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Biomedical subjects

B Lindqvist

Publications and source records attributed to B Lindqvist.

At least 19 recordsLinked to original sources
PubMed2006

High levels of hepatitis B virus DNA in body fluids from chronic carriers.

Chronic infection with hepatitis B virus (HBV) is a major global health problem. Transmission is mainly blood-borne, although the route of infection during horizontal transmission in childhood is unclear. Nosocomial outbreaks of HBV have been widely reported, but have mainly focused on blood-borne transmission. There is limited knowledge of the viral load levels in other body fluids. In the present study, chronic HBV carriers were tested for the presence of HBV DNA in serum, saliva, nasopharyngeal fluid, urine and tears by means of qualitative and quantitative polymerase chain reaction (PCR) methods. Twenty-five patients who were positive for HBV DNA with both PCRs were included. Low titres in real-time PCR corresponded with weak bands in the qualitative assay. HBV DNA was found in two urine samples, 10 saliva samples, five nasopharyngeal swabs and in tear fluid from four patients. One highly viraemic HBeAg-positive carrier with serum HBV DNA levels of 7 x 10(9) genome copies had high copy numbers detected in both saliva and nasopharyngeal fluid. These results demonstrate that highly viraemic HBV carriers may have high titres of HBV DNA in other body fluids. This has particular importance for infection control programmes and regulations, underlining the importance of aiming towards regular HBV DNA testing and thus infectivity assessment of chronic carriers in order to prevent transmission.

Adult↗
PubMed2006

Novel mutation in Hepatitis B virus preventing HBeAg production and resembling primate strains.

Chronic carriers of hepatitis B infection often harbour virus strains with mutations in the precore region. These mutations are temporally associated with the development of HBeAg loss and seroconversion to anti-HBe. The most common precore mutation is a stop codon at position 1896, but other mutations leading to abolished HBeAg secretion have been described. Here, a novel precore mutation introducing a lysine in the precore position 28, a sequence shared by non-human primates but not by other human isolates, is described. However, the insertion causes a frame-shift preventing the expression of HBeAg by introducing a stop codon 5 aa downstream of the mutation. Analysis of the predicted RNA secondary structure indicates that the insertion could occur without fatally affecting the stability of the stem-loop encapsidation signal.

Animals↗
PubMed2000

Distinct cellular receptor interactions in poliovirus and rhinoviruses.

Receptor binding to human poliovirus type 1 (PV1/M) and the major group of human rhinoviruses (HRV) was studied comparatively to uncover the evolution of receptor recognition in picornaviruses. Surface plas- mon resonance showed receptor binding to PV1/M with faster association and dissociation rates than to HRV3 and HRV16, two serotypes that have similar binding kinetics. The faster rate for receptor association to PV1/M suggested a relatively more accessible binding site. Thermodynamics for receptor binding to the viruses and assays for receptor-mediated virus uncoating showed a more disruptive receptor interaction with PV1/M than with HRV3 or HRV16. Cryo-electron microscopy and image reconstruction of receptor-PV1/M complexes revealed receptor binding to the 'wall' of surface protrusions surrounding the 'canyon', a depressive surface in the capsid where the rhinovirus receptor binds. These data reveal more exposed receptor-binding sites in poliovirus than rhinoviruses, which are less protected from immune surveillance but more suited for receptor-mediated virus uncoating and entry at the cell surface.

Animals↗
PubMed2000

Variability in methotrexate serum and cerebrospinal fluid pharmacokinetics in children with acute lymphocytic leukemia: relation to assay methodology and physiological variables.

Methotrexate (MTX) steady state concentrations were evaluated in 42 children who had received high-dose infusions (6-8 g/m2) for acute lymphocytic leukemia. Concentrations in serum and cerebrospinal fluid (CSF) measured by immunoassay were found to be highly variable. Reanalysis by a reference high-pressure liquid chromatography method ruled out analytical factors as a source of this variability. The correlation coefficient between the analytical methods was 0.77 for the serum data and 0.88 for the CSF data. The variability of serum and CSF concentrations was higher in younger patients (serum; P = 0.05 and CSF; P = 0.18), and the CSF concentration decreased with decreasing age and in later courses. Body surface area, body mass index, weight, and gender were not significantly related to MTX variability. We conclude that the pronounced pharmacokinetic variability seen during MTX infusions remains largely unexplained.

Antimetabolites, Antineoplastic↗
PubMed1998

A region from the medium chain adaptor subunit (mu) recognizes leucine- and tyrosine-based sorting signals.

Tyrosine-based sorting signals in the cytosolic tails of membrane proteins have been found to bind directly to the medium chain subunit (mu) of the adaptor complexes AP-1 and AP-2. For the leucine-based signals, an interaction with AP-1 and AP-2 has been reported, but no specific interacting subunit has been demonstrated. After searching for molecules interacting with the leucine-based sorting signals within the cytosolic tail of the major histocompatibility complex class II-associated invariant chain using a phage display approach, we identified phage clones with homology to a conserved region of the AP-1 and AP-2 mu chains. To investigate the relevance of these findings, we have expressed regions of mouse mu1 and mu2 chains on phage gene product III and investigated the binding to tail sequences from various transmembrane proteins with known endosomal targeting signals. Enzyme-linked immunosorbent binding assays showed that these phages specifically recognized peptides containing functional leucine- and tyrosine-based sorting signals, suggesting that these regions of the mu1 and mu2 chains interact with both types of sorting signals.

Amino Acid Sequence↗
PubMed1998

A three-dimensional photographic method for documentation and measurement of dental conditions.

A 3-D photographic technique was developed for the registration of bite conditions. This technique may replace plaster models for archiving purposes. To achieve this, photographic equipment and computer programs should be user friendly, not too expensive, and allow measurements that satisfy scientific demands. This purpose was fulfilled by combining the following elements: a photographic unit with standardized conditions for 3-D photography and a reference object with known coordinates where bite impressions or models are placed during photography. To reconstruct 3-D coordinates from photographs these are placed on a digitizer connected to a computer programmed for reconstructing 3-D coordinates from the digitized 2-D data. The accuracy of the 3-D reconstruction of coordinates, x, y, z, was tested by means of 3-D photographs of a test object with reference points having a precision of +/- 0.5 micron. The mean error for distances of 5 mm and 15 mm varied between -0.17 mm and +0.15 mm. Measurements of 45 degrees and 90 degrees angles had an accuracy that varied from -0.5 degree to +0.9 degree and from -1.2 degrees to +1.5 degrees respectively. An angle between lines and a plane of 54.7 degrees displayed a mean error of +/- 1.6 degrees. The test of the accuracy of the 3-D photographic technique for calculating distances and angles demonstrated that it fulfills demands for scientific applications on clinical material.

Calibration↗
PubMed1998

Selection of phage displayed peptides from a random 10-mer library recognising a peptide target.

BACKGROUND: Peptide display libraries are powerful tools in the search for detailed information about protein-protein interactions. Usual targets for isolation of phage displayed peptide ligands include antibodies, various receptors, other full size proteins or larger fragments thereof. Smaller protein fragments such as synthetic peptides have not been reported as targets for screening of peptide display libraries. OBJECTIVES: To investigate whether a protein target used for screening of a peptide display library could be scaled down to peptide size. As the peptide target we wanted to use a sequence derived from the cytosolic tail of MHC class II associated invariant chain containing a leucine class endosomal sorting signal, known to be recognised as an autonomous functional unit during targeting of class II complexes to antigen processing compartments. STUDY DESIGN: A screening procedure where a synthetic 15-mer invariant chain peptide was coupled to a methacrylate matrix of high binding capacity was developed, and three rounds of selection were performed from a random 10-mer fUSE5 display library. RESULTS: The peptide display library was successfully enriched for phage clones with affinity for the invariant chain peptide. Furthermore, the binding phage clones were able to distinguish between a functional and a mutated form of the target. These clones therefore displayed possible peptide mimetics of signal recognition sites in the cellular sorting machinery. CONCLUSION: The size of a protein target may be scaled down to peptide size and be recognised by a 10-mer peptide displayed on filamentous phage. This approach may particularly be useful when the peptide target contains a functional unit for recognition.

Amino Acid Sequence↗
PubMed1997

On the prognostic value of systemic methotrexate clearance in childhood acute lymphocytic leukemia.

The prognostic value of systemic methotrexate clearance (ClMTX) during high-dose therapy was evaluated in a cohort of 42 children with acute lymphocytic leukemia (ALL). As part of an extensive chemotherapy protocol, they had received a total of 293 methotrexate (MTX) infusions in the 6-8 g/m2 dose range. At the termination of the study, when they had all been followed up for 3.5 years or more, 26 of these patients were still in continuous complete remission, whereas 16 had suffered relapse. The intrapatient variability in ClMTX during the eight courses was up to six-fold. In 67% of the patients, the maximum level of ClMTX reached at least twice the minimum value. The coefficients of variation for the intra- and interindividual variability in ClMTX were 9-57% and 26-41%, respectively. The cumulative probability of relapse, estimated by the Kaplan-Meier procedure, was increased for patients with a high ClMTX during the initial treatment course, but the difference was not significant on a 5% level. There was no significant relationship between high individual median ClMTX and subsequent relapse of ALL. However, ClMTX during the initial infusion, the time-dependent mean for ClMTX, and the individual patient's median ClMTX, were significant predictors for event-free survival in a Cox proportional hazards regression analysis. The present study demonstrates gross pharmacokinetic variability and unpredictable values of ClMTX in subsequent courses after standardized administration of MTX to paediatric patients with ALL. In spite of the association between ClMTX and prognosis shown by some of the analyses, estimates of ClMTX rates may not necessarily be related to disease outcome in a way that can be exploited to the benefit of the individual patient.

Adolescent↗
PubMed1997

Prerectal peritoneal pouch with herniating small bowel -- a unique cause of severe constipation in a child.

We report a 14-year-old boy with severe constipation with a four-year history of no spontaneous bowel movements. Defecography, with synchronously administered barium enema and barium meal, showed that the small bowel could slide down in front of the rectum obstructing defecation. He was operated and a prerectal peritoneal pouch was found, which was resected. Postoperatively he has had daily spontaneous bowel movements. We have found no similar case described in the literature.

Adolescent↗
PubMed1997

[Birth-time of the year now and hundred years ago].

In Umea, in norther Sweden, 1984-94 many more children were born in March, April and May, than in October, November, December. 1895-1904 child birth were common in June, September, October and least in January, February. Contraceptives probably have caused the change, but other factors may have had some influence.

Environment↗
PubMed1995

The reaction between epichlorohydrin and polysaccharides: Part 2, Synthesis of some model substances, with cyclic substituents.

Eight derivatives of methyl alpha-D-glucopyranoside, in which the substituents are part of cyclic structures, have been prepared as model substances for possible structural elements formed on reaction of polysaccharides with epichlorohydrin. The substances were converted into the permethylated alditol-1-d acetates and characterised by CIMS and EIMS.

Epichlorohydrin↗
PubMed1995

Mandibular function before and after orthodontic treatment.

To determine the influence of orthodontic treatment on mandibular function, a longitudinal study was initiated on 245 consecutive prospective orthodontic patients before and after the orthodontic treatment. Of the 245 referred patients, eight declined treatment and 27 moved to other parts of the country before the treatment was completed. Thus, the longitudinal study was based on 210 patients. The functional examination was made according to Carlsson and Helkimo (1972) and Helkimo (1974), and by the same person (MO). Before the orthodontic treatment, symptoms of temporomandibular disorders (TMD) were found in 16.7 per cent of the patients and in 6.7 per cent after treatment. The number of subjects without signs or symptoms of TMD increased from 26.7 per cent before treatment to 46.2 per cent after. According to the dysfunction index (Helkimo, 1974), 31.4 per cent of the patients had a moderate and 13.8 per cent a severe mandibular dysfunction before the start of orthodontic treatment. After the treatment, the corresponding figures were 14.3 and 5.7 per cent, respectively. The material was divided into groups, consisting of boys and girls younger than 13 years, and 13 years and older at the start of treatment. Before treatment there was a higher prevalence of signs and symptoms of TMD in the older age group than in the younger, and higher in girls than in boys. After the orthodontic treatment, the prevalence was still higher in girls than in boys in both age groups, but not higher in the older age group than in the younger group.

Adolescent↗
PubMed1994

A tyrosine-based motif in the cytoplasmic domain of the alphavirus envelope protein is essential for budding.

The budding of enveloped viruses from cellular membranes is believed to be dependent on the specific interaction between transmembrane spike proteins and cytoplasmic core components of the virus. We found that the cytoplasmic domain of the E2 transmembrane spike glycoprotein of Semliki Forest virus contains two essential determinants which are absolutely needed for budding. The first constitutes a single tyrosine residue in the context of a direct pentapeptide repeat. The tyrosine could only partially be substituted for other residues with aromatic or bulky hydrophobic side chains, although these immediately reverted to the original genotype. The second determinant involves palmitylated cysteine residues flanking the tyrosine repeat motif. The function of these is probably to anchor the tail against the inner surface of the membrane so that the tyrosine-containing motif is properly presented to the nucleocapsid. This is the first example where a membrane virus employs a tyrosine signal for the selective incorporation of spike proteins into budding structures.

Amino Acid Sequence↗
PubMed1994

The reaction between epichlorohydrin and polysaccharides: Part 1. Syntheses of some model substances with non-cyclic substituents.

Five derivatives of methyl alpha-D-glucopyranoside, in which the substituents form noncyclic structures, have been prepared as model substances for possible structural elements formed on reaction of polysaccharides with epichlorohydrin. The substances were converted into the permethylated alditol-1-d derivatives and characterised by CIMS and EIMS.

Carbohydrate Sequence↗
PubMed1994

The prevalence of circulating anti-tubular basement membrane-antibody in renal diseases, and clinical observations.

Anti-tubular basement membrane antibodies were determined by ELISA in 217 patients with different renal diseases. The assay for antibodies in serum was based on a 58 kD bovine tubular basement membrane antigen. Sera were studied from 69 patients with different forms of interstitial nephritis; 15 patients (10 women, 5 men) had anti-tubular basement membrane titers above the normal (compared with a reference group of healthy blood donors). Three patients are presented in greater detail. Thirty-four patients with pyelonephritis (confirmed by intravenous urogram) were investigated; one serum was positive. Sera from 114 patients with renal glomerular and/or vascular disease were studied; 12 had positive titers for tubular basement membrane and glomerular basement membrane or other kidney disease antibodies. This study supports the opinion that damage in the renal medulla can be caused by an autoimmune process. Circulating anti-TBM antibodies may be of value in the investigation of patients with tubulo-interstitial diseases but the cause and prognosis of this condition is, however, not known.

Adult↗