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Biomedical subjects

E Samuelsson

Publications and source records attributed to E Samuelsson.

At least 19 recordsLinked to original sources
PubMed2000

Visual cognitive tests, central auditory function and auditory communication.

A cognitive, text-based test battery, presented as text on a computer screen (TIPS), was used to assess properties of central cognitive processing relevant for visual and audiovisual speech comprehension. TIPS was compared and contrasted with another, purely auditory, battery, ACE, aimed at assessing afferent (A), central (C) and efferent (E) auditory communicative functions. The results show that there is no overlap with the 'A' component, but some overlap between TIPS parameters and the 'C' component, especially when the auditory-language tests are used in the C estimate. However, the TIPS parameters show high correlations with the 'E' component (i.e. measuring output and phonological parameters), suggesting that the efferent component may be composed of an interesting central feature. TIPS parameters do not fare as well in the predictions of the auditory ecological test performances, but the ACE parameters do, especially when organized according to a cognitive complexity parameter. In order to optimize the conceptual and practical benefit of the TIPS and ACE concepts, TIPS needs to be adapted auditorily and ACE tests need to be audiovisual. These developments will become important for ecological audiology.

Adult↗
PubMed2000

Anal sphincter tears: prospective study of obstetric risk factors.

OBJECTIVE: To evaluate intrapartum risk factors for anal sphincter tear. DESIGN: A prospective observational study. SETTING: Delivery unit at the University Hospital in Göteborg, Sweden. PARTICIPANTS: 2883 consecutive women delivered vaginally during the period between 1995 and 1997. Information was obtained, from patient records and from especially designed protocols which were completed during and after childbirth. MAIN OUTCOME MEASURES: Anal sphincter (third and fourth degree) tear. RESULTS: Anal sphincter tear occurred in 95 of 2883 women (3.3%). Univariate analysis demonstrated that the risk of anal sphincter tear was increased by nulliparity, high infant weight, lack of manual perineal protection, deficient visualisation of perineum, severe perineal oedema, long duration of delivery and especially protracted second phase and bear down, use of oxytocin, episiotomy, vacuum extraction and epidural anaesthesia. After analysis with stepwise logistic regression, reported as odds ratio, 95% confidence interval, the following factors remained independently associated with anal sphincter tear: slight perineal oedema (0.40, 0.26-0.64); manual perineal protection (0.49, 0.28-0.86); short duration of bear down (0.47, 0.24-0.91); no visualisation of perineum (2.77, 1.36-5.63); parity (0.59, 0.40-0.89); and high infant weight (2.02, 1.30-3.16). Analysis of variance showed that manual perineal protection had a stronger influence on lowering the frequency, and lack of visualisation of perineum and infant weight had a stronger influence on raising the frequency, of anal sphincter tears in nulliparous compared with parous women. CONCLUSIONS: Perineal oedema, poor ocular surveillance of perineum, deficient perineal protection during delivery, protracted final phase of the second stage, parity and high infant weight all constitute independent risk factors for anal sphincter tear. Such information is essential in order to reduce perineal trauma during childbirth.

Adult↗
PubMed2000

Determinants of urinary incontinence in a population of young and middle-aged women.

BACKGROUND: Urinary incontinence and genital prolapse are prevalent conditions in the female population. The aim of this study was to study possible determinants of female urinary incontinence in a population-based sample of young and middle-aged women. METHODS: Of 641 eligible women aged 20-59 years in a primary health care district, 487 (76%) responded to a questionnaire and accepted an invitation to a gynecological examination. The examination included digital assessment of the pelvic floor muscle strength (PFMS). Genital prolapse presence (cystocele, rectocele, uterine prolapse or absence of the urethrovesical crease) was graded in relation to the vaginal introitus. RESULTS: The prevalence of urinary incontinence was 28%, 3.5% having daily leakage. Stress urinary incontinence was the dominant type. The odds ratio (OR) of having incontinence increased from 1 to 3.5 with increasing age and from 1 to 2.7 with increasing parity. The OR also increased with decreasing PFMS; from 1 in the group with the best PFMS to 3.4 in the group unable to contract their pelvic musculature. In addition, women with cystocele and/or absence of the urethrovesical crease had a 2.5-fold increased OR of incontinence (95% CI 1.5-4.2), smoking increased the OR 1.9 times (95% CI 1.1-3.2) and estrogen replacement therapy (ERT) increased the OR 2.9 times (95% CI 1.4-5.9). There were no significant correlations with the presence of chronic disease, episiotomy or the birth weights of children but small non-significant correlations with performed hysterectomy and the woman's weight. CONCLUSIONS: Urinary incontinence is a frequent symptom in the female general population and related to age, pelvic floor muscle strength, genital prolapse, smoking, parity and estrogen replacement therapy.

Adult↗
PubMed2000

Audiometric characterization of a family with digenic autosomal, dominant, progressive sensorineural hearing loss.

In this study, a non-syndromic progressive bilateral high frequency hearing loss is described in a family with 141 identified members. Recent genetic analyses indicated a digenic inheritance with linkage to the gene loci DFNA2 and DFNA12. The affected family members who shared haplotypes at both loci (type I) showed an early postlingual onset and a more rapid rate of progress compared with those with one either of the two disease associated haplotypes (type II). The audiometric pattern was cochlear without a vestibular involvement. Auditory brainstem response audiometry and magnetic resonance imaging indicated normal retrocochlear features. The otoacoustic emissions were affected for both type I and type II, whereas the acoustic stapedius reflex thresholds were normal in most cases. It is concluded that both types had an outer hair cell/micro-mechanical abnormality, but that the DFNA 2 type might have an additional dysfunction at the level of the inner hair cells. It is furthermore pointed out that the application of refined audiometric techniques as well as a further development of new techniques is needed in order to characterize the phenotypes of the rapidly expanding number of genetically defined inner ear abnormalities.

Adult↗
PubMed1999

Communicative ability in an audiological perspective. Theory and application to post-secondary school students.

The underlying assumption in the present study is that the individual's speech and hearing communicative ability is composed of three components, each corresponding to different functional systems of the brain: afferent functions (A) represent the auditory activity and sound perception largely corresponding to activity in the ascending auditory pathways. The central functions (C) include cortical auditory and language abilities controlled in parts of the left temporal lobe and subcortical centres. The efferent functions (E) consist of speech motor processes and articulation. A test battery of 20 tests measuring several aspects of afferent, central and efferent functions was applied to 11 hearing-impaired post-secondary school students and several control groups. All data were normalized with the normal materials as references. Individual communicative profiles were obtained from these primary data, which consisted of audiometric tests (tone and speech audiometry, impedance tests, brainstem response audiometry and phase audiometry), sound environmental tests with hearing aids (directional speech-in-noise, word localization, sound environment identification test), and language tests (reading tests, prosody, auditory memory and recall, phonology and articulation). Since the central functions cannot truly and directly be determined in hearing-imparied subjects, they were assessed under optimal listening conditions. Furthermore, central functions were estimated according to three different models: distributive, parallel model (model 1), multiplicative, serial model (model 2) and compensatory model (model 3). On the basis of these models, a three-component description of the communicative ability consisting of A,C and E functions was obtained. It was found that C and E functions were largely independent of the adult afferent functions, but C functions were negatively correctly to hearing in childhood. A preliminary comparison between the tests and a comparison between the models was performed by predicting benefit of hearing aid. Model 3 gave the best prediction. Beyond the three-component A,C, and E characterization of the students, a total communicative ability score could be calculated giving values from 37% to 79% of the normal mean. On the basis of the conceptual and statistical analyses, the test battery could be reduced to include tone 0-12 years, tone adults, word localization test (afferent); word chain, lecture test (central), articulatory test (efferent) and audiovisual test. The simple algorithm of adding the normalized loss of afferent (peripheral) function to the normalized results of the acoustic central tests seems to be promising for isolation for the central auditory capacity even in cases with peripheral impairment. It is concluded that a wider perspective is desirable in the diagnostic evaluation of the hearing-impaired individual in order to understand his communicative abilities and form a cornerstone in the planning of rehabilitation in conjunction with social and psychological factors.

Adolescent↗
PubMed1998

Towards an ecological audiology: stereophonic listening chamber and acoustic environmental tests.

An acoustic laboratory for reproduction of speech and acoustic environments is presented along with two sound field tests. Its design has been inspired by the LEDE (Living End Dead End) principle for construction of radio and music control rooms. The equipment and the 12 loudspeakers can simultaneously reproduce several stereophonic and monophonic recordings. The interesting feature is that the delayed first reflex in the LEDE room allows for a realistic perception of the recording room. A preliminary presentation of two newly developed tests for sound field listening is given. In DSIN. Directional Speech In Noise, the JFC (just follow conversation) threshold for continuous discourse is determined in 12 directions in quiet and in noise from +/- 60 degrees azimuth. In SEIT (Sound Environmental Identification Test), stereophonic acoustic environments are presented and the subject is asked to identify specific components and to characterize each environment as closely as possible. Results from tests with normal hearing subjects and examples of results with hearing impaired subjects are presented. The potential of the technique for use in aural rehabilitation, functional definition of auditory communication and quality assessment of hearing aids is discussed. It is pointed out that the term ecological audiology is suitable for describing the interaction between the communicating individual and the environment in a broad sense.

Acoustics↗
PubMed1998

Evidence for digenic inheritance of nonsyndromic hereditary hearing loss in a Swedish family.

We investigated a Swedish family with nonsyndromic progressive bilateral sensorineural hearing loss. Thirteen candidate loci for autosomal dominant nonsyndromic hearing loss were tested for linkage in this family. We found significant LOD scores (>3) for markers at candidate locus DFNA12 (11q22-q24) and suggestive LOD scores (>2) for markers at locus DFNA2 (1p32). Our results for markers on chromosome 11 narrowed down the candidate region for the DFNA12 locus. A detailed analysis of the phenotypes and haplotypes shared by the affected individuals supported the notion that two genes segregated together with hearing impairment in the family. Severely affected family members had haplotypes linked to the disease allele on both chromosomes 1 and 11, whereas individuals with milder hearing loss had haplotypes linked to the disease allele on either chromosome 1 or chromosome 11. These observations suggest an additive effect of two genes, each gene resulting in a mild and sometimes undiagnosed phenotype, but both together resulting in a more severe phenotype.

Adult↗
PubMed1997

A population study of urinary incontinence and nocturia among women aged 20-59 years. Prevalence, well-being and wish for treatment.

BACKGROUND: The aim was to study urinary incontinence (UI) and nocturia in a female population; prevalence, effect on well-being, wish for treatment and result of treatment in primary health care. METHODS: A postal questionnaire was sent to all women aged 20-59 years who were scheduled for gynecological health examination by midwives in a primary health care district during one year. Questions concerning well-being were based on the Gothenburg QOL instrument. All women with incontinence were offered treatment by a midwife and a family doctor. RESULTS: Of the included 641 women, 491 (77%) answered the questionnaire. The prevalence of urinary incontinence was 27.7%, 3.5% having daily leakage. Nocturia occurred in 32 women (6.5%), 12 of whom were also incontinent. Self-assessed health, sleep, fitness and satisfaction with work situation decreased significantly with increased frequency of incontinence. Well-being was not correlated to type of incontinence. Nocturia correlated to poor health and sleep. About a quarter of the incontinent women started treatment when offered and 80% of those who completed the treatment program were subjectively improved. Wish for treatment was directly correlated to frequency of incontinence but not to type. CONCLUSIONS: Urinary incontinence and nocturia affect well-being in a negative way. Well-being and wish for treatment correlate to frequency of incontinence but not to type of incontinence. Most women with UI accept it, only about a quarter of incontinent women, or 6-7% of all women in the studied age group, want treatment. Treatment of female urinary incontinence in primary health care is successful.

Adult↗
PubMed1996

Integrated production of human insulin and its C-peptide.

The potential for the development of an integrated process for production of human insulin and its C-peptide in Escherichia coli has been investigated. Human proinsulin was produced intracellularly in E. coli fused to two synthetic IgG-binding domains (ZZ) derived from staphylococcal protein A. High expression levels (3 g/l culture) of the gene product, which accumulated as inclusion bodies, was obtained. Solubilization of inclusion bodies by oxidative sulfitolysis and subsequent renaturation was performed directly after cell lysis and pellet wash. IgG affinity chromatography was used for efficient recovery of pure proinsulin fusion protein in a single step. Monomers of the proinsulin fusion protein constituted approximately 70%. A single step conversion of the fusion protein into insulin and C-peptide by trypsin and carboxypeptidase B treatment was achieved by engineering the junction between proinsulin and its affinity handle, ZZ. Characterization of the cleavage products by reversed phase chromatography (RPC) verified that human insulin and C-peptide were generated and that the ZZ affinity handle was resistant to cleavage. Human insulin and C-peptide were recovered with high yields by preparative reversed-phase high performance liquid chromatography (RP-HPLC). The potential use of the presented scheme for large-scale production of recombinant insulin and/or its C-peptide is discussed.

Biotechnology↗
PubMed1996

Chaperone-like effect during in vitro refolding of insulin-like growth factor I using a solubilizing fusion partner.

A fusion partner, ZZ, derived from staphylococcal protein A, has earlier been shown facilitate the in vitro folding of human insulin-like growth factor I (IGF-I). Although no solubilizing agents were used, there was no problem with precipitation, even at relatively high protein concentrations. We have here investigated this phenomenon further by characterizing the in vitro refolding of IGF-I fused to one or two solubilizing Z domains. The comparison also included IGF-I without a solubilizing fusion partner. Solubility studies of the reduced proteins were performed, in addition to an evaluation of the aggregation occurring during the refolding process. Fusion to one or two Z domains increased the solubility of reduced IGF-I more than 100-fold. In addition, the Z or ZZ fusion partners decreased aggregation of the IGF-I moieties during the renaturation. The fusion partner has an effect resembling that of a cis-acting chaperone during in vitro refolding and may be an alternative to overcome the problems of insolubility and aggregation.

Cloning, Molecular↗
PubMed1996

Single-step trypsin cleavage of a fusion protein to obtain human insulin and its C peptide.

The kinetics for trypsin cleavage of different fusion proteins, consisting of human proinsulin and two IgG-binding domains (ZZ), were investigated. To achieve simultaneous removal of the fusion tag and processing of proinsulin to insulin and free C peptide, three versions of the ZZ-proinsulin fusion protein were generated, having different trypsin-sensitive cleavage sites, Arg, Lys-Arg or Lys. The ZZ-proinsulin fusion proteins which accumulated as inclusion bodies in Escherichia coli cells were solubilized, refolded and purified by IgG affinity chromatography. The yield of ZZ-proinsulin monomers exceeded 90%. The kinetics for the trypsin cleavage revealed unexpected differences when comparing the three linkers and it was found that the single arginine linker was most efficiently processed. Characterization of the cleavage products by reverse-phase chromatography, mass spectrometry and N-terminal sequencing verified that human insulin and C peptide were generated. The results demonstrate that high yields of native insulin, C peptide and affinity tag can be achieved by simultaneous cleavage of a fusion protein at three different trypsin-sensitive sites in a single step. The implications for production and recovery of various recombinant proteins are discussed.

Amino Acid Sequence↗
PubMed1996

Affinity-assisted in vivo folding of a secreted human peptide hormone in Escherichia coli.

We show that coexpression of a specific binding protein in Escherichia coli can significantly improve the relative yields of correctly folded human insulin-like growth factor I (IGF-I). A glutathione redox buffer was used during growth to allow formation and breakage of disulfide bonds in the periplasm of the bacterial host. Both the binding protein and the peptide hormone were produced as affinity fusions, which allowed purification of the in vivo formed heterodimer by alternative affinity purification methods. The use of affinity-assisted in vivo folding has general implications for expression, folding, and purification of recombinant proteins.

Affinity Labels↗
PubMed1995

Hydrophobicity engineering to increase solubility and stability of a recombinant protein from respiratory syncytial virus.

Site-directed mutagenesis has been employed to engineer the hydrophobic properties of a 101-amino-acid fragment from the human respiratory syncytial virus (RSV) major glycoprotein (G protein). When this protein was produced in Escherichia coli, more than 70% of the gene product was found as inclusion bodies, and the product recovered from the soluble fraction was severely degraded. Substitution of two cysteine residues for serine residues, did not significantly change the solubility or stability of the gene product. In contrast, a dramatic increase in both solubility and stability was achieved by multiple engineering of hydrophobic phenylalanine residues. As compared to the non-engineered protein, the fraction of soluble protein in vivo could be increased from 27% to 75%. Surprisingly, this effect was accompanied by a remarkable increase in stability. The in vitro solubility of the purified gene products was similarly increased approximately fivefold. Structural studies using circular dichroism suggest that the two engineered fragments have a distribution of secondary-structure elements similar to the non-engineered fragment. In addition, the two engineered G-protein variants were demonstrated to be at least in part antigenically authentic to the non-engineered gene product. These results demonstrate that engineering of hydrophobic residues can be used as a tool to increase the solubility and proteolytic stability of poorly soluble and labile proteins.

Amino Acid Sequence↗
PubMed1994

Enhanced in vitro refolding of insulin-like growth factor I using a solubilizing fusion partner.

We have previously shown that human insulin-like growth factor I (IGF-I), fused to ZZ (two domains derived from staphylococcal protein A), can be refolded at relatively high concentrations, without the use of solubilizing agents [Samuelsson, E., Wadensten, H., Hartmanis, M., Moks, T., & Uhlén, M. (1991) Bio/Technology 9, 363-366]. Here we have studied this phenomenon in detail by characterizing the in vitro refolding of IGF-I, fused to one or two solubilizing Z domains and without a solubilizing fusion partner. The characterization included solubility studies of the reduced proteins and an evaluation of the aggregation occurring during the refolding process. The results suggest that the applied fusion protein strategy can be used to obtain a cis-acting chaperone-like effect during refolding in vitro. Fusion to one or two Z domains resulted in more than a 100-fold increase in the solubility of reduced IGF-I. In addition, the Z or ZZ fusion partners decrease multimerization of the IGF-I moieties during the renaturation. The fusion protein strategy may be an option to overcome the obstacles of insolubility and aggregation, frequently encountered when designing in vitro refolding processes.

Humans↗
PubMed1991

Characterization of an extended form of recombinant human insulin-like growth factor II.

To investigate the biological role of variants of human insulin-like growth factor II (IGF-II), an extended form designated IGF-IIE21, with a molecular mass of 9.8 kDa, was produced in Escherichia coli as a stable and soluble secreted fusion protein. After site-specific cleavage of the affinity purified fusion protein, followed by purification using ion exchange and reversed phase chromatography, it could be demonstrated that IGF-IIE21 and IGF-II have similar or identical activities according to radioimmunoassay and radioreceptor assay. However, IGF-IIE21 showed only 1% growth promotion activity as compared with IGF-II in a clonal expansion assay using human K562 cells which lacks IGF-I receptors. These results suggest that this extended variant of IGF-II can bind to the receptor but has limited growth promoting activity.

Amino Acid Sequence↗
PubMed1991

Facilitated in vitro refolding of human recombinant insulin-like growth factor I using a solubilizing fusion partner.

We describe a new approach to refolding recombinant proteins in which an affinity fusion partner, consisting of two IgG-binding domains (ZZ) derived from staphylococcal protein A, is used to solubilize misfolded molecules before, during and after reduction and reoxidation. We show that human insulin-like growth factor I (IGF-I) can be refolded as a fusion protein at a concentration as high as 1-2 mg/ml without the use of denaturing agents. A process scheme suitable for large scale application is described in which the yield of correctly folded human IGF-I with full biological activity is substantially increased.

Immunoglobulin G↗