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Biomedical subjects

C Hafner

Publications and source records attributed to C Hafner.

18 recordsLinked to original sources

[Hemorrhagic dengue fever after trip to Malaysia].

A 39-year-old patient developed a disseminated rash with scattered petechiae, fever, malaise and arthralgia after a trip to Malaysia. The patient displayed increasing dengue IgG titers and borderline dengue IgM titers. Dengue fever with a hemorrhagic course is a rare condition in adult patients. Patients who have previously had dengue fever and retained non-neutralizing heterotypic antibodies are more likely to develop this complication via the phenomenon of antibody-dependent enhancement.

Adult↗

Primary cutaneous cryptococcosis and secondary antigenemia in a patient with long-term corticosteroid therapy.

We report a case of a 71-year-old male who developed severe cellulitis of his right forearm and hand after he had an accidental injury from the sharp edge of a metal plate of a birdhouse. The patient suffers from chronic asthma and has been treated with systemic corticosteroids for years. Culture of aspirates from two sites of the wound area revealed growth of Cryptococcus neoformans in one and Acinetobacter lwoffii in the other. After combined treatment including antibiotics, antifungal therapy with fluconazole 400 mg/d and surgical debridement followed by a mesh graft, the patient achieved complete healing of the wound. Five months after the infection, the patient was still positive for cryptococcal antigen at a titer of 1:64 despite oral treatment with fluconazole 50 mg/d, and maintenance therapy with fluconazole 200 mg/d was recommended for 6 months, or longer depending on further results. The clinical and microbiological characteristics of this patient as well as therapeutical and epidemiological aspects of primary cutaneous cryptococcosis (PCC) are discussed.

Aged↗

Characterization of cross-reactive bell pepper allergens involved in the latex-fruit syndrome.

BACKGROUND: Between 30% and 50% of individuals who are allergic to latex products are also allergic to specific plant foods, a fact that is well documented as the latex-fruit syndrome. Simultaneous sensitization to latex and bell pepper has been previously reported. Although bell pepper fruits are frequently consumed raw, cooked or as a spice, little is known about the cross-reactive allergens. OBJECTIVE: In this study we wished to identify bell pepper allergens involved in the latex-fruit syndrome. METHODS: Sera of four patients who displayed clinical symptoms to latex and bell pepper were used in immunoblot studies on protein extracts of three different cultivars of fresh bell pepper and fresh Hevea latex. Cross-reactive allergens were identified by inhibition experiments using recombinant Hev b 8 (latex profilin), and natural Hev b 2 (latex beta-1,3-glucanase) in addition to the protein extracts. A novel cross-reactive IgE-reactive 30 kDa protein was subjected to sequence analysis. RESULTS: Three patients displayed IgE to profilins from bell pepper fruits and latex. Two patients possessed IgE to Hev b 2, a latex beta-1,3-glucanase, and a homologous protein in bell pepper. One patient possessed IgE reactive with a protein of 30 kDa identified by N-terminal sequencing as an l-ascorbate peroxidase and another patient to a protein of 38 kDa. Additionally, IgE binding proteins in two higher molecular weight ranges showed cross-reactive capacities. CONCLUSION: Our findings show on the molecular level that bell pepper is part of the latex-fruit syndrome. For the first time we have identified the major latex allergen Hev b 2, a beta-1,3-glucanase, and the bell pepper l-ascorbate peroxidase as cross-reactive allergens. We were also able to show that profilins are responsible for some of the IgE cross-reactivity.

Adult↗

Identification of differentially expressed genes in models of melanoma progression by cDNA array analysis: SPARC, MIF and a novel cathepsin protease characterize aggressive phenotypes.

Currently, the scale and consistency of changes of gene expression profiles in models of melanoma progression are largely unknown. Therefore, we investigated siblings of cell lines or malignant melanomas (MM), which have been selected by nude mouse passages for (a). increased tumorigenicity (local ECM-independent growth), (b). metastatic potential, or (c). selected for increase invasiveness using the Boyden chamber. cDNA array analysis surveying more than 27.000 transcripts per cell line showed that 1.5-2.8% of all detectable transcripts were consistently differentially regulated during selection process in those models. Using array analysis, we identified 33 individual transcripts that exhibited significant differential hybridization paralleling the increased aggressiveness of the selected progeny. Because some of those genes could play a significant functional role in the progression of MM, we additionally proved their regulative pattern using Northern blotting. Among others, progressive overexpression of osteonectin/SPARC, a angiogenesis, was found in the selected offspring from all three experimental models and may therefore be considered as a potential marker for aggressive MM as well a promising therapeutic target. We further show that the selection of MM cells for increased ECM-independent local growth was accompanied by overexpresssion of macrophage migration inhibiting factor (MIF), an important modulator of both cell cycle progression and angiogenesis, and cathepsin Z, a novel member of the family of matrix degrading proteinases.

Animals↗

Monovalent fusion proteins of IgE mimotopes are safe for therapy of type I allergy.

By screening phage display random peptide libraries with purified immunoglobulin E (IgE) from birch pollen-allergic patients, we previously defined peptides mimicking natural IgE epitopes (mimotopes) of the major birch pollen allergen Bet v 1. The present study aimed to define a monovalent carrier for the IgE mimotopes to induce protective antibodies directed to the IgE epitopes, suitable for mimotope-specific therapy. We expressed the selected mimotopes as fusion proteins together with streptococcal albumin binding protein (ABP). The fusion proteins were recognized specifically by anti-Bet v 1 human IgE, which demonstrated that the mimotopes fused to ABP resemble the natural IgE epitope. Bet v 1-specific IgG was induced by immunization of BALB/c mice with fusion proteins. These IgG antibodies could inhibit IgE binding to Bet v 1. Skin testing of Bet v 1 allergic mice showed that the ABP mimotope constructs did not elicit type I skin reactions, although they possess IgE binding structures. Our data suggest that IgE mimotopes are safe for epitope-specific immunotherapy of sensitized individuals, when presented in a monovalent form. Therefore, ABP-fused mimotopes are promising candidates for a new type of immunotherapy based on the precise induction of blocking antibodies.

Allergens↗

Evidence for oligoclonality and tumor spread by intraluminal seeding in multifocal urothelial carcinomas of the upper and lower urinary tract.

Multifocality and recurrence of urothelial carcinoma may result from either the field effect of carcinogens leading to oligoclonal tumors or monoclonal tumor spread. Previous molecular studies, favoring the monoclonality hypothesis, are mostly limited to the urinary bladder. We investigated genetic alterations in a total of 94 synchronous or metachronous multifocal tumors from 19 patients with at least one tumor both in the upper and lower urinary tract. Loss of heterozygosity (LOH) was determined using eight markers on chromosome 9 and one marker on 17p13 (p53). Microsatellite instability was investigated at six loci and protein expression of MSH2 and MLH1 was evaluated by immunohistochemistry. In addition, exons 5-9 of the p53 gene were sequenced. Deletions at chromosome 9 were found in 73% of tumors and at 17p13 in 18% of tumors. There was no significant difference in the frequency of LOH in the upper and lower urinary tract. Deletions at 9p21 were significantly correlated with invasive tumor growth. The pattern of deletion revealed monoclonality of all tumors in nine patients. In five patients there were at least two tumor clones with different genetic alterations. In four of these patients the different clones occurred in the bladder and subsequently in the ureter and renal pelvis. All four patients with p53 mutations revealed identical mutations in all tumors. Thus, multifocal urothelial carcinomas are frequently monoclonal, whereas others show oligoclonality, providing molecular evidence for field cancerization. Intraluminal tumor cell seeding appears to be an important mechanism of multifocal occurrence and recurrence of urothelial carcinomas.

Chromosomes, Human, Pair 9↗

Hev b 7 is a Hevea brasiliensis protein associated with latex allergy in children with spina bifida.

BACKGROUND: In addition to their disease-associated handicaps, patients with spina bifida (SB) are at high risk of developing latex allergy. Individuals with SB represent a special group of latex-allergic patients, inasmuch as their IgE-binding patterns differ from those of other populations of latex-allergic individuals. Two allergens strongly associated with latex allergy in patients with SB--Hev b 1 and Hev b 3--have already been identified. OBJECTIVE: We intended to identify a predominant IgE-binding band--in addition to Hev b 1 and 3--at 43 kDa in a study population of 38 latex-allergic (IgE antibodies to latex and symptoms on provocation with latex gloves) and 15 latex-sensitized (IgE antibodies to latex but no symptoms on provocation) children with SB (mean age, 12.3 years) and to determine its frequency of recognition. METHODS: Sera of latex-sensitized or latex-allergic patients with SB were tested on latex C extract containing natural Hev b 1, Hev b 3, and Hev b 7 and with the recombinant 43-kDa Hev b 7 in immunoblot and inhibition studies. RESULTS: Natural Hev b 1 was recognized by 82% and natural Hev b 3 by 79% of the latex-allergic children with SB. In addition to some other proteins, 15 (39.5%) of 38 latex-allergic and 2 (13%) of 5 latex-sensitized children with SB revealed IgE binding to a 43-kDa band in the latex protein extract. We identified this 43-kDa IgE-binding band as natural Hev b 7 by immunoblotting and inhibition experiments using recombinant Hev b 7. CONCLUSION: From these data, we conclude that Hev b 7, the patatin-like Hevea latex protein, is the third SB-associated latex allergen. Future immunotherapy for latex-allergic individuals with SB will have to include Hev b 7 in addition to Hev b 1 and Hev b 3.

Adolescent↗

Molecular and immunologic characterization of new isoforms of the Hevea brasiliensis latex allergen hev b 7: evidence of no cross-reactivity between hev b 7 isoforms and potato patatin and proteins from avocado and banana.

BACKGROUND: Hev b 7 is a Hevea brasiliensis latex allergen with sequence identities of 39% to 42% to patatins recently identified as potato allergens. The complementary DNAs encoding 2 different Hev b 7 isoforms were previously reported. OBJECTIVE: The aim of this study was to determine the sequence variation of Hev b 7 and to compare the IgE reactivity of individual isoforms in vitro and in vivo. A further objective was to evaluate possible cross-reactivities between Hev b 7 and patatins and proteins from banana and avocado. METHODS: An H brasiliensis lambda ZAP complementary DNA (cDNA) library was screened with use of a Hev b 7 cDNA probe. Four Hev b 7 isoforms were produced in recombinant form and their IgE-binding capacities were compared. IgE immunoblot inhibitions and ELISA inhibition assays were used to investigate the possible cross-reactivity between Hev b 7 and recombinant potato patatin and proteins from avocado and banana. RESULTS: Two new isoforms, S2 and D2, were identified by sequencing 32 cDNA clones with full-length coding regions. All 4 recombinant isoforms displayed esterase activity and identical IgE-binding capacities. The new isoforms S2 and D2 were evaluated in skin prick tests and provoked responses equivalent to natural Hev b 7. No cross-reactivity was observed between Hev b 7 isoforms and potato patatin and proteins from avocado and banana. CONCLUSIONS: All 4 recombinant Hev b 7 isoforms have equivalent IgE-binding capacity and therefore represent suitable reagents for the development of in vitro and in vivo diagnostic tests. Hev b 7, patatins, and their homologs appear not to contribute to cross-reactivity in the latex-fruit syndrome.

Adult↗

Evaluation of genotoxicity of emissions from municipal waste incinerators with Tradescantia-micronucleus bioassay (Trad-MCN).

A 4-year study was conducted to investigate the suitability of the Tradescantia-micronucleus bioassay (Trad-MCN) to detect genotoxicity of emissions from municipal waste incinerators. The genotoxic potential of emissions was assessed in three ways: (i) direct fumigation of Tradescantia with diluted incinerator emissions, (ii) exposure of Tradescantia to smoke condensates and (iii) in situ monitoring of genotoxicity of emissions near a municipal incinerator. The results of direct fumigation with smoke emissions varied over the course of the study. In 1992, significantly higher micronuclei frequencies (MCN) were always observed in treated plants than in control plants, regardless of length of fumigation period. Furthermore, MCN frequencies were significantly higher in plants fumigated for 24 h than those fumigated for 8 h, and MCN frequencies were also higher in plants fumigated in chamber 1 (low dilution, high stack gas concentration) than those in chamber 2 (P<0.05). MCN frequencies were substantially lower in 1993 and 1994, and in only 1 out of the 5 fumigation experiments were MCN frequencies significantly higher in treated plants than in controls. This drop in MCN frequencies was possibly due to the installation of better pollution control devices in the incinerator in 1993. Exposure to smoke condensates induced significant increases in MCN frequencies in most exposure trials. A drop in MCN frequencies over the course of the 4-year study was also attributed to the installation of new smoke scrubbing devices. This was further confirmed by the chemical analysis of the condensate, which showed a significant reduction in organic pollutants after the installation of the new devices. The results of in situ monitoring of genotoxicity near a municipal waste incinerator showed that MCN frequencies of Tradescantia depended on the distance from the incinerator, and the direction of wind. Because exposure periods of 6 h were insufficient to elicit significant responses, periods of 10 to 24 h are recommended for in situ monitoring.

Air Pollutants↗

Turnover of microfilariae in small mammals 2. Disintegration of microfilariae (Acanthocheilonema viteae) (Filarioidea: Nematoda) after intravenous injection into the jird, Meriones unguiculatus.

After i.v. injection of 305 x 10(3) microfilariae (mf) per animal (50 g) into naive jirds, 50.8% of them could be recovered at autopsy 15 min later. Of these, 65.8% were calculated to be in the peripheral circulating blood (PCB) and were completely intact; 18.6% were recovered by perfusion of the lungs and 13.6% from the liver. In both organs about half the mf were associated with adherent lymphocytes and neutrophils but a few were partly disintegrated. Only 2.6% were recovered from the kidneys and the spleen. In long-term injection experiments using the same inoculum size the autopsy was done 15 min and 1, 3 and 6 weeks post-injection (p.i.) of mf into naive jirds. Throughout the experimental period the density of mf remained more or less constant in the PCB, but 3 weeks p.i. the density in the lungs increased up to 14 times to that in the PCB, whereas in the liver it decreased at the same time to a density similar to that in the PCB. In patent animals with adult worms delivering mf these were distributed as follows: 34.7% were calculated to be in the PCB; 24.4% were obtained by perfusion from the lungs and 22.0% from the liver; the rest were found in the kidneys (16.6%) and spleen (2.3%). In the lungs and the liver about 5/6 were associated with adherent cells, partly disintegrated or as fragments. In view of the fact that very few mf become disintegrated immediately after i.v. injection and also from their extremely long sojourn in the PCB, a low turnover rate of mf is presumed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Extracranial carotid artery aneurysms.

Carotid artery aneurysms are rare, however, serious complications may result--namely, rupture, thrombosis, or emboli. Five distinct clinical types of aneurysms are reported with different symptoms and treatment. Fusiform, saccular, false, and mycotic aneurysms are best treated with interposition autogenous vein grafting. Spontaneous dissection aneurysms are best treated initially with anticoagulation and follow-up angiography. Recanalization is the usual result. Meticulous surgical technique to prevent perioperative emboli is essential to prevent central nervous system complications.

Adult↗

Cloning of the patatin-like latex allergen Hev b 7, its expression in the yeast Pichia pastoris and its immunological characterization.

The 43-kD latex allergen Hev b 7 was purified from the latex of Hevea brasiliensis and identified by N-terminal and internal peptide sequences as highly homologous to patatins. Patatins are storage proteins encoded by a multigene family found in plants such as potato and tomato. We have obtained a cDNA clone coding for a cytoplasmic form of Hev b 7. The recombinant protein was expressed in the methylotrophic yeast Pichia pastoris at 10 mg/l culture supernatant. Both natural Hev b 7 and rHev b 7 were recognized by IgE in 11% of the latex-allergic patients. rHev b 7 inhibited binding to its counterpart in natural rubber latex extracts. Purified rHev b 7 used at concentrations of 10 micrograms/ml in skin prick tests produced wheal-and-flare reactions of sizes equal to those produced by nHev b 7. Furthermore, we were able to show that rHev b 7 possessed esterase activity. A plant expression system for the production of larger quantities of recombinant latex allergens as an alternative to the preparation from H. brasiliensis sap is discussed.

Allergens↗