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Biomedical subjects

L Holm

Publications and source records attributed to L Holm.

At least 91 records · Page 5Linked to original sources

Elevated serum levels of soluble CD30 in patients with atopic dermatitis (AD).

The immunopathology of AD is still unclear, but evidence for an immune response polarized towards Th2 activity has been provided. The CD30 molecule belongs to the tumour necrosis factor (TNF) receptor family and is expressed on activated T cells with a sustained expression in Th2 cells. This molecule also exists in a soluble form (sCD30). Elevated serum levels of sCD30 have been found in patients with Hodgkin's disease, chronic hepatitis B infection and HIV infection. Studies were undertaken to compare the serum levels of sCD30 in patients with AD (n=49) and healthy non-atopic controls (n=94). The presence of sCD30 was analysed with ELISA. A significantly higher concentration of sCD30 was noted in AD patients, median sCD30 level 29 U/ml (range 1-708 U/ml), compared with healthy non-atopic controls (P<0.001), where the median level was 11 U/ml with a range of 1-1042 U/ml. No correlation was found between sCD30 levels and total serum IgE, or between the AD patients' SCORAD values and concentration of sCD30. sCD30 levels were also analysed in 20 AD patients, which during ketoconazole treatment had improved their clinical scores and reduced their serum IgE and eosinophil cationic protein levels. However, no significant decrease in sCD30 levels was noted after treatment. The results show that patients with AD have elevated levels of sCD30, but without correlation to total serum IgE or disease activity.

Adolescent↗

An evolutionary treasure: unification of a broad set of amidohydrolases related to urease.

The recent determination of the three-dimensional structure of urease revealed striking similarities of enzyme architecture to adenosine deaminase and phosphotriesterase, evidence of a distant evolutionary relationship that had gone undetected by one-dimensional sequence comparisons. Here, based on an analysis of conservation patterns in three dimensions, we report the discovery of the same active-site architecture in an even larger set of enzymes involved primarily in nucleotide metabolism. As a consequence, we predict the three-dimensional fold and details of the active site architecture for dihydroorotases, allantoinases, hydantoinases, AMP-, adenine and cytosine deaminases, imidazolonepropionase, aryldialkylphosphatase, chlorohydrolases, formylmethanofuran dehydrogenases, and proteins involved in animal neuronal development. Two member families are common to archaea, eubacteria, and eukaryota. Thirteen other functions supported by the same structural motif and conserved chemical mechanism apparently represent later adaptations for different substrate specificities in different cellular contexts.

Amidohydrolases↗

Definitions of 'healthy' eating: a pan-EU survey of consumer attitudes to food, nutrition and health.

OBJECTIVE: To describe the perceptions of a healthy diet across Europe and to explore the socio-cultural factors that influence these perceptions. DESIGN: A cross-sectional study in which quota-controlled, nationally-representative samples of approximately 1000 adults from each country completed a face-to-face interview-assisted questionnaire. SETTING: The survey was conducted between October 1995 and February 1996 in the 15 member states of the European Union. SUBJECTS: 14331 subjects (aged 15 y upwards) completed the questionnaire. Data were weighted by population size for each country and by sex, age and regional distribution within each member state. RESULTS: Responses were grouped into broad categories; overall 80% (specific country rates varied from 67-91%) of respondents mentioned either more fruit and vegetables or less fat, fatty foods, or a low fat diet, or balance and variety. The effects of age, gender and level of education were also explored: educational level appeared to have the strongest influence on perceptions of a healthy diet. Respondents who mentioned the family as a key influence on food choice, were more likely to mention eating more fruit and vegetables as part of a healthy diet. Respondents who stated that they did not have any source of information about diet were less likely to mention balance and variety or less fat or more vegetables. CONCLUSIONS: The results of the present study suggest that many people defined healthy eating in a way which would suggest that the healthy dietary guidelines are having some impact. The results also show, however, that there may be specific groups who are missed by current national campaigns, and that any European wide campaigns to change attitudes about healthy eating need to consider the baseline perception of healthy eating reported here.

Adolescent↗

Difficulties in trying to eat healthier: descriptive analysis of perceived barriers for healthy eating.

OBJECTIVE: To determine the factors which are perceived to be important barriers to healthy eating among European adults. DESIGN: A cross sectional study in which quota-controlled, nationally-representative samples of approximately 1000 adults from each country completed a face-to-face interview-assisted questionnaire. SETTING: The survey was conducted between October 1995 and February 1996 in the 15 member states of the European Union. SUBJECTS: 14,331 subjects (aged 15 y upwards) completed the questionnaire. Data were weighted by population size for each country and by sex, age and regional distribution within each member state. RESULTS: The study demonstrates a great variability in the perceived barriers to healthy eating between different EU countries. Lack of time was the most frequently mentioned difficulty among EU subjects for not following nutritional advice (24% of total EU sample). This barrier was frequently reported by the younger and the higher education people. Other frequently reported barriers were giving up favourite foods (23%) and willpower (18%). Thus healthy diets do not appear to be viewed as an easy or attractive alternative to current diets. There was wide geographical variation in the number of subjects mentioning price as an important barrier to healthy eating (15% in overall EU sample) ranging from less than 10% in Germany and Italy to 23% in the UK and 24% in Luxembourg.

Adolescent↗

Decision support system for the evolutionary classification of protein structures.

The structures of nearly a thousand sequence-unique proteins represent only 300 different 3D shapes. Is structural resemblance between proteins with little sequence similarity the result of physical convergence to favourable folding patterns, or does it reflect a memory of common evolutionary history? Separating these two processes is important for organizing genome data in terms of protein families and for theoretical approaches to protein structure prediction by fold recognition techniques. Achieving separation requires a combination of structure, sequence and functional analysis of proteins. For this purpose, we are developing a decision support system that scans heterogeneous protein sequence and structure related databases, and collects or calculates characters indicative of common functional constraints. The criteria include sequence homology, analysis of 3D clusters of conserved residues, conservation of active sites, and keyword analysis of biological function. Even without extensive refinement, application of a combination of these criteria to a test set representing all currently known protein structures yields 87% coverage with 7% false positives, compared to 53% coverage by only 1D sequence criteria. Thus, the semiautomatic prototype system significantly enhances the efficiency of unifying families of functionally related proteins in spite of long evolutionary distances.

Binding Sites↗

[Food consumption of the population. Trends followed via telephone interviews].

This study aimed at establishing and evaluating a simple method for surveilling trends in consumption of 10 nutritionally important foods. The method is based on food frequency questions combined with questions on the previous days intake, collected through telephone interviews. Participants (461 men, 546 women, 15-60+ yrs) came from a population sample. Between 22 and 69% consumed the foods in question as frequently as prescribed by the Danish food recommendations (lowest for fish and for vegetables, highest for potatoes/rice/pasta). Characteristic sex and age differences were observed, similar to findings from traditional, quantitative food surveys in Denmark. The food frequency results were confirmed by results from the previous day's intake. Crossing of frequencies for different foods gave additional information on consumption patterns. The results indicate that this very simple method may be a useful supplement to traditional quantitative dietary surveys for surveilling trends in food consumption. The Danish Nutrition Council therefore aims at doing similar surveys every other year.

Adolescent↗

Mapping the protein universe.

The comparison of the three-dimensional shapes of protein molecules poses a complex algorithmic problem. Its solution provides biologists with computational tools to organize the rapidly growing set of thousands of known protein shapes, to identify new types of protein architecture, and to discover unexpected evolutionary relations, reaching back billions of years, between protein molecules. Protein shape comparison also improves tools for identifying gene functions in genome databases by defining the essential sequence-structure features of a protein family. Finally, an exhaustive all-on-all shape comparison provides a map of physical attractor regions in the abstract shape space of proteins, with implications for the processes of protein folding and evolution.

Algorithms↗

The FSSP database: fold classification based on structure-structure alignment of proteins.

The FSSP database presents a continuously updated classification of 3-D protein folds based on an all-against-all comparison of structures currently in the Protein Data Bank (PDB) [Bernstein et al. (1977) J. Mol. Biol., 112, 535- 542]. The database currently contains an extended structural family for each of 600 representative protein chains which have <25% mutual sequence identity. The results of the exhaustive pairwise structure comparisons are reported in the form of a fold tree generated by hierarchical clustering and as a series of structurally representative sets of folds at varying levels of uniqueness. For each query structure from the representative set, there is a database entry containing structure-structure alignments with its structural neighbours in the representative set and its sequence homologs in the PDB. All alignments are based purely on the 3-D co-ordinates of the proteins and are derived by an automatic structure comparison program (Dali). The FSSP database is accessible electronically on the World Wide Web and by anonymous ftp.

Amino Acid Sequence↗

Consumers' views on food quality. A qualitative interview study.

The study investigated the themes consumers discuss when describing their everyday considerations about food quality. Twenty Copenhagen families with young children were interviewed open-endedly concerning daily food-related practices and thoughts, making particular use of narrative descriptions of specific meals. Respondents expressed both positive and negative opinions about a broad variety of processed and unprocessed foods. Positive opinions about food quality related mainly to personal criteria such as taste or convenience. Negative comments mainly related to how foods were processed or distributed. The study suggests that concerns about food safety are integrated in everyday concepts of food quality, and that consumers individually develop strategies to deal with this. However, feelings of uncertainty, helplessness and self reproach were frequently reported. The results suggest that choices of foods often reflect compromises in everyday life rather than the consumers' preferences.

Attitude↗

Power of one: nurses and tobacco control.

OBJECTIVES: To review major events in cigarette marketing and smoking practices, and to examine courses of action that can be taken by nurses to impact public health and safety. DATA SOURCES: Journal articles and news reports relating to the tobacco industry and tobacco regulations. CONCLUSION: Every segment of society suffers economic and health consequences of tobacco use, yet the tobacco industry continues to successfully market and promote the use of tobacco. Successful approaches to control tobacco use can be initiated at the federal, state, or local level. IMPLICATIONS FOR NURSING PRACTICE: Any nurse can take positive action toward tobacco control in numerous ways: by increasing awareness of the need for tobacco control; initiating personal action such as education and contacting legislators; and supporting public action through joining groups or coalitions whose efforts are directed at tobacco control.

Advertising↗

Localisation of carbonic anhydrase in the sperm storing regions of the domestic hen oviduct.

In the female bird sperm is stored in a quiescent mode, but full motility is needed for successful fertilisation. Regulation of sperm motility is thus of vital interest and the pH is a factor of importance. For this reason the localisation of carbonic anhydrase in the vagina, uterovaginal junction and infundibulum was studied with a histochemical method. Carbonic anhydrase catalyses the reaction CO2 + H2O <--> H+ + HCO3- and is known to take significant part in acid-base regulation in the body. The enzyme was found in all regions with the highest activity, both cytoplasmic and membrane-bound, in the non-ciliated cells of the uterovaginal surface epithelium. Intense membrane-bound activity was also found in the infundibular grooves and glands with slightly less in the sperm storage tubules and vaginal epithelium. Occasionally cytoplasmic and nuclear staining was seen. Changes in pH affect sperm motility and our results provide the first evidence for cellular mechanisms that makes rapid changes of the pH possible in these regions. Judging from the distribution of carbonic anhydrase we suggest two possible functions: (1) increasing pH and/or adding bicarbonate ions to stimulate sperm motility needed for the transfer to the storage sites and at fertilisation, and (2) a lowering of the pH in the sperm storage sites to keep the sperm quiescent during storage.

Animals↗

Evolutionary link between glycogen phosphorylase and a DNA modifying enzyme.

We report here an unexpected similarity in three-dimensional structure between glucosyltransferases involved in very different biochemical pathways, with interesting evolutionary and functional implications. One is the DNA modifying enzyme beta-glucosyltransferase from bacteriophage T4, alias UDP-glucose:5-hydroxymethyl-cytosine beta-glucosyltransferase. The other is the metabolic enzyme glycogen phosphorylase, alias 1.4-alpha-D-glucan:orthophosphate alpha-glucosyltransferase. Structural alignment revealed that the entire structure of beta-glucosyltransferase is topographically equivalent to the catalytic core of the much larger glycogen phosphorylase. The match includes two domains in similar relative orientation and connecting helices, with a positional root-mean-square deviation of only 3.4 A for 256 C alpha atoms. An interdomain rotation seen in the R- to T-state transition of glycogen phosphorylase is similar to that observed in beta-glucosyltransferase on substrate binding. Although not a single functional residue is identical, there are striking similarities in the spatial arrangement and in the chemical nature of the substrates. The functional analogies are (beta-glucosyltransferase-glycogen phosphorylase): ribose ring of UDP-pyridoxal ring of pyridoxal phosphate co-enzyme; phosphates of UDP-phosphate of co-enzyme and reactive orthophosphate; glucose unit transferred to DNA-terminal glucose unit extracted from glycogen. We anticipate the discovery of additional structurally conserved members of the emerging glucosyltransferase superfamily derived from a common ancient evolutionary ancestor of the two enzymes.

Amino Acid Sequence↗

The cytidylyltransferase superfamily: identification of the nucleotide-binding site and fold prediction.

The crystal structure of glycerol-3-phosphate cytidylyltransferase from B. subtilis (TagD) is about to be solved. Here, we report a testable structure prediction based on the identification by sequence analysis of a superfamily of functionally diverse but structurally similar nucleotide-binding enzymes. We predict that TagD is a member of this family. The most conserved region in this superfamily resembles the ATP-binding HiGH motif of class I aminoacyl-tRNA synthetases. The predicted secondary structure of cytidylyltransferase and its homologues is compatible with the alpha/beta topography of the class I aminoacyl-tRNA synthetases. The hypothesis of similarity of fold is strengthened by sequence-structure alignment and 3D model building using the known structure of tyrosyl tRNA synthetase as template. The proposed 3D model of TagD is plausible both structurally, with a well packed hydrophobic core, and functionally, as the most conserved residues cluster around the putative nucleotide binding site. If correct, the model would imply a very ancient evolutionary link between class I tRNA synthetases and the novel cytidylyltransferase superfamily.

Amino Acid Sequence↗

Mucus and alkali secretion in the rat duodenum: effects of indomethacin, N omega-nitro-L-arginine, and luminal acid.

BACKGROUND & AIMS: Duodenal mucus and bicarbonate secretion appear to play an essential role in the protection of the duodenum. The aim of this study was to examine duodenal bicarbonate and mucus secretion and the effects of cyclooxygenase inhibition, nitric oxide synthase inhibition, and luminal acid. METHODS: Duodenal mucus gel thickness was measured using microelectrodes during intravital microscopy in anesthetized rats. Bicarbonate secretion was measured using back-titration. RESULTS: A continuous layer of mucus with a mean thickness of 284 +/- 11 microns (n = 35) and a mean alkaline secretion of 0.18 +/- 0.01 mumol.cm-2.min-1 were found in untreated animals. Indomethacin decreased both mucus and bicarbonate secretion by about 35%. NO synthase inhibition with N omega-nitro-L-arginine reduced mucus secretion by about 21% but increased bicarbonate secretion by 39%. Exposure of the mucosal surface to 10 mmol/L HCI increased mucus secretion by 44% and bicarbonate secretion by 22%. CONCLUSIONS: The duodenal mucus layer is continuous. It can be easily removed, and new secretion can be followed. Duodenal mucus secretion is strongly stimulated by luminal acid and endogenous prostanoids and less markedly by NO, whereas bicarbonate secretion is stimulated by acid and endogenous prostanoids and inhibited by endogenous NO.

Acids↗

Villus tip microcirculation in the rat duodenum.

Duodenal microvascular perfusion was measured in anaesthetized rats both as erythrocyte velocity (rcv) in capillaries in the tip of duodenal villi and by laser-Doppler flowmetry (LDF). Rcv increased transiently by about 40% during the first 5 min of luminal exposure to 10 mM (NaCl to isotonicity) hydrochloric acid, while LDF measurements only showed a transient increase of about 7%, followed by a prolonged reduction by about 11%. Since the LDF signal is a measure not only of villus microcirculation but also of blood flow in the deeper layers, our results may suggest that blood flow is transiently redistributed towards the villi from deeper layers. Hypovolaemia (bleeding by approximately 10% of the blood volume) reduced rcv in the capillaries by 63% during the first 5 min of hypotension, but reduced LDF only by about 12%, a discrepancy which suggests a shift in blood flow from the tip to deeper layers. The experiments were performed under atmospheric oxygen tension, but rcv in the villus capillaries exposed to abdominal PO2 (approximately 45 mmHg) did not differ significantly from the values obtained under the atmospheric oxygen condition, either in the resting situation or during hypotension. In conclusion, we have developed an animal model in which red cell velocity in the tip of the duodenal villi can be studied for several hours and in which alkaline secretion from the duodenum is similar to previously reported levels. Our results show that the villus tip microcirculation in the duodenum may respond differently from that of deeper layers of the duodenal wall.

Animals↗