PubMed Health⌕ Search

Biomedical subjects

L Danielsson

Publications and source records attributed to L Danielsson.

At least 19 recordsLinked to original sources
PubMed2002

Small bowel biopsy in Swedish paediatric clinics.

AIM: A correct diagnosis of coeliac disease, one of the most common chronic diseases in Swedish children, demands small bowel biopsy, which can be performed endoscopically or by means of a peroral capsule. Recently there was a debate among Swedish paediatric gastroenterologists, with some advocating the cessation of capsule biopsy in favour of endoscopic biopsies. To gain information on which to base a recommendation for which technique to use, the Swedish Working Group for Childhood Coeliac Disease was commissioned to carry out a national questionnaire study on current small bowel biopsy routines in Swedish paediatric clinics. METHODS: A questionnaire concerning biopsy routines in the year 2000 was sent to all paediatric clinics performing biopsies. A reply was obtained from 39 of 40 clinics, covering 98% of the Swedish population. RESULTS: Some 1400 biopsies were performed, 64% of which were capsule biopsies and 36% endoscopic. Three clinics performed all biopsies endoscopically and 11 clinics all via a capsule. At endoscopy all children were under deep sedation or full anaesthesia, while most children undergoing capsule biopsy were under light or deep sedation. The oxygen saturation was monitored during endoscopy but less often or never during routine capsule biopsy. The presence of the parents during biopsy varied according to the degree of sedation: at 97% of the clinics performing capsule biopsy on children under light sedation, the parents were present during the whole procedure, whereas no parents were present at clinics where the biopsy was performed endoscopically under anaesthesia. CONCLUSION: Compared with the results of a similar questionnaire concerning biopsy routines performed in the early 1990s, children are now more effectively sedated. Furthermore, there is an obvious trend from capsule towards endoscopic biopsy. Both the endoscopic and the capsule biopsy techniques are useful and satisfactory for obtaining small bowel mucosal samples providing that the children are effectively sedated. For practical and economic reasons the capsule biopsy technique will probably continue to be used, although to a lesser extent than today.

Biopsy↗
PubMed2001

A central core structure in an antibody variable domain determines antigen specificity.

Antibody binding sites provide an adaptable surface capable of interacting with essentially any molecular target. Using CDR shuffling, residues important for the assembly of mucin-1 specific paratopes were defined by random recombination of the complementarity determining regions derived from a set of mucin-1 specific clones, previously selected from an antibody fragment library. It was found that positions 33 and 50 in the heavy chain and 32, 34, 90, 91 and 96 in the light chain were conserved in many of the clones. These particular residues seem to be located centrally in the binding site as indicated by a structure model analysis. The importance of several of these conserved residues was supported by their presence in a mouse monoclonal antibody with a known structure and the same epitope specificity. Several of these corresponding residues in the mouse monoclonal antibody are known to interact with the antigen. In conclusion, critical residues important for maintaining a human antigen-specific binding site during the process of in vitro antibody evolution were defined. Furthermore, an explanation for the observed restricted germline gene usage in certain antibody responses against protein epitopes is provided.

Animals↗
PubMed2000

Recombining germline-derived CDR sequences for creating diverse single-framework antibody libraries.

We constructed a single-chain Fv antibody library that permits human complementarity-determining region (CDR) gene fragments of any germline to be incorporated combinatorially into the appropriate positions of the variable-region frameworks VH-DP47 and VL-DPL3. A library of 2 x 109 independent transformants was screened against haptens, peptides, carbohydrates, and proteins, and the selected antibody fragments exhibited dissociation constants in the subnanomolar range. The antibody genes in this library were built on a single master framework into which diverse CDRs were allowed to recombine. These CDRs were sampled from in vivo-processed gene sequences, thus potentially optimizing the levels of correctly folded and functional molecules, and resulting in a molecule exhibiting a lower computed immunogenicity compared to naive immunoglobulins. Using the modularized assembly process to incorporate foreign sequences into an immunoglobulin scaffold, it is possible to vary as many as six CDRs at the same time, creating genetic and functional variation in antibody molecules.

Germ-Line Mutation↗
PubMed2000

Late-diagnosed DDH: a prospective 11-year follow-up of 71 consecutive patients (75 hips).

I have prospectively studied 71 consecutive patients (75 hips) with late-diagnosed DDH (developmental dysplasia of the hip) treated uniformly with special reference to the development of the femoral head and the acetabulum. The age at the start of treatment was 10 (2-64) months. The follow-up time was 11 (6-18) years. After tenotomy and traction, closed reduction failed in 7 hips. These cases were treated by open reduction with or without Salter innominate osteotomy-in 2 hips femoral osteotomy was also done (shortening, varus and derotation). 1 hip subluxated and 1 re-dislocated after closed reduction. Avascular necrosis occurred in 4 hips and additional surgery was required in 12 hips--11 Salter osteotomies, 1 varus femoral osteotomy. In the first year after reduction, the acetabular angle improved rapidly--faster in the younger children. When treatment started between 12 and 22 months, the improvement was slower and the final outcome more unpredictable. The femoral head continued to grow irrespective of the age at reduction and became normal in almost all cases. Salter's innominate osteotomy stabilized hips after open reduction and gave excellent results in cases with an increasing acetabular angle. At the last re-examination, all but 2 patients were asymptomatic. Radiographically, 65 hips were rated Severin group I, 9 group II and 1 group III.

Age Factors↗
PubMed2000

Epidemic of coeliac disease in Swedish children.

Coeliac disease has emerged as a public health problem. The aim of the present study was to analyse trends in the occurrence of symptomatic coeliac disease in Swedish children from 1973 to 1997, and to explore any temporal relationship to changes in infant dietary patterns. We established a population-based prospective incidence register of coeliac disease in 1991, and, in addition, retrospective data from 1973 were collected. A total of 2151 cases fulfilled the diagnostic criteria. Furthermore. We collected national data on a yearly basis on duration of breastfeeding, intake of gluten-containing cereals and recommendations on when and how to introduce gluten into the diet of infants. From 1985 to 1987 the annual incidence rate in children below 2 y of age increased fourfold to 200-240 cases per 100000 person years, followed from 1995 by a sharp decline to the previous level of 50-60 cases per 100000 person years. This epidemic pattern is quite unique for a chronic disease of immunological pathogenesis, suggesting that prevention could be possible. The ecological observations made in this study are compatible with the epidemic being the result, at least in part, of a change in and an interplay among three factors within the area of infant feeding, i.e. amount of gluten given, age at introduction of gluten, and whether breastfeeding was ongoing or not when gluten was introduced. Other factor(s) may also have contributed, and the search for these should be intensified.

Adolescent↗
PubMed1998

Cystatin F is a glycosylated human low molecular weight cysteine proteinase inhibitor.

A previously undescribed human member of the cystatin superfamily called cystatin F has been identified by expressed sequence tag sequencing in human cDNA libraries. A full-length cDNA clone was obtained from a library made from mRNA of CD34-depleted cord blood cells. The sequence of the cDNA contained an open reading frame encoding a putative 19-residue signal peptide and a mature protein of 126 amino acids with two disulfide bridges and enzyme-binding motifs homologous to those of Family 2 cystatins. Unlike other human cystatins, cystatin F has 2 additional Cys residues, indicating the presence of an extra disulfide bridge stabilizing the N-terminal region of the molecule. Recombinant cystatin F was produced in a baculovirus expression system and characterized. The mature recombinant protein processed by insect cells had an N-terminal segment 7 residues longer than that of cystatin C and displayed reversible inhibition of papain and cathepsin L (Ki = 1.1 and 0.31 nM, respectively), but not cathepsin B. Like cystatin E/M, cystatin F is a glycoprotein, carrying two N-linked carbohydrate chains at positions 36 and 88. An immunoassay for quantification of cystatin F showed that blood contains low levels of the inhibitor (0.9 ng/ml). Six B cell lines in culture secreted barely detectable amounts of cystatin F, but several T cell lines and especially one myeloid cell line secreted significant amounts of the inhibitor. Northern blot analysis revealed that the cystatin F gene is primarily expressed in peripheral blood cells and spleen. Tissue expression clearly different from that of the ubiquitous inhibitor, cystatin C, was also indicated by a high incidence of cystatin F clones in cDNA libraries from dendritic and T cells, but no clones identified by expressed sequence tag sequencing in several B cell libraries and in >600 libraries from other human tissues and cells.

Amino Acid Sequence↗
PubMed1998

[Proposed criteria for diagnosis of celiac disease in children].

At a seminar arranged in September 1997 by the Swedish Paediatric Working Group for Coeliac Disease, a diagnostic protocol proposed by the working group was approved by a majority of the paediatricians present, representing almost all paediatric units in Sweden. Briefly, a small bowel biopsy is called for in all children, both at presentation and as a control during gluten-free dieting. Subsequent gluten challenge and biopsy are mandatory only in cases of atypical presentation or if the diagnosis is questioned at some future date. Serum antigliadin and anti-endomysial antibody tests are complementary tools. Agreement was also reached regarding the institution of a national coeliac disease registry.

Antibodies↗
PubMed1997

Prevalence of coxarthrosis in an urban population during four decades.

In the current study, in a survey of 4121 double contrast radiographs of the colon performed from 1987 through 1995, the hip joints were examined and classified with regard to the presence or absence of primary coxarthrosis. The data collection was performed in precisely the same manner as in two earlier studies undertaken on 3903 radiographs of the colon covering the years 1956 through 1962 and 4027 radiographs of the colon covering the years 1975 through 1982. In the current study the prevalence of coxarthrosis, the gender ratio, and distribution between bilateral and unilateral cases had not changed compared with the data from the two earlier studies. When pooling the three investigations, the age specific prevalence of primary coxarthrosis based on the 12,051 radiographs fits an exponential curve for which the prevalence of primary coxarthrosis increased from below 1% in the age group younger than 55 years to 10% in the age group older than 85 years. In the current study approximately half of the patients (55%) had undergone total hip arthroplasty. This was more than in the study from 1984 (35%). Among the surgically treated patients, lateral coxarthrosis was more common than was medial coxarthrosis.

Adult↗
PubMed1996

Small bowel biopsy in Swedish paediatric clinics.

The capsule technique for small bowel biopsy performed at Swedish paediatric clinics was evaluated using two questionnaires in 1990 and 1993, respectively. Replies were received from all 45 centres which together perform approximately 2300 biopsies per year. Clotting function tests prior to biopsy were carried out in 42% of the centres. The biopsies were performed under intubation anaesthesia in 13% of the centres. The most striking difference between the answers to the two questionnaires was the mode of sedation. The use of intravenous sedatives increased from 40% of the centres in the first questionnaire to 59% in the second one. The use of the oral, rectal and intramuscular routes decreased correspondingly. The most frequently used drugs for intravenous sedation were benzodiazepines, in the first questionnaire diazepam and in the second one midazolam. The failure rate was approximately 5%. In the first questionnaire, no complication was encountered. In the second questionnaire, three cases of intramural duodenal haematoma were reported, one of which led to pancreatitis. We conclude that by focusing on questions of sedation these rather simple questionnaires may have resulted in more effective sedation of children undergoing small bowel biopsy.

Biopsy↗
PubMed1995

Induction of primary antigen-specific immune reponses in SCID-hu-PBL by coupled T-B epitopes.

Adoptive transfer of human lymphoid cells into immunodeficient (SCID) mice lacking the ability to functionally rearrange T- and B-cell receptor genes constitutes a unique model to study and manipulate human immunocytes. We have investigated this model for the purpose of generating an antigen-specific primary humoral immune response. Peripheral blood lymphocytes (PBL) derived from blood donors were used to repopulate SCID mice, which subsequently were immunized with different B-cell epitopes coupled to either tetanus toxoid (TT), or to a promiscuous helper epitope of TT, or by incorporating the antigens into a liposome construct. By recruiting the necessary T-cell help found in the T-cell memory compartment against TT, primary immune responses were obtained against the hapten dinitrophenyl (DNP), the V3 loop peptide derived from glycoprotein (gp120) (HIV-1), the melanoma-associated GD2 ganglioside and ovine submaxillary mucin. The primary immune response against the GD2 ganglioside was induced by incapsulating TT into GD2-containing liposomes. These liposome constructs also allowed us to induce a high human IgG serotitre (3000-4000) against this normally not very immunogenic ganglioside.

Animals↗
PubMed1993

Chaperonin assisted phage display of antibody fragments on filamentous bacteriophages.

We have used the GroE chaperonins to assist in the packing of a new phage display vector, pEXmide3. Titers of the packed phagemid increased almost 200-fold from approximately 4 x 10(11) cfu/ml, without coexpression of the GroE proteins, to approximately 7 x 10(13) cfu/ml with their coexpression. Equal titers of non-assisted and assisted phagestocks exhibited the same antigen specificity and ELISA reactivity, indicating the same frequency of displayed Fab-fragments. While the diversity of antibody libraries depends on the bacterial transformation efficiency, the copy number of each antibody is determined by subsequent amplification of the phage, thus chaperonin assisted phagemid packing in bacteriophage M13 can be used as a general and simple tool to increase the amplification level of expressed Fab fragments. pEXmide3 was developed for display of Fab and single chain Fv-fragments (scFv), using restriction enzymes that do not cut, or cut with low frequencies, in genes encoding immunoglobulin variable domains. The vector allows cloning of genes for the variable domains linking these to predetermined human constant domains or cloning of the entire light and heavy Fab chains. A modification of the pelB leader sequence, with a glutamine to alanine substitution at residue 18, was used for export of the light chain.

Bacterial Proteins↗
PubMed1992

Kinetic analysis of recombinant antibody-antigen interactions: relation between structural domains and antigen binding.

The relation between domain structures of recombinant monoclonal antibody fragments and their reaction kinetics was studied for the first time using a novel biosensor based on surface plasmon resonance technology. The association and dissociation rate constants of Fab, Fv and single domain (VH fragment) anti-lysozyme antibodies were determined and compared to the intact monoclonal antibody. Fab and Fv fragments showed similar reaction kinetics and had affinity constants of 6 x 10(9) M-1 and 25 x 10(9) M-1, respectively. The single domain antibody had significantly different reaction kinetics compared to the fragments consisting of paired heavy and light chain domains. The VH domain had both a higher dissociation and a lower association rate constant, which resulted in an affinity constant approximately 250 times lower than the Fab fragment. This rapid evaluation of antibody reaction kinetics should prove to be an important selection parameter when comparing antibody fragments for their utility in therapeutic or other applications.

Antibodies, Monoclonal↗
PubMed1992

Allergic symptoms up to 4-6 years of age in children given cow milk neonatally. A prospective study.

In a previously published prospective study, we followed the development of allergic symptoms in term infants with a slightly reduced birthweight (-1 SD to -2 SD). These children received, according to local routine, early feeding with cow milk formula in order to diminish such neonatal problems as hypoglycemia and hyperbilirubinemia. Of 216 infants 207 were observed for allergic symptoms up to 18 months of age. One group (F) received cow milk formula during the first days of life before the mother's breastmilk production started and was then breastfed; the other (B) was not given any formula before normal breastfeeding started. Unexpectedly, we found fewer allergic symptoms, in particular allergic skin problems, in the group fed cow milk, the difference being concentrated to children with a family history of allergic symptoms. At 5 years of age 183 of the 207 children have been reinvestigated. Mild symptoms of allergy (suspected and obvious) were found in 22% (F) and 27% (B) respectively (NS). Moderate and severe symptoms of allergy (obvious) were found in 4.2% (F) and 4.5% (B). In the subgroup with a double family history of allergic symptoms, 28% (7/25, F) and 59% (10/17, B) had symptoms of allergy (p less than 0.05). This difference was even more pronounced when laboratory tests in favour of atopic diagnosis were included, 14% (F) and 53% (B) respectively (p less than 0.05). Thus at 5 years we still find a significantly lower frequency of allergic symptoms in the subgroup fed cow milk formula early with a family history of allergic symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗