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Biomedical subjects

A Hoffmann

Publications and source records attributed to A Hoffmann.

At least 55 records · Page 3Linked to original sources
PubMed2002

Influence of food processing on the allergenicity of celery: DBPCFC with celery spice and cooked celery in patients with celery allergy.

BACKGROUND: Celery root is often consumed in a processed form as a cooked vegetable or as a spice. So far, however, there has been no information about the allergenicity of processed celery in celery-allergic patients. METHODS: In 12 patients with a history of allergic reactions to raw or raw and cooked celery, double-blind placebo-controlled food challenges (DBPCFCs) with raw celery (n = 10), cooked celery (110 degrees C/15 min; n = 11), and celery spice (n = 5) were performed. Nine patients underwent an open mucosal challenge with four samples of canned celery retorted at Co-values (cooking effect) of 7.45-76.07 (corresponding to the time periods in minutes at a thermal influence of 100 degrees C). IgE immunoblot analysis of celery extract was performed with sera of all challenged patients. The thermal stability of celery allergen was investigated by enzyme allergosorbent test (EAST) inhibition. Furthermore, intraperitoneal immunization of mice followed by a rat basophil leukemia (RBL) cell mediator release assay was used as a biological in vitro model to assess the allergenicity of processed celery. RESULTS: Six out of 11 patients showed a positive DBPCFC to cooked celery and five out of five patients to celery spice. Allergenicity of celery was preserved in four patients with a positive DBPCFC to cooked celery even if celery was treated at a Co-value of 76.07. Patients with positive DBPCFC to cooked celery reacted to known celery allergens (Api g 1, Api g 4, cross-reactive carbohydrate determinants CCD). EAST inhibition showed that heat resistance of celery allergens decreases in the following order: CCD > Api g 4 > Api g 1. Accordingly, five of six patients with a positive DBPCFC to cooked celery were sensitized to profilin and/or CCD. The murine model reflected the reactivity of patients sensitized to the major allergen Api g 1. CONCLUSIONS: 1) In a subset of patients with a positive DBPCFC to cooked celery, celery remains allergenic even after extended thermal treatment (76.07 min/100 degrees C). 2) Celery spice is allergenic for patients with an allergy to raw celery. 3) RBL cells sensitized with mouse IgE to raw celery may serve as a useful tool for screening the potential allergenicity of heat-processed products containing celery.

Adult↗
PubMed2002

Assessment of ADRs associated with lipid-lowering agents recorded in the Department of Internal Medicine, University Hospital, Jena.

Drug-related illness is an important cause of admission to hospital. Little information is available regarding the frequency of ADRs caused by antilipidemic agents classified as HMG-CoA reductase inhibitors (statins). Treatment with statins has been associated with the occurrence of myopathy or liver toxicity in case reports. Recent lipid intervention studies have involved the implementation of lipid lowering therapy with HMG-CoA reductase inhibitors in cardiovascular risk management. Since January 1997 we have been involved in a study, the aim of which was to improve the spontaneous drug information reporting system in Germany. The study was supported by the German Federal Institute for Drugs and Medical Devices, the "Bundesinstitut für Arzneimittel und Medizinprodukte", Berlin BfArM. Between early 1997 and late 2000, as a result of this monitoring of ADRs, we analyzed all patient histories concerning therapy with statins. A total of 550 ADR patients were evaluated, (209 male, 341 female) with a mean age of 66.4 years. 27 (4.9%) of all patients had received statins (atorvastatin = 12, fluvastatin = 7, simvastatin as well as pravastatin = 3, lovastatin = 2). Only 2 of the 27 patients admitted to hospital for typical ADRs of statins such as skeletal muscle toxicity (e.g. myalgia, rhabdomyolysis) or disorders involving hepatic structure or function were receiving statins (atorvastatin). An increased risk of rhabdomyolysis has been reported in the case of several statins, following concomitant use with erythromycin, cyclosporine or itraconazole, all of which are potent inhibitors of CYP3A4 enzyme. But only 1 atorvastatin patient had received cyclosporine as a CYP3A4 inhibitor. After discontinuing medication, signs of intoxication disappeared. The antihyperlipidemic drugs available are generally safe and effective, and rate of ADRs is low if concomitant intake of other drugs and the differing pharmacokinetic profiles of the statins are considered.

Adverse Drug Reaction Reporting Systems↗
PubMed2002

Assessment of frequencies of lifestyle factors and polymorphisms of drug-metabolizing enzymes (NAT2, CYP2E1) in human hepatocellular carcinoma (HCC) patients in a department of surgical medicine--a pilot investigation.

The pathogenesis of human hepatocellular carcinoma (HCC) is a multistage process with the involvement of a multifactorial etiology. The role of drugs as risk factors has not been conclusively ascertained, but it appears that the use of oral contraceptives can be included. In the multifactorial etiology of human hepatocellular carcinoma (HCC), an association and interaction between genetic polymorphisms of xenobiotic metabolizing enzymes, lifestyle factors and cancer risk has been postulated. This pilot investigation examines the frequency of polymorphisms in selected genes (NAT2, CYP2E1) coding for xenobiotic metabolizing enzymes, and life-style habits (cigarette smoking, alcohol consumption) in 38 HCC patients. Genotyping of xenobiotic metabolizing enzymes was carried out using polymerase chain reaction--restriction fragment length polymorphism methods and DNA extracted from peripheral blood cells. In addition, HCC patients were interviewed with regard to their cigarette smoking habits and alcohol consumption using a standardized questionnaire. The results of this pilot investigation showed that the majority of the HCC patients smoke and consume alcohol. We found no predominance of slow acetylators (45%) or rapid acetylators (55%). 70.6% of slow acetylators were smokers. 86.5% of all patients with homozygote PstI/RsaI genotype also carried the homozygote DraI genotype, whereas 10.8% of all subjects with heterozygote PstI/RsaI genotype also carried the heterozygote DraI genotype. These genotype frequencies remain to be confirmed in a larger ethnic group. Whether polymorphisms of xenobiotic metabolizing enzymes is an important risk factor in (cigarette smoking-/alcohol consumption) HCC or not is currently being investigated in a case-control study in the same ethnic group.

Alcohol Drinking↗
PubMed2002

Replacement of murine sera by allergen-specific monoclonal IgE antibodies: a new approach for the characterisation of allergen extracts.

Allergen characterisation that is based on patients' sera or monoclonal allergen-specific IgG antibodies has several disadvantages. Current methods such as immunoblotting or allergen-specific EUSA are non-functional assays and cannot be used to evaluate the biological allergenic activity of allergen products. We have established an in vitro assay based on polyclonal murine IgE and allergen-dependent mediator release of rat basophilic leukaemia (RBL) cells as an alternative to passive cutaneous anaphylaxis (PCA), an animal model of IgE-mediated allergic reactions. The RBL assay is a functional in vitro test which enables the measurement of biological potency of allergen extracts to be made. Up to now, allergen-specific IgE-containing murine sera were used for sensitisation of RBL cells. Sensitisation with allergen-specific IgE monoclonal antibodies (IgE mAbs) would reduce the number of animals necessary for the production of allergen-specific IgE. In addition, IgE mAbs are better defined and will offer more exact determination of allergens. Since allergen-specific IgE mAbs were not available, the aim of this study was to produce such antibodies. As a new strategy to select IgE-producing hybridomas the RBL mediator release assay was used: the cells were incubated with hybridoma supernatant and stimulated with allergen and crosslinking allergen-specific polyclonal IgG antibodies. By this technology IgE mAbs specific for the birch pollen allergens Bet v 1 and Bet v 6 were produced. In conclusion, this novel strategy enables the production of panels of allergen-specific IgE mAbs by immunisation of a limited number of mice to be made. These IgE mAbs in combination with the RBL mediator release assay may serve as new tools for the evaluation of diagnostic and therapeutic allergen extracts.

Allergens↗
PubMed2001

Catalepsy and hypolocomotion induced by a nitric oxide donor: attenuation by theophylline.

Nitric oxide (NO) promotes adenosine release in the striatum and hippocampus. Behavioral effects of the nitric oxide donor sodium nitroprusside were studied in mice and included an examination of spontaneous locomotion and catalepsy, which are behaviors modulated by adenosine. Sodium nitroprusside caused a dose-dependent (2, 4 and 6 mg/kg) decrease in locomotor activity and catalepsy at the dose of 6 mg/kg. These effects were substantially attenuated by pretreatment with the non-selective adenosine receptors antagonist theophylline (10 and 30 mg/kg). Moreover, combined treatment with theophylline (30 mg/kg) and sodium nitroprusside (6 mg/kg) induced limbic seizures in 23% of animals. The pretreatment with the selective adenosine A(1) receptor antagonist 8-cyclopentyl-1, 3-dimethylxanthine (CPT) (1.2 mg/kg) caused no effect on the spontaneous or sodium nitroprusside-induced behavior. These data suggest that these behavioral effects of sodium nitroprusside are at least partially mediated by adenosine in the striatum and hippocampus, probably via adenosine A(2A) receptors.

Animals↗
PubMed2001

Molecular cloning, expression and characterization of the Canis familiaris interleukin-4.

Interleukin 4 (IL-4) is an important regulatory cytokine produced by activated T lymphocytes and mast cells, and regulates the growth and differentiation of cells such as B and T lymphocytes. The rapid amplification of cDNA ends (RACE) was used to clone the canine IL-4 gene. It was expressed in mammalian cells and Escherichia coli. Monoclonal antibodies were raised to rcIL-4 for use in an enzyme-linked immunosorbent assay (ELISA). This will facilitate studies on the role of cIL-4 in inflammatory diseases, particularly rheumatoid arthritis.

Animals↗
PubMed2001

Relationship between cerebro-spinal fluid pH and pulmonary ventilation of the South American lungfish, Lepidosiren paradoxa (Fitz.).

The respiratory control in land vertebrates (Tetrapoda) is mainly linked to regulation of acid-base status, which involves peripheral and central chemoreceptors. The lungfish (Dipnoi) might constitute the sister group of all land vertebrates (Tetrapoda) and possess a combination of real lungs and reduced gills. In this context, we evaluated the possible presence of central respiratory chemoreceptors in the South American Lungfish, Lepidosiren paradoxa. Pulmonary ventilation and respiratory frequency increased significantly with reductions of CSF pH by means of mock CSF solutions. This suggests that Lepidosiren possess central acid-base receptors.

Acid-Base Equilibrium↗
PubMed2001

Two-stage magnetization reversal in exchange biased bilayers.

MnF(2)/Fe bilayers exhibit asymmetric magnetization reversal that occurs by coherent rotation on one side of the loop and by nucleation and propagation of domain walls on the other side of the loop. Here, we show by polarized neutron reflectometry, magnetization, and magnetotransport measurements that for samples with good crystalline "quality" the rotation is a two-stage process, due to coherent rotation to a stable state perpendicular to the cooling field direction. The result is remarkably asymmetrically shaped hysteresis loops.

Journal Article↗
PubMed2001

Alternative splicing of the imprinted candidate tumor suppressor gene ZAC regulates its antiproliferative and DNA binding activities.

ZAC encodes a zinc finger protein with antiproliferative activity, is maternally imprinted and is a candidate for the tumor suppressor gene on 6q24. ZAC expression is frequently lost in breast and ovary tumor-derived cell lines and down-regulated in breast primary tumors. In this report, we describe ZACDelta2, an alternatively spliced variant of ZAC lacking the sequence encoding the two N-terminal zinc fingers. Messenger RNAs encoding ZAC or ZACDelta2 were equally abundant and both proteins were nuclear. ZACDelta2 displayed an improved transactivation activity and an enhanced affinity for a ZAC binding site, suggesting that the two N-terminal zinc fingers negatively regulated ZAC binding to its target DNA sequences. Both proteins were equally efficient in preventing colony formation, indicating similar overall antiproliferative activities. However, these activities resulted from a differential regulation of apoptosis vs cell cycle progression since ZACDelta2 was more efficient at induction of cell cycle arrest than ZAC, whereas it was the reverse for apoptosis induction. Hence, these data further underline that ZAC gene is critically controlled, both at the transcriptional level through imprinting and at the functional level through alternative splicing.

Alternative Splicing↗
PubMed2001

[Rhabdomyolysis as a rare complication of theophylline poisoning].

CASE REPORT: A case of a 73-year-old male with theophylline overdose complicated by rhabdomyolysis is reported. After uncontrolled self-medication with an unknown number of theophylline slow release 350 mg tablets and furosemide 40 mg tablets he was admitted with unspecific clinical signs like tachyarrhythmia, vomiting and restlessness. Maximum theophylline concentration was 66.5 mg/l, other abnormal laboratory findings included hypokalemia (2.8 mmol/l) and hyponatremia (123 mmol/l). The maximum creatinkinase level was measured after admission (32.29 mumol/s/l) accompanied by a serum myoglobin level of 3,789 micrograms/l. Immediate treatment with oral activated charcoal and continuous veno-venous hemodialysis (CVVH) was instituted, together with intravenous potassium and sodium chloride substitution, forced diuresis and continuous administration of intravenous metoprolol. The theophylline, creatinkinase and myoglobin levels decreased rapidly and there was no second rise in theophylline found. The patient survived without sequelae. CONCLUSION: Rhabdomyolysis is a rare complication of theophylline intoxication. In literature only a small number of cases are reported. Our results illustrate the necessity of a purposeful and fast management to successfully prevent renal failure or death. Some pathogenetic mechanisms of theophylline-induced rhabdomyolysis, epidemiologic data, risk factors and therapeutical principles will be demonstrated by a detailed literature survey.

Aged↗
PubMed2001

Hypoxia-induced upregulation of eNOS gene expression is redox-sensitive: a comparison between hypoxia and inhibitors of cell metabolism.

Several papers report a hypoxia-induced upregulation of the endothelial nitric oxide synthase (eNOS) mRNA expression. Since there is no known hypoxia-sensitive element binding site in the eNOS promoter, we reasoned that the effect of hypoxia could be simulated by a metabolically elicited alteration of the redox state. Therefore, cultured porcine aortic endothelial cells (PAEC) were exposed to hypoxia (1-10% O(2)) or inhibitors of cellular energy metabolism including rotenone, 2, 4 dinitrophenol (DNP) and 2-deoxyglucose for 6 to 24 h. Additionally, cells were treated with lactate and nicotinic acid to alter the cellular NAD(P)H/NAD(P) ratio without changes of energy supply. The cellular NAD(P)H/NAD(P) ratio was used as an index of the cellular redox state and determined using the MTT-assay. Hypoxia increased eNOS mRNA transcription and MTT-reduction in a manner inversely proportional to pO(2). Exposure to rotenone, DNP, and lactate increased the NAD(P)H/NAD(P) ratio, MTT-reduction, and eNOS mRNA also in parallel. In contrast, 2-deoxyglucose and nicotinic acid attenuated both MTT-reduction and eNOS mRNA expression. In order to study a potential role of the redox regulated transcription factor complex AP-1 in hypoxia-induced eNOS mRNA transcription, c-jun expression was determined and decoy experiments were performed. c-jun expression paralleled changes of eNOS mRNA expression and MTT-reduction. Furthermore, in the presence of oligodeoxynucleotides corresponding to the AP-1 binding sites of the eNOS promoter, the hypoxia and chemically induced eNOS mRNA expression was completely abolished. We propose that hypoxia, by altering cellular metabolism, leads to an increase in the cellular NAD(P)H/NAD(P) ratio which favors enhanced eNOS expression by redox-sensitive AP-1 mediated transcriptional control.

Animals↗
PubMed2001

Perspectives in the biological function, the technical and therapeutic application of bone morphogenetic proteins.

The bone morphogenetic proteins (BMPs) belong to the transforming growth factor beta superfamily of growth and differentiation factors and have been characterized by their ability to induce new bone formation in ectopic (non-skeletal) sites. BMPs are secreted molecules and are key regulators in early embryogenesis and organogenesis. One of the many functions of BMPs is to induce cartilage, bone, and connective tissue formation in vertebrates. This osteo-inductive capacity of BMPs has long been considered very promising for applications in bone repair, in the treatment of skeletal diseases, and in oral applications such as dentiogenesis and cementogenesis during regeneration of periodontal wounds. We discuss here biological roles of the BMPs in the organism and their signaling cascades leading to bone and cartilage formation in particular. It is also the aim of this review to evaluate the potential and the problems of BMPs in skeletal tissue engineering for the regeneration of bone damaged by disease or trauma and to serve as therapeutic agents for periodontal defects.

Animals↗
PubMed2001

Basal midbrain modulation of tonic immobility in the toad Bufo paracnemis.

Tonic immobility (TI) is considered to be a final stage in a sequence of defensive responses occurring in the prey/predator encounter. It is known that the basal midbrain of toads is involved in the organization of defensive behavior and analgesia. This study investigated the effect of electrolytic or neurotoxic lesions of two mesencephalic regions [tegmentum (TEG) and interpeduncular nucleus (IPN)] on the latency and duration of TI (induced by postural inversion and by movement restriction) and on the latency of the motor response to a nociceptive stimulus (hot plate) in toads. Electrolytic lesions of TEG and IPN promoted an increase in the duration of TI episodes. Neurotoxic lesion of these two regions also caused an increase in the duration of TI episodes. The effect was more intense in the animals with electrolytic lesion, possibly due to more extensive damage associated with this procedure or to damage of passage fibers. The results suggest that lesions of the midbrain TEG liberate basic circuits placed caudally and are involved in the organization of the TI response. It remains to be determined if the IPN exerts its effect directly on the caudal levels or by acting via the mesencephalic TEG. Lesions do not interfere with the latency of the motor response to a thermal noxious stimulus, indicating that the lesioned regions do not affect the reflexive response and are not essential for the perception of the noxious stimulus.

Animals↗
PubMed2001

[Organizational and medical aspects of transition of juveniles with congenital heart defects to adult cardiology care].

A growing, heterogeneous group of children with congenital heart disease is surviving into adulthood due to advances in medicine. These patients including those with simple and complex congenital heart disease and operated on during childhood are facing long-term complications. Superspecialist care and expertise are required during their life to deal with their unique problems the most common being ventricular failure, arrhythmias, valve and conduit longevity. Teenagers and adolescents disappear from both medical and parental care because of the lack of transition programs. Transition of care from pediatric to adult cardiologists must be organized in each country and must reflect regional history, regional politics and realities. Transition of care requires goodwill from parents, adolescents, pediatric and adult cardiologists. Transition clinics being held jointly by pediatric and adult cardiologists between the age of 16 and 18 years are essential to encourage the adolescents to take charge of their own life and health issues. Adequate information about their heart defect, their operations and their residual lesions may help them understand the implications for the future and improve their compliance. A transition program must include counseling on education, career, endocarditis prophylaxis, insurance and lifestyle issues such as sexuality and reproduction (including anticonception, pregnancy), cardiovascular risk factors and sports activities. Medical reports including operative reports and heart catheterization reports must be transferred to the adult cardiologists. In Switzerland, care of adults with congenital heart disease is based on three levels: 1) primary caregivers including general practiioners, internists and community cardiologists; 2) cardiologists with special commitment and expertise to patients with congenital heart disease who organize regional outpatient clinics; 3) supraregional referral centers with cardiologists trained in pediatric and adult congenital heart disease and experienced in the special needs, problems and management of this unique population. A close collaboration between pediatric and adult cardiologists participating jointly in the care of congenital heart disease patients is very important. An interdisciplinary team offers all non-invasive and invasive facilities for diagnostic and therapeutic procedures in a supraregional referral center. A close collaboration among all physicians is crucial for optimal care and management. Integration of adolescents with congenital heart disease into an adult medical system improves both compliance and quality of care and supports the patient's esteem because many medical aspects and lifestyle issues are completely different from those during childhood.

Adolescent↗
PubMed2001

Nucleosome remodeling at the IL-12 p40 promoter is a TLR-dependent, Rel-independent event.

Lipopolysaccharide (LPS) induction of the gene encoding interleukin 12 p40 requires remodeling of a promoter-encompassing nucleosome and the Toll-like receptor (TLR)-mediated activation of a c-Rel-containing complex. Analysis of TLR4-mutant mice revealed that remodeling requires TLR signaling. However, Rel proteins and other proteins required for transcription of an integrated p40 promoter were insufficient for remodeling. c-Rel was also unnecessary for remodeling, as remodeling was observed in c-Rel-/- macrophages, which lack p40 transcripts. These results suggest that remodeling requires TLR signaling pathways that diverge from the c-Rel activation pathways. The factors that stimulate remodeling may represent, therefore, newly identified targets of TLR signaling and of agents that regulate inflammatory responses and TH1 development.

Animals↗
PubMed2001

Novel point mutations, deletions, and polymorphisms in the cathepsin C gene in nine families from Europe and North Africa with Papillon-Lefèvre syndrome.

Papillon-Lefèvre syndrome is an autosomal recessive disorder characterized by palmoplantar keratoderma, periodontitis, and premature loss of dentition. Mutations in the CTSC gene that encodes cathepsin C have been described in families affected with Papillon--Lefèvre syndrome. Cathepsin C is the least understood of the lysosomal cysteine proteases; it has been reported to participate in both intracellular and extracellular cleavage of proteins and activation of serine proteases in immune and inflammatory cells. We report here eight new mutations in Papillon-Lefèvre syndrome families: four deletions and four point mutations, including a missense mutation in the propeptide chain that could help elucidate structure-function relationships in this protein. We also found that the 458C > T mutation, first reported in two families by Hart et al (2000c), was a neutral polymorphism in our families, as suggested by Allende et al (Cathepsin C gene: first compound heterozygous patient with Papillon--Lefèvre syndrome and novel symptomless mutation. Hum Mutat 17:152-153, 2001).

Africa, Northern↗