Biomedical subjects

L Holm

Publications and source records attributed to L Holm.

At least 55 records · Page 3Linked to original sources

PubMed2000

Estimating the significance of sequence order in protein secondary structure and prediction.

MOTIVATION: How critical is the sequence order information in predicting protein secondary structure segments? We tried to get a rough insight on it from a theoretical approach using both a prediction algorithm and structural fragments from Protein Databank (PDB). RESULTS: Using reverse protein sequences and PDB structural fragments, we theoretically estimated the significance of the order for protein secondary structure and prediction. On average: (1) 79% of protein sequence segments resulted in the same prediction in both normal and reverse directions, which indicated a relatively high conservation of secondary structure propensity in the reverse direction; (2) the reversed sequence prediction alone performed less accurately than the normal forward sequence prediction, but comparably high (2% difference); (3) the commonly predicted regions showed a slightly higher prediction accuracy (4%) than the normal sequences prediction; and (4) structural fragments which have counterparts in reverse direction in the same protein showed a comparable degree of secondary structure conservation (73% identity with reversed structures on average for pentamers). CONTACT: jong@biosophy.org; dietmann@ebi.ac.uk; heger@ebi.ac.uk; holm@ebi.ac.uk

Algorithms↗

PubMed2000

Sequence search algorithm assessment and testing toolkit (SAT).

MOTIVATION: The Sequence Search Algorithm Assessment and Testing Toolkit (SAT) aims to be a complete package for the comparison of different protein homology search algorithms. The structural classification of proteins can provide us with a clear criterion for judgment in homology detection. There have been several assessments based on structural sequences with classifications but a good deal of similar work is now being repeated with locally developed procedures and programs. The SAT will provide developers with a complete package which will save time and produce more comparable performance assessments for search algorithms. The package is complete in the sense that it provides a non-redundant large sequence resource database, a well-characterized query database of proteins domains, all the parsers and some previous results from PSI-BLAST and a hidden markov model algorithm. RESULTS: An analysis on two different data sets was carried out using the SAT package. It compared the performance of a full protein sequence database (RSDB100) with a non-redundant representative sequence database derived from it (RSDB50). The performance measurement indicated that the full database is sub-optimal for a homology search. This result justifies the use of much smaller and faster RSDB50 than RSDB100 for the SAT. AVAILABILITY: A web site is up. The whole packa ge is accessible via www and ftp. ftp://ftp.ebi.ac.uk/pub/contrib/jong/SAT http://cyrah.ebi.ac.uk:1111/Proj/Bio/SAT http://www.mrc-lmb.cam.ac.uk/genomes/SAT In the package, some previous assessment results produced by the package can also be found for reference. CONTACT: jong@ebi.ac.uk

Algorithms↗

PubMed2000

RSDB: representative protein sequence databases have high information content.

MOTIVATION: Biological sequence databases are highly redundant for two main reasons: 1. various databanks keep redundant sequences with many identical and nearly identical sequences 2. natural sequences often have high sequence identities due to gene duplication. We wanted to know how many sequences can be removed before the databases start losing homology information. Can a database of sequences with mutual sequence identity of 50% or less provide us with the same amount of biological information as the original full database? RESULTS: Comparisons of nine representative sequence databases (RSDB) derived from full protein databanks showed that the information content of sequence databases is not linearly proportional to its size. An RSDB reduced to mutual sequence identity of around 50% (RSDB50) was equivalent to the original full database in terms of the effectiveness of homology searching. It was a third of the full database size which resulted in a six times faster iterative profile searching. The RSDBs are produced at different granularity for efficient homology searching. AVAILABILITY: All the RSDB files generated and the full analysis results are available through internet: ftp://ftp.ebi.ac. uk/pub/contrib/jong/RSDB/http://cyrah.e bi.ac.uk:1111/Proj/Bio/RSDB

Algorithms↗

PubMed2000

DaliLite workbench for protein structure comparison.

SUMMARY: DaliLite is a program for pairwise structure comparison and for structure database searching. It is a standalone version of the search engine of the popular Dali server. A web interface is provided to view the results, multiple alignments and 3D superimpositions of structures.

Computational Biology↗

PubMed2000

Localization of calcium and zinc in the sperm storage tubules of chicken, quail and turkey using X-ray microanalysis.

Sperm storage tubules from the utero-vaginal junction of chickens, quails and turkeys were analysed for calcium and zinc using X-ray microanalysis of ultra-rapidly frozen tissue in a scanning electron microscope. This technique enabled the tubular fluid surrounding the stored spermatozoa and the intracellular content of the cells of the sperm storage tubules to be analysed separately and, by using standards with known concentrations, their elemental concentrations were estimated. The mean (+/- SEM) concentration of calcium in the tubular fluid from chickens, quails and turkeys was 17 +/- 3, 19 +/- 3 and 17 +/- 4 mmol kg(-1) wet weight, respectively. The intracellular calcium concentration of the cells of the tubules did not differ significantly from these values and was also similar in the mucosal epithelial cells of the utero-vaginal junction. Zinc was localized in the cells of turkey sperm storage tubules and tubular fluid, but at low concentrations. No zinc could be detected in corresponding structures from chickens and quails. The concentration of calcium in the tubular fluid is within the range known to inhibit the motility of spermatozoa, supporting this function for calcium during storage. Zinc is known to depress turkey sperm metabolism and it may also be involved in inducing quiescence of spermatozoa during storage in this species.

Animals↗

PubMed1999

[Changes in food habits among the population from 1995 to 1998].

In order to survey trends in food habits the Danish Nutrition Council initiated two food frequency surveys, comprising ten nutritionally important foods, in 1995 and in 1998. Participants were men and women, 15-90 yrs, from similar population samples (n = 1007 in 1995, 1024 in 1998). Participation rate was 62% in 1995 and 63% in 1998. Data were collected by telephone interview. For six of the ten foods significant changes in consumption frequencies were observed: salad/raw vegetables, rice/pasta and fish were consumed more frequently in 1998, whereas consumption of meat, potatoes and fresh fruit had become less frequent. Average frequencies differed by 4-13%. In 1998 low-fat milk had become more common, whereas whole milk was now less common. More subjects now skipped fat spreads on their bread, but more chose spreads containing butterfat. Some, but not all, of the observed changes point in the right direction compared to recommendations. The results demonstrate that food habits are currently in a dynamic process.

Adolescent↗

PubMed1999

Protein folds and families: sequence and structure alignments.

Dali and HSSP are derived databases organizing protein space in the structurally known regions. We use an automatic structure alignment program (Dali) for the classification of all known 3D structures based on all-against-all comparison of 3D structures in the Protein Data Bank. The HSSP database associates 1D sequences with known 3D structures using a position-weighted dynamic programming method for sequence profile alignment (MaxHom). As a result, the HSSP database not only provides aligned sequence families, but also implies secondary and tertiary structures covering 36% of all sequences in Swiss-Prot. The structure classification by Dali and the sequence families in HSSP can be browsed jointly from a web interface providing a rich network of links between neighbours in fold space, between domains and proteins, and between structures and sequences. In particular, this results in a database of explicit multiple alignments of protein families in the twilight zone of sequence similarity. The organization of protein structures and families provides a map of the currently known regions of the protein universe that is useful for the analysis of folding principles, for the evolutionary unification of protein families and for maximizing the information return from experimental structure determination. The databases are available from http://www.embl-ebi.ac.uk/dali/

Databases, Factual↗

PubMed1999

Nordic meals: methodological notes on a comparative survey.

This article discusses some methodological aspects of the project "Eating and Modern Everyday Life. A Comparative Survey of Nordic Countries". Data were collected in April 1997 with computer assisted telephone interviews in Denmark, Finland, Norway and Sweden. Questionnaires included a record of the informant's eating on the day before the interview, attitudes related to current food discourses, socio-demographic information and a few open-ended questions. The emphasis was on social and cultural aspects of eating. One aim of this study is to investigate whether regular meals are substituted by irregular eating patterns. In order to avoid any predefined meal concepts the questionnaire therefore focused on eating events. The reconstruction of data is based on a model called the eating system. The model has three dimensions: the eating pattern (the rhythm and the number of eating events, the alternations of hot and cold eating events), the meal format (the composition of the main course, the sequence of the whole meal) and the social organization of eating (where and with whom people are eating, who did the cooking). Some preliminary results are presented suggesting that the questionnaire and the analytical model suit the purpose of studying modernization through the field of food.

Denmark↗

PubMed1999

Sensitization to allergens of house-dust mite in adults with atopic dermatitis in a cold temperature region.

BACKGROUND: An IgE-mediated contact reaction to airborne allergens has been suggested as one important pathogenetic mechanism in atopic dermatitis (AD). The house-dust mite (HDM) might be a common allergen involved. In Scandinavia, sensitization to HDM has been rare, probably because of the cold, dry climate. However, recent studies indicate high levels of domestic mites and HDM allergen in 15-20% of homes in central and northern Sweden. METHODS: To evaluate the importance of the HDM in patients with AD in the Stockholm region, we screened 81 adult Stockholm residents with AD, for the prevalence and degree of sensitization to the HDM, according to specific IgE (RAST), skin prick test (SPT), and atopy patch test (APT). We also assessed the HDM exposure in their homes and correlated the results with clinical history, severity of the dermatitis, and type of residence during childhood and today. RESULTS: The sensitization rate to HDM was high (56% according to RAST, 24% according to SPT, and 47% according to APT), and 20% of the patients were exposed to HDM allergens in their beds. Mite exposure seemed to aggravate the dermatitis in highly sensitized patients. CONCLUSIONS: The results indicate that we have to take the HDM into account when discussing aggravating factors in adult patients with AD in the Stockholm region.

Adolescent↗

PubMed1999

Preferences, quantities and concerns: socio-cultural perspectives on the gendered consumption of foods.

A review of the sociological research regarding the gendered features of food consumption is presented. The focus is upon differences between women and men in regard to their preferences for particular foods and types of meals, seen in relation to the cultural function of foods as symbolic markers of femininity or masculinity, assessments of the quantities of food consumed by women and men respectively, and differences between women and men in regard to concerns with food safety, health, weight reduction and fitness. Some methodological limitations of this research are discussed with particular reference to the need for interdisciplinary cooperation between sociologists and nutritionists in the design and analysis of dietary surveys. Suggestions are made in regard to future directions for sociological research in this field, with particular reference to the issue that dietary recommendations appear to focus upon increasing the consumption of foods that are markers of femininity and decreasing the consumption of foods that are markers of masculinity in Western food culture.

Culture↗

PubMed1999

Coenzyme Q10 in health and disease.

The literature concerning the importance of coenzyme Q10 in health and disease has been reviewed. Usual dietary intake together with normal in vivo synthesis seems to fulfil the demands for Q10 in healthy individuals. The importance of Q10 supplementation for general health has not been investigated in controlled experiments. The literature allows no firm conclusions about the significance of Q10 in physical activity. In different cardiovascular diseases, including cardiomyopathy, relatively low levels of Q10 in myocardial tissue have been reported. Positive clinical and haemodynamic effects of oral Q10 supplementation have been observed in double-blind trials, especially in chronic heart failure. These effects should be further examined. No important adverse effects have been reported from experiments using daily supplements of up to 200 mg Q10 for 6-12 months and 100 mg daily for up to 6 y.

Cardiovascular Diseases↗

PubMed1999

Randomized trial on protein vs carbohydrate in ad libitum fat reduced diet for the treatment of obesity.

OBJECTIVE: To study the effect on weight loss in obese subjects by replacement of carbohydrate by protein in ad libitum consumed fat-reduced diets. DESIGN: Randomized dietary intervention study over six months comparing two ad libitum fat reduced diets (30% of total energy) strictly controlled in composition: High-carbohydrate (HC, protein 12% of total energy) or high-protein (HP, protein 25% of total energy). SETTING AND PARTICIPANTS: Subjects were 65 healthy, overweight and obese subjects (50 women, 15 men, aged 18-55 y) randomly assigned to HC (n = 25), HP (n = 25) or a control group (C, n = 15). All food was provided by self-selection in a shop at the department, and compliance to the diet composition was evaluated by urinary nitrogen excretion. MAIN OUTCOME MEASURE: Change in body weight, body composition and blood lipids. RESULTS: More than 90% completed the trial. Weight loss after six months was 5.1 kg in the HC group and 8.9 kg in the HP group (difference 3.7 kg, 95% confidence interval (CI)(1.3-6.2 kg) P < 0.001), and fat loss was 4.3 kg and 7.6 kg, respectively (difference 3.3 kg (1.1-5.5 kg) P < 0.0001), whereas no changes occurred in the control group. More subjects lost > 10 kg in the HP group (35%) than in the HC group (9%). The HP diet only decreased fasting plasma triglycerides and free fatty acids significantly. CONCLUSIONS: Replacement of some dietary carbohydrate by protein in an ad libitum fat-reduced diet, improves weight loss and increases the proportion of subjects achieving a clinically relevant weight loss. More freedom to choose between protein-rich and complex carbohydrate-rich foods may allow obese subjects to choose more lean meat and dairy products, and hence improve adherence to low-fat diets in weight reduction programs.

Adolescent↗

PubMed1999

Helicobacter pylori extracts reduce gastric mucosal blood flow by a nitric oxide-independent but mast cell- and platelet-activating factor receptor-dependent pathway in rats.

BACKGROUND: We have previously shown that water extracts from Helicobacter pylori reduce gastric mucosal blood flow by approximately 15%. It has also been suggested that H. pylori can inhibit endogenous nitric oxide (NO) biosynthesis. Our aim was to examine whether the reduction in blood flow induced by H. pylori is the direct consequence of an NO synthase inhibition and the possible involvement of mast cell degranulation. METHODS: A water extract was produced from wildtype strain 88-23. The extract was applied on the exteriorized gastric corporal mucosa in inactin-anesthetized rats, after removing as much as possible of the mucus layer, during intravital microscopy. Blood flow was measured with laser-Doppler flowmetry. RESULTS: In rats pretreated with the NO synthase inhibitor N-nitro-L-arginine there was a 19% +/- 6% reduction in blood flow 40 min after application of the extract, and a 27% +/- 9% reduction after another 20 min with saline. The reduction was abolished by concomitant pretreatment with the mast cell stabilizer ketotifen or the platelet-activating factor (PAF) receptor antagonist WEB2086. CONCLUSION: The reduction in mucosal blood flow induced by the extract was probably mediated through an acute inflammatory response involving mast cell degranulation with consequent PAF secretion. The effect on blood flow was not the result of a decrease in vascular tone due to an inhibition of endogenous NO biosynthesis.

Animals↗

PubMed1999

Impairment and work disability due to whiplash injury following traffic collisions. An analysis of insurance material from the Swedish Road Traffic Injury Commission.

A study was set up to determine the trends in medical impairment and work disability ratings for persons affected by whiplash associated disorders (WAD) and other injuries secondary to road traffic collisions, and into the influence of age, gender, professional status, and final medical impairment rating on final work disability. A cross-sectional study was carried out of insurance files of 2,523 subjects in 1989 and 3,223 subjects in 1994 judged to have a permanent medical impairment of 10% or more and work disability due to road traffic injury. Files were obtained from the Swedish Road Traffic Injury Commission. The main outcome measures were the crude frequency and age-specific, standardized percentage of traffic injuries with a medical impairment of 10% or more for the years 1989 and 1994. Final work disability status was analysed with respect to age, gender, type of injury, degree of medical impairment, and professional status. The proportion of medical impairment due to WAD was found to have increased from 16% in 1989 to 28% in 1994, but the proportion of work disability was found to have remained the same. Age over 40 years, low professional status, and having a medical impairment judgement of 15% or more were independently associated with reduced or full work disability.

Accidents, Traffic↗

PubMed1999

Sweat production and localisation of carbonic anhydrase in the equine sweat gland during exercise at two ambient temperatures.

The aim of this investigation was to study sweat production during exercise at 2 ambient temperatures (20 degrees C and 35 degrees C) and the concurrent localisation of carbonic anhydrase (CA) in the sweat gland. Horses develop alkalosis during prolonged exercise and the sweat contains HCO3-. Carbonic anhydrase is therefore of interest since it catalyses the reaction CO2 + H2O<-->HCO3- + H+. Four standardbred trotters performed an exercise test. Skin biopsies were taken from the neck, and sweat rate, blood and skin temperatures were measured. There was a close relationship between sweat rate, temperatures and work intensity at 20 degrees C. Temperatures and sweat rate were higher at 35 degrees C and did not fall when the work intensity dropped. A significant decrease in the sweat gland cell area was found after exercise at 35 degrees C with an accompanying decrease of vesicles. Strong CA activity was present at the luminal cell membrane and weaker basolaterally. The staining intensity increased after exercise. We suggest that CA might be of importance for counteracting the alkalosis developed after exercise by delivering HCO3- for generation of the alkaline pH in sweat.

Animals↗

PubMed1998

The effect of pH on the motility of spermatozoa from chicken, turkey and quail.

At 40 degrees C in a NaCl-based buffer the motility of spermatoza from chicken, turkey and quail was inhibited at pH values below 7.8, 7.2 and 7.2, respectively. At these pH values the percentage motile and velocity of spermatoza were relatively low, but the motility became vigorous when the pH was raised by 0.2 units and increased even more following further alkalinization. Spermatozoa from all three species stored motionless at pH 6.0 for 3 h could be reactivated by dilution in an alkaline solution (pH 9.0). These findings support the hypothesis that a change in the environmental pH could be implicated in the suppression and stimulation of sperm motility during oviducal sperm storage and transport.

Animals↗

PubMed1998

[Despite better knowledge of pathogenesis and treatment: atopic eczema--a disease with increasing incidence in Sweden].

The past twenty years have witnessed an increasing incidence of atopic dermatitis in Western Europe. The article consists in a discussion of the pathogenesis, clinical signs and treatment of this common skin disease. Both an IgE-mediated reaction on epidermal Langerhans cells, and a physiological/biochemical defect of the skin barrier structure may be crucial factors of the multifactorial pathogenesis. Local treatment with corticosteroids and moisturisers remains the basic approach, though the development of new more specific treatments is under way. Although much remains to be learned about atopic dermatitis, today all patients can be offered effective treatment resulting in improved quality of life.

Adult↗

PubMed1998

Dictionary of recurrent domains in protein structures.

The rapid growth in the number of experimentally determined three-dimensional protein structures has sharpened the need for comprehensive and up-to-date surveys of known structures. Classic work on protein structure classification has made it clear that a structural survey is best carried out at the level of domains, i.e., substructures that recur in evolution as functional units in different protein contexts. We present a method for automated domain identification from protein structure atomic coordinates based on quantitative measures of compactness and, as the new element, recurrence. Compactness criteria are used to recursively divide a protein into a series of successively smaller and smaller substructures. Recurrence criteria are used to select an optimal size level of these substructures, so that many of the chosen substructures are common to different proteins at a high level of statistical significance. The joint application of these criteria automatically yields consistent domain definitions between remote homologs, a result difficult to achieve using compactness criteria alone. The method is applied to a representative set of 1,137 sequence-unique protein families covering 6,500 known structures. Clustering of the resulting set of domains (substructures) yields 594 distinct fold classes (types of substructures). The Dali Domain Dictionary (http://www.embl-ebi.ac.uk/dali/) not only provides a global structural classification, but also a comprehensive description of families of protein sequences grouped around representative proteins of known structure. The classification will be continuously updated and can serve as a basis for improving our understanding of protein evolution and function and for evolving optimal strategies to complete the map of all natural protein structures.

Amino Acid Sequence↗