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L Holm

Publications and source records attributed to L Holm.

At least 37 records · Page 2Linked to original sources
PubMed2001

Disrupted carbonic anhydrase distribution in the avian shell gland following in ovo exposure to estrogen.

Eggshell thinning among wild birds has been an environmental concern for almost half a century and the underlying mechanisms are still not fully understood. Previously we showed that exposure of quail embryos to ethynylestradiol (EE2) caused disorganization of the tubular glands in the shell gland of adult birds. In this study, we have examined the effect of in ovo exposure to EE2 on carbonic anhydrase (CA) localization, especially in the shell gland, because CA is required for shell formation. In the control birds, CA was localized in the cell membranes of the tubular gland cells of the shell gland, whereas the surface epithelium was always devoid of CA. In ovo treatment with 20ng EE2/g egg resulted in a loss of CA activity in the tubular glands while the surface epithelium showed strong induction of both membrane bound and cytoplasmic CA activity in 49+/-1% of the cells. The dose 2ng EE2/g egg resulted in partial loss of tubular gland CA and strong induction of CA activity in 2.5+/-0.5% of the surface epithelial cells and weaker induction in 22+/-2% of the epithelial cells. In conclusion, this study shows that embryonic exposure to a xenoestrogen disrupts CA distribution in the adult shell gland. We propose that eggshell thinning in avian wildlife could reflect a functional malformation in the shell gland, already induced by xenoestrogen during embryonic development rather than being caused solely by exposure of the adult bird.

Animals↗
PubMed2001

Effectiveness of occlusive bedding in the treatment of atopic dermatitis--a placebo-controlled trial of 12 months' duration.

BACKGROUND: Several studies on avoidance of house-dust-mite (HDM) and cat allergens have been carried out, most of them in asthmatic patients and only a few in patients with atopic dermatitis (AD). No study so far has focused on which subgroup of AD patients benefits from avoidance measures. METHODS: Forty adult patients with AD completed the 12-month avoidance study. They were divided into an active treatment (n = 22) and a placebo (n = 18) group. Active treatment comprised use of polyurethane-coated cotton encasings for bedding, and placebo use of cotton covers. Patients came for regular checkups during the 12-month period, when eczema severity was assessed and blood samples were analyzed for total IgE, HDM- and cat-specific IgE and soluble CD30 (sCD30) in serum. Dust samples were collected from mattresses before treatment and after 3, 6, and 12 months, and analyzed for content of HDM and cat allergen. RESULTS: Eczema severity decreased significantly in both groups (P < 0.001), with a more pronounced decrease in patients with active covers. The HDM exposure decreased significantly in the active treatment group (P < 0.001), and the levels of HDM-specific IgE were reduced (P<0.05). Exposure to cat allergens was unchanged in the active treatment group but decreased, albeit not significantly (P=0.19), in the placebo group. sCD30 levels were significantly reduced in both groups (P<0.001). Patients not sensitized to HDM allergens benefited from the bedcovers as much as sensitized patients. CONCLUSIONS: Occlusive bedding significantly reduced HDM exposure in bed (P<0.001) and eczema severity, and sCD30 levels decreased significantly (P<0.001). Patients not sensitized to HDM and not exposed to HDM allergens benefited equally from use of the bedcovers, a result which could be due to a reduction of other important allergens, superantigens, or irritants in bed. We therefore recommend the use of bedcovers as part of treatment for AD.

Adult↗
PubMed2001

The safety and efficacy of MenoTreat, a new balloon device for thermal endometrial ablation.

BACKGROUND: An evaluation of the performance and safety of the prototype of a new device, MemoTreat (Atos Medical) for thermal endometrial balloon ablation in patients with menorrhagia. The evaluation was performed at four Swedish hospitals. METHODS: In total 51 consecutive, premenopausal patients, suffering from menorrhagia due to benign causes and not responding to conventional treatment, were treated between March 1997 and March 1998. The treatment entailed heated (85 degrees C) sterile saline circulated in a uterine balloon at a treatment pressure of 200 mmHg for 11 minutes. The procedure was performed mainly under general anesthesia and no pre-treatment endometrial thinning was performed. A validated pictorial assessment technique was used to evaluate changes in menstrual blood loss before and after treatment. Changes in quality of life and severity of dysmenorrhea were also evaluated. Data analysis was based on the 'intention to treat' method. RESULTS: The success rate in terms of a 50% reduction in menstrual bleeding was 84.3% at 6 months after treatment. Five patients became amenorrheic. The quality of life assessment showed substantial improvement and the severity of dysmenorrhea was markedly reduced. No intra-operative treatment complications occurred and the post-treatment morbidity was similar to that reported for other similar treatment methods. CONCLUSIONS: MenoTreat significantly reduced menstrual bleeding in menorrhagic patients, with a concomitant improvement in quality of life. The findings in this study resulted in a redesigned device with a thinner balloon catheter, improved cervical protection and treatment temperatures kept at a constant level.

Adult↗
PubMed2001

Identification of homology in protein structure classification.

Structural biology and structural genomics are expected to produce many three-dimensional protein structures in the near future. Each new structure raises questions about its function and evolution. Correct functional and evolutionary classification of a new structure is difficult for distantly related proteins and error-prone using simple statistical scores based on sequence or structure similarity. Here we present an accurate numerical method for the identification of evolutionary relationships (homology). The method is based on the principle that natural selection maintains structural and functional continuity within a diverging protein family. The problem of different rates of structural divergence between different families is solved by first using structural similarities to produce a global map of folds in protein space and then further subdividing fold neighborhoods into superfamilies based on functional similarities. In a validation test against a classification by human experts (SCOP), 77% of homologous pairs were identified with 92% reliability. The method is fully automated, allowing fast, self-consistent and complete classification of large numbers of protein structures. In particular, the discrimination between analogy and homology of close structural neighbors will lead to functional predictions while avoiding overprediction.

Automation↗
PubMed2001

Monitoring of dietary changes by telephone interviews: results from Denmark.

OBJECTIVES: To monitor trends in Danish food habits with respect to selected key elements, from 1995 to 1998, and to evaluate the appropriateness of the method developed for that purpose. DESIGN AND METHOD: Two cross-sectional population surveys, in 1995 and 1998. Data collection by computer-assisted telephone interviews including 10 food-frequency questions, questions on type of fat used on sandwiches and drinking milk, and check questions on the previous day. Reproducibility was tested in a subgroup (n = 222) in the 1998 survey. SETTING: The Danish Nutrition Council initiated the survey. SUBJECTS: Men and women aged 15-90 years, 1007 in 1995 and 1024 in 1998. Samples of private telephone numbers were drawn from regional telephone registers, geographically stratified. Participation rates were 62%. RESULTS: Significant differences were observed between 1995 and 1998, some of these in accordance with dietary guidelines (decreased use of whole milk and fat spread on bread, increased use of skimmed milk, salad vegetables, rice/pasta and fish). Other changes were opposite to dietary guidelines (increased use of soft butter, decreased use of soft margarine and low-fat spreads, potatoes, and fresh fruit). Differences in average consumption frequency amounted to 4-13%. Several results were confirmed by comparison with other data, and the reproducibility of the method was acceptable. Data were suitable for analysis of food use patterns, a relevant approach when assessing food habits in a lifestyle context. CONCLUSIONS: The changes observed illustrate the dynamics of food habits and the need for frequent monitoring. This simple telephone method may be a valuable tool for that purpose, as a supplement to national dietary surveys, also in a public health context.

Adolescent↗
PubMed2001

Monitoring improvement using a patient-rated depression scale during treatment with anti-depressants in general practice. A validation study on the Goldberg Depression Scale.

OBJECTIVE: To perform a pilot study on the value of the Goldberg Depression Scale as an instrument for monitoring improvement in depressed patients treated with anti-depressants in general practice. DESIGN: A comparative study using simultaneous ratings on the observer-based 17-item Hamilton Depression Scale and the patient-rated Goldberg Depression Scale. SETTING: General practice. PATIENTS: Twenty-one patients meeting the ICD-10 criteria of a moderate depressive episode were assessed at the time of inclusion and through three follow-up visits. MAIN OUTCOME MEASURES: Scores on the Goldberg Depression Scale compared to the Hamilton Depression Scale. RESULTS: An acceptable internal and external validity of the Goldberg Depression Scale was demonstrated. The Loevinger coefficient varied from 0.25 at the time of diagnosis to 0.57, 0.65 and 0.69 by visits two, three and four. Factor analysis identified only one general factor explaining 50% or more of the variants, except at visit 1. When the Goldberg Depression Scale was correlated to the Hamilton Depression Scales, a coefficient of 0.74 was obtained (p < 0.001). CONCLUSION: This pilot study indicates that the Goldberg Depression Scale is suitable for monitoring improvement in depressed patients treated in general practice. Further studies are recommended.

Antidepressive Agents↗
PubMed2001

Picasso: generating a covering set of protein family profiles.

MOTIVATION: Evolutionary classification leads to an economical description of protein sequence data because attributes of function and structure are inherited in protein families. This paper presents Picasso, a procedure for deriving a minimal set of protein family profiles that cover all known protein sequences. RESULTS: Picasso starts from highly overlapping sequence neighbourhoods revealed by all-on-all pairwise Blast alignment. Overlaps are reduced by merging sequences or parts of sequences into multiple alignments. For maximum unification, the multiple alignments must reach into the twilight zone of sequence similarity. Sensitive and selective profile-profile comparison allows unification down to about 15% pairwise sequence identity. Families unified through a short conserved sequence motif are associated with multiple full-length alignments describing different subfamilies. Domains that are mobile modules are identified based on their association with different sets of neighbours. The result is 10000 unified domain families (excluding singletons) representing functionally related proteins and recovering classical prolific domain types in high numbers. The classification is useful, for example, in developing strategies for efficient database searching and for selecting targets to complete the map of all 3-D structures.

Algorithms↗
PubMed2001

Generating protein interaction maps from incomplete data: application to fold assignment.

MOTIVATION: We present a framework to generate comprehensive overviews of protein-protein interactions. In the post-genomic view of cellular function, each biological entity is seen in the context of a complex network of interactions. Accordingly, we model functional space by representing protein-protein-interaction data as undirected graphs. We suggest a general approach to generate interaction maps of cellular networks in the presence of huge amounts of fragmented and incomplete data, and to derive representations of large networks which hide clutter while keeping the essential architecture of the interaction space. This is achieved by contracting the graphs according to domain-specific hierarchical classifications. The key concept here is the notion of induced interaction, which allows the integration, comparison and analysis of interaction data from different sources and different organisms at a given level of abstraction. RESULTS: We apply this approach to compute the overlap between the DIP compendium of interaction data and a dataset of yeast two-hybrid experiments. The architecture of this network is scale-free, as frequently seen in biological networks, and this property persists through many levels of abstraction. Connections in the network can be projected downwards from higher levels of abstraction down to the level of individual proteins. As an example, we describe an algorithm for fold assignment by network context. This method currently predicts protein folds at 30% accuracy without any requirement of detectable sequence similarity of the query protein to a protein of known structure. We used this algorithm to compile a list of structural assignments for previously unassigned genes from yeast. Finally we discuss ways forward to use interaction networks for the prediction of novel protein-protein interactions. AVAILABILITY: http://www.ebi.ac.uk/~lappe/FoldPred/.

Algorithms↗
PubMed2001

Beliefs, knowledge and attitudes as predictors of sunbathing habits and use of sun protection among Swedish adolescents.

In 1996, a random population sample of 2615 adolescents completed a questionnaire concerning habitual sun-related behaviours, attitudes towards sunbathing, and knowledge about skin cancer. Females, older adolescents, those with less sun-sensitive skin, those with higher knowledge and those with a positive attitude towards sunbathing were more likely to be frequent sunbathers. Younger adolescents, those who today sunbathe moderately, and those with sensitive skin were more likely to believe that they would sunbathe more often in the future. Males, adolescents with less sensitive skin, those with a positive attitude towards sunbathing and those sunbathing often, were less likely to use protection when sunbathing. Interventions to decrease sun exposure among adolescents should focus on changing attitudes toward sunbathing and having a tan, since knowledge of skin cancer and the damaging affect of sunbathing did not seem to effect current sunbathing habits, or use of sun protection.

Adolescent↗
PubMed2001

Intraluminal acid and gastric mucosal integrity: the importance of blood-borne bicarbonate.

The acid-secreting gastric mucosa resists intraluminal acid better than the nonsecreting. Here we investigated pH at the epithelial cell surface, mucosal permeability, and blood flow during intraluminal administration of acid (100 mM) in acid-stimulated and nonstimulated gastric corpus mucosae. Surface pH (H(+)-selective microelectrodes), permeability (clearance of (51)Cr-EDTA), and mucosal blood flow (laser-Doppler flowmetry) were studied in Inactin-anesthetized rats. Acid secretion was stimulated with pentagastrin (40 microg. kg(-1). h(-1)) or impromidine (500 microg. kg(-1). h(-1)), or HCO(3)(-) (5 mmol. kg(-1). h(-1)) given intravenously. Surface pH was only slightly reduced by intraluminal acid in acid secretion-stimulated or HCO(3)(-)-treated rats but was substantially lowered in nonstimulated rats. Clearance increased threefold and blood flow increased by approximately 75% in nonstimulated rats. During stimulated acid secretion or intravenous infusion of HCO(3)(-), clearance was unchanged and blood flow increased by only approximately 30% during intraluminal acid. Increased epithelial transport of HCO(3)(-) buffering the mucus gel is most probably the explanation for the acid-secreting mucosa being less vulnerable to intraluminal acid than the nonsecreting.

Acid-Base Equilibrium↗
PubMed2001

The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo.

Divergent results from in vitro studies on the thickness and appearance of the gastrointestinal mucus layer have previously been reported. With an in vivo model, we studied mucus gel thickness over time from stomach to colon. The gastrointestinal tissues of Inactin-anesthetized rats were mounted luminal side up for intravital microscopy. Mucus thickness was measured with a micropipette before and after mucus removal by suction. The mucus layer was translucent and continuous; it was thickest in the colon (approximately 830 microm) and thinnest in the jejunum (approximately 123 microm). On mucus removal, a continuous, firmly adherent mucus layer remained attached to the epithelial surface in the corpus (approximately 80 microm), antrum (approximately 154 microm), and colon (approximately 116 microm). In the small intestine, this layer was very thin (approximately 20 microm) or absent. After mucus removal, there was a continuous increase in mucus thickness with the highest rate in the colon and the lowest rate in the stomach. In conclusion, the adherent gastrointestinal mucus gel in vivo is continuous and can be divided into two layers: a loosely adherent layer removable by suction and a layer firmly attached to the mucosa.

Animals↗
PubMed2001

Anatomical and histological changes in the oviducts of Japanese quail, Coturnix japonica, after embryonic exposure to ethynyloestradiol.

Oestrogen is needed for normal oviductal development in female birds, but excessive early exposure to oestrogen can cause oviductal abnormalities and impair egg-laying ability. In this study, the anatomical and histological effects of in ovo exposure to the synthetic oestrogen ethynyloestradiol on the oviducts of immature and adult female Japanese quail, Coturnix japonica, were investigated. A series of abnormalities was observed after injection of ethynyloestradiol (2 or 20 ng g(-1) egg) into the yolk on day 3 of incubation. Ethynyloestradiol induced precocious differentiation of the luminal epithelium and tubular glands in immature chicks. Right-side oviduct retention occurred at all the ages studied, whereas certain other effects were not evident until sexual maturity. The left oviduct was reduced in size and tubular gland density in the uterus (shell gland) was reduced in sexually mature birds that had been treated with ethynyloestradiol. The utero-vaginal junction was longer than in control birds and had a higher tubular gland density. The epithelial cells in the magnum were taller in birds treated with ethynyloestradiol. Embryonic exposure to the environmental contaminant ethynyloestradiol may cause persisting structural malformations in oviducts of quails, which can impair fertility. As oviductal malformations are indicative of embryonic exposure to exogenous oestrogen, they are potentially useful as biomarkers of xenooestrogen exposure in wild bird populations.

Aging↗
PubMed2000

Rapid automatic detection and alignment of repeats in protein sequences.

Many large proteins have evolved by internal duplication and many internal sequence repeats correspond to functional and structural units. We have developed an automatic algorithm, RADAR, for segmenting a query sequence into repeats. The segmentation procedure has three steps: (i) repeat length is determined by the spacing between suboptimal self-alignment traces; (ii) repeat borders are optimized to yield a maximal integer number of repeats, and (iii) distant repeats are validated by iterative profile alignment. The method identifies short composition biased as well as gapped approximate repeats and complex repeat architectures involving many different types of repeats in the query sequence. No manual intervention and no prior assumptions on the number and length of repeats are required. Comparison to the Pfam-A database indicates good coverage, accurate alignments, and reasonable repeat borders. Screening the Swissprot database revealed 3,000 repeats not annotated in existing domain databases. A number of these repeats had been described in the literature but most were novel. This illustrates how in times when curated databases grapple with ever increasing backlogs, automatic (re)analysis of sequences provides an efficient way to capture this important information.

Algorithms↗
PubMed2000

The role of meat in everyday food culture: an analysis of an interview study in Copenhagen.

Interviews undertaken in a study of consumers' views on food quality were re-analysed with special reference to the narrative themes raised by consumers when describing their views on the quality of meat and meat products. Negative attitudes towards meat were frequently expressed, and with more emotion than comments about any other food. Being based on interviews made prior to the BSE crisis, the study gives evidence that the popularity of meat was in a process of decline already before this crisis. It was found that critical attitudes centred around the following four themes: the manner in which meat is produced and processed in modern agriculture and industry, the fact that meat derives from animals, the food culture associated with meat eating and the perceived unhealthiness of meat. In spite of their critical attitudes, the interviewees nevertheless consumed meat on a daily basis. This study suggests that negative attitudes towards meat are not necessarily associated with decreased meat consumption, but are associated with a tendency to re-structure meals with special reference to the role assigned to meat.

Attitude↗
PubMed2000

Towards a covering set of protein family profiles.

Evolutionary classification leads to an economical description of the protein sequence universe because attributes of function and structure are inherited in protein families. Efficient strategies of functional and structural genomics therefore target one representative from each family. Enumerating all families and establishing family membership consistently based on sequence similarities are nontrivial computational problems. Emerging concepts and caveats of global sequence clustering are reviewed. Explicit multiple alignments coupled with neighbourhood analysis lead to domain segmentation, and hierarchical unification helps to resolve conflicts and validate clusters. Eventually, every part of every sequence will be assigned to a domain family which is uniquely associated with a fold and a molecular function.

Amino Acid Sequence↗
PubMed2000

Acid transport through channels in the mucous layer of rat stomach.

BACKGROUND & AIMS: We have reported previously that secreted acid moves through the mucous layer in restricted areas above the gastric crypts. The aim of this study was to visualize and study the dynamics of this event. METHODS: Anesthetized rats prepared for intravital microscopy of the gastric mucosa were divided in the following groups with respect to acid secretion: spontaneous; stimulated (pentagastrin, 40 microg. kg(-1). h(-1)); transiently inhibited (omeprazole, 400 micromol. kg(-1) for 7 days); and totally inhibited (omeprazole, 3 x 200 micromol. kg(-1) for 7 days). The mucus was stained with Congo red (blue, pH < 3; red, pH > 5.2), and photographs were taken through a stereomicroscope. RESULTS: During acid secretion, blue-colored crypt openings with attached thread-like (5-7 microm wide) structures (designated channels) were seen passing from the crypt openings through the mucus to the lumen. Red-colored channels and crypt openings were observed when acid secretion was transiently inhibited. Red-colored crypt openings but no channels were found after total inhibition of acid secretion for a week. CONCLUSIONS: The results suggest that secreted acid is transported through channels within the mucus. These channels are probably created by the high intraglandular pressure pushing acid and glandular mucus into the gel.

Animals↗
PubMed2000

Carbonic anhydrase in the utero-vaginal junction of immature and mature ostriches.

1. Sperm storage tubules in the ostrich start to develop at an early stage of oviductal growth. Concurrently, membrane-bound carbonic anhydrase was found in the cells of the storage tubules. 2. In mature ostriches the utero-vaginal junction averaged 11.5+/-2.1 cm in length and primary mucosal folds were extremely long and slender. Membrane-bound carbonic anhydrase was present in the cells of the sperm storage tubules. In the non-ciliated cells of the surface epithelium both membrane-bound and cytoplasmic activity was detected. 3. The possible role of carbonic anhydrase in the stimulation/inhibition of sperm motility by altering the pH was discussed.

Age Factors↗