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Biomedical subjects

P Fritsch

Publications and source records attributed to P Fritsch.

At least 181 records · Page 10Linked to original sources
PubMed1986

Transfer of Np(V) nitrate from gastrointestinal segments of the adult rat.

The transfer of soluble Np(V) nitrate was measured in gastrointestinal segments from adult rats by two procedures: instillation, in segments in which the physico-chemical form of Np might be modified by gastrointestinal factors; and perfusion, in segments in which the luminal state of Np remains constant. These assays allowed accurate measurement of the Np(V) transferred from the intestine to the whole body. The amount measured was proportional to segment length and to the duration of the experiments, which lasted for periods of 0.25 to 2 h. Under these experimental conditions, hourly transfer values were about 2 percent, both per millilitre of Np(V) solution instilled and per 10 cm of jejunum perfused. This flux is very much greater than that which may be deduced from studies in which Np was gavaged into intact rats. Intestinal transfer of Np was constant for Np concentrations ranging from 5 X 10(-12) M to 1 X 10-4) M. Raising the concentration of Np(V) to more than 1 X 10(-4) M reduced its intestinal transfer. Addition of Fe(II) also reduced it. The small intestine was the main site of Np(V) absorption, since the transfer from instilled jejunum was about 20 times that observed from the stomach, and no difference was noted between jejunal and duodenal transfer.

Animals↗
PubMed1986

Ontogeny of Ia-positive and Thy-1-positive leukocytes of murine epidermis.

Murine epidermis harbors 2 populations of dendritic leukocytes: Langerhans cells (LC) and Thy-1-positive dendritic epidermal cells (Thy-1 +DEC). In the adult mouse these cell types are morphologically distinct and display highly characteristic phenotypes. LC bear Ia-antigens and a group of markers typical for mononuclear phagocytes: Fc- and C3bi-receptors, macrophage-specific antigen F4/80, and membrane ATPase. Thy-1 +DEC, in contrast, lack these markers but express high levels of Thy-1 and asialo-GM1 (asGM1) antigen. Since LC and Thy-1 +DEC share a common origin from the bone marrow we expected to gain insight into their relationship by studying their ontogenetic development. Epidermal sheets from fetal and newborn C3H/He and C57B1/6 mice obtained at defined ages from day 17 of gestation up to day 30 of postnatal life were monitored for the emergence of the above-mentioned markers for LC and Thy-1 +DEC. In double-labeling experiments LC markers were first detected by visualizing the monoclonal antibodies by a sensitive triple-layer rhodamine-immunofluorescence technique; in a second step, after appropriate blocking procedures, Thy-1 and asGM1 antigens were demonstrated by direct and indirect immunofluorescence. We found that in fetal epidermis, only few cells expressed either Thy-1 or Ia (4 and 1 cells/mm2, respectively, on day 18 of gestation). The bulk of Thy-1 +DEC and Ia +EC appeared only after birth. Adult proportions of Thy-1 +DEC and Ia +EC were reached at around 1 month of postnatal life. In contrast, all the other LC markers were expressed on a substantial number of fetal dendritic cells (280 cells/mm2 on day 18 of gestation), indicating the presence of phenotypically immature Ia-negative LC in fetal epidermis. By day 4 of postnatal life all F4/80 +EC and ATPase +EC (i.e., LC) had acquired Ia-antigens. Surprisingly, LC also bore asGM1 antigens, which in the adult epidermis are strictly confined to Thy-1 +DEC, up to day 5 of postnatal life. Thus, LC in fetal and early newborn epidermis are not yet fully differentiated. As they differentiate, they acquire Ia antigens and lose asGM1 antigens. In contrast, a phenotypically immature Thy-1 +DEC population could not be traced with the markers used. Thy-1 +DEC appear to be characterized by a stable phenotype (Thy-1+/asGM1+) throughout their lifetime.

Age Factors↗
PubMed1986

Apoptotic keratin bodies as autoantigen causing the production of IgM-anti-keratin intermediate filament autoantibodies.

The presence of numerous keratin bodies in the upper dermis is a characteristic finding in skin lesions of patients with various dermatoses such as cutaneous graft-versus-host disease, lichen planus, or chronic discoid lupus erythematosus. These keratin bodies are generated by apoptotic keratinocyte death, consist largely of keratin intermediate filaments (KIF), and are constantly covered with immunoglobulins, mainly IgM. Apoptosis is also thought to occur under physiologic conditions in the skin as it does in other organs, but keratin bodies are not frequently reported as being found in nonlesional skin. In order to assess the frequency of keratin bodies in normal skin, we examined serial sections of 10 normal human skin specimens and 5 dermal sheets prepared from normal human skin for the presence of keratin bodies. They were visualized by direct immunofluorescence using a fluorescein isothiocyanate (FITC) rabbit antihuman IgM conjugate. In addition the KIF origin of keratin bodies was demonstrated by a double-staining immunofluorescence procedure using a FITC-conjugated rabbit antihuman IgM followed by a mouse monoclonal antibody against keratin and a sheep antimouse immunoglobulin conjugated with Texas Red. One specimen was also examined for keratin bodies at the ultrastructural level. In serial sections, all 10 normal human skin specimens had numerous keratin bodies as assessed by visualization of globular IgM deposits. Evaluated on dermal sheets, the number of keratin bodies ranged from 39-262 per mm2. Nearly all keratin bodies also stained with the antikeratin antibodies. Ultrastructurally the remarkable number of keratin bodies, which consist of filaments measuring approximately 10 nm in diameter or of more granular material, in normal human skin was confirmed. In order to investigate the capacity of KIF material in keratin bodies to function as autoantigen, we examined the sera of the 10 skin donors and, in addition, of 30 normal healthy individuals and 10 patients with rheumatoid arthritis for the occurrence and specificity of IgM-anti-KIF autoantibodies by an enzyme-linked immunosorbent assay and by immunoblot. IgM-anti-KIF autoantibodies were found in all 50 test sera. In the majority of the sera the specificity of these autoantibodies included the 51 kD and the 58 kD KIF protein, which are constituents of KIF in keratin bodies and basal keratinocytes. Quantitatively, the antibody activity of the IgM-anti-KIF autoantibodies varied from serum to serum, being highest in the sera of patients with rheumatoid arthritis.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗
PubMed1986

HLA-DR expression on keratinocytes is a common feature of diseased skin.

Biopsy specimens from 185 patients with 52 different skin disorders were investigated by indirect immunofluorescence staining for the presence of HLA-DR bearing keratinocytes and their association with an underlying inflammatory infiltrate and in particular with activated (HLA-DR-positive, Leu-4-positive) T lymphocytes. HLA-DR expression on keratinocytes was demonstrated in 38 dermatoses, including lymphocytic vasculitis, lupus erythematosus, morphea, vitiligo, lichen planus, cutaneous T-cell lymphoma, various infectious dermatoses, allergic contact dermatitis, granulomatous dermatoses, Sweet's syndrome, lichen sclerosus and erythema nodosum. In 27 of these this had not previously been reported. Occurrence of HLA-DR on keratinocytes was invariably linked to the presence of a lymphocytic infiltrate containing numerous activated T-cells (Leu-4 +, HLA-DR +) whereas such infiltrates were not accompanied by HLA-DR expression on keratinocytes in all the dermatoses investigated, as in pseudolymphoma and erythema anulare centrifugum. However, HLA-DR positive keratinocytes were consistently absent in skin disorders lacking any significant lymphocytic infiltration (e.g. leukocytoclastic vasculitis, bullous autoimmune dermatoses, genodermatoses and mastocytosis). Although it has been suggested that HLA-DR-positive keratinocytes are involved in various immune responses of the skin, their exact functional significance is, as yet, unknown.

Epidermis↗
PubMed1986

Gastrointestinal absorption of neptunium in primates: effect of ingested mass, diet, and fasting.

Absorption and retention of neptunium were determined in baboons after intragastric administration of neptunium nitrate solutions at pH 1. The effects of mass, diet, and fasting on absorption were studied. At higher mass levels (400-800 micrograms Np/kg), absorption was about 1%; at lower mass intakes (0.0009-0.005 micrograms Np/kg), absorption was reduced by 10- to 20-fold. The addition of an oxidizing agent (Fe3+) increased gastrointestinal absorption and supported the hypothesis of a reduction of Np (V) when loss masses were ingested. Diets depleted of or enriched with hydroxy acids did not modify retention of neptunium but increased urinary excretion with increasing hydroxy acid content. The diet enriched with milk components reduced absorption by a factor of 5. Potatoes increased absorption and retention by a factor 5, not necessarily due to the effect of phytate. Fasting for 12 or 24 h increased retention and absorption by factors of about 3 and 10, respectively. Data obtained in baboons when low masses of neptunium were administered suggest that the f1 factor used by ICRP should be decreased. However, fasting as encountered in certain nutritional habits is a factor to be taken into consideration.

Animals↗
PubMed1985

Human interferon-gamma induces expression of HLA-DR on keratinocytes and melanocytes.

Primary human epidermal cell cultures composed of keratinocytes and melanocytes were exposed to supernatants of phytohaemagglutinin (PHA)-stimulated T cells, various lymphokines and interferon-beta, and checked for the emergence of HLA-DR antigen using immunofluorescence and immunoelectron microscopy. HLA-DR expression was induced by the supernatants and human recombinant interferon-gamma (rIFN-gamma), whereas recombinant interferon-alpha 2, interleukin-2 and non-recombinant human interferon-beta had no such effect. The threshold concentration of rIFN-gamma required to induce this phenomenon was 10 IU/ml; no further increase of reaction intensity was observed using doses of more than 100 IU/ml. Maximum reaction intensity was achieved after 72 h of incubation; a minimum of 3 h of incubation with rIFN-gamma followed by 72 h incubation in rIFN-gamma-free medium proved sufficient to induce HLA-DR expression. The inductive effect of the supernatants and rIFN-gamma could be completely abrogated by pretreatment with excess doses of the monoclonal antibody GZ4 specific for human IFN-gamma. Keratinocytes and melanocytes reacted in an identical fashion both qualitatively and quantitatively in all experiments. These data indicate that IFN-gamma possesses specific signal functions in the induction of HLA-DR expression on epidermal cells.

Cells, Cultured↗
PubMed1985

Excretion of nitrates and nitrites in saliva and bile in the dog.

The kinetics of salivary and biliary excretion of inorganic nitrates and nitrites was studied in mongrel dogs after iv injection of these compounds labelled with 15N. There was strong salivary excretion of 15NO-3 after injection of Na15NO3 but little or no nitrites were excreted in the saliva, indicating that the nitrites present in the mouth are mainly the result of in situ transformation of nitrates into nitrites. In the bile, large quantities of nitrates were excreted when the dogs received 15NO-2, indicating endogenous oxidation of the nitrite.

Animals↗
PubMed1985

[Allergic granulomatosis (Churg-Strauss syndrome)].

Allergic granulomatosis is a rare life-threatening systemic disorder of unknown origin, which represents a variant of systemic necrotizing vasculitis affecting medium-sized arteries and venules. Histologically, allergic granulomatosis is characterized by vascular and extravascular necrotizing palisading granulomas with prominent eosinophilia (Churg-Strauss granulomas). The clinical criteria include atopy with severe allergic asthma, pronounced peripheral eosinophilia, and nodular infiltrates of the skin and internal organs (Churg-Strauss granulomas). The internal organs most commonly involved are the lungs, gastrointestinal tract and, less often, the peripheral nerves, heart, and kidneys. Associated symptoms include fever, arthralgias and skin rashes, such as erythema multiforme, necrotizing venolitis, fixed drug eruption, and urticaria. Allergic granulomatosis shares common features with Wegener's granulomatosis and polyarteritis nodosa and may be related to the latter condition; overlap syndromes are a well-known occurrence. Similar to the other manifestations of systemic necrotizing vasculitis, immune complexes have been detected in fresh lesions and are suspected of being the basic pathogenetic findings. The causative antigens are likely to be respiratory antigens. The prognosis of untreated allergic granulomatosis is poor (mortality of approximately 50% within the first year). Systemic corticosteroids and cyclophosphamide are effective; complete remissions following cyclophosphamide treatment have been reported.

Adult↗
PubMed1985

[Autohistoradiographic study of the pulmonary retention of almitrine bismesylate].

The histo-autoradiographic distribution of labelled Almitrine was quantitatively assessed on semi-fine cuts of rat lung. The experimental set-up consisted of an isolated heart-lung preparation, perfused for two hours with homologous blood containing 10 microCi per ml of H3 almitrine (990 mCi/mM) et 0.1 microCi per ml of C14 almitrine (9.9 mCi/MM). Sequential histological biopsies were made. There was an apparent heterogeneous radioactivity of the tissues overall with no observed increase in fixation with perfusion time (v.i.). Nevertheless the auto-radiograph enabled this conclusion to be rectified by revealing the cause of the heterogeneity, the embolisation of micro-aggregates of the labelled product. After correction was made for this factor the scattering of the fixed radioactivity in the samples was weak. The localisation of the labelled product showed a good stability for the fixed marker in the tissues, and identified the distribution of the tracers H3 and C14, a preferential fixation by alveolar macrophages, type-2 pneumocytes, Clara cells and adipocytes. A remarkable fixation was noted in the cardiac fibres of the pulmonary veins. Amongst the cells of the bronchi, the mucus cells were notably active for the fixation of Almitrine. There was no detectable fixation associated with the nervous tissues and the neuro-epithelial body was not labelled. A sequential analysis showed that only fixation in smooth muscle fibres rose significantly with perfusion time.

Almitrine↗
PubMed1985

[Mycetoma caused by Petriellidium boydii: treatment with ketoconazole].

A case of mycetoma of the lower leg (Madura foot) with bone involvement caused by Petriellidium boydii is presented. After an initially favourable therapeutic response to ketoconazole (2 X 200 mg/die) the process recurred despite proven sensitivity of the fungus in vitro. It could not be controlled with conservative treatment and ultimately necessitated amputation of the lower leg. A striking, hitherto unreported feature of mycetoma was the episodic occurrence of circulating immune complexes with febrile monoarthritis of the adjacent ankle.

Adult↗
PubMed1984

Treatment of localized scleroderma and lichen sclerosus with etretinate.

Eight patients with lichen sclerosus and 8 patients with localized scleroderma were treated with etretinate (Tigason) at doses of 0.5 mg/kg body weight for between 3 and 12 months: 2 of 3 patients with juvenile type lichen sclerosus cleared, whereas the lesions of 5 patients with balanitis xerotica obliterans, kraurosis vulvae and extragenital lichen sclerosus were unchanged or even progredient. 2 of the patients with localized scleroderma cleared with slight atrophy. The lesions of 5 others failed to resolve but progression was halted under continued therapy; after drug withdrawal, the lesions resumed progression in 2 patients. We conclude that only moderate therapeutic effects can be achieved with etretinate in both lichen sclerosus and localized scleroderma.

Adult↗
PubMed1984

[Cheilitis granulomatosa (Melkersson-Rosenthal syndrome): treatment with clofazimine].

A pilot study with the anti-leprosy agent clofazimine was conducted on seven patients with cheilitis granulomatosa or complete Melkersson-Rosenthal syndrome. Beneficial effects were observed in all patients, dependent on the degree of the clinical expression of the disease: the variable attacks of lip swelling, characteristic for the edematous phase of this disease, were suppressed promptly and completely in all patients. Persistent residual swelling of the lips, caused by cellular inflammatory infiltrates, which was present in four patients prior to therapy, responded much less rapidly and--in three out of four--only incompletely. After drug withdrawal, four patients remained free of symptoms for periods ranging from 5 to 45 months; the remaining three patients relapsed after intervals of 3-18 months. The mode of action clofazimine takes in cheilitis granulomatosa is not understood at the present time but is likely to be linked to the phagocytosis-stimulating effect of this drug on macrophages.

Adolescent↗
PubMed1984

[Xeroderma pigmentosum: prevention of tumors with etretinate].

A 46-year-old woman with xeroderma pigmentosum has had more than one hundred skin tumours in her life, in recent years largely keratoacanthomas. Two and a half years ago, a low-dose prophylactic treatment with etretinate (25 mg/day) was initiated. Since then, no further skin tumours have arisen except for several very small, rapidly resolving keratoacanthomas.

Etretinate↗