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Biomedical subjects

E Lindahl

Publications and source records attributed to E Lindahl.

At least 19 recordsLinked to original sources
PubMed2001

Isolated hypervariable regions derived from streptococcal M proteins specifically bind human C4b-binding protein: implications for antigenic variation.

Antigenic variation in microbial surface proteins represents an apparent paradox, because the variable region must retain an important function, while exhibiting extensive immunological variability. We studied this problem for a group of streptococcal M proteins in which the approximately 50-residue hypervariable regions (HVRs) show essentially no residue identity but nevertheless bind the same ligand, the human complement regulator C4b-binding protein (C4BP). Synthetic peptides derived from different HVRs were found to retain the ability to bind C4BP, implying that the HVR corresponds to a distinct ligand-binding domain that can be studied in isolated form. This finding allowed direct characterization of the ligand-binding properties of isolated HVRs and permitted comparisons between different HVRs in the absence of conserved parts of the M proteins. Affinity chromatography of human serum on immobilized peptides showed that they bound C4BP with high specificity and inhibition experiments indicated that different peptides bound to the same site in C4BP. Different C4BP-binding peptides did not exhibit any immunological cross-reactivity, but structural analysis suggested that they have similar folds. These data show that the HVR of streptococcal M protein can exhibit extreme variability in sequence and immunological properties while retaining a highly specific ligand-binding function.

Amino Acid Sequence↗
PubMed2000

Identification of related proteins on family, superfamily and fold level.

Proteins might have considerable structural similarities even when no evolutionary relationship of their sequences can be detected. This property is often referred to as the proteins sharing only a "fold". Of course, there are also sequences of common origin in each fold, called a "superfamily", and in them groups of sequences with clear similarities, designated "family". Developing algorithms to reliably identify proteins related at any level is one of the most important challenges in the fast growing field of bioinformatics today. However, it is not at all certain that a method proficient at finding sequence similarities performs well at the other levels, or vice versa.Here, we have compared the performance of various search methods on these different levels of similarity. As expected, we show that it becomes much harder to detect proteins as their sequences diverge. For family related sequences the best method gets 75% of the top hits correct. When the sequences differ but the proteins belong to the same superfamily this drops to 29%, and in the case of proteins with only fold similarity it is as low as 15%. We have made a more complete analysis of the performance of different algorithms than earlier studies, also including threading methods in the comparison. Using this method a more detailed picture emerges, showing multiple sequence information to improve detection on the two closer levels of relationship. We have also compared the different methods of including this information in prediction algorithms. For lower specificities, the best scheme to use is a linking method connecting proteins through an intermediate hit. For higher specificities, better performance is obtained by PSI-BLAST and some procedures using hidden Markov models. We also show that a threading method, THREADER, performs significantly better than any other method at fold recognition.

Algorithms↗
PubMed2000

Mesoscopic undulations and thickness fluctuations in lipid bilayers from molecular dynamics simulations.

Molecular dynamics simulations of fully hydrated Dipalmitoylphosphatidylcholine bilayers, extending temporal and spatial scales by almost one order of magnitude, are presented. The present work reaches system sizes of 1024 lipids and times 10-60 ns. The simulations uncover significant dynamics and fluctuations on scales of several nanoseconds, and enable direct observation and spectral decomposition of both undulatory and thickness fluctuation modes. Although the former modes are strongly damped, the latter exhibit signs of oscillatory behavior. From this, it has been possible to calculate mesoscopic continuum properties in good agreement with experimental values. A bending modulus of 4 x 10(-20) J, bilayer area compressibility of 250-300 mN/m, and mode relaxation times in the nanosecond range are obtained. The theory of undulatory motions is revised and further extended to cover thickness fluctuations. Finally, it is proposed that thickness fluctuations is the explanation to the observed system-size dependence of equilibrium-projected area per lipid.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1997

Descriptions of suffering in connection with life values. Healthy individuals' reflections in interviews.

Nine semistructured interviews with attendant questions were conducted with the purpose of elucidating how healthy individuals describe suffering and life values in their reflections upon active euthanasia. In order to find the intended meaning in utterances, the interviews were interpreted step by step. The point of departure was the following question: What expressions of suffering and what expressions of life values can be found in the text? A connection was found between the interviewees' descriptions of suffering and life values in their reflections upon active euthanasia. The interviewees who considered close relations to be a value of life expressed suffering as dependence, compassion, violation, abandonment and feelings of guilt, while those to whom health was a value of life expressed suffering as torment, dependence, physical pain, feebleness, hopelessness and dying. Those who saw autonomy as a value of life expressed suffering as dependence and violation and those to whom doing good was a value of life expressed suffering as compassion. When organizing health care and deciding about the response to suffering, it seems important to strive for a response built upon the individual patient's description of suffering and life values.

Adult↗
PubMed1996

The influence of tail biting on performance of fattening pigs.

In comparison to 29 non bitten animals, severe tail biting was found to decrease the daily weight gain (DWG) by 25% in 8 fattening pigs during the period of biting. However, when comparing the weight gain of the lifetime between bitten and non bitten pigs, no influence of the tail biting was found. It is of interest that severely wounded pigs were parenterally treated with prokainpenicillin G for 3 consecutive days in connection with the tail biting, which could be suggested to promote the growth by reducing the influence of infections gained by the tail biting as well as of other infections present in herds rearing conventional pigs. Despite penicillin treatment, abscesses were more frequently recorded in tail bitten pigs than in non bitten animals. The tail biting was not equally distributed between the sexes, as barrows were more frequently bitten than gilts. Among the unbitten pigs, barrows were also found to grow faster than gilts. Indeed, when comparing tail bitten and non bitten barrows, a negative influence of tail biting on DWG was not only shown during the period of biting, but could also be monitored as a reduced DWG from that period until slaughter by 11% and during lifetime by 5% (the tail bitten gilts were too few to allow statistical calculations). These results clearly indicate that tail biting affects the growth rate of the lifetime despite penicillin treatment. However, it should be stressed that this decreased lifetime DWG may not be monitored when evaluating abattoir data because the sex distribution of the pigs may not be known in such materials.

Abscess↗
PubMed1990

Prenatal diagnosis in Pelizaeus-Merzbacher disease using RFLP analysis.

Pelizaeus-Merzbacher disease (PMD) is a rare X-linked recessive disorder with severe psychomotor retardation and neurological symptoms due to an inborn abnormality of proteolipid protein (PLP), the major protein component of myelin. A tight linkage between the gene of PLP and PMD locus has been suggested. We have carried out a series of RFLP studies using a cDNA probe for PLP and an anonymous DNA-fragment DXYS12 in a large Finnish family with at least three affected individuals. DNA analysis on chorionic villus specimens allowed us to exclude the disease in a male fetus of a possible carrier mother and, likewise, to demonstrate carrier status in a female fetus in another at-risk pregnancy.

Adolescent↗
PubMed1988

Neonatal risk factors and later neurodevelopmental disturbances.

Background factors of developmental outcome in a group of 386 neonatal 'at-risk' infants and 107 controls were examined in a prospective nine-year follow-up study. Dichotomized outcome variables were computed for each of the assessments; neurodevelopmental, motor, psycholinguistic, cognitive and school progress. In the study group, 17 to 29 per cent were found to have significant problems, compared with 10 to 17 per cent of the control group. Children with low birthweight, neonatal neurological symptoms or several neonatal disorders were found to have most problems at the age of nine years. In stepwise logistic regression analyses, smallness for gestational age, neonatal signs of cerebral depression and low social-class were found to be the most significant predictors of neurodevelopmental problems at age nine. Factors suggesting intra-uterine hypoxia or poor nutrition were also associated with developmental problems. The background pathology of the neonatal conditions seemed to be of more importance than the neonatal manifestations themselves.

Brain↗
PubMed1988

Prediction of early school-age problems by a preschool neurodevelopmental examination of children at risk neonatally.

A group of 350 children who had had neonatal developmental risk-factors were assessed at the age of five years with a neurodevelopmental examination. At nine years they were assessed again for neuropaediatric, motor, psycholinguistic, cognitive and school-achievement problems. (Children with major handicaps were excluded). Poor performance at age five was significantly associated with failure in the nine-year examinations and with school problems. Sensitivity of the five-year neurodevelopmental examination in predicting problems at nine years was 0.30 to 0.50, and its predictive value for an abnormal performance was 0.30 to 0.60. Predictively, the neurodevelopmental examination was accurate in defining children without later problems, but less satisfactory in defining those who did develop problems. Multiple linear regression analyses between the neurodevelopmental examination and the scores at nine years revealed low explanatory power. A shortened neurodevelopmental examination, based on the best predictors, seemed to be as efficient as the full examination.

Brain Damage, Chronic↗
PubMed1987

Motor performance of neonatal risk and non-risk children at early school-age.

The motor skills of 382 children with neonatal risk factors and 107 children with no risk factors, in the age group 8-9 years, were studied using the Test of Motor Impairment (Stott-Moyes-Henderson). Neonatal disturbances, such as low birthweight and neurological symptoms were associated with marked clumsiness. The test performance was found, unexpectedly, to be significantly affected by age and sex in both the study and the control group. The test items were the same for an age range of one whole year, with no allowance for continuous development of skills. The need of normative data for each country is stressed.

Age Factors↗
PubMed1986

Neurodevelopmental significance of minor and major congenital anomalies in neonatal high risk children.

Minor and major congenital anomalies were studied in 395 neonatal risk children and 107 normal school children at the age of nine in the context of follow-up of the risk children. The purpose of the study was to evaluate the impact of early prenatal disturbances on the long term prognosis. Minor physical anomalies (MPA) were scored by a weighted scoring system modified from that of Waldrop and Halverson. The children with minor or major congenital anomalies performed worse in a cognitive test (WISC) and in a motor performance test. The differences were significant in the neonatal risk group. There were more small for gestational age (SGA) children in the anomaly group of the neonatal risk group as a whole and in the low birthweight group than in the non-anomaly group. Hyperactivity was associated with a high MPA score in the comparison group, but not in the study group. The results are consistent with earlier reports of associations between intrauterine growth disturbance and minor physical anomalies. Our findings suggest an additive effect of prenatal insults and neonatal risk factors in the origin of neurodevelopmental disturbances.

Attention Deficit Disorder with Hyperactivity↗
PubMed1986

Precocious puberty associated with oral-facial-digital syndrome type I.

A girl with the oral-facial-digital syndrome type I (OFD I) developed precocious puberty at early infancy. This is presumed to be due to a hamartoma in the tuber cinereum region. Hypothalamic hamartomas have not been described in OFD I earlier, whereas lingual hamartomas are a common feature in this condition.

Abnormalities, Multiple↗
PubMed1984

Further delineation of the Cohen syndrome; report on chorioretinal dystrophy, leukopenia and consanguinity.

Six new patients with the Cohen syndrome are reported from Finland and 25 published cases from elsewhere are reviewed. New findings are consanguinity among two pairs of parents, granulocytopenia, and marked ophthalmological changes: decreased visual acuity, hemeralopia, constricted visual fields, chorioretinal dystrophy with bull's-eye-like maculae and pigmentary deposits, optic atrophy, and isoelectric electroretinogram. Previously known features of the Cohen syndrome (non-progressive mental retardation, short stature, microcephaly, peculiar facies, slender hands and feet, floppiness, delayed puberty) are confirmed or revised. The ophthalmological features merit attention in the previous and future suspected cases of the Cohen syndrome. Autosomal recessive inheritance can be taken for granted.

Abnormalities, Multiple↗
PubMed1984

Nine-year follow-up of infants weighing 1 500 g or less at birth.

A nine-year follow-up of 116 children born consecutively in 1971-74 with a birthweight of 1 500 g or less showed that 59 had died. Of those who were alive, four had severe motor and/or mental handicaps and three were blind because of retrolental fibroplasia. The low birthweight children without severe handicaps were found to have impaired motor function, speech defects and impaired school achievement more often than the controls. There was a significant correlation between the test results at the age of five and nine years, which indicates that children with school failure can be recognized and early remedial treatment started before school or on starting school.

Birth Weight↗