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L Holm

Publications and source records attributed to L Holm.

At least 73 records · Page 4Linked to original sources
PubMed1998

[The sociopsychological importance of food in hospital. Evaluation of a new meal system in a children's cancer ward].

Malnutrition of patients in hospitals is a subject that is fairly well described in the medical literature, but less attention has been paid to the social significance of food in hospitals. This article describes a study of the social and psychological impact of the introduction of a new meal delivery system in a children's cancer ward. A traditional centralized meal system was replaced by a staffed local kitchen. The evaluation involved questionnaires to the children, parents and staff members; qualitative, indepth, semi-structured interviews with subgroups; observations of meals. Children, staff and parents greatly preferred the new meal system, which changed the significance of food and meals in the hospital: from an arena of conflict and problems to one with a greatly enhanced social status. The article underlines that it is important to integrate socio-psychological and nutritional aspects of food and eating if malnutrition in hospitals is to be overcome.

Child↗
PubMed1998

Touring protein fold space with Dali/FSSP.

The FSSP database and its new supplement, the Dali Domain Dictionary, present a continuously updated classification of all known 3D protein structures. The classification is derived using an automatic structure alignment program (Dali) for the all-against-all comparison of structures in the Protein Data Bank. From the resulting enumeration of structural neighbours (which form a surprisingly continuous distribution in fold space) we derive a discrete fold classification in three steps: (i) sequence-related families are covered by a representative set of protein chains; (ii) protein chains are decomposed into structural domains based on the recurrence of structural motifs; (iii) folds are defined as tight clusters of domains in fold space. The fold classification, domain definitions and test sets for sequence-structure alignment (threading) are accessible on the web at www.embl-ebi.ac.uk/dali . The web interface provides a rich network of links between neighbours in fold space, between domains and proteins, and between structures and sequences leading, for example, to a database of explicit multiple alignments of protein families in the twilight zone of sequence similarity. The Dali/FSSP organization of protein structures 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.

Computer Communication Networks↗
PubMed1998

Prostaglandin E2 and aggressive factors increase the gland luminal pressure in the rat gastric mucosa in vivo.

BACKGROUND & AIMS: The gastroprotective properties of prostaglandins in low concentrations are still unclear. In this study, we investigated the effects of prostaglandin E2 (PGE2), indomethacin, and intraluminally applied HCl or ethanol on intraglandular pressure, mucus thickness, acid secretion, and gastric mucosal blood flow. METHODS: Glandular pressure and mucous gel thickness were measured with microelectrodes during intravital microscopy in thiobutabarbital sodium-anesthetized rats. Gastric blood flow was measured with laser Doppler flowmetry. RESULTS: In pentagastrin-treated rats, glandular pressure increased significantly in response to topical (1 micrograms/mL) or intra-arterial (12 micrograms.kg-1.h-1) PGE2 from approximately 17 to 69 and 18 to 57 mm Hg, respectively, whereas blood flow, mucus thickness, and acid secretion were unaltered. Indomethacin (3 mg/kg intravenously) significantly decreased glandular pressure from approximately 20 to 11 mm Hg. Intraluminal application of 10 and 100 mmol/L HCl or 20% and 40% ethanol significantly increased glandular pressure but had no effect after indomethacin pretreatment. CONCLUSIONS: Endogenous PGE2 is important for maintaining a high glandular pressure, and exogenous PGE2 potently increases glandular pressure at concentrations not altering blood flow, mucus thickness, or acid secretion. This suggests that high intraglandular pressures might be involved in gastroprotection.

Administration, Topical↗
PubMed1998

Gastric mucosal smooth muscles may explain oscillations in glandular pressure: role of vasoactive intestinal peptide.

BACKGROUND & AIMS: Oscillating (3-7 cycles/min) high pressures in gastric glands during acid secretion suggest the existence of rhythmically contracting mucosal muscles. The aim of this study was to study vasoactive intestinal peptide (VIP), an inhibitory neurotransmitter in the gastrointestinal tract, in relation to mucosal muscles, glandular pressure, and blood flow. METHODS: Rat, dog, and human mucosae were examined immunocytochemically for smooth muscle actin and VIP. Glandular pressure was measured using microelectrodes, red blood cell velocity (V[RBC]) was measured using a cross-correlation technique, and blood flow was measured using laser Doppler flowmetry in exposed gastric mucosa of thiobutabarbital sodium-anesthetized rats. RESULTS: Actin immunostaining showed muscle strands arising from muscularis mucosae, extending toward the gastric pits. VIP-immunoreactive nerve fibers were found in close relation to these muscles. VIP, administered intra-arterially close to the stomach (2 microg/kg bolus, followed by 10 microg x kg[-1] x h[-1]), significantly decreased glandular pressure from 18.2 +/- 1.6 to 8.9 +/- 1.6 mm Hg and almost eliminated the pressure oscillations. VIP infusion also abolished the oscillations in V(RBC) and significantly increased blood flow by approximately 35%. CONCLUSIONS: Contracting mucosal muscles may be responsible for oscillations in glandular pressure and possibly also in V(RBC). VIP probably relaxes these muscles.

Animals↗
PubMed1998

Unification of protein families.

Computational biology exploits the evolutionary connectivity between proteins and protein families to predict structural and functional properties of uncharacterized gene products. In the past year, conceptual and statistical refinements have substantially improved algorithms for the detection of remote homologues. In conjunction with the rapid growth of biological databases, the global organization of proteins into sequence families, functional families and structural families has become both pertinent and feasible.

Amino Acid Sequence↗
PubMed1998

Localization of carbonic anhydrase in the sperm-storing regions of the turkey and quail oviduct.

The localization of carbonic anhydrase in the sperm storage regions of turkey and quail was investigated using a histochemical method showing the activity of all the isozymes present. Intense carbonic anhydrase activity was found in the turkey sperm storage tubules and infundibular storage glands, whereas no activity could be detected in the quail at these sites. Both species did, however, show strong membrane-bound and cytoplasmic activity in the non-ciliated cells of the utero-vaginal surface epithelium and scattered cells of the vaginal epithelium. The enzyme catalyses the reaction CO2 + H2O <--> H+ + HCO3-, and the presence of carbonic anhydrase in these regions makes rapid changes in pH possible. It is suggested that increasing pH and/or the addition of bicarbonate stimulates sperm motility needed during transfer of the oviducal lumen. A lowering of the pH would keep the sperm quiescent during storage. The duration of sperm storage is considerably longer in the turkey than in the quail. The high quantity of carbonic anhydrase in the turkey sperm storage tubules may, thus, play a role in the duration of sperm storage.

Aging↗
PubMed1998

Pityrosporum orbiculare-reactive T-cell lines in atopic dermatitis patients and healthy individuals.

The yeast Pityrosporum orbiculare is one of the factors that may contribute to atopic dermatitis (AD). In the present study we compared the T-cell response to P. orbiculare in 12 AD patients with specific immunoglobulin (Ig)E antibodies (Ab) in serum against P. orbiculare with that of six non-atopic healthy controls. Freshly isolated peripheral blood mononuclear cells (PBMC) were cultured for 3 days in the presence of P. orbiculare extract. The proliferative response as measured by [3H]-thymidine incorporation was significantly higher in the AD patients than in the healthy controls (P < 0.05). Furthermore, significantly higher levels of interleukin (IL)-5 (P < 0.05), as analyzed by ELISA, were produced by PBMC from the AD patients compared to the healthy controls. Pityrosporum orbiculare-reactive T-cell lines (TCL) established by P. orbiculare stimulation of PBMC for 11 days produced significantly higher levels of IL-4 and IL-5 after stimulation with anti-CD3 Ab and showed a higher IL-4/interferon (IFN)-gamma ratio (P < 0.05) in the AD patients compared to the healthy controls. The higher proliferative PBMC response to P. orbiculare and the Th2-like cytokine production by P. orbiculare-stimulated TCL from AD patients indicate that P. orbiculare may play a role in maintaining skin inflammation in AD.

Adolescent↗
PubMed1998

Effectiveness of a dietary intervention strategy in general practice: effects on blood lipids, health and well-being.

OBJECTIVES: To evaluate the effect of a dietary treatment programme on blood cholesterol concentration in hypercholesterolaemic patients in general practice and to analyse subjectively experienced side-effects. DESIGN: A 1-year parallel trial comparing a new treatment programme with conventional treatment. SETTING: General practitioners in Roskilde county, Denmark. SUBJECTS: 355 men and women, aged 20-60 years, with a persistent blood cholesterol concentration above age- and gender-specific cut-off points (265 in an intervention group and 90 in a control group). INTERVENTION: A treatment strategy based on collaboration between doctor and dietitian using individual dietary advice and feedback from measured biological parameters. MAIN OUTCOME MEASURES: Serum lipids, body weight, blood pressure, dietary behaviour, health parameters, quality of life parameters and acceptance by patients and general practitioners. RESULTS: Total blood cholesterol concentration decreased by 14% (1.07 mmol l(-1), P < 0.0001) in 159 patients in the intervention group, not having any lipid altering drug during treatment, in addition to 3% from screening to start of treatment. In 65 patients in the control group, without any lipid altering drug, the reduction of cholesterol concentration was 4% (0.27 mmol l(-1), P < 0.01; intervention vs. control P < 0.001). In the intervention group overweight subjects (body mass index > 30) reduced body weight by 6% (P < 0.0001). Systolic blood pressure was reduced by 11% (P < 0.0001) and diastolic blood pressure by 10% (P < 0.0001) and 19% (P < 0.003) for intervals 90-110 mmHg and > 110 mmHg, respectively. Risk score decreased and self-assessed health, physical and psychological well-being improved. CONCLUSIONS: The treatment strategy tested proved to be efficient, without side-effects and well accepted by patients and general practitioners. The results strongly suggest that hypercholesterolaemia can efficiently be treated non-pharmacologically in general practice.

Adult↗
PubMed1998

Extracts of Helicobacter pylori reduce gastric mucosal blood flow through a VacA- and CagA-independent pathway in rats.

BACKGROUND: Helicobacter pylori may interfere with gastroduodenal protective mechanisms. Such effects could be due to a direct interaction with gastric epithelial cells but also to the action of a wide range of secreted and membrane-bound virulence factors. Our aim was to study the acute effects of water extracts produced from H. pylori on gastric mucosal blood flow and acid secretion and to relate them to VacA and CagA activity. METHOD: Extracts were produced from strains 88-23 and A5, both wild type; A5VacA, an isogenic mutant lacking expression of the vacuolating cytotoxin (VacA) and the immunodominant antigen (CagA); and Escherichia coli strain ATCC-25922. Bacterial extracts were applied on the exteriorized gastric corporal mucosa in inactin-anaesthetized rats after removal of as much as possible of the mucus layer, during intravital microscopy. Blood flow was measured by means of laser-Doppler flowmetry. RESULTS: All H. pylori extracts, including the extract from 88-23 heated to 100 degrees C for 30 min, significantly reduced blood flow by 15%-19%, whereas E. coli had no significant effect on blood flow. CONCLUSION: A factor or a combination of factors, other than VacA and CagA released from H. pylori, might compromise the natural defence of the gastric corporal mucosa by reducing mucosal blood flow. The factor is heat-stable and lacking or less potent in E. coli.

Animals↗
PubMed1998

COFFEE: an objective function for multiple sequence alignments.

MOTIVATION: In order to increase the accuracy of multiple sequence alignments, we designed a new strategy for optimizing multiple sequence alignments by genetic algorithm. We named it COFFEE (Consistency based Objective Function For alignmEnt Evaluation). The COFFEE score reflects the level of consistency between a multiple sequence alignment and a library containing pairwise alignments of the same sequences. RESULTS: We show that multiple sequence alignments can be optimized for their COFFEE score with the genetic algorithm package SAGA. The COFFEE function is tested on 11 test cases made of structural alignments extracted from 3D_ali. These alignments are compared to those produced using five alternative methods. Results indicate that COFFEE outperforms the other methods when the level of identity between the sequences is low. Accuracy is evaluated by comparison with the structural alignments used as references. We also show that the COFFEE score can be used as a reliability index on multiple sequence alignments. Finally, we show that given a library of structure-based pairwise sequence alignments extracted from FSSP, SAGA can produce high-quality multiple sequence alignments. The main advantage of COFFEE is its flexibility. With COFFEE, any method suitable for making pairwise alignments can be extended to making multiple alignments. AVAILABILITY: The package is available along with the test cases through the WWW: http://www. ebi.ac.uk/cedric CONTACT: cedric.notredame@ebi.ac.uk

Algorithms↗
PubMed1998

Removing near-neighbour redundancy from large protein sequence collections.

MOTIVATION: To maximize the chances of biological discovery, homology searching must use an up-to-date collection of sequences. However, the available sequence databases are growing rapidly and are partially redundant in content. This leads to increasing strain on CPU resources and decreasing density of first-hand annotation. RESULTS: These problems are addressed by clustering closely similar sequences to yield a covering of sequence space by a representative subset of sequences. No pair of sequences in the representative set has >90% mutual sequence identity. The representative set is derived by an exhaustive search for close similarities in the sequence database in which the need for explicit sequence alignment is significantly reduced by applying deca- and pentapeptide composition filters. The algorithm was applied to the union of the Swissprot, Swissnew, Trembl, Tremblnew, Genbank, PIR, Wormpep and PDB databases. The all-against-all comparison required to generate a representative set at 90% sequence identity was accomplished in 2 days CPU time, and the removal of fragments and close similarities yielded a size reduction of 46%, from 260 000 unique sequences to 140 000 representative sequences. The practical implications are (i) faster homology searches using, for example, Fasta or Blast, and (ii) unified annotation for all sequences clustered around a representative. As tens of thousands of sequence searches are performed daily world-wide, appropriate use of the non-redundant database can lead to major savings in computer resources, without loss of efficacy. AVAILABILITY: A regularly updated non-redundant protein sequence database (nrdb90), a server for homology searches against nrdb90, and a Perl script (nrdb90.pl) implementing the algorithm are available for academic use from http://www.embl-ebi.ac. uk/holm/nrdb90. CONTACT: holm@embl-ebi.ac.uk

Algorithms↗
PubMed1997

[Efficacy and safety of dietary supplementation containing Q10].

The literature concerning the importance of Q10 for health and disease has been reviewed. Dietary intake together with normal in vivo synthesis seems to fulfil the body's demands for Q10 in younger, healthy individuals. The importance of Q10 in general well-being 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 a positive effect of oral Q10 supplementation has been reported, especially in chronic heart failure. These effects should be further examined. No important adverse side effects have been reported from experiments using daily supplements of up to 200 mg of Q10 for six to twelve months, and 100 mg daily for up to six years.

Cardiovascular Diseases↗
PubMed1997

Dali/FSSP classification of three-dimensional protein folds.

The FSSP database presents a continuously updated structural classification of three-dimensional protein folds. It is derived using an automatic structure comparison program (Dali) for the all-against-all comparison of over 6000 three-dimensional coordinate sets in the Protein Data Bank (PDB). Sequence-related protein families are covered by a representative set of 813 protein chains. Hierachical clustering based on structural similarities yields a fold tree that defines 253 fold classes. For each representative protein chain, there is a database entry containing structure-structure alignments with its structural neighbours in the PDB. The database is accessible online through World Wide Web browsers and by anonymous ftp (file transfer protocol). The overview of fold space and the individual data sets provide a rich source of information for the study of both divergent and convergent aspects of molecular evolution, and define useful test sets and a standard of truth for assessing the correctness of sequence-sequence or sequence-structure alignments.

Amino Acid Sequence↗
PubMed1997

Predicting protein structure using hidden Markov models.

We discuss how methods based on hidden Markov models performed in the fold-recognition section of the CASP2 experiment. Hidden Markov models were built for a representative set of just over 1,000 structures from the Protein Data Bank (PDB). Each CASP2 target sequence was scored against this library of HMMs. In addition, an HMM was built for each of the target sequences and all of the sequences in PDB were scored against that target model, with a good score on both methods indicating a high probability that the target sequence is homologous to the structure. The method worked well in comparison to other methods used at CASP2 for targets of moderate difficulty, where the closest structure in PDB could be aligned to the target with at least 15% residue identity.

Markov Chains↗
PubMed1997

Omeprazole induces high intraglandular pressure in the rat gastric mucosa.

BACKGROUND & AIMS: In a few patients receiving high doses of omeprazole for a prolonged period, cystic changes have developed in the gastric mucosa, possibly consisting of enlarged gland lumina. To investigate this question, the luminal pressure in gastric glands was studied after omeprazole treatment in Inactin-anesthetized rats. METHODS: The gland luminal pressure and mucus thickness were measured with microelectrodes. For pressure measurements (servo-null technique) the microelectrode was inserted into a gland at an angle of approximately 30 degrees to the mucosal surface. RESULTS: Animals given omeprazole by gavage, 400 micromol/kg daily for 1 week, showed high gland luminal pressures (27.4 +/- 2.4 mm Hg). Similar values were found in animals given an intravenous omeprazole injection (40 micromol/kg). Much lower pressures were noted after vehicle or pentagastrin infusion. The thickness of the lower, firm mucus layer was not altered by omeprazole treatment. CONCLUSIONS: The significantly higher gland luminal pressure after treatment with omeprazole, compared with the values during pentagastrin or vehicle infusion, cannot be explained by increased mucus thickness. The results suggest accumulation of fluid in the gland lumen caused by increased resistance to outflow from the gland. This might explain the proposed enlargement of gland lumina.

Animals↗
PubMed1997

Enzyme HIT.

Explore the source record for details and available documents.

Acid Anhydride Hydrolases↗
PubMed1997

Effect of inhibition of pentagastrin-stimulated acid secretion on gastric mucosal gland luminal pressure.

We demonstrated previously that hydrochloric acid secreted from the gastric glands traverses the mucus layer in channels above the gland openings. The driving force for creation of these channels is most probably the hydrostatic pressure generated in the gastric gland lumen during stimulation of acid secretion. Here we investigated the effect of total inhibition of acid secretion on gland luminal pressure. Glandular pressure was measured in vivo with a pressure-sensitive microelectrode technique in Inactin-anaesthetized Sprague Dawley or Lewis x DA F1 rats. Glandular pressure was significantly reduced after ranitidine inhibition of acid secretion, from 17.2 +/- 2.1 mmHg during pentagastrin stimulation to 11.2 +/- 1.2 mmHg. This was also true when pentagastrin infusion was continued after inhibition of secretion with ranitidine. Omeprazole, however, did not significantly alter gland luminal pressure although it totally inhibited acid secretion. With continuation of pentagastrin infusion after omeprazole inhibition, glandular pressure increased significantly from 17.6 +/- 3.4 to 20.1 +/- 3.3 mmHg. In conclusion, total inhibition of acid secretion with ranitidine reduces but does not abolish gland luminal pressure. After omeprazole inhibition of acid secretion the gastric gland luminal pressure persisted or even increased. Since the volume secretion is lower after omeprazole administration than during pentagastrin stimulation, the outflow resistance most probably had increased after omeprazole injection. Suggestions for increased outflow resistance are narrowing in the upper part of the gland lumen by conformational changes of the cells or muscle contractions, and/or an increase in mucus secretion or viscosity.

Animals↗