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Biomedical subjects

L Jäger

Publications and source records attributed to L Jäger.

At least 37 records · Page 2Linked to original sources

Quantification of group 5 grass pollen allergens in house dust.

BACKGROUND: It is widely known and accepted that grass pollen is a major outdoor cause of hay fever. However, it is of virtual importance for grass pollen allergic patients with symptoms all the year round to know the concentration of grass pollen allergens in their homes. OBJECTIVE: The main objective of this study was to quantify the amount of grass pollen allergen in mass units (microg Phl p 5) in dust settled indoors and to detect the distribution of allergenic activity in different sampling locations of homes. Furthermore, we studied the seasonal fluctuation of allergen content in dust samples. METHODS: We adapted the two site binding assay for detection of group 5 grass pollen allergens in samples from randomly selected homes in Hamburg (n = 371), Erfurt (n = 396), Hettstedt (n = 353), Zerbst (n = 289) and Bitterfeld (n = 226), Germany. Dust samples were collected from floor of living room (LR), bedroom (BR) or children's room (CR) and mattress (MA) during period of June 1995 to August 1998. The amount of the major grass group 5 allergens was detected in microg/g dust. RESULTS: Phl p 5 was detected in 67% of the samples analysed (n = 4760). The range was between undetectable (< 0.03 microg/g dust) and 81 microg/g dust. Phl p 5 levels were significantly higher in the dust from LR (geometric mean 0.117 microg/g dust) or BR/CR floors (geometric mean 0.098 microg/g dust) than in mattresses (geometric mean 0.043 microg/g dust). We observed seasonal fluctuation of indoor Phl p 5 levels with peak in June but also annual differences. Thus Phl p 5 content indoors reflects also the different quantities of pollen counts of annual courses. During pollination period we found two times higher Phl p 5 levels (0.172 microg/g dust, P < 0.001) than outside of grass pollination season (0.095 microg/g dust). The indoor Phl p 5 levels outside of season seem to be independent of pollination before. We suppose that settled pollen grains or allergenic material from outdoor particles carried indoors via footwear and clothes accumulates in house dust. CONCLUSION: Although we not known how the allergens in settled dust are equilibrated with those in the air, the considerable high level of Phl p 5 in indoor dust even during periods when no grass pollen is present in the atmosphere may be an important cause of pollen-allergy symptoms outside of season.

Air Pollution, Indoor↗

Magnetic resonance imaging-based joint space measurements in temporomandibular joints with disk displacements and in controls.

OBJECTIVE: Previous studies have discussed a posterior displacement of the condyle as a possible risk factor for the development of disk displacements (DDs) of the temporomandibular joint (TMJ). The objective of this study was to compare the posterior and anterior joint spaces in healthy TMJs with those of patients who present different forms of DDs. STUDY DESIGN: The anterior and posterior joint spaces from 58 patients with unilateral or bilateral DD with reduction (DDR) or without reduction (DDNR) and from 30 healthy volunteers were measured with 3 sagittal magnetic resonance images (MRIs) from each TMJ in the maximum intercuspid position. RESULTS: Measurements of anterior and posterior joint spaces showed a good interexaminer reproducibility (rank correlation coefficients ranging from 0.88 to 0.95). Patients with bilateral DDR demonstrated a significantly more posterior position of the condyle, as compared with controls and patients with bilateral DDNR. DDNR presented a significant reduction of the anterior and the posterior joint spaces, leading to a mean concentric position of the condyle. Patients with unilateral DDR or DDNR demonstrated a greater variability of anterior and posterior joint spaces, compared with patients with a bilaterally identical type of DD. CONCLUSIONS: The data of this MRI-based clinical study indicate that different stages of disk displacements are associated with significant changes of condylar position. The variation of anterior and posterior joint spaces was influenced by the diagnosis of the contralateral joint.

Adolescent↗

Sialolithiasis: MR sialography of the submandibular duct--an alternative to conventional sialography and US?

PURPOSE: To determine the value of magnetic resonance (MR) sialography for the diagnosis of sialolithiasis by comparing results prospectively with those of ultrasonography (US) and digital sialography. MATERIALS AND METHODS: MR sialography was prospectively performed with T2-weighted three-dimensional (3D) constructive interference in steady-state (CISS) and rapid acquisition with relaxation-enhancement (RARE) sequences in 24 patients suspected of having sialolithiasis. Evoked salivation was used as contrast material. T1-weighted spin-echo and T2-weighted turbo spin-echo MR imaging also were performed. The results were then compared with those of US and digital sialography, with the latter as standard of reference. RESULTS: The 3D CISS images were significantly (P: <.05) superior to RARE images for demonstrating the submandibular ductal system, followed by T2-weighted turbo spin-echo images (P: <.01) and T1-weighted spin-echo images (P: <.001). The sensitivity and specificity were 100% and 80%, respectively, for CISS MR sialography and 80% and 100%, respectively, for RARE MR imaging. The sensitivity and specificity of US were both 80%. CONCLUSION: MR sialography with evoked salivation is noninvasive and allows delineation of the submandibular ductal system and detection of sialoliths with accuracy that is similar to that of digital sialography and superior to that of US.

Humans↗

Bacterial meningitis in adults: demonstration of inner ear involvement using high-resolution MRI.

OBJECTIVE: To visualize the sites involved in audiovestibular dysfunction during bacterial meningitis in adults and to relate these findings to the extent of hearing impairment and vestibular dysfunction. BACKGROUND: Hearing impairment is among the most frequent complications of bacterial meningitis. METHODS: High-resolution MRI (HR-MRI) of the inner ear was performed in seven adult patients with hearing loss as a complication of bacterial meningitis. RESULTS: Five patients had unilateral (n = 1) or bilateral (n = 4) contrast enhancement of vestibulocochlear structures. The structures most frequently involved were the cochlear nerve (n = 9), the first cochlear turn (n = 9), the vestibulum (n = 9), and the semicircular canals (n = 7). There was a significant correlation between clinical and MRI findings: all nine ears with cochlear enhancement were deaf (hearing loss >90 dB), whereas none of the five ears with normal MRI findings had hearing losses of more than 90 dB (range, 30 to 70 dB; p = 0.0005). Vestibular dysfunction as revealed clinically and by quantitative vestibular function testing was found in six of seven patients (11 of 14 ears). Five of these patients (nine ears) also demonstrated enhancement of the vestibular organ on high-resolution MRI of the inner ear. CONCLUSIONS: High-resolution MRI can visualize the involvement of vestibulocochlear structures in bacterial meningitis in both cooperative and consciously impaired patients. These findings suggest a correlation between abnormalities on MRI and the extent of cochlear dysfunction.

Adolescent↗

"Allergen engineering": variants of the timothy grass pollen allergen Phl p 5b with reduced IgE-binding capacity but conserved T cell reactivity.

One problem of conventional allergen-specific immunotherapy is the risk of anaphylactic reactions. A new approach to make immunotherapy safer and more efficient might be the application of engineered allergens with reduced IgE-binding capacity but retained T cell reactivity. Using overlapping dodeca-peptides, the dominant T cell epitopes of the timothy grass pollen allergen Phl p 5b were identified. By site-directed mutagenesis outside these regions, point and deletion mutants were generated. Allergen variants were analyzed for IgE-binding capacity with sera of different grass pollen allergic patients by Western blotting, Dot blotting, and EAST inhibition test, and for histamine releasing capacity with peripheral blood basophils from different patients. The deletion mutants revealed significantly reduced IgE reactivity and histamine releasing capacity, compared with the wild-type Phl p 5b. Furthermore, in vivo skin prick tests showed that the deletion mutants had a significantly lower potency to induce cutaneous reactions than the wild-type Phl p 5b. On the other hand, T cell clones and T cell lines from different allergic patients showed comparable proliferation after stimulation with allergen variants and wild-type Phl p 5b. Considering their reduced anaphylactogenic potential together with their conserved T cell reactivity, the engineered allergens could be important tools for efficient and safe allergen-specific immunotherapy.

Allergens↗

HepG2 human hepatoma cells express multiple cytokine genes.

Although cytokines are known to be involved in the regulation of a variety of hepatocellular functions, hepatocytes themselves are generally considered only targets but not producers of these important mediators. In order to investigate whether cells of hepatocellular linages are a potential source of various regulatory cytokines we have estimated the multiple cytokine gene expression in the culture of well differentiated human HepG2 hepatoma cells using RT-PCR. Our findings demonstrate that HepG2 cells express mRNAs for interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), macrophage colony-stimulating factor (M-CSF), oncostatin-M (OSM), intercellular adhesion molecule (ICAM-1), interleukin 4 (IL-4), IL-5, IL-7, IL-10, IL-11, IL-12 and IL-6 receptor (IL-6R). At the same time the expression of IL-1, IL-2, IL-3, IL-6, CD40 ligand and IL-2R genes was not detected. It was concluded that hepatocytes are potential producers of a variety of cytokines, some of them being able to regulate hepatocellular functions directly, while others are important regulators of leukocyte activity. Thus, on the one hand, hepatocytes may express autoregulatory cytokines and on the other hand, influence the functions of other liver cells like Kupffer, Ito or endothelial cells. Due to their large amount, liver parenchymal cells could be an important source of sytemically acting pro- and anti-inflammatory and other regulatory cytokines.

CD40 Antigens↗

Procalcitonin expression in human peripheral blood mononuclear cells and its modulation by lipopolysaccharides and sepsis-related cytokines in vitro.

Procalcitonin (PCT), the precursor of calcitonin, was recently put forward as a diagnostic marker of systemic bacterial infection and sepsis. The major PCT production site in sepsis still remains unclear. Because of a certain association between increased levels of PCT and leukocyte-derived cytokines during sepsis, we assessed the possible expression of PCT in human peripheral blood mononuclear cells (PBMCs) and the modulation of PCT by lipopolysaccharides (LPS) and various sepsis-related cytokines by reverse transcriptase-polymerase chain reaction (RT-PCR) by using a novel primer set and flow cytometric analysis with intracellular staining with antibodies to the PCT components calcitonin and katacalcin. RT-PCR and flow cytometric analysis demonstrated that PBMCs express PCT both on mRNA and on protein levels. LPS and various proinflammatory cytokines (interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), IL-2) had pronounced stimulatory effects on the expression of PCT mRNA. Under identical experimental conditions the anti-inflammatory cytokine IL-10 had no effect on the expression of mRNA for PCT. Flow cytometric analysis demonstrated increased intracellular amounts of PCT components after LPS stimulation. Thus we demonstrate for the first time that PCT is expressed in PBMCs. This expression is modulated by bacterial LPS and sepsis-related cytokines. Therefore PBMCs may be among the sources of elevated PCT levels in patients with sepsis.

Base Sequence↗

Katacalcin and calcitonin immunoreactivity in different types of leukocytes indicate intracellular procalcitonin content.

PURPOSE: Procalcitonin is a new marker of severity of nonviral, in particular, bacterial infections. In respect of sepsis its site of production remains unknown. This study was carried out to determine whether subsets of human leukocytes contain procalcitonin. MATERIALS AND METHODS: Blood samples of 17 patients who had demonstrated various degrees of serum procalcitonin levels on the day before evaluation were analyzed for serum procalcitonin by immunoluminometry and for intracellular reaction of monocytes, granulocytes, B-, and T-lymphocytes against katacalcin- or calcitonin-sensitive antibodies. Katacalcin and calcitonin are part of the procalcitonin molecule. Associations of these reactions with serum procalcitonin levels as well as differences between groups with a normal or elevated serum level were analyzed. RESULTS: Intracellular antibody reaction against katacalcin was demonstrated in all cell types. We also found a lower rate of intracellular antibody reaction against calcitonin. Associations of serum procalcitonin with the two antibody reactions were demonstrated. Differences in intracellular reactions in the group with elevated serum procalcitonin were seen with both antibodies compared with a normal control. CONCLUSION: Intracellular antibody reaction against katacalcin supports the notion that various types of leukocytes contain procalcitonin.

Antibody Formation↗

Allergens in house-dust samples in Germany: results of an East-West German comparison.

The background of this study is the finding of several studies that the frequency of respiratory allergies was significantly higher in the former West Germany than the former East Germany. The present study investigated the levels of allergens of house-dust mite (Der p 1 and Der f 1), cat (Fel d 1), and cockroach (Bla g 2) in the household dust of 201 homes in Hamburg (West Germany) and 204 homes in Erfurt (East Germany), and examined the factors that affect these levels. The characteristics of homes were assessed by a questionnaire. The allergen levels were studied in dust from living rooms (LR), bedrooms (BR), and mattresses (MA). We detected in samples from Hamburg significantly higher allergen concentrations than in Erfurt: three times higher Der p 1, five times higher Der f 1, and three times higher Fel d 1. For Bla g 2, no comparison was possible because the concentrations were below the detection limit in 93% of the samples. Most of the differences could be explained by differences in housing and living characteristics between both cities. The mean ratio of Der p 1 levels in mattress dust between Hamburg and Erfurt decreased from 4.1 to 1.54 (NS) after adjustment for season, building material, age of the house, story of the dwelling, type of heating, age of carpet/mattress, presence of dogs, and indoor climate (temperature, humidity). The mean ratio of Der f 1 levels decreased from 6.9 to 2.78 (P<0.05) after adjustment for these factors. The mean ratio for Fel d 1 in mattress dust decreased fom 4.03 to 1.65 (P<0.05) after adjustment for season, building material, story of dwelling, size of dwelling, ventilation, cleaning routines, and pets. A similar reduction was seen for floor dust (LR plus BR). Our results indicate that the differences between the concentrations of mite and cat allergens found in Hamburg and Erfurt are explicable mainly, but not completely, by different building characteristics (age of houses, building material, story, and size of the dwelling) which affected the indoor climate, as well as by differences in other individual living habits (keeping of pets, age of carpets or mattresses, and cleaning routines).

Air Pollution, Indoor↗

[Rapidly progressing course of cutaneous angiosarcoma in the area of the head-neck].

INTRODUCTION: Angiosarcomas are rare, aggressive tumors of vascular origin, most commonly affecting older males. An optimum treatment strategy has not yet been defined. CASE REPORT: We report on a 68-year-old male patient who initially presented with a small, bruise-like macule of the cheek. He was treated with different antibiotics and steroids for a few weeks. Due to failure of any clinical improvement, a biopsy was taken revealing an undifferentiated malignant tumor. Subsequently, the patient was referred to our department, where the lesion was excised. Histology showed an extensive, well-differentiated angiosarcoma. According to oncological protocols, the patient underwent 5 cycles of chemotherapy with etoposid, ifosphamid and adriamycine. Despite therapy, tumor size remained unchanged. After therapy was discontinued, tumor growth rapidly proceeded with semicircular infiltration of the right face and neck. A few weeks later the patient died. DISCUSSION: About 50 percent of cutaneous angiosarcomas are found in the head and neck region of the elderly. No clear etiology has been implicated with respect to the origin of this tumor. Traumatic bruises, infections, and allergic reaction may be confused clinically with angiosarcoma. Differential diagnosis also comprises other vascular neoplastic diseases, i.e. lymphangioma, hemangiopericytoma and Kaposi's sarcoma. If complete excision is possible, radical surgery is the treatment of choice. The effectiveness of chemotherapy is unclear. The role of radiation therapy is also under discussion due to the technical problems of administering radiotherapy to the extensive volume at risk. As the late diagnosis adversely affects the prognosis, the importance of early biopsy in suspicious lesions is mandatory.

Aged↗

[Role of diagnostic imaging in chronic recurrent parotitis in childhood].

BACKGROUND: Chronic recurrent parotitis represents a disease of still uncertain etiology that can be divided into a childhood and an adult form. Sialography is still the imaging procedure of choice. METHOD: We report about a nine-year-old girl who had had six episodes of parotitis in the past two years. MR sialography is presented as an alternative to conventional sialography. MR was performed with a 1.5 T wholebody tomograph using a high resolution 3D-CISS sequence. RESULTS AND CONCLUSION: MR sialography does not require any contrast medium. It primarily images liquid structures, and the flow of saliva can be adequately demonstrated after stimulation with ascorbic acid. These special features of MR sialography allow its use also during acute episodes of sialadenitis, thus providing a significant improvement over conventional sialography. Furthermore, no overlapping occurs as in conventional summation images, due to the multiplanar reconstruction features.

Adult↗

Cogan's syndrome: clinical significance of antibodies against the inner ear and cornea.

The aim of this study was to evaluate the pathological significance of antibodies against cornea and inner ear tissue in the development of audiovestibular and ocular symptoms in patients with Cogan's syndrome (CS). We analysed the serum of 5 CS patients for binding of IgM and IgG to fresh cryosections of rat labyrinth (semicircular canals, ampulla, utricle, saccule) and cornea by indirect immunofluorescence (IF). The predominant pattern of anti-corneal IgM was staining of the superficial cell layer of the non-keratinizing squamous epithelium. IgM against cornea was found in 3 patients, all of whom had bilateral inflammatory eye signs at the start of the disease. However, IgM was also detected in the chronic stage of the disease when no clinical signs of eye involvement were apparent. The study includes the first follow-up examination of anti-corneal IgM and IgG antibodies during a complete episode of active CS. During the first episode of CS in 1 patient, anti-corneal IgM became detectable 1 week after the onset of interstitial keratitis and 3 weeks after the onset of audiovestibular symptoms. It increased over several weeks and then fell to very low levels. However, at no time was anti-corneal IgG found. In the course of follow-up examinations, the serum of 4 patients intermittently contained low titre IgG antibodies against inner ear labyrinthine tissue, but without any clear correlation with the active stages of CS. In addition, high-resolution MRI (HR-MRI) of the inner ear was performed in the acute and chronic stages of CS to evaluate the activity of CS. In the acute stage, HR-MRI revealed abnormal MRI signals in the vestibule, semicircular canals, vestibular nerve, or cochlea. In the chronic stage, patients showed narrowing or occlusion of semicircular canals and the cochlea on the 3D-CISS images, but no high signal lesions (T1) and no enhancement. Antibodies against cornea or labyrinthine tissue were not consistently detected in CS and the level of organ-specific antibodies did not correlate with the activity of the disease.

Acute Disease↗

A comparison of digital luminescence mammography and conventional film - screen system: preliminary results of clinical evaluation.

The objective of this study was to determine if digital luminescence mammography can be used as a diagnostic tool. We investigated twenty-two patients with mammographically suspicious findings using a conventional film-screen system and a digital phosphor storage plate in order to compare these two techniques. Four radiologists experienced in mammography reviewed each pair of images. Our results indicate that detectability of microcalcifications and solid masses with digital systems is superior to conventional film-screen mammography due to the increased contrast enhancement associated with digital systems. We did, however, find that characterization of morphological details is inferior with the digital system, presumably due to reduced spatial resolution. In addition, we found no statistically significant difference in the differentiation of benign from malignant lesions with both techniques. The accuracy of mammographic diagnosis was investigated in a receiver operating characteristic study and similar values were found with both techniques. Our results indicate that digital mammography will become an acceptable diagnostic tool although improvement, especially in spatial resolution, is desirable.

Aged↗

Detection and quantification of group 4 allergens in grass pollen extracts using monoclonal antibodies.

BACKGROUND: Grass pollen extracts are complex mixtures consisting of different major allergenic and non-allergenic components. Phl p 4 is an important allergen, because more than 75% of grass pollen allergic patients produce specific IgE antibodies against group 4 allergens. OBJECTIVE: This study was designed to investigate the specificity of monoclonal antibodies (MoAbs) produced against Phl p 4 and to verify the presence of group 4-like proteins in different grass pollen. Furthermore the usefulness of MoAbs for quantification of group 4 allergens was studied. METHODS: Group 4 analogues were investigated by immunoblotting and ELISA inhibition using three MoAbs. The specificity of antibodies was studied using isolated group 1 and group 5 allergens. Quantification of group 4 allergen was achieved by a two-site solid-phase ELISA. Phl p 4 was purified from whole pollen extract by chromatographic or electrophoretic techniques and used as standard. RESULTS: The MoAbs studied bound strongly to proteins from timothy grass pollen extract at a mw of 55 kDa and a pI of 9.0-9.3. Phl p 4 homologes with similar mw were detected in Dactylis glomerata, Festuca pratensis, Holcus lanatus, Poa pratensis, Lolium perenne. Epitope mapping showed that all three MoAb recognized unrelated regions on Phl p 4. A two-site binding ELISA using MoAbs was developed for determination of Phl p 4 in Phleum pratense extracts. The method was able to evaluate group 4 in mass units with a working range between 150 and 2000 ng/mL. The absolute amounts of group 4 in extracts of several grasses varied considerably but was always-less than 1% of the total protein. CONCLUSION: Group 4 homologes are present in the various grass extracts but to different extents. The group 4 ELISA could be very useful as a additional tool for providing information concerning the composition of grass pollen extracts.

Allergens↗

Mapping of T-cell epitopes of Phl p 5: evidence for crossreacting and non-crossreacting T-cell epitopes within Phl p 5 isoallergens.

BACKGROUND: Group 5 allergens represent major grass pollen allergens because of their high sensitization indices. The identification of T-cell epitopes of these allergens is a prerequisite for the design of immunotherapeutic strategies based on peptide vaccination or modified allergens with conserved T-cell epitopes. OBJECTIVE: This study was undertaken to determine T-cell epitopes on Phl p 5 major pollen allergen of timothy grass (Phleumn pratense). METHODS: T-cell lines (TCLs) and T-cell clones (TCCs), specific to Phl p 5, were established from the peripheral blood of 18 patients allergic to grass pollen. All TCCs were mapped for epitope specificities using 178 overlapping dodecapeptides representing the primary structures of two isoforms of Phl p 5 (Phl p 5a and Phl p 5b). Phenotype and cytokine production profiles of TCCs were tested. Selected TCCs were analysed for HLA class II restriction. RESULTS: A total of 82 TCCs were isolated. All TCCs displayed the helper cell (TH) phenotype. Their reactivity with two recombinant expressed isoforms of Phl p 5a and Phl p 5b was heterogeneous. The epitope specificity of the TCCs was then revealed. Nineteen T-cell epitopes could be identified on Phl p 5. Eighty-one percent of mapped TCCs recognized three T-cell reactive regions on the Phl p 5 allergen. Some TCCs were reactive with isoepitopes presenting on Phl p 5a as well as Phl p 5b. Allergen-specific stimulation induced a TH0-like type of cytokine production in 25 of 50 TCCs. Almost all TCCs secreted high concentrations of interleukin-13. CONCLUSION: Phl p 5, a major grass pollen allergen, contains several T-cell epitopes. Some epitope regions were recognized by several patients. Epitope recognition pattern could not be correlated with special HLA class II haplotypes. T-cell stimulating isoepitopes were found at corresponding regions of Phl p 5a and Phl p 5b isoforms.

Adult↗

Tree-pollen allergy is efficiently treated by short-term immunotherapy (STI) with seven preseasonal injections of molecular standardized allergens.

The efficacy and tolerance of short-term immunotherapy (STI) by seven preseasonal injections of tree-pollen allergens (ALK7 Frühblühermischung) was investigated in a double-blind, placebo-controlled, multicenter study with 111 rhinoconjunctivitis patients. Nasal and bronchial symptoms simultaneously analyzed, and nasal symptoms as a single end point, but not the overall score of nasal, bronchial, and conjunctival symptoms, showed a significantly lower increase with STI during birch-pollen exposure (both P=0.033, n=105, Mann-Whitney U-test). However, a selective analysis with patients from centers with high recruitment figures (n> or =10 patients, n=29 STI, n=32 placebo) showed a significantly lower increase of nasal, bronchial, and overall symptom score (STI 11.0 vs placebo 18.0, P=0.001, U-test). STI had equidirected effects on conjunctival, nasal, and bronchial symptoms analyzed as multiple end points, although conjunctival symptoms were not significantly different as a single end point. The seasonal increase in drug use was reduced by 62% in the STI group compared with placebo (P=0.032, t-test). Specific IgG4 increased only after STI (P<0.001); IgE was not significantly different. Eosinophil cationic protein remained unchanged with STI, but significantly increased with placebo in the pollen season (P=0.003). STI was well tolerated. In conclusion, STI was shown to be efficacious and safe for the treatment of patients with tree-pollen rhinoconjunctivitis.

Adolescent↗