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Biomedical subjects

H Hansson

Publications and source records attributed to H Hansson.

At least 19 recordsLinked to original sources

An intervention program for university students who have parents with alcohol problems: a randomized controlled trial.

AIM: To study the effects of alcohol and coping intervention among University students who have parents with alcohol problems. METHODS: A total of 82 university students (56 women and 22 men, average age 25) with at least one parent with alcohol problems were included. The students were randomly assigned to one of three programs: (i) alcohol intervention program, (ii) coping intervention program, and (iii) combination program. All programs were manual based and individually implemented during two 2-h sessions, 4 weeks apart. This assessment contained both a face-to-face interview and six self-completion questionnaires; AUDIT, SIP, EBAC, coping with parents' abuse questionnaire, SCL-90 and ISSI. Follow-up interviews were conducted after 1 year. RESULTS: All participants finished the baseline assessment, accepted and completed the intervention, while 95% of the students completed the 12-month follow-up assessment. The two groups that received alcohol intervention improved their drinking pattern significantly more than the group that did not receive alcohol intervention [change of standardized scores -0.27 (CI -0.53 to -0.03)]. The groups receiving coping intervention did not differ from the group not receiving coping intervention concerning their ability to cope with their parents' alcohol problems. Nor did they differ regarding changes in their own mental health or in their social interaction capacity. CONCLUSION: The intervention improved drinking patterns in adult children of alcoholics.

Adaptation, Psychological↗

Clinical pharmacology of clemastine in healthy dogs.

The pharmacokinetic properties of clemastine were investigated in six healthy dogs and compared with the effect of the drug recorded as inhibition of wheal formation induced by intradermal injections of histamine. Clemastine clearance was high (median: 2.1 L h(-1) kg(-1)) and the volume of distribution large (13.4 L kg(-1)). The half-life after intravenous administration was 3.8 h and the plasma protein binding level in vitro was 98%. After oral administration, the bioavailability was only 3%. Given intravenously, clemastine (0.1 mg kg(-1)) inhibited wheal formation completely for 7 h, whereas the effect after oral administration (0.5 mg kg(-1)) was minor. The data show that most dosage regimens suggested in the literature for the oral administration of clemastine to dogs are likely to give too low a systemic exposure of the drug to allow effective therapy.

Administration, Oral↗

Both proline-rich sequences in the TH region of Bruton's tyrosine kinase stabilize intermolecular interactions with the SH3 domain.

The Tec homology (TH) region located N-terminal to the Src homology 3 (SH3) domain of Bruton's tyrosine kinase (Btk) contains two proline-rich SH3-binding sequences (PRRs). We have previously demonstrated that the TH region acts to stabilize intermolecular interactions in N-terminally extended SH3 (PRR-SH3) fragments. Here, we analyze six PRR-SH3 fragments with different proline-to-alanine substitutions in the two PRRs. Gel permeation chromatography and nuclear magnetic resonance spectroscopy show that both PRRs can stabilize self-association. This observation provides an explanation to why the TH region of Btk makes intermolecular interactions, whereas the corresponding interaction in the related Itk kinase with only one PRR, is intramolecular.

Agammaglobulinaemia Tyrosine Kinase↗

Intermolecular interactions between the SH3 domain and the proline-rich TH region of Bruton's tyrosine kinase.

The SH3 domain of Bruton's tyrosine kinase (Btk) is preceded by the Tec homology (TH) region containing proline-rich sequences. We have studied a protein fragment containing both the Btk SH3 domain and the proline-rich sequences of the TH region (PRR-SH3). Intermolecular NMR cross-relaxation measurements, gel permeation chromatography profiles, titrations with proline-rich peptides, and (15)N NMR relaxation measurements are all consistent with a monomer-dimer equilibrium with a dissociation constant on the order of 60 microM. The intermolecular interactions do, at least in part, involve proline-rich sequences in the TH region. This behavior of Btk PRR-SH3 may have implications for the functional action of Btk.

Agammaglobulinaemia Tyrosine Kinase↗

Bilateral hearing aids--effects and consequences from a user perspective.

The present study assesses the experiences with bilateral amplification in a group of 144 people provided with two hearing aids between May 1994 and July 1997. Two-thirds of the participants preferred to use both prescribed hearing aids. The participants reported that they used their hearing aids frequently. Bilateral amplification was appreciated especially for recognizing speech, for sound localization and for superior sound quality. Situations in which the subjects showed the highest appreciation of two hearing aids were when attending lectures and theatre performances and for communication in noisy background situations. There were statistically significant differences between users of bilateral and unilateral hearing aids regarding judgement of sound quality of hearing aid processed signals and localization ability in favour of bilateral hearing aid amplification. The self-assessed advantages of bilateral amplification demonstrated in this study should motivate a generous prescription strategy of two hearing aids.

Acoustic Stimulation↗

Effects of coping skills training, group support, and information for spouses of alcoholics: a controlled randomized study.

Our aim was to compare the effect of three different interventions in spouses of alcoholics with regard to coping strategies, mental symptoms, hardship, and drinking patterns. The spouses were randomized to three different interventions: 1) information, 2) individual coping skills training, and 3) group support. Follow-up periods were at 12 and 24 months. In this paper the 12-month results are presented. Thirty-nine spouses attended the study. They were recruited from the services of the Department of Alcohol and Drug Diseases, Malmö University Hospital, Malmö, Sweden, and advertisements in the local daily press. The spouses were randomized to 1) 1 standard information session, 2) 4 individual coping skills training sessions, once a month, and 3) 12 group sessions, twice a month. Background data were obtained, and four self-report scales-the Coping Behaviour Scale, Hardship Scale, SCL-90, and AUDIT-were administered at admission and follow-up examinations. At follow-up all three groups had improved significantly with regard to coping behaviour, hardship, and mental symptoms. The coping skills training group and the support group together showed a stronger decrease in psychiatric symptoms (P = 0.1) than the single information session group. The three groups did not differ in coping behaviour and hardship. The findings indicate that changing of coping strategies in spouses of alcoholics can be successful with only one single information session, whereas the reduction of mental symptoms may need longer treatment.

Adaptation, Psychological↗

Calorimetry a method to be used to characterise pyrolytically decarboxylated bicarbonate and assess its stability at elevated humidities.

Microcalorimetry was used to characterise bicarbonate after treatment at high temperatures. By measuring the heat flow from a sample of bicarbonate at 100% relative humidity, the net exothermic contribution could be used to estimate the fraction of pyrolytically formed Na(2)CO(3). The enthalpy value corresponding to the heat of solution of Na(2)CO(3) was also applicable to a physical mixture of NaHCO(3)/Na(2)CO(3). However, from the characteristic peaks of the heat flow versus time curve, pyrolytically formed Na(2)CO(3) could be distinguished from that present in the physical mixture. The different bicarbonate batches of varying degree of pyrolytic decarboxylation were also observed at an elevated relative humidity of 54%. From these measurements it could be inferred that a decarboxylation of up to 4.5% could be allowed without any significant effect on the stability of bicarbonate at 54%.

Calorimetry↗

Antinuclear antibodies: presence and specificity in autoimmune connective tissue disease in the dog.

Autoimmune connective tissue disease in both animals and humans present as multi-systemic disorders. Clinical signs referable to joints, musculoskeletal system and Dermatopathies are present. Autoantibody production is a regular feature of systemic autoimmune disease and these antibodies have diagnostic value in both human and veterinary medicine. In this study, we demonstrate that many of the commonly used diagnostic techniques developed for use with human patients may also be adapted for use in dogs. However, in some instances, 'canine specific' autoantibodies, distinct from analogous human antibodies may be detected in sera from dogs with a diagnosis of autoimmune disease. This finding indicates that dogs may develop 'dog-specific' autoimmune connective tissue disease.

Animals↗

Measures of the binaural interaction component in human auditory brainstem response using objective detection criteria.

The occurrence of binaural interaction in humans has been demonstrated using auditory brainstem response (ABR). A distinctly binaural potential, beta, is derived by subtracting the ABR recording evoked by binaural clicks from the monaural aggregate, i.e., the sum of the two corresponding ABR recordings evoked by monaural clicks. However, few clinical data are available, possibly because the beta-wave is considered an elusive response due to a low signal-to-noise-ratio. In the present study, beta-wave latency, amplitude and area were evaluated for 10 subjects with normal hearing using automatic analysis and averaging based on a large number of stimulations. The efficacy of the beta-wave measures was assessed using different stimulus rates, as binaural interaction is known to decrease with increasing stimulus rate. It was found that the beta-wave given by automatic analysis demonstrated known characteristics of binaural interaction in human ABR, i.e. the absence of binaural interaction during wave III, significant binaural interaction during wave V and a significant decrease in binaural interaction when the stimulus rate was increased. These findings suggest that a beta-wave in the binaural difference waveform can be detected and quantified using automatic analysis, thus it is suitable for clinical studies, at least for patients with normal hearing thresholds.

Adult↗

Verification of a pencil beam based treatment planning system: output factors for open photon beams shaped with MLC or blocks.

The accuracy of monitor unit calculations from a pencil beam based, three-dimensional treatment planning system (3D TPS) has been evaluated for open irregularly shaped photon fields. The dose per monitor unit was measured in water and in air for x-ray beam qualities from 6 to 15 MV. The fields were shaped either with a multileaf collimator (MLC) or with customized alloy blocks. Calculations from the 3D TPS were compared with measurements. The agreement between calculated and measured dose per monitor unit depended on field size and the amount of blocking and was within 3% for the MLC-shaped fields. The deviation could be traced to limitations in head scatter modelling for the MLC. For fields shaped with alloy blocks, the dose per monitor unit was calculated to be within 1.6% of measured values for all fields studied. The measured and calculated relative phantom scatter for fields with the same equivalent field size were identical for MLC and alloy shaped fields. These results indicate that the accuracy in the TPS calculations for open irregular fields, shaped with MLC or blocks, is satisfactory for clinical situations.

Algorithms↗

Canine antinuclear antibodies: comparison of immunofluorescence staining patterns and precipitin reactivity.

The occurrence of antinuclear antibodies (ANAs) against several specific nuclear antigens is clearly associated with certain systemic rheumatic disorders in human patients. Determination of ANAs on a routine basis, usually by indirect immunofluorescence (IIF) technique, has therefore become an important diagnostic tool. The subdividing of positive ANA-sera into different nuclear IIF staining patterns often gives clues to antibody specificity. The present investigation aimed at studying whether such subgroups of staining patterns in IIF ANA positive canine sera may represent certain specific ANAs that can be verified by standard methods used for specificity determination in humans. The presence of precipitating antibodies, determined by the Ouchterlony immunodiffusion (ID) technique, was found to be strictly associated with a positive IIF ANA, exhibiting a speckled staining pattern without any chromosomal reactivity. None of the sera with chromosomal reactivity contained precipitating antibodies. Among the ID positive serum samples, different antigenic reactivities were detected, represented by different ID subgroups. Only 1 of the 4 main subgroups obtained by ID showed identity with any of the common and disease-associated human ANA specificities, exhibiting anti-RNP reactivity. One of these serum samples concomitantly exhibited precipitating antibodies against the Sm antigen.

Animals↗

Thermodynamic characterization of non-sequence-specific DNA-binding by the Sso7d protein from Sulfolobus solfataricus.

We used isothermal titration calorimetry and fluorescence spectroscopy to investigate the thermodynamics of non-sequence-specific DNA-binding by the Sso7d protein from the archaeon Sulfolobus solfataricus. We report the Sso7d-poly(dGdC) binding thermodynamics as a function of buffer composition (Tris-HCl or phosphate), temperature (15 to 45 degrees C), pH (7.1 to 8.0), osmotic stress and solvent (H2O/2H2O), and compare it to poly (dAdT) binding; and we have previously also reported the salt concentration dependence. Binding isotherms can be represented by the McGhee-von Hippel model for non-cooperative binding, with a binding site size of four to five DNA base-pairs and binding free energies in the range DeltaG degrees approximately -7 to DeltaG degrees approximately -10 kcal mol-1, depending on experimental conditions. The non-specific nature of the binding is reflected in similar thermodynamics for binding to poly(dAdT) and poly(dGdC). The native lysine methylation of Sso7d has only minor effects on the binding thermodynamics. Sso7d binding to poly(dGdC) is endothermic at 25 degrees C with a binding enthalpy DeltaH degrees approximately 10 kcal mol-1 in both phosphate and Tris-HCl buffers at pH 7.6, indicating that DeltaH degrees does not include large contributions from coupled buffer ionization equilibria at this pH. The binding enthalpy is temperature dependent with a measured heat capacity change DeltaCp degrees=-0.25(+/-0.01) kcal mol-1 K-1 and extrapolations of thermodynamic data indicate that the complex is heat stable with exothermic binding close to the growth temperature (75 to 80 degreesC) of S. solfataricus. Addition of neutral solutes (osmotic stress) has minor effects on DeltaG degrees and the exchange of H2O for 2H2O has only a small effect on DeltaH degrees, consistent with the inference that complex formation is not accompanied by net changes in surface hydration. Thus, other mechanisms for the heat capacity change must be found. The observed thermodynamics is discussed in relation to the nature of non-sequence-specific DNA-binding by proteins.

Archaeal Proteins↗

Solution structure of the SH3 domain from Bruton's tyrosine kinase.

X-linked agammaglobulinemia (XLA) is a heritable immunodeficiency caused by mutations in the gene coding for Bruton's tyrosine kinase (Btk). Btk belongs to the Tec family of tyrosine kinases. Each member of the family contains five regions and mutations causing XLA have been isolated in all five regions. We have determined the solution structure of the Src homology 3 (SH3) domain of Btk using two- and three-dimensional nuclear magnetic resonance (NMR) spectroscopy on natural abundance and 15N-labeled protein material. The structure determination is complemented by investigation of backbone dynamics based on 15N NMR relaxation. The Btk SH3 forms a well-defined structure and shows the typical SH3 topology of two short antiparallel beta-sheets packed almost perpendicular to each other in a sandwich-like fold. The N- and C-termini are more flexible as are peptide fragments in the RT and n-Src loops. The studied Btk SH3 fragment adopts two slowly interconverting conformations with a relative concentration ratio of 7:1. The overall fold of the minor form is similar to that of the major form, as judged on the basis of observed NOE connectivities and small chemical shift differences. A tryptophan (W251) ring flip is the favored mechanism for interconversion, although other possibilities cannot be excluded. The side chain of Y223, which becomes autophosphorylated upon activation of Btk, is exposed within the potential SH3 ligand binding site. Finally, we compare the present Btk SH3 structure with other SH3 structures.

Agammaglobulinaemia Tyrosine Kinase↗

Autoantibody profiles in canine ANA-positive sera investigated by immunoblot and ELISA.

Canine systemic lupus erythematosus (SLE) has a similar disease expression as human SLE, but the serological characterisation of the canine disease is as yet incomplete. In the present study, we examined the specificity of antinuclear antibodies (ANA) in indirect immunofluorescence (IIF) positive canine sera. Sixty-four canine IIF ANA positive sera were characterised using HeLa cell nuclear extract immunoblots and recombinant U1-70K ELISA. We compared these results with a previously shown concordance between indirect immunofluorescence and immunodiffusion in canine SLE serological diagnosis. One canine serum reacting with Sm proteins was observed, and five canine sera presented anti-RNP autoantibodies against the antigens 70K, A, C, and/or B/B'. The autoantigen most frequently recognised was a 43 kDa nuclear protein, previously described as hnRNP G. This prominent canine autoantigen was missing in the commercially available extract designed for immunodiffusion testing of human sera. Other prominent canine autoantigens were found not to be identical with the principal human ones, thus making present human test systems deficient for the use in canine systemic connective disease diagnosis. The development of antigenic extract designed for canine autoimmune autoantigens is necessary in order to make immunodiffusion a useful method in canine diagnosis. The anti-RNP positive canine sera were examined in more detail and we found that the human major antigenic region of the most prominent RNP antigen, the U1-70K protein, also is targeted by canine autoantibodies. Thus, the response against the RNP antigen seems to be conserved between man and dog.

Animals↗

Adverse effects after radical external beam radiotherapy of localized prostatic adenocarcinoma using two-dimensional dose-planning and a limited field technique.

Adverse effects were assessed after definitive limited field, 2-dimensional CT-planned radiation treatment of localized prostatic adenocarcinoma. In 66 surviving patients, out of a total of 176 treated patients, personal interviews were performed and self-administered questionnaires distributed. The average follow-up was 6.6 years. Adverse effects with regard to bowel function and micturition were investigated, and graded 0-4 with increasing severity and impact on performance status, essentially according to the RTOG toxicity scoring system. Sexual functions were registered on visual analogue scales. The majority of adverse effects were considered minor (grade 1) and did not require any treatment. Late adverse effects on bowel and bladder or urethra that required treatment (grade 2-4) were reported in up to 8% (n = 5) of cases respectively. Late bowel side-effects that interfered with life style (grade 3-4) occurred in up to 3% (n = 2) of patients; the majority were rectal complications. Corresponding urinary side-effects were registered in up to 6% (n = 4) of the patients. Major surgical interventions were not required. Sexual functions were substantially affected in 60% of cases not administered endocrine treatment. Multivariate analyses could not identify patient or treatment risk factors related to complications.

Adenocarcinoma↗

Systemic autoimmunity due to mercury vapor exposure in genetically susceptible mice: dose-response studies.

Six groups of genetically mercury-susceptible female SJL/N (H-2s) mice were exposed to mercury vapor at a concentration of 0.3-1.0 mg Hg/m3 air for 0.5-19 hr/day 5 days a week for 10 weeks. The absorbed doses were calculated to be between 75 and 2365 micrograms Hg/week/kg body wt (micrograms Hg/week/kg). The correlation between the dose and the concentration of Hg in kidney, spleen, and thymus was highly significant (p < 0.0001; Spearman's rank correlation test). The lowest observed adverse effect level (LOAEL) for serum IgG antinucleolar antibodies (ANoA) was 170 micrograms Hg/week/kg, corresponding to a renal mercury concentration of 4.0 +/- 0.76 micrograms Hg/g wet wt. The correlation between the absorbed dose and the ANoA titer was highly significant (p < 0.0001; Spearman's rank correlation test), and all mice were ANoA-positive at a dose of 480 micrograms Hg/week/kg. High-titer ANoA targeted the nucleolar 34-kDa protein fibrillarin. The LOAEL for B-cell stimulation, measured as an increase in serum IgG2a and IgG1 concentrations, was 360 micrograms Hg/week/kg, but the increase was fivefold higher and also included IgE at a dose of 690 and 2365 micrograms Hg/week/kg. The serum Ig concentrations peaked after 2-4 weeks and then slowly declined but, except for IgE, remained significantly increased during the entire exposure time. Glomerular, mesangial IgG immune complex (IC) deposits, accompanied by systemic vessel wall IC deposits, were first detected at a dose of 480 micrograms Hg/week/kg. The mesangium also showed increased titers of IgM IC deposits and complement factor C3c. The correlation between the absorbed dose, and the individual titer of IgG, IgM, and C3c, was highly significant (p < 0.0001; Spearman's rank correlation test). In conclusion, mercury vapor efficiently induced an autoimmune syndrome in genetically susceptible mice, and the LOAEL for the adverse effects varied in the order ANoA < B-cell stimulation < IC deposits. Comparing the body burden of mercury in mice at the LOAEL for autoantibodies with the body burden in populations of occupationally exposed humans suggests that the safety margin may be narrow for genetically susceptible individuals.

Administration, Inhalation↗

Transrectal ultrasonically-guided core biopsies in the assessment of local cure of prostatic cancer after radical external beam radiotherapy.

Fifty-five patients were included in an extended follow-up after radical radiation therapy (RRT) for localized prostatic cancer (T1-3, Nx, M0). Local cure was assessed by a combination of digital rectal examination (DRE), transrectal ultrasound (TRUS) and systematic 'mapping' with TRUS-guided core biopsies (TGCB). After a mean follow-up of 6.8 years, 33% (18/55) of the patients were locally free of tumour, while in 67% (37/55) of cases residual cancer was demonstrated in the biopsies. Endocrine treatment did not influence the local cure rate, nor did the T stage of tumour grade at diagnosis or the cumulative radiation effect (CRE) values within the range of the present study. The sensitivity of DRE and TRUS was low; 37% and 20% respectively, while the specificity of the DRE and TRUS methods was 83% and 94% respectively. The conclusion of the study is that residual tumour was found in the high proportion of biopsied patients nearly 7 years after RRT and that multiple, TRUS-guided core biopsies are mandatory in the assessment of local cure in patients irradiated for prostatic cancer; both DRE and TRUS on their own are less reliable.

Biopsy↗