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Biomedical subjects

B Lindqvist

Publications and source records attributed to B Lindqvist.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

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

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

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

Ultrafiltration failure and dialysate glucose in CAPD.

This study was performed to evaluate the use of the glucose concentration versus glucose absorption in the dialysate to estimate ultrafiltration efficacy. In 26 patients (16 men, 10 women) on continuous ambulatory peritoneal dialysis, a total of 128 dwells were investigated. Each dwell lasted 5 hours, using 2 L of peritoneal dialysis fluid containing 140 mmol/L glucose. After the dwell, the removed peritoneal dialysis fluid was weighted. The concentrations of creatinine and glucose and the total amount of glucose were analyzed. The mean concentration of dialysate glucose for the whole group after a 5-hour dwell was 38.9 +/- 8.9 (SD) mmol/L. The ultrafiltration volume was inversely correlated to the glucose absorbed (r = -0.59, p = 0.002), but was not significantly correlated to the glucose concentration in the dialysate (r = 0.40, p = 0.057). The ultrafiltration volume was not related to the creatinine concentration in the dialysate or the body weight. The average dialysate glucose did not change during a one-year observation time. Patients with diabetes mellitus had significantly lower glucose absorption than nondiabetics (p = 0.045), and patients with low ultrafiltration efficacy had significantly greater glucose absorption than those with normal and high ultrafiltration (p = 0.038). There was no difference between those who had those who had not suffered from peritonitis. The results indicate that the glucose absorption from the dialysis fluid is the best parameter to calculate the peritoneal ultrafiltration efficacy and not the glucose concentration currently used.

Adult

Bacteriophage P2 and P4 morphogenesis: protein processing and capsid size determination.

An interesting feature of the bacteriophage P2-P4 system is the switch in size between a large P2 (60 nm) and a small P4 (45 nm) capsid. We have investigated whether the protein processing reactions cleaving the primary translation product gpN to several capsid proteins (h1, h2, and N*) are involved in this switch. Using antibodies specific against gpN and its derivatives we have identified all the structural components of mature P2 and P4 particles that are derived from gpN. Our estimate of the relative amounts of gpN derivatives suggests that the previously identified minor capsid proteins h1 and h2 can only be essential structural components of the P4, and not the P2, capsid. Nevertheless, the relative amounts are similar in vivo during a P2 and a P4 infection. This indicates that the switch in head size is not caused by the presence of elevated amounts of h1 and h2 during P4 morphogenesis. We have also identified the sites where gpN is cleaved to its derivatives h1, h2, and N*, ascertaining that the cleavage sites are the same in P2 and P4. Our results indicate that the processing reactions are not directly involved in the head size determination mechanism.

Amino Acid Sequence

Mandibular function before orthodontic treatment.

Two-hundred-and-forty-five consecutive prospective orthodontic patients and 245 controls matched for age, sex, and residence, but with minor need of orthodontic treatment, were examined. The functional examination of the masticatory system was made according to Carlsson and Helkimo (1972), and Helkimo (1974). According to dysfunction index (Helkimo, 1974), 33.5 per cent of the patients and 21.6 per cent of the controls had a moderate, and 18.9 and 7.8 per cent respectively, a severe dysfunction. The corresponding figures for symptoms were 16.7 and 4.9 per cent respectively. In the patient group the frequency of signs and symptoms was higher in the older age group and in the girls. Orthodontic patients appeared to be at greater risk of craniomandibular disorders (CMD) than individuals with minor need of treatment.

Adolescent