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Biomedical subjects

Wolfgang Hemmer

Publications and source records attributed to Wolfgang Hemmer.

At least 19 recordsLinked to original sources
PubMed2007

Mapping of Malus domestica allergens by 2-D electrophoresis and IgE-reactivity.

The importance of apple allergens has been repeatedly emphasized, and their presence has been confirmed both in pollen and in fruits. In the present study, a combination of proteomic tools have been used to build a complete allergen map of apple. The water-soluble fraction of an apple extract was precipitated using a phenol-based procedure and separated by 2-DE. Initially four previously classified allergens, Mal d 1, Mal d 2, Mal d 3 and Mal d 4, could be identified in Western blots with polyclonal rabbit antibodies directed to the four respective allergens, and subsequently matched to the bands recognized by several patient sera. Further, all four known apple allergens were localized on a 2-DE map and they were matched with spots recognized by sera of patients with different allergic patterns. Moreover, a new, putative allergen could be identified using MS. We evaluated the influence of post-translational modifications and the immunoreactivity under different analytical conditions. The comparison of different visualization methods for 2-DE gels and blots revealed that even very low concentrations of the intact epitopes are detectable by IgEs of patients, and therefore might be sufficient to trigger allergic symptoms in sensitized individuals.

Allergens↗
PubMed2006

Is the Ross operation still an acceptable option in children and adolescents?

BACKGROUND: The Ross operation is increasingly accepted as an alternative to conventional valve prostheses for children, adolescents, and young adults. We review patients younger than 20 years of age. METHODS: Of 404 Ross operations done before November 2004, 60 were young patients with a median age of 12 years (range, 1 to 20 years). The pulmonary autograft technique universally was as a free root. A cryopreserved pulmonary homograft reconstructed the right ventricular outflow tract. RESULTS: Early postoperative complications were reentry for bleeding in 2 patients and one pacemaker insertion. No thromboembolic or hemorrhagic events occurred during the follow-up of 42 +/- 27 months. Two late deaths occurred, one from myocardial infarction after 3 months and another sudden death after 5 years, probably from critical pulmonary homograft stenosis. Echocardiographic follow-up revealed a median peak gradient of 6.3 +/- 3 mm Hg across the autograft. The median pulmonary homograft peak gradient of 19.1 +/- 13.7 mm Hg was increased to more than 30 mm Hg in 6 patients. Another 6 patients had moderate but clinically insignificant pulmonary homograft regurgitation. Altogether, 6 patients required reoperation for replacement of stenotic homografts. No autograft related reoperation occurred. CONCLUSIONS: Young patients with the Ross operation had good mid-term autograft function and no perioperative mortality. Factors that justify the choice of the Ross operation for young patients are the normal physiologic hemodynamics and growth of the autograft as well as freedom from anticoagulation. A 10% reoperation rate, elevated pulmonary homograft gradients, and the surgical complexity remain limiting factors.

Adolescent↗
PubMed2005

Mimotopes identify conformational epitopes on parvalbumin, the major fish allergen.

Parvalbumin, the major fish allergen, is recognized by allergen-specific IgE of more than 90% of all fish-allergic patients. A detailed knowledge of allergenic structures is crucial for developing a vaccine inducing blocking antibodies specifically directed towards the IgE binding epitopes. In the present study we aimed to use the phage display technique to generate mimotopes, which mimic epitopes on parvalbumin. Parvalbumin-specific IgE was purified from sera of fish-allergic patients and used for screening of a constrained decamer phage library. After four rounds of biopanning using parvalbumin-specific IgE, five phage clones were selected which were specifically recognized by parvalbumin-specific IgE as well as IgG. DNA sequencing and peptide alignment revealed a high degree of sequence similarities between the mimotopes. Interestingly, on the surface of natural parvalbumin three regions could be defined by computational mimotope matching. In accordance, previously defined allergenic peptides of cod parvalbumin highlighted areas in close proximity or overlapping with the mimotope matching sites. From the presented data we conclude that our approach identified conformational epitopes of parvalbumin relevant for IgE and IgG binding. We suggest that these mimotopes are suitable candidates for an epitope-specific immunotherapy of fish-allergic patients.

Allergens↗
PubMed2005

Ross procedure and left ventricular mass regression.

BACKGROUND: Return of left ventricular mass to normal is considered to be a favorable result of aortic valve replacement. The Ross procedure provides near normal hemodynamics and thus allows studies of left ventricular (LV) reverse remodeling. LV mass regression may be influenced by surgical technique (subcoronary [SC] versus root replacement [RR]). METHODS AND RESULTS: Data from the German Ross Registry were analyzed. A total of 646 patients (mean age: 43.6+/-12.7 years, range: 16 to 71 years; SC technique n=295, RR technique n=351) underwent a Ross procedure in 7 participating centers from 1990 to 2004. The patients underwent preoperative and postoperative echocardiographic evaluations. Mean follow-up time was 3.5+/-2.5 years (range 0.12 to 13.7 years). Follow-up completeness was 97%. The LV mass index (LVMI) decreased significantly during follow-up in both groups (SC: 209+/-53 preoperatively to 154+/-48 at 1-year follow-up, [P<0.01 versus preoperative values] to 149+/-51 g/m2 at 2-year follow-up, [P=NS 1-year versus 2-year follow-up] versus RR: from 195+/-56 preoperatively to 144+/-51 at 1-year follow-up [P<0.01 versus preoperative values] to 140+/-49 g/m2 [P=NS 1-year versus 2-year follow-up]). LVMI regression remained stagnant 1 year after the Ross procedure in most patients in both groups. On the basis of multivariate analysis, predictors for incomplete LVMI regression after the autograft procedure were high preoperative LVMI, smoking, and uncontrolled diastolic hypertension. CONCLUSIONS: At mid-term echocardiographic follow-up, patients of both groups had favorable autograft hemodynamics. Risk factors for incomplete postoperative LVMI regression in our study were smoking and persistent diastolic hypertension. This emphasizes the importance of cessation of smoking and treatment of arterial hypertension, even in younger patients, after corrected aortic valve disease.

Adolescent↗
PubMed2005

Fruit cross-reactive allergens: a theme of uprising interest for consumers' health.

Regular consumption of fruits has a positive influence on human health by disease prevention. However parallel to dietetic benefits, IgE-mediated fruit allergies have been shown to be an increasing health risk for children and adults in the Northern hemisphere. The spectrum of food allergies ranges from chronic symptoms to more acute problems and even anaphylaxis. Fruit proteins with high primary sequence similarity display also homologous tertiary structures, resulting in similar epitopes to IgEs and consequently in cross-reactivity. In this review we present the major allergens of stone and pome fruits and discuss the presence of homologous proteins in small fruits. Interestingly these proteins, which might pose an allergenic potential for pre-sensitised individuals are expressed also in strawberry, raspberry and blueberry, otherwise rich in beneficial biofactors.

Allergens↗
PubMed2005

Plasma levels of polyunsaturated fatty acids in children with atopic dermatitis and in atopic and nonatopic controls.

BACKGROUND: Atopic dermatitis has been thought to be associated with a disturbance in n-6 polyunsaturated fatty acid (PUFA) metabolism, but randomized trials investigating the clinical efficacy of oral supplementation with gammalinolenic acid have revealed conflicting results. AIM OF THE STUDY: To re-investigate the proposed linkage between PUFA dysregulation and atopic dermatitis. MATERIALS AND METHODS: Plasma levels of linoleic acid (LA), gammalinolenic acid (GLA), dihomogammalinolenic acid (DGLA) and arachidonic acid (AA) were measured using HPLC in 22 children with atopic dermatitis. Patients were subdivided into those with elevated total serum IgE (group A, n = 15, IgE > +1 SD of age-specific normal values) and those with normal IgE (group B, n = 7) and compared with children suffering from allergic rhinitis/asthma (group C, n = 8) and with non-atopic controls (group D, n = 6). RESULTS: GLA levels were significantly lower (p < 0.05) in eczema patients with elevated IgE (A, 0.19 +/- 0.06%) and in atopic controls (C, 0.23 +/- 0.06%) than in eczema patients with low IgE (B, 0.42 +/- 0.19%) and non-atopic controls (D, 0.43 +/- 0.16%). There were no significant differences between groups for LIN, DGLA and AA, except for lower LIN levels in atopic controls. Correlation of individual LA and GLA values showed significantly steeper regression lines in low-IgE responders (B and D, k(x) = 0.058) than in high-IgE responders (A and C, k(x) = 0.012; p < 0.02), suggesting impaired delta-6-desaturase function in the latter. For the study population as a whole, there was a clear negative correlation between total levels of IgE and GLA (r(s) = -0.64) and a moderate negative correlation between total IgE and AA (r(s) = -0.38). CONCLUSIONS: Dysregulation of n-6 PUFA metabolism is neither consistently found in nor specifically associated with atopic dermatitis but rather appears to be associated with IgE production and atopy in general. The finding of decreased GLA levels in eczema patients with elevated total IgE and in children with allergic rhinitis and asthma but not in eczema patients with normal total IgE questions the proposed pathophysiologic role of fatty acid dysregulation in atopic dermatitis.

Asthma↗
PubMed2005

The N-glycans of yellow jacket venom hyaluronidases and the protein sequence of its major isoform in Vespula vulgaris.

Hyaluronidase (E.C. 3.2.1.35), one of the three major allergens of yellow jacket venom, is a glycoprotein of 45 kDa that is largely responsible for the cross-reactivity of wasp and bee venoms with sera of allergic patients. The asparagine-linked carbohydrate often appears to constitute the common IgE-binding determinant. Using a combination of MALDI MS and HPLC of 2-aminopyridine-labelled glycans, we found core-difucosylated paucimannosidic glycans to be the major species in the 43-45 kDa band of Vespula vulgaris and also in the corresponding bands of venoms from five other wasp species (V. germanica, V. maculifrons, V. pensylvanica, V. flavopilosa and V. squamosa). Concomitant peptide mapping of the V. vulgaris 43 kDa band identified the known hyaluronidase, Ves v 2 (SwissProt P49370), but only as a minor component. De novo sequencing by tandem MS revealed the predominating peptides to resemble a different, yet homologous, sequence. cDNA cloning retrieved a sequence with 58 and 59% homology to the previously known isoform and to the Dolichovespula maculata and Polistes annularis hyaluronidases. Close homologues of this new, putative hyaluronidase b (Ves v 2b) were also the major isoform in the other wasp venoms.

Amino Acid Sequence↗
PubMed2004

Triple-coated stents (Hirudin/Iloprost/Paclitaxel): an in vitro approach for characterizing the antiproliferative potential of each individual compound.

BACKGROUND: Hirudin (H)/iloprost (I)/paclitaxel (P)-coated stents represent a multifactorial approach to reducing the proliferative response caused by ballooning and stenting. The study presented compares the net effect of each individual compound of HIP-coated stents with the summed effect of the compounds in the stent coating. METHODS AND RESULTS: For proliferation prescreening studies, human coronary smooth muscle cells were incubated with H (0.005-500 microg/ml), I (0.00001-1 microg/ml), and P (0.0001-10 microg/ml). After 5 days, cell number was studied in a cell analyzer system. Secondly, 8-mm stents were coated with (1) HI, (2) HIP-10 microg/20 microg/40 microg (HIP5%/10%/20%), (3) P-40 microg (P), (4) IP-40 microg (IP), and (5) HP-40 microg (HP). After 5 days, the effect on cell proliferation and cytoskeletal structures was studied. No antiproliferative effect was found after incubation with H; significant inhibition was seen after incubation with I (p<0.05) or lipophilically dissolved P (p<0.001). After 5 days incubation with HIP5%-, HIP10%-, HIP20%-, P20%-, IP20%-, and HP20%-coated stents, cell proliferation was inhibited by 55.5% (p<0.05), 61% (p<0.05), 57.9% (p<0.05), 59.5% (p<0.001), 59.8% (p<0.001), and 63.3% (p<0.001), respectively. HI- and HIP-coated stents caused a severe destruction of the cytoskeletal structures smooth muscle alpha-actin and alpha-tubulin; despite the destruction, vital cells could be identified with positive FDA staining. CONCLUSIONS: Although both lipophilically dissolved P and hydrophilically dissolved I contributed to the antiproliferative effect, no additive effect of the two compounds was detected. In vivo P can be released more easily from the coating material due to the permanent lipophilic contact of the stent struts with the vessel wall. The current study is the first report on a clear and uncomplicated technique to obtain information on the antiproliferative potential of coated stents before large experimental studies are initiated.

Antineoplastic Agents, Phytogenic↗
PubMed2004

Specificity of IgG and IgE antibodies against plant and insect glycoprotein glycans determined with artificial glycoforms of human transferrin.

Cross-reactive carbohydrate determinants of plants are essentially a mixture of N-glycans containing beta1,2-xylose and core alpha1,3-fucose, the latter also found in insect glycoproteins. To determine the relative contributions of these two sugar residues to antibody binding, we prepared an array of glycomodified forms of human apo-transferrin. Using core-alpha1, 3-fucosyltransferase (EC 2.4.1.214) and beta1,2-xylosyltransferase (EC 2.4.2.38) recombinantly expressed in Pichia pastoris and suitable glycosidases, glycoforms containing either only fucose (MMF), only xylose (MMX), both (MMXF), or neither (MM) linked to the common pentasaccharide core were generated. Additional glycoforms were obtained by enzymatic removal of the alpha1,3-linked mannosyl residue. These transferrin glycoforms served to define the binding specificity of antibodies in western blot, ELISA, and inhibition ELISA. Rabbit anti-horseradish peroxidase serum bound to both the fucosylated (MMF) and the xylosylated (MMX) glycoforms. Inhibition studies indicated two independent highly specific populations reacting with either of the two epitopes. In contrast, the monoclonal antibody YZ1/2.23 appears to recognize a larger structure including both the fucosyl and the xylosyl residue. The mannose-deficient glycoform was a poorer inhibitor for both antibodies. Terminal GlcNAc residues prevented antibody binding. Rabbit anti-bee venom serum reacted with fucosylated forms (MMF and MMXF) only. Experiments with sera from allergic patients suggest that glycomodified human transferrin, especially the MMXF glycoform, is a suitable reagent for the detection of antibodies against cross-reactive carbohydrate determinants. Within the panel studied, several sera contained high levels of fucose-reactive IgE but only a few sera showed any binding to MMX-transferrin.

Animals↗
PubMed2004

[Adverse reaction to the azo dye Pigment Red 170 in a tattoo].

A 30-year old white male presented with sharply demarcated pruritic lesions in a black and red tattoo on his wrist. The strongly infiltrated and slightly scaly eruptions started four months after tattoo application and were notably restricted to the red-colored areas. Symptoms got worse after UV exposure. Patch testing and photo patch testing with the used azo dye Pigment Red 170 (C.I. 12475) was negative. Histology revealed lichenoid dermatitis without signs of a granulomatous reaction. The verification of allergic sensitization in hypersensitivity reactions to tattoos by patch testing may be difficult due to the poor penetration into the skin of the applied azo pigments. Intradermal testing may be more sensitive but bears the risk of long lasting skin reactions.

Adult↗
PubMed2004

Hemodynamic performance following the Ross operation: comparison of two different techniques.

BACKGROUND AND AIM OF THE STUDY: The Ross operation as aortic valve replacement has undergone technical evolution. Originally described as a subcoronary implant, the full-root replacement technique is now more common worldwide. It remains unclear which of the two techniques has the better results. Hence, the hemodynamic performances of the two implantation methods, as applied by two experienced centers, were compared as part of the German Ross Registry. METHODS: In total, 132 (Group 1, root replacement, mean age 40 +/- 14 years) and 249 (Group 2, subcoronary implant, mean age 48 +/- 14 years) consecutively operated patients were compared clinically and echocardiographically. Data were analyzed focusing on pulmonary autograft and homograft function at mid-term (2.78 +/- 1.89 versus 2.26 +/- 2.11 years). RESULTS: Echocardiography revealed autograft peak systolic gradients of 5.0 +/- 2.7 mmHg for Group 1 and 6.7 +/- 3.7 mmHg for Group 2 (p < 0.05), and an indexed effective orifice area (EOA) of 1.98 +/- 0.57 cm2/m2 and 1.64 +/- 0.43 cm2/m2 (p < 0.05), respectively. Homograft peak systolic gradients were 15.6 +/- 9.0 mmHg and 11.7 +/- 6.8 mmHg for Groups 1 and 2 (p < 0.05) respectively, and the indexed EOA with regard to the homograft was 1.08 +/- 0.49 cm2/m2 and 1.26 +/- 0.50 cm2/m2 (p < 0.05). Autograft insufficiency grade > I was present in 1.5% (2/132) of Group 1 and 2.8% (7/249) of Group 2 patients. Pulmonary insufficiency grade > I was 17.4% (23/132) for Group 1 and 4.8% (12/249) for Group 2 (p < 0.05). CONCLUSION: Although both groups enjoyed excellent hemodynamics in the mid-term, the root replacement technique had the advantage of larger annulus diameters and greater aortic EOA. Clinically relevant autograft regurgitation in both groups was gratifyingly rare, and seemed to be independent of surgical technique. Long-term durability of the more demanding subcoronary technique versus the problems of larger dimensions of the sinus of Valsalva and sinotubular junction in the free-root technique, remains to be proven. Apparent differences in pulmonary homograft hemodynamics can most likely be explained by surgical differences, younger patients in Group 1, and by homograft variation.

Adult↗
PubMed2003

Older patients fare better with the Ross operation.

BACKGROUND: The Ross operation has an established position in young patients. We address the question of whether any age group profits most from the Ross operation, and we compare the results in various ages. METHODS: From February 1995 to August 2001 we performed 250 Ross operations. Group 1 consisted of 46 patients, ages 2 to 25 years (median age, 15 years). Group 2 consisted of 123 patients, ages 26 to 49 years (median age, 39 years). Group 3 consisted of 81 patients, ages 50 to 67 years (median age, 55 years). Echocardiography was performed perioperatively, at 2 to 6 months, and then yearly. RESULTS: Mean follow-up for the three groups was 32, 31, and 28 months, respectively (p = 0.36). One patient from group 2 died after 25 months caused by suppurative pneumonia and 3 patients from group 3 died (1 from suspected acute thoracic aorta dissection at 40 months, 1 from ventricular fibrillation after 25 months, and 1 from an undiagnosed sudden death at 5 months). Autograft replacement was necessary for 3 patients from group 2 and 1 from group 3. Autograft repair was necessary for 1 patient from group 2, and pulmonary homograft reoperation was necessary for 1 patient from group 1. All other autografts currently have physiologic gradients and clinically insignificant regurgitation. Median peak gradient across the right ventricular outflow tract was 23.6 +/- 18 mm Hg for group 1, 14.6 +/- 8 mm Hg for group 2, and 11.5 +/- 7 mm Hg, which was significantly lower for group 3 patients (p < 0.001). Eleven patients are under close follow-up for right ventricular outflow tract gradients > or = 40 mm Hg; eight of these patients are from group 1, 3 are from group 2, and there are none from group 3. CONCLUSIONS: Although the Ross operation provides excellent results in all age groups, the problem of right ventricular outflow tract stenosis has not been seen in patients older than 50 years, which implies that it offers superior results for aortic valve disease in middle aged and older patients.

Adolescent↗