Biomedical subjects

U Baumann

Publications and source records attributed to U Baumann.

At least 19 recordsLinked to original sources

PubMed2007

Skin surveillance of a U.K. paediatric transplant population.

BACKGROUND: Solid organ transplant recipients are at increased risk of skin cancer. Melanoma is less common than nonmelanoma skin cancer (NMSC) although the relative proportion of melanoma among skin cancers has been shown to be higher in paediatric than adult recipients. Multiple melanocytic naevi and/or atypical naevi may be a risk factor for the development of melanoma. The relationship between naevus counts and phenotypic characteristics, disease-related variables and sun exposure has not been explored in paediatric transplant patients. OBJECTIVES: To determine the prevalence of premalignant and malignant skin lesions and to identify known risk factors associated with benign and atypical melanocytic naevi in a U.K. paediatric transplant population. METHODS: Paediatric (< or = 19 years) renal and liver transplant patients, who were 5 or more years post-transplantation, were reviewed over 12 months. Lifetime history of sun exposure, episodes of sunburn, sunny holidays, sunscreen use, sun bed use, demographic and transplantation details were collected using interview, questionnaire and case note review. A skin examination was performed for regional counts of malignant lesions, benign and atypical naevi. RESULTS: Ninety-eight patients (82 liver, 13 renal, three multiorgan) with a median follow up of 9 years (range 5-16) were reviewed. Neither skin cancer nor premalignant lesions for NMSC were detected in this group. Eighty-five patients had benign naevi (median 6, range 1-57). Clinical risk factors for increased counts of benign naevi included increasing age (P = 0.03), more episodes of sunburn (P = 0.003) and prolonged treatment with cyclosporin (P = 0.009). The presence of atypical naevi in six patients was significantly associated with more episodes of sunburn (P = 0.006) and more transplants (P = 0.04). Other variables including phenotype, skin type, sun exposure, holidays abroad, residence abroad and total duration of immunosuppression did not correlate with benign or atypical naevus counts. CONCLUSIONS: Skin cancer was not observed in paediatric solid organ transplant recipients who were 5-16 years post-transplantation. Both benign and atypical naevus counts were higher in children with frequent episodes of sunburn. As both naevi and sunburn are risk factors for melanoma, we should target fair-skinned transplant recipients with naevi for intensive sun avoidance education. A prospective, longitudinal follow-up study should determine the onset of skin cancer post-transplantation and the significance of benign and atypical naevus counts in this cohort.

Adolescent↗

PubMed2006

The usefulness of bone marrow aspiration in the diagnosis of Niemann-Pick disease type C in infantile liver disease.

BACKGROUND: Niemann-Pick disease type C (NPC) is a fatal, autosomal recessive lysosomal storage disease which may present in infancy with cholestatic jaundice and/or hepatosplenomegaly. In cholestatic patients with splenomegaly, a bone marrow aspirate has been advocated as a relatively accessible tissue to demonstrate storage phenomena. Typically in patients with NPC, macrophages with abnormal cholesterol storage, so called foam cells, can be detected in the bone marrow. AIM: To review our experience of bone marrow aspiration in children with NPC presenting with infantile liver disease. METHODS: A retrospective analysis of 11 consecutive children (8 males) from Birmingham Children's Hospital with NPC presenting with infantile liver disease was undertaken. The diagnosis of NPC was confirmed in all cases by demonstrating undetectable or low rates of cholesterol esterification and positive filipin staining for free cholesterol in cultured fibroblasts. RESULTS: The median age at presentation was 1.5 months (range 0.5-10). Bone marrow aspirates showed storage cells in only 7/11 cases. Bone marrow aspirates which had storage cells were undertaken at a median age of 11 months while those with no storage cells were undertaken at median age 2.3 months. The overall sensitivity of bone marrow aspirates for detecting storage cells in children presenting with infantile liver disease was 64%; however, for children who had bone marrow aspirates in the first year of life it was only 57%. CONCLUSIONS: The sensitivity of bone marrow aspirate for the diagnosis of NPC disease in patients presenting with infantile liver disease was lower than previously reported. Where NPC is suspected clinically, definitive investigations should be undertaken promptly. There is a need to develop sensitive screening methods for NPC in children presenting with infantile liver disease.

Age Factors↗

PubMed2006

Small substrate, big surprise: fold, function and phylogeny of dihydroxyacetone kinases.

Dihydroxyacetone (Dha) kinases are a family of sequence-conserved enzymes which utilize either ATP (in animals, plants and eubacteria) or phosphoenolpyruvate (PEP, in eubacteria) as their source of high-energy phosphate. The kinases consist of two domains/subunits: DhaK, which binds Dha covalently in hemiaminal linkage to the Nepsilon2 of a histidine, and DhaL, an eight-helix barrel that contains the nucleotide-binding site. The PEP-dependent kinases comprise a third subunit, DhaM, which rephosphorylates in situ the firmly bound ADP cofactor. DhaM serves as the shuttle for the transfer of phosphate from the bacterial PEP: carbohydrate phosphotransferase system (PTS) to the Dha kinase. The DhaL and DhaK subunits of the PEP-dependent Escherichia coli kinase act as coactivator and corepressor of DhaR, a transcription factor from the AAA(+) family of enhancerbinding proteins. In Gram-positive bacteria genes for homologs of DhaK and DhaL occur in operons for putative transcription factors of the TetR and DeoR families. Proteins with the Dha kinase fold can be classified into three families according to phylogeny and function: Dha kinases, DhaK and DhaL homologs (paralogs) associated with putative transcription regulators of the TetR and DeoR families, and proteins with a circularly permuted domain order that belong to the DegV family.

Citrobacter freundii↗

PubMed2005

[HIV infections and children].

The HIV infection in children is not easily characterized and, because of this, may remain undetected for a long time. Guiding symptoms could be chronic skin eczema, respiratory tract infections, otitides, diarrhea or parotitis. The German AIDS Pediatric Association (PAAD) has made recommendations for the treatment of HIV infections in children. The treatment of HIV-positive children should be conducted in connection with an experienced institution. The untreated HIV infection is associated with an especially high mortality during the first year of life. Antiretroviral therapy using liquid confections is also possible in children of every age other than premature infants and its efficacy has been demonstrated through studies. A specific feature of the treatment of HIV infections in children is the concealment of the diagnosis from the young patients to prevent an unintentional passing on of the diagnosis onto third parties. The subsequent necessary concealment strategy means an additional burden on the family concerned.

AIDS-Related Opportunistic Infections↗

PubMed2005

Hyperinsulinism in tyrosinaemia type I.

Tyrosinaemia type I (TT I) (McKusick 276700) is a heterogeneous disorder with a broad spectrum of clinical phenotypes. Although histological abnormalities of the pancreas are well recognized, there are only incidental reports of pancreatic dysfunction manifested as insulin-dependent diabetes mellitus. We report three subjects with TT I and acute liver dysfunction who had hyperinsulinism in early infancy. Hypoglycaemia persisted despite dietary treatment and one patient had inadequate lipolysis at the time of hypoglycaemia. All three patients were successfully treated with diazoxide (10 mg/kg per day) and chlorthiazide (35 mg/kg per day) and treatment was gradually withdrawn after 9, 13 and 34 months, respectively. The mechanism of pancreatic dysfunction in TT I is unknown but may be related to the toxic metabolites that accumulate in this condition. We conclude that hyperinsulinism is not a rare complication in TT I. In patients with persistent hypoglycaemia, C-peptide should always be measured. Treatment with diazoxide and chlorthiazide is highly effective, appears to be safe, and does not need to be continued lifelong.

Blood Glucose↗

PubMed2004

Recombinant OprF-OprI as a vaccine against Pseudomonas aeruginosa infections.

A vaccine against Pseudomonas aeruginosa based on recombinant outer membranes has been developed. After intramuscularly injecting into patients with severe burns, antibodies against P. aeruginosa were induced. Vaccination was well tolerated. Intranasal application of the vaccine into volunteers, induced specific s-IgA antibodies. We conclude that the newly developed vaccine may be suitable for protection of the main risk groups of P. aeruginosa infections. In particular, for the protection of burn patients and patients with cystic fibrosis.

Administration, Intranasal↗

PubMed2004

Accumulation and distribution of platinum and rhodium in the European eel Anguilla anguilla following aqueous exposure to metal salts.

The platinum group metals (PGM) Pt and Rh are emitted into the environment mainly by catalytic exhaust gas converters of cars and by effluents of hospitals, which use Pt based anti-cancer drugs. However, there is still a lack of information on the availability of these precious metals to the biosphere. As PGM accumulate in sediments of aquatic ecosystems we focused our study on the uptake of the noble metals by European eels, Anguilla anguilla. Therefore, eels were exposed in tap water and humic water containing Pt(4+) and Rh(3+) at a concentration of 170 and 260 microg/l, respectively. After an exposure period of 6 weeks the mean Pt levels in bile, liver, kidney and intestine of the exposed eels ranged between 68 ng/g and 840 ng/g and the mean Rh levels between 35 ng/g and 155 ng/g whereas the PGM levels of the unexposed controls were below the detection limit of 50 ng/g for Pt and 5 ng/g for Rh. Rh was also taken up by gill and spleen. No PGM uptake was found for muscle and blood. The pattern of metal distribution within the eel differed between Pt and Rh and was dependent on the water type. Due to their accumulation capacity for PGM eels are suitable as accumulation indicators to detect PGM pollution in aquatic ecosystems.

Anguilla↗

PubMed2004

Late eczematous reactions to food in children with atopic dermatitis.

BACKGROUND: Food allergy is a common problem in patients with atopic dermatitis (AD), particularly in children. While immediate reactions to food are well characterized, the importance of food as a provocation factor for late eczematous reactions has been a subject of debate for several decades. OBJECTIVE: To investigate the importance of food for the induction of late eczematous reactions in children with AD and to correlate the clinical outcome to the results of specific IgE determinations and atopy patch tests (APTs). METHODS: One hundred and six double-blind placebo-controlled food challenges (DBPCFCs) to cow's milk, hen's egg, wheat and soy in 64 children with AD (median age 2 years) were analysed retrospectively. Total and food-specific IgE were determined by CAP RAST FEIA and APTs with native foodstuff were performed. The diagnostic values of specific IgE and APT results were calculated. RESULTS: Forty-nine (46%) of the challenges were related to a clinical reaction. An exacerbation of AD (late eczematous reaction) commonly occurred 24 h after the ingestion of food. Isolated late eczematous reactions were seen in 12% of all positive challenges. Forty-five percent of the positive challenges were associated with late eczematous responses, which followed immediate-type reactions. The sensitivity of food-specific IgE and the APT was 76% and 70%, respectively. Specific IgE and APT were often false positive, which resulted in low positive predictive values (64% and 45%, respectively). CONCLUSIONS: Late eczematous reactions may often be observed upon food challenge in children with AD. Due to the poor reliability of food-specific IgE and APT results DBPCFCs have still to be regarded as the gold standard for the appropriate diagnosis of food responsive eczema in children with AD.

Child, Preschool↗

PubMed2004

High-resolution mapping of the S and Z loci of Phalaris coerulescens.

Self incompatibility (SI) in Phalaris coerulescens is gametophytically determined by two unlinked multi allelic loci (S and Z). Neither the S nor Z genes have yet been cloned. As part of a map-based cloning strategy, high-resolution maps of the S and Z regions were generated from distorted segregating populations using RFLP probes from wheat, barley, oat, and Phalaris. The S locus was delimited to 0.26 cM with two boundary markers (Xwg811 and Xpsr168) and cosegregated with Xbm2 and Xbcd762. Xbcd266 was the closest marker linked to Z (0.9 cM). A high level of colinearity in the S and Z regions was found in both self-incompatible and -compatible species. The S locus was localized to the subcentromere region of chromosome 1 and the Z locus to the long arm end of chromosome 2. Several rice BAC clones orthologous to the S and Z locus regions were identified. This opens the possibility of using the rice genome sequence data to generate more closely linked markers and identify SI candidate genes. These results add further support to the conservation of gene order in the S and Z regions of the grass genomes.

Centromere↗

PubMed2002

Plant thioredoxins: the multiplicity conundrum.

Thioredoxins are small proteins distinguished by the presence of a conserved dicysteine active site. In oxidized thioredoxin, the two cysteines form a disulfide bond that is targeted by the enzyme thioredoxin reductase. Together with an electron donor, thioredoxin and thioredoxin reductase form the 'thioredoxin system' that is present in all organisms. Thioredoxins participate in dithiol/disulfide exchange reactions with a large range of cellular substrates. Higher plants possess a very complex thioredoxin profile consisting of at least two different thioredoxin systems that contain distinct, multigenic thioredoxin classes which have different intracellular localizations. In this review we summarise the current state of knowledge regarding the function of plant thioredoxins representing all systems and classes.

Amino Acid Sequence↗

PubMed2002

[Moving into a residential home -- experiences of the elderly and their relatives].

The change of ones habitual living conditions in favor of institutionalized living in a residential home is for an old person usually connected with many difficulties. Psychological studies support the argument that unprepared or sudden relocation leads to dramatic somatic and psychic reactions of the old person (anxiety, depression), as well as his care-givers. In this context we examined 45 elderly and 34 relatives about their experiences and changes in their life during the moving process. The most striking findings the positive experiences of the elderly and relatives during the relocation process, the low amount of information about residential home especially of the elderly, the positive attitude of elderly and relatives towards the residential home and finally the well-developed processes of short-term accommodation and subjective well-being.

Adult↗

PubMed2001

Cross cultural differences in health related quality of life in adolescents with cystic fibrosis.

PURPOSE: Quality of Life (QoL) is an important outcome measure in health care and pharmacological trials. The trend towards multinational clinical trials may be problematic because it is unclear as to whether, or to what extent, QoL-measures are comparable across cultures. This study compared QoL between English and German adolescents with Cystic Fibrosis (CF) and their healthy peers. METHOD: The study comprised a cross-sectional design. The English subjects formed two groups; 58 adolescents with CF and 49 healthy controls. The German subjects consisted of 26 adolescents with CF and 75 healthy controls. Quality of life was measured using the English and German versions of the SF-36. Demographic (age and gender) and clinical data (FEV1% predicted and BMI) were also recorded. RESULTS: The English and German CF groups had similar age-adjusted lung function and body mass index. Both the English CF and control groups reported a poorer quality of life than their respective German counterparts across several domains of the SF-36. These were limitations in activities due to physical health problems and emotional difficulties, social functioning, energy and vitality and pain. CONCLUSIONS: The differences in quality of life between English and German adolescents with CF appear to be either culturally determined or due to idiosyncrasies in the translations of the SF-36. rather than a consequence of their disease or its management.

Adolescent↗

PubMed2001

Protease C of Erwinia chrysanthemi: the crystal structure and role of amino acids Y228 and E189.

PrtC, a metallo-protease secreted by Erwinia chrysanthemi, is a member of the serralysin family and hence belongs to the metzincin superfamily. While the crystal structures of representatives of all metzincin subfamilies have been elucidated in the past, there is still some controversy about the reaction mechanism and the role of certain characteristic amino acids in the active centre. In this study, we probed the role of Tyr228 and Glu189 by site-directed mutagenesis and X-ray crystallography. There is evidence that these residues participate in catalysis, although conflicting hypotheses have been proposed. The crystal structures of wild-type and mutants have been refined to an R(free) of about 0.20 at resolutions of 2.0 A or better. Exchange of Glu189 versus alanine reduces the catalytic efficiency to less than 0.5 % using resorufin casein as substrate and to about 3 % using an assay utilising the thiol ester Ac-Pro-Leu-Gly-[(S)Leu]-Leu-Gly-OEt. The drop in activity is caused by a reduction in k(cat) while the K(M) values are virtually the same. In the resorufin casein assay, the mutant Y228F shows about 3 % of the wild-type activity and in the thiol ester assay this increases to about 56 %. In the latter case, the K(M) value of the mutant is increased from 5.3 mM to 9.0 mM with only little reduction in k(cat). The different behaviour of this mutant with respect to the two substrates can be explained by a switch in the rate-determining step during catalysis. The study presented here provides clear evidence that Glu189 of the HEXXHXXGXXH motif is the catalytic base, while Tyr228 is more likely involved in substrate binding and the stabilisation of the tetrahedral transition state.

Amino Acid Motifs↗

PubMed2001

The conserved methionine residue of the metzincins: a site-directed mutagenesis study.

The metalloprotease clan of the metzincins derive their name from the presence of a conserved methionine residue that is located on the C-terminal side of the zinc-binding consensus sequence HEXXHXXGXXH. This methionine residue is located in a rather divergent part of the primary sequence but is structurally very well conserved. It is located under the pyramidal base of the three histidine residues that coordinate the catalytic zinc ion and is not involved in any direct contact with the metal nor the substrate. In order to clarify its role, this methionine residue (M226) of the protease C from Erwinia chrysanthemi has been mutated to various other amino acids. The mutants M226L, M226A, M226I were sufficiently stable to be isolated, while the mutants M226H, M226S and M226N could not be purified. The kinetic properties of these mutants were analysed. All mutants showed decreased activity, whereby increases in K(M) as well as decreases in k(cat) were observed. The M226L mutant and M226C-E189 K double mutant, which has the catalytic glutamic acid substituted as well, could be crystallised. The structure of the M226L mutant was determined to a resolution of 2.0 A and refined to R(free) of 0.20. The structure is isomorphous to the wild-type and does not show large differences, with the exception of a very small movement of the zinc-liganding histidine residues. The M226C-E189 K double mutant crystal structure has been refined to an R(free) of 0.20 at 2.1 A resolution. A small rearrangement of the zinc-liganding histidine residues can be detected, which leads to a slightly different zinc coordination and could explain the decrease in activity.

Amino Acid Substitution↗

PubMed2001

Distinct tissue site-specific requirements of mast cells and complement components C3/C5a receptor in IgG immune complex-induced injury of skin and lung.

We induced the passive reverse Arthus reaction to IgG immune complexes (IC) at different tissue sites in mice lacking C3 treated or not with a C5aR-specific antagonist, or in mice lacking mast cells (Kit(W)/Kit(W-v) mice), and compared the inflammatory responses with those in the corresponding wild-type mice. We confirmed that IC inflammation of skin can be mediated largely by mast cells expressing C5aR and FcgammaRIII. In addition, we provided evidence for C3-independent C5aR triggering, which may explain why the cutaneous Arthus reaction develops normally in C3(-/-) mice. Furthermore, some, but not all, of the acute changes associated with the Arthus response in the lung were significantly more intense in normal mice than in C3(-/-) or Kit(W)/Kit(W-v) mice, indicating for C3- and mast cell-dependent and -independent components. Finally, we demonstrated that C3 contributed to the elicitation of neutrophils to alveoli, which corresponded to an increased synthesis of TNF-alpha, macrophage-inflammatory protein-2, and cytokine-induced neutrophil chemoattractant. While mast cells similarly influenced alveolar polymorphonuclear leukocyte influx, the levels of these cytokines remained largely unaffected in mast cell deficiency. Together, the phenotypes of C3(-/-) mice and Kit(W)/Kit(W-v) mice suggest that complement and mast cells have distinct tissue site-specific requirements acting by apparently distinct mechanisms in the initiation of IC inflammation.

Animals↗

PubMed2001

Crystal structure of a complex between Pseudomonas aeruginosa alkaline protease and its cognate inhibitor: inhibition by a zinc-NH2 coordinative bond.

Serralysins are a family of metalloproteases secreted by Gram-negative bacteria into the medium in the form of inactive zymogens. Usually, all serralysin secretors have on the same operon a gene coding for a periplasmic 10-kDa protein, which is an inhibitor of the secreted protease. The recent characterization of the inhibitor of the alkaline protease from Pseudomonas aeruginosa revealed a surprisingly low dissociation constant of 4 pm, contrary to earlier studies on homologous systems, where inhibition constants in the microm range were reported. To approach a more accurate understanding, the crystal structure of the complex between inhibitor and protease from P. aeruginosa was determined at 1.74 A resolution and refined to R(free) = 0.204. The structure reported here shows clearly that the N terminus of the inhibitor forms a coordinative bond to the catalytic Zn(2+) ion with a nitrogen-zinc distance of 2.17 A. We conclude that this interaction adds substantially to the complex stability and show also that similar interactions are found in other metzincin-inhibitor complexes.

Amino Acid Sequence↗

PubMed2001

Biochemical characterization of the structure-specific DNA-binding protein Cmb1 from Schizosaccharomyces pombe.

Cmb1, a novel HMG box protein from Schizosaccharomyces pombe, has been characterized biochemically using glutaraldehyde cross-linking, gel-filtration and analytical ultracentrifugation. It was identified as a monomeric, non-spherical protein, with a tendency to aggregate in solution. Limited proteolysis with trypsin and chymotrypsin showed that the C-terminal HMG box was a compact, proteolytically stable domain and the N-terminal region of Cmb1 was relatively unstructured and more easily digested. As Cmb1 was previously identified as a potential mismatch-binding protein, the binding constants and stoichiometry for both homoduplex and heteroduplex DNA were determined using an IASys resonant mirror biosensor. Cmb1 indeed demonstrated a tighter association with mismatched DNA, especially with the C/Delta-mismatch. Expression constructs of Cmb1 were made to study the sections of the protein involved in DNA binding. Constructs with the N-terminal region absent revealed that the C-terminal HMG box was the primary DNA-binding region. The presence of the N-terminal region did, however, facilitate tighter binding to both homoduplex and heteroduplex DNA. The amino acid residues isoleucine 14 and leucine 39 were located as putative intercalating residues using structure guided homology modelling. The model templates were derived from two distinct HMG:DNA complexes: HMG-D bound to homoduplex DNA and HMG 1 bound to cisplatin DNA. Binding studies using the Cmb1 HMG box with point mutations in these residues showed that isoleucine 14 was important for the binding of Cmb1 to homoduplex DNA, but affected binding to mismatches to a lesser extent. In contrast, leucine 39 appeared to have a more significant function in binding to mismatched DNA.

Amino Acid Sequence↗

PubMed2001

The dihydroxyacetone kinase of Escherichia coli utilizes a phosphoprotein instead of ATP as phosphoryl donor.

The dihydroxyacetone kinase (DhaK) of Escherichia coli consists of three soluble protein subunits. DhaK (YcgT; 39.5 kDa) and DhaL (YcgS; 22.6 kDa) are similar to the N- and C-terminal halves of the ATP-dependent DhaK ubiquitous in bacteria, animals and plants. The homodimeric DhaM (YcgC; 51.6 kDa) consists of three domains. The N-terminal dimerization domain has the same fold as the IIA domain (PDB code 1PDO) of the mannose transporter of the bacterial phosphoenolpyruvate:sugar phosphotransferase system (PTS). The middle domain is similar to HPr and the C-terminus is similar to the N-terminal domain of enzyme I (EI) of the PTS. DhaM is phosphorylated three times by phosphoenolpyruvate in an EI- and HPr-dependent reaction. DhaK and DhaL are not phosphorylated. The IIA domain of DhaM, instead of ATP, is the phosphoryl donor to dihydroxyacetone (Dha). Unlike the carbohydrate-specific transporters of the PTS, DhaK, DhaL and DhaM have no transport activity.

Adenosine Triphosphate↗