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Biomedical subjects

T Fischer

Publications and source records attributed to T Fischer.

At least 217 records · Page 12Linked to original sources

Regulation of the human immune response to ragweed pollen by immunotherapy. A controlled trial comparing the effect of immunosuppressive peptic fragments of short ragweed with standard treatment.

A new allergenic preparation consisting of peptic fragments of short ragweed has been tested for its clinical effectiveness. Such enzymatically derived fragments have been shown in prior murine studies to retain the T epitopes of the original allergen but to have a severe reduction in the number of B epitopes. Three groups of ragweed hayfever patients were placed on pre-seasonal immunotherapy. One group received a conventional ragweed preparation that had been enriched for antigen E (Amb a I), designated as Pool 2. The second group was given fragments of Pool 2 (fSRW) prepared by peptic digestion and the third group was injected with histamine as a placebo. Groups treated with the fSRW and Pool 2 had significantly reduced symptom-medication scores compared with the placebo-treatment group. However, fSRW-treated patients fared significantly better than Pool 2 patients (P less than 0.02). fSRW injections caused a significant rise in preseasonal specific IgG, antibodies as well as suppression of the seasonal anamnestic specific IgE increase. Similar, but not quite as marked changes occurred with Pool 2 treatment. fSRW was well tolerated and non-toxic. Thus, allergen modification by enzymatic degradation, as demonstrated here, appears to be a promising new approach for allergen immunotherapy.

Adult↗

Evaluation of customers' complaints about sunscreen cosmetics sold by the Swedish pharmaceutical company.

Sweden's pharmacies hold more than a 1/3 of the country's market for sunscreen cosmetics (sunscreens). Customers complaining of skin problems associated with the use of sunscreens obtained from the pharmacies were offered dermatological investigation and tests with standard allergens and sunscreens. 27 of 58 complaining customers were fully investigated, and another 8 partly tested. 2 disease entities, a burning sensation and erythema for one or a few days, and dermatitis with scaling lasting for up to 3 weeks, were about equally common. Contact or photocontact allergy to 2-hydroxy-4-methoxybenzophenone caused severe contact dermatitis in 3 individuals.

Benzophenones↗

Regulation of IFN-gamma-receptor expression in human monocytes by granulocyte-macrophage colony-stimulating factor.

The regulation of human IFN-gamma receptor (IFN-gamma-R) expression by granulocyte-macrophage CSF (GM-CSF) was investigated. On monocytic cell lines (U937, HL60) and peripheral blood monocytes, IFN-gamma-binding capacity was down-regulated upon incubation with GM-CSF. Scatchard plot analyses revealed that down-regulation was caused by a decrease in IFN-gamma-R number rather than by a change in affinity. GM-CSF treatment did not reduce IFN-gamma-R-specific mRNA levels, but reduced the half-life of membrane-expressed IFN-gamma-R, indicating a post-translational control of IFN-gamma-R by GM-CSF. Because both IFN-gamma and GM-CSF are crucially involved in activation of monocytic function, the data presented suggest that down-regulation of IFN-gamma-R by GM-CSF may represent a potential negative feedback control of monocyte activation. Further studies of IFN-gamma binding characteristics and isolation of IFN-gamma-R by immunoprecipitation revealed that IFN-gamma binding to human peripheral blood monocytes is mediated by a receptor protein structurally and functionally identical to that previously characterized in several established cell lines of other tissue origin.

Blotting, Northern↗

Glycosylation of the human interferon-gamma receptor. N-linked carbohydrates contribute to structural heterogeneity and are required for ligand binding.

The contribution of N-linked carbohydrates to human interferon-gamma receptor (hIFN-gamma-R) structure and function was investigated in four tumor cell lines of various tissue origin. Western and ligand blotting of native and deglycosylated, affinity-purified hIFN-gamma-R of the monocytic cell line U937 and the lymphoid cell line Raji revealed that the different sizes of hIFN-gamma-R from U937 (103 kDa) and Raji (90 kDa) cells are reduced upon either metabolic inhibition or enzymatic deglycosylation of N-linked carbohydrates to a common size of the receptor molecule with an apparent molecular mass of 73 kDa for both cell lines, indicating that heterogeneity in hIFN-gamma-R size is largely due to differential glycosylation. In all cell lines investigated, inhibition of N-linked glycosylation or modulation of carbohydrate processing did not prevent receptor transport to the cell membrane, but blocked hIFN-gamma binding capacity of membrane-expressed receptor molecules, as revealed by specific binding of hIFN-gamma-R-specific monoclonal antibody and specific binding of 125I-labeled hIFN-gamma. These data suggest that a lack of complex-type N-linked carbohydrates is associated with a complete loss of receptor function, i.e. high affinity binding capacity. Recovery of hIFN-gamma binding of deglycosylated receptors was achieved upon affinity purification and adsorption to nitrocellulose membranes, indicating that the carbohydrate side chains themselves do not directly contribute to the ligand binding epitope but seem to be essential for appropriate conformation of the receptor protein in the cell membrane.

Alkaloids↗

Human chromosome 21 is necessary and sufficient to confer human IFN gamma responsiveness to somatic cell hybrids expressing the cloned human IFN gamma receptor gene.

The human interferon (IFN) gamma receptor cDNA has been stably expressed in human/mouse somatic cell hybrids, which differ in their content of human chromosome 21. Despite high affinity IFN gamma binding-capacity of all receptor transfectants, biological responsiveness to IFN gamma, as determined by enhancement of mouse-MHC class I gene expression, required the presence of chromosome 21. These data suggest complementation of at least two functionally distinct components in order to create a biologically active IFN gamma receptor.

Animals↗

Multiple sclerosis and other immunologic diseases.

A characteristic feature of immunologic diseases is their association with each other. For multiple sclerosis (MS), several retrospective studies reported increased as well as expected coincidence rates with other immunologic diseases. We conducted a prospective case-control study of MS patients and healthy volunteers and found 13/101 MS patients and 2/97 controls with such diseases (P = 0.009, chi-square test), as well as 47/88 MS patients versus 31/95 controls with a variety of circulating autoantibodies (P = 0.004, chi-square test). These results speak for an increased coincidence of MS with other immunologic diseases and support the idea that MS is also an immunologic disease.

Adolescent↗

Relationship of one form of human histamine-releasing factor to connective tissue activating peptide-III.

We have previously reported purification of three forms of histamine-releasing factors (HRFs) from mixtures of streptokinase-streptodornase stimulated human mononuclear cells and platelets with apparent molecular masses of 10-12, 15-17, and 40-41 kD (1989. J. Clin. Invest. 83:1204-1210). We have also prepared mouse MAbs against the 10-12-kD HRF (1989. J. Allergy Clin. Immunol. 83:281). Affinity-purified 10-12-kD HRF appears as a broad band upon polyacrylamide gel electrophoresis in the presence of SDS. We determined the NH2-terminal amino acid sequence of the top and bottom halves of this broad band. Sequence analysis revealed striking homology between this HRF and connective tissue activating peptide-III (CTAP-III), a platelet-derived 8-10-kD protein known to cause mitogenesis and extracellular matrix formation in fibroblast cultures. 19 of 21 NH2-terminal residues in the top half of the HRF band were identical to the NH2-terminal sequence of CTAP-III. 20 of 21 NH2-terminal residues in the bottom half were identical to the NH2-terminal sequence of neutrophil-activating peptide-2, which is derived from CTAP-III by proteolytic cleavage between residues 15 and 16. Purified CTAP-III also released histamine from basophils. Rabbit antiserum raised against either native or recombinant CTAP-III recognized affinity-purified HRF in immunodot blot assays, and MAb against HRF recognized CTAP-III in both dot blot and microtiter plate based immunoassays. These data demonstrate the first structural, functional, and immunologic relationship between one form of human HRF and a previously described cell product.

Amino Acid Sequence↗

Influence of topical metal binding substances, vehicles, and corticosteroid creams on the allergic patch test reaction in metal-sensitive patients.

Persons known to be allergic to nickel, cobalt, or both were patch tested with serial dilutions of cobalt chloride or nickel sulfate either in petrolatum on skin treated with topical preparations with and without metal-binding compounds or incorporated into such special preparations. A decreased response was found in patients tested with Vioform (clinquinol) and cobalt chloride simultaneously, whereas rutin (3,3',4',5,7-pentahydroxyflavon 3-rhamnoglucosid) increased the response, and polyfloretin phosphate had no effect. The vehicles proved significant: "Ung Merck" and "W/O Cream Base" increased reactivity, whereas polyethylene glycol gave good protection against metal ions. As expected, corticosteroid creams suppressed the inflammatory response.

Administration, Topical↗

The effects of cryogenic blockade of the centrifugal, bulbopetal pathways on the dynamic and static response characteristics of goldfish olfactory bulb mitral cells.

The responses of single goldfish olfactory bulb mitral cells were studied by extracellular recordings before and during cryogenic blockade of the efferent, centrifugal pathways in the ipsilateral olfactory tract. In each experiment the same odour was presented 40 times before and then 40 times during cooling. Each stimulus period (at least 30 s) was preceded by a stimulus-free interval (at least 30 s), during which a steady stream of tap water was applied. These procedures allow the investigation of activity changes of single neurons and of cell ensembles using statistical methods. i) In comparison with the pre-cooling activity, cooling of the efferent pathways did not cause a generalized disinhibition in mitral cell responses. Significant disinhibitory, significant inhibitory and indifferent effects occurred in about the same proportion during repetitive water and odour applications. ii) Abrupt or slow changes of single mitral cell discharge patterns during the 40 water and odour applications were observed before and during blocking of the efferent fibre systems: These pattern changes are therefore not necessarily a consequence of the efferent signals, and may thus have been a result of intrabulbar plasticity. iii) The most notable effect of efferent fibre blockade across all experiments was a significant (Wilcoxon-rank-test, P = 0.01) decrease of the signal to noise ratio i.e., the ratio between the activity during the "spontaneous" (water) and the stimulus (odour) phase, which could be demonstrated for both the phasic (immediately after stimulus onset) and tonic (during long term stimulation) components of the mitral cell responses.

Action Potentials↗

Easier patch testing with TRUE Test.

TRUE Test, a standardized, ready-to-apply patch test system, is made from polyester covered with a film of allergens incorporated in a hydrophilic polymer. The patches are mounted on nonwoven cellulose tape with acrylic adhesive, covered with siliconized plastic, and packed in an air-tight and light-impermeable envelope. When the test strip is taped on the skin, perspiration hydrates the film and transforms it to a gel, which causes the allergen to be released. The first panel of 12 allergens and allergen mixes is standardized and tested for stability in vitro and in vivo. The accuracy of the test panel has been certified in international multicenter studies by comparing it with present patch test techniques. A second panel of 11 more allergens was completed in 1988. The two test panels include the full standard panel of the North American Contact Dermatitis Group.

Dermatitis, Contact↗

Patch testing technique.

The patch test is a necessary tool to evaluate contact dermatitis and other pruritic dermatoses. To obtain accurate test results, however, high-quality test material must be used, the application technique must be correct, and the results must be evaluated with skill and criticism. The relevance of the test should be related to the patient's history: both positive and negative test results are of importance.

Allergens↗

Chemical, pharmaceutical and clinical standardization of the TRUE Test caine mix.

The development of the caine mix patch of the TRUE TestTM involved extensive formulation work to obtain optimal release, stability and clinical function. Hydroxypropyl cellulose, ordinarily used in the TRUE TestTM, induced crystallization and inadequate release of benzocaine. Addition of the crystal poison glucose caused rapid degradation of the caines. Polyvinylpyrrolidone (PVP) proved to be a vehicle which incorporated the caines in a stable preparation on the patch. Rapid release of the caines from this vehicle when applied on membranes was confirmed by in vivo patch test studies.

Adult↗

N-glycosidase treatment of Colo 205 cells interferes with hIFN-gamma induced HLA-DR expression.

We investigated the effects of N-glycosidase treatment on the interferon-gamma (IFN-gamma) induced HLA-DR expression of Colo 205 cells. N-glycosidase treatment resulted in a significant decrease of IFN-gamma induced HLA-DR specific immunofluorescence intensity ranging from complete reduction to approximately 30% of that of untreated control cells depending on the IFN-gamma dose. IFN-gamma binding studies showed that this was due to a severe reduction in IFN-gamma binding capacity of N-glycosidase treated cells. Since the number of cell membrane IFN-gamma receptors (IFN-gamma-Rs) was virtually unchanged as revealed by immunofluorescence analysis with a hIFN-gamma-R specific monoclonal antibody this indicates that N-linked carbohydrates play an important role in signal transduction and ligand binding capacity of the hIFN-gamma-R and strengthens the view that carbohydrate moieties of receptor proteins are of greater functional significance than originally anticipated.

Cell Line↗

Serum alpha fetoprotein in 714 mentally retarded carriers of hepatitis B surface antigen.

Sera from 714 mentally retarded carriers of hepatitis B surface antigen were screened for alpha fetoprotein (AFP) by monoclonal radioimmunoassay. Serum AFP levels were less than 20 mcg/L in 708 (99.2%) carriers. One 29-year-old carrier with normal liver function had serum AFP level of 1500 mcg/L, which increased to 12,500 mcg/L after 72 days. She died of multifocal hepatocellular carcinoma (HCC) with cirrhosis. Five other carriers with serum AFP levels between 20 and 165 mcg/L are alive without clinical HCC. No correlation was found between serum AFP level and race, age, sex, Down's syndrome, serum alanine aminotransferase level, and hepatitis B e antigen positivity. Single cross-sectional serum AFP screening by itself is not sufficient for early diagnosis of HCC.

Adolescent↗

European multicenter study of the TRUE Test.

A new, standardized, ready-to-apply patch test, the TRUE Test, has been evaluated on 698 consecutive patients with suspected contact dermatitis. The patients were tested with 12 different allergens. Simultaneously, the same 12 allergens in pet. (Trolab) were applied symmetrically to the opposite side of the upper back using the conventional Finn Chamber technique. There were positive test reactions to all 12 allergens tested in the patient group. The concordance of positive reactions between the TRUE Test and the Finn Chamber test was 67%; 13% of all positive reactions were recorded only for the TRUE Test and 20% only for the Finn Chamber method. The frequency of questionable and irritant reactions was of the same low order of magnitude for both test methods; such reactions were recorded in around 2% of all test patches.

Allergens↗