22%, lower than the proportions testing HIV seropositive found in 1985 at each of the two clinics, which suggests that the speed of the spread of the epidemic of HIV infection among IVDUs has slowed in our region. Counseling of IVDUs should emphasize the risks of sexual acquisition, particularly among persons with steady relationships who may not perceive their risk.

Adult

Histologic and immunohistochemical study comparing xanthoma disseminatum and histiocytosis X.

BACKGROUND AND DESIGN: As xanthoma disseminatum and histiocytosis X share clinicopathologic features, difficulties in diagnosis can arise. The use of immunocytochemical markers for S100 protein, factor XIIIa, lysozyme, alpha 1-antitrypsin, for adherence of peanut agglutinin and of antibodies LN3 (HLA-DR), Leu-M1 (CD15), QBEnd/10 (CD34), MAC 387, and KP1 (CD68) as an aid to conventional histology has been studied in routinely fixed skin biopsy specimens from seven patients with xanthoma disseminatum and 12 patients with histiocytosis X. RESULTS: Typically xanthoma disseminatum occurs in discrete foci below an intact epidermis with individual cells set within a delicate fibrillary connective tissue stroma. In contrast, histiocytosis X usually occurs as a diffuse lichenoid infiltrate that can extend to deeper tissues. Epidermal invasion is common and the cells tend to lie free separated by edema fluid. Characteristic histiocytosis X cells are ovoid with an indented or kidney-shaped nucleus that occupies half or more of the cell. Xanthoma disseminatum cells differ in showing irregular scalloped borders, a more extensive cytoplasm, and an ovoid vesicular nucleus. Most xanthoma disseminatum cells labeled strongly for factor XIIIa and with KP1; a few cells labeled only weakly with peanut agglutinin. In contrast, most histiocytosis X cells labeled for S100 protein and with LN3 and peanut agglutinin. All the other markers remained negative in both conditions and were thus noncontributory for differentiating xanthoma disseminatum from histiocytosis X. CONCLUSIONS: We conclude that the differences in labeling patterns are a useful aid to histologic diagnosis of histiocytosis X and xanthoma disseminatum and they also reflect their separate histiogenesis.

Adolescent

[Typing of infiltration cells in primary, localized, nodular, cutaneous amyloidosis].

Amyloid tumours in two patients with primary localized nodular cutaneous amyloidosis contained very dense infiltrates consisting mainly of plasma cells and lymphocytes. In one case IgM was detected on many cells of the infiltrate, while in the other IgA was found in morphologically apparently normal plasma cells. Immunohistochemical investigations did not reveal any immunoglobulin light chain restriction in either of the tumours. Numerous cells expressed B cell markers, such as CD20 or CD38. Rearrangement studies on material from the amyloid tumour of one of the patients confirmed the monoclonality of plasma cells. This observation indicates that the nodules of primary localized nodular cutaneous amyloidosis indeed represent an extramedullary plasmocytoma, which consists of amyloid-producing plasma cells. Of special interest was the unexpectedly high proportion of cells expressing T cell markers (CD3, CD5, CD4 greater than CD8) in the amyloid nodules of both patients. After excluding co-expression of B and T cell markers on identical cells by immunohistochemical studies on serial sections and also after molecular biological studies, we assume that this is a separate T cell population that may have a regulatory effect on the production of amyloid.

Aged

[Package contaminations].

In this chapter, the authors consider the problems originating from packaging for foods and the possible risks of contamination. The methods available for evidencing the possible migrations from package to food are considered. Dealing with package safety, toxicological tests (animal, cells...) are described. Then, the different classes of materials, as well that are usual (wood, paper, cardboard, glass, ceramic, metal, ...) as the new materials (plastic, elastomer, ...) are described. The authors emphasis the importance of package and of its development in food industries. Safety control from toxicologist is critical.

Food Contamination

High risk of developing toxoplasmic encephalitis in AIDS patients seropositive to Toxoplasma gondii.

We studied 41 AIDS patients in the Austrian Tyrol with respect to toxoplasma antibody titers and the presence of CNS toxoplasmosis. In no patient had primary Pneumocystis carinii pneumonia (PcP) prophylaxis with either trimethoprim/sulfamethoxazole or pyrimethamine/sulfadoxine been applied; the degree to which CNS toxoplasmosis is influenced by this kind of PcP chemoprophylaxis, widely used elsewhere, is still unclear. In this study 47.4% of toxoplasma-seropositive patients developed CNS toxoplasmosis, compared to the previously estimated risk of 12%-28% for developing CNS involvement in such patients. In view of the high risk of toxoplasma-seropositive patients with AIDS, increased efforts in developing a well-tolerated chemoprophylaxis to combat CNS toxoplasmosis are required.

Acquired Immunodeficiency Syndrome

Modulation of exudate inflammation parameters in rat carrageenan-induced granuloma by modification of exudate iron levels.

We have used the carrageenan-induced pouch-granuloma in rats to investigate how changes in low-molecular-mass iron chelate levels in the exudate, induced by iron loading (iron-dextran) or chelation (desferrioxamine) influence cellular and systemic inflammatory parameters. In the iron-treated group we observed a rapid decrease in the number of leukocytes and exudate volume; there was also an increase in ferritin iron and low-molecular-mass iron chelates, and on the eighth day a systemic response. In the desferrioxamine-treated group we detected a decrease in low-molecular-mass iron chelates, ferritin iron, and an increase in the number of leukocytes. We describe the protective effects of desferrioxamine against the deleterious effects of ferrous iron and relate this to its chelating and scavenging activity. The results suggest that the levels of low-molecular-mass iron chelates modulate the inflammatory response, possibly through their contribution to the oxygen free radical generation, which is responsible for the cell membrane damage and subsequently its death. The modulatory action of iron-dextran and desferrioxamine support our hypothesis.

Animals

Mechanism of allergic cross-reactions--I. Multispecific binding of ligands to a mouse monoclonal anti-DNP IgE antibody.

A recently developed solid-phase binding assay was used to investigate the specificity of ligand binding to a mouse monoclonal anti-dinitrophenyl IgE [IgE(aDNP)]. All DNP-amino acids, that were tested, inhibited the binding of radio-labeled IgE(aDNP) to DNP covalently attached to polystyrene microtiter plates; however, the concentration for 50% inhibition varied within four orders of magnitude, DNP-L-serine being the most, DNP-proline the least potent inhibitor. In addition to DNP analogues a large number (2074) of drugs and other compounds were tested for their ability to compete with DNP for the binding site of IgE(aDNP). At the concentrations used for screening 59% of the compounds had no significant inhibition; 19% inhibited the binding of IgE(aDNP) more than 50%. Several families of compounds (tetracyclines, polymyxines, phenotiazines, salicylates and quinones) of effective competitors were found. Within these families change in the functional groups attached to the "family stem" had major effects on the affinity of ligand binding. The occurrence frequencies of interactions of ligands with IgE(aDNP) is in good agreement with a semi-empirical model for multispecific antibody-ligand interactions.

Amino Acids

Mechanism of allergic cross-reactions--II. Cross-stimulation, by chemically unrelated ligands, of rat basophilic leukemia cells sensitized with an anti-DNP IgE antibody.

Serotonin release from rat basophilic leukemia (RBL) cells, sensitized with a DNP-binding monoclonal IgE, was stimulated with solid surface (polystyrene)-bound DNP-amino acids. The stimulatory potency of DNP-amino acids was dependent on the structure of amino acid attached to DNP. Generally, DNP-amino acids with high affinities to the sensitizing IgE (I(50) less than 10 microM) were stimulatory in polystyrene-bound form; DNP-amino acids with lower affinities (Pro, Cys, Trp), and aliphatic aromatic DNP-amino acid derivatives were inactive. In addition to structural analogues of DNP, lymecycline, that is chemically unrelated to DNP but was found to have high affinity to IgE(aDNP), was also stimulatory in this system. This drug, and various quinones (e.g. acenaphthene-quinone) in BSA-conjugated forms also stimulated serotonin release from RBL cells sensitized with IgE(aDNP). These studies suggest that (1) There is a threshold of intrinsic ligand binding affinities at approximately I(50) = 10-100 microM; ligands with lower affinities do not stimulate mediator release even if they are presented in multivalent forms; (2) The above affinity threshold for mediator cell stimulation is valid for various ligands, irrespective of their chemical similarity to the immunogen; (3) Multispecific stimulation of mediator release may contribute to the frequently observed allergic cross-reactions, false positive tests for allergies, and anaphylactic reactions to drugs upon first exposure.

Acenaphthenes

Photochemotherapy for severe psoriasis without or in combination with acitretin: a randomized, double-blind comparison study.

In a randomized, double-blind comparative study 60 patients with severe, widespread psoriasis were treated either with photochemotherapy (PUVA) alone or in combination with acitretin. Forty-eight patients completed the study; of these, 25 received placebo combined with PUVA and 23 received acitretin with PUVA. Marked or complete clearing of psoriasis occurred in 80% of the patients (20 of 25) without acitretin and in 96% of the patients (22 of 23) with adjunctive acitretin administration. The mean cumulative UVA dose given to patients in the acitretin-PUVA group was 42% less than that required for patients in the placebo-PUVA group. We conclude that acitretin substantially augments the efficacy of photochemotherapy in the treatment of severe psoriasis.

Acitretin

Markers for disease progression in intravenous drug users infected with HIV-1.

We evaluated the number and percentage of CD4+ T cells, the ratio of CD4+ T cells to CD8+ T cells, the serum levels of beta 2- microglobulin and urinary levels of neopterin for their ability to predict disease progression (defined as clinical AIDS and/or oral candidiasis in combination with a CD4+ T cell count less than 400 x 10(6)/l). Thirty-eight intravenous drug users (IVDU) infected with HIV-1 without HIV-1-related symptoms were followed for a median observation period of 45 months. Cumulative incidence of disease progression was computed by the product-limit approach. The CD4+: CD8+ T-cell ratio (P = 0.001), the number (P = 0.002) and percentage (P = 0.05) of CD4+ T cells, and urinary neopterin (P = 0.007) were significant predictors for disease progression. Serum beta 2-microglobulin, which has been found to be of similar prognostic value as neopterin in homosexual men, did not show predictive power in this study of IVDU. The urinary neopterin concentrations obtained at entry of the study correlated with the values of the CD4+:CD8+ T-cell ratio and number and percentage of CD4+ T cells which were obtained at the end of the follow-up. These findings should help to identify, among HIV-1-infected IVDU, those at high risk of disease progression.

Adult