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Biomedical subjects

G Andersson

Publications and source records attributed to G Andersson.

At least 19 recordsLinked to original sources
PubMed2001

Mutational analysis of the interaction between active site residues and the loop region in mammalian purple acid phosphatases.

Mammalian purple acid phosphatases (PAPs) can be divided into two groups, which exhibit distinct spectroscopic and kinetics properties: PAPs that consist of a single 36 kDa polypeptide, and PAPs that have undergone limited proteolysis to give two fragments with masses of 16 and 20 kDa, respectively. Proteolysis results in an increase in enzymatic activity, an increase in the optimal pH for activity, and a change in the g(z)() value of the characteristic EPR spectrum of the mixed-valence binuclear iron center. It has been proposed that these changes are due to the loss of interactions between Asp146 in an exposed loop region and active site residues upon proteolysis. In the present study, site-directed mutagenesis of Asp146 in recombinant rat bone PAP (recRPAP) has confirmed this hypothesis. Conversion of Asp146 into Ala, which eliminates the interaction of the side chain with the active site, resulted in an enzyme with properties typical of PAPs isolated in proteolytically cleaved forms. The Asp146Asn and Asp146Glu mutants were also prepared and examined to assess the effects of altered electrostatic interactions and side-chain length. Limited proteolysis of all three mutant enzymes with cathepsin L resulted in a significant increase in catalytic activity. Thus, although the interaction between Asp146 and (an) active site residue(s) is the major factor responsible for the low catalytic activity of uncleaved PAPs, other interactions are also important. Since both p-nitrophenyl phosphate and osteopontin, a potential in vivo substrate, show the same level of activation, the observed increase in catalytic activity upon proteolysis is likely to be due to electrostatic rather than steric effects. EPR spectra of FeZn-recRPAP before and after cleavage by cathepsin L suggest that cleavage primarily affects the divalent metal site. The observation that pK(es,1) is also sensitive to changes at the divalent site is consistent with the proposal that the nucleophilic hydroxide is that bridging the divalent and trivalent metals.

Acid Phosphatase↗
PubMed2001

Different roles of spermine in glucocorticoid- and Fas-induced apoptosis.

Two experimental systems representative of the mitochondrial and death receptor apoptotic pathways are the dexamethasone-induced programmed cell death in mouse thymocytes and the antibody-mediated cross-ligation of the Fas receptor in the human leukemic T-cell line Jurkat, respectively. In both cell systems, caspase-9, -8, and -3 were activated upon induction of apoptosis and a sub-G(1) peak appeared as a sign of ongoing DNA fragmentation. Addition of 1 mM spermine together with dexamethasone inhibited caspase activation and the appearance of the sub-G(1) peak in mouse thymocytes. In contrast, Fas-induced cell death was totally unaffected by spermine addition. Spermine addition significantly elevated the spermine concentration in both thymocytes and Jurkat cells. Thus, spermine per se did not inhibit the caspases but rather their activation. The fact that spermine inhibited caspase activation only in the thymocytes implies that spermine inhibited dexamethasone-induced apoptosis upstream of caspase-9 activation.

Animals↗
PubMed2001

Longitudinal follow-up of tinnitus complaints.

OBJECTIVE: To investigate the long-term outcome of patients with tinnitus, the long-term effects of cognitive behavioral therapy, and what properties of tinnitus predict distress at follow-up. DESIGN: A longitudinal follow-up of a consecutive sample of patients with tinnitus initially seen by a clinical psychologist. SETTING: Department of Audiology, University Hospital, Uppsala, Sweden. PARTICIPANTS: A consecutive series of 189 patients with tinnitus treated between January 1988 and March 1995 were sent a postal questionnaire booklet. One hundred forty-six (77 women and 69 men) provided usable responses, in all yielding a 77% response rate. MAIN OUTCOME MEASURES: A questionnaire was derived from a structured interview "Questions About Your Tinnitus." Also included were the Tinnitus Reaction Questionnaire and tinnitus-matching data. RESULTS: Questionnaire data showed that many patients with tinnitus still experienced distress an average of 4.9 years after admission. Tolerance of tinnitus increased over time overall. For patients who had received cognitive behavioral therapy (59%), there was a reduction in tinnitus-related distress. Further, an open-ended question showed that the benefits from treatment outnumbered the deficits. Multiple regression analysis showed that tinnitus maskability at admission was a significant predictor of distress at follow-up. CONCLUSIONS: Severe tinnitus shows some signs of improvement over time, especially when psychological treatment has been given. Tinnitus maskability is an important prognostic factor of future tinnitus annoyance.

Adult↗
PubMed2001

Lack of integration, and seasonal variations in demand explained performance problems and waiting times for patients at emergency departments: a 3 years evaluation of the shift of responsibility between primary and secondary care by closure of two acute hospitals.

In 1996, Stockholm County decided to reduce the costs of health care in order to release resources for upcoming medical needs. The method was both structural changes and transfer of low technology care from hospitals to other settings. The effects of interventions on service quality for patients and organisational performance of departments of internal medicine, orthopaedics and surgery were evaluated. Three cross-sectional studies were performed for comparison over time. Details on all individuals who visited A&E departments during 1 week in May 1997, May 1998 and May 1999 were recorded prospectively, and 16246 visits were registered. From 1995 to 1999 the total number of visits increased by 21% according to annual statistics. The utilisation of emergency care rose by 40/1000, and was not associated with the growth of population by 4.5%. Hospitals responded to peaks of demand by stringent prioritisation. Median waiting times were unchanged, but mean waiting times were prolonged over time, in particular for younger, not-referred patients. There was a direct correlation between waiting times and number of visitors. Total length of stay at A&E departments was related mainly to the waiting time for the first examination by a physician and cycle time for X-rays. Increased number of visits strained the capacity of hospitals and led to temporary loss of service quality for patients. The expected chain-reaction of integrated care did not take place, since providers outside hospitals were resistant to the shift of responsibility. Hospitals were utilised as primary care centres. The sub-optimal integration and fragmented care with an inappropriate balance between providers seems a universal problem.

Cross-Sectional Studies↗
PubMed2001

Randomized controlled trial of vestibular rehabilitation combined with cognitive-behavioral therapy for dizziness in older people.

OBJECTIVE: To evaluate the effectiveness of vestibular rehabilitation combined with cognitive behavioral therapy in the treatment of dizziness in older people. STUDY DESIGN AND SETTING: A randomized controlled design was used with patients recruited via an advertisement. Nine patients completed treatment and 10 served as waiting-list controls. The intervention lasted 7 weeks with 5 weekly group sessions and consisted of vestibular exercises. Cognitive behavioral therapy components were added to promote relaxation, reduce anxiety, and avoidance of feared situations and movements. RESULTS: Statistically significant improvements on walking time, 2 dizziness provocative movements, and on the Dizziness Handicap Inventory, but no effects on the Romberg or anxiety and depression. Of the treated patients, 89% reached statistical significant improvement on the total inventory score. CONCLUSION: Cognitive behavioral therapy combined with vestibular rehabilitation decreases dizziness in older people. SIGNIFICANCE: These findings indicate that cognitive behavioral therapy can be combined with vestibular rehabilitation in the treatment of dizziness.

Aged↗
PubMed2001

Development of a brief version of the Burn Specific Health Scale (BSHS-B).

BACKGROUND: The Burn Specific Health Scale (BSHS) is an outcome scale designed specifically for burn patients. The scale has been abbreviated (BSHS-A) and revised (BSHS-R). We used a factor analytic approach to further improve the scale for clinical use. METHODS: Two hundred forty-eight of 350 former patients (70.9%) treated at the Uppsala Burn Unit between 1980 and 1995 responded to 94 questions from previous versions of the BSHS. RESULTS: Principal components factor analyses were used to derive an instrument with 40 items called the Burn Specific Health Scale-Brief (BSHS-B), resulting in nine well-defined domains with intercorrelations ranging from 0.11 to 0.56, and Chronbach's factor alphas ranging from 0.75 to 0.93. The domains describe function with respect to Heat Sensitivity, Affect, Hand Function, Treatment Regimens, Work, Sexuality, Interpersonal Relationships, Simple Abilities, and Body Image. CONCLUSION: The BSHS-B is a valid but shorter alternative to the previously described BSHS-A. Important domains of postburn distress are captured better in the BSHS-B than in the BSHS-R.

Adult↗
PubMed2001

Identification of novel porcine endogenous betaretrovirus sequences in miniature swine.

PCR amplification of genomic DNA from miniature swine peripheral blood lymphocytes, using primers corresponding to highly conserved regions of the polymerase (pol) gene, allowed the identification of two novel porcine endogenous retrovirus (PERV) sequences, PMSN-1 and PMSN-4. Phylogenetic analyses of the nucleotide sequences of PMSN-1 and PMSN-4 revealed them to be most closely related to betaretroviruses. The identification of PERVs belonging to the Betaretrovirus genus shows that endogenous retroviruses of this family are more broadly represented in mammalian species than previously appreciated. Both sequences contained inactivating mutations, implying that these particular loci are defective. However, Southern blot analysis showed additional copies of closely related proviruses in the miniature swine genome. Analyses of fetal and adult miniature swine tissues revealed a broad mRNA expression pattern of both PMSN-1 and PMSN-4. The most abundant expression was detected in whole bone marrow c-kit(+) (CD117(+)) progenitor bone marrow cells, fetal liver, salivary gland, and thymus. It appears unlikely that functional loci encoding these novel PERV sequences exist, but this remains to be established. The betaretrovirus sequences described in this report will allow such investigations to be actively pursued.

Animals↗
PubMed2001

Mechanisms of estrogen action.

Our appreciation of the physiological functions of estrogens and the mechanisms through which estrogens bring about these functions has changed during the past decade. Just as transgenic mice were produced in which estrogen receptors had been inactivated and we thought that we were about to understand the role of estrogen receptors in physiology and pathology, it was found that there was not one but two distinct and functional estrogen receptors, now called ER alpha and ER beta. Transgenic mice in which each of the receptors or both the receptors are inactive have revealed a much broader role for estrogens in the body than was previously thought. This decade also saw the description of a male patient who had no functional ER alpha and whose continued bone growth clearly revealed an important function of estrogen in men. The importance of estrogen in both males and females was also demonstrated in the laboratory in transgenic mice in which the aromatase gene was inactivated. Finally, crystal structures of the estrogen receptors with agonists and antagonists have revealed much about how ligand binding influences receptor conformation and how this conformation influences interaction of the receptor with coactivators or corepressors and hence determines cellular response to ligands.

Animals↗
PubMed2001

Chromosomal distribution, localization and expression of the human endogenous retrovirus ERV9.

ERV9 is a class I family of human endogenous retroviral sequences. Somatic cell hybrid genomic hybridization experiments using a mono-chromosomal panel indicate the presence of approximately 120 ERV9 loci in the human genome distributed on most chromosomes. Fluorescence in situ hybridization (FISH) using an ERV9 cDNA probe containing gag, pol and env sequences, verified this observation and a consistent signal was found at the chromosome region 11q13.3-->q13.5. By analysis of a panel of radiation hybrids, an ERV9 locus was mapped to within a 300-kbp region at the chromosome site 11q13. The marker cCLGW567 and the locus MAP3K11/D11S546 centromeric and telomeric flanked it, respectively. Northern blot analysis, using an ERV9 LTR probe, indicated that most normal tissues examined expressed low abundant ERV9 LTR driven mRNAs of various sizes. The most prominent expression was found in adrenal glands and testis. However, the level of expression varied in the same tissues among different individuals indicating that ERV9 mRNA expression probably is inducible in certain tissues or at various cell stages.

Animals↗
PubMed2001

Expression and distribution of tartrate-resistant purple acid phosphatase in the rat nervous system.

Tartrate-resistant purple acid phosphatase (TRAP) of osteoclasts and certain cells of the monocyte-macrophage lineage belongs to the family of purple acid phosphatases (PAPs). We provide here evidence for TRAP/PAP expression in the central and peripheral nervous systems in the rat. TRAP/PAP protein was partially purified and characterized from the trigeminal ganglion, brain, and spinal cord. The TRAP activity (U/mg tissue) in these tissues was about 10-20 times lower than in bone. Reducing agents, e.g. ascorbate and ferric iron, increased the TRAP activity from the neural tissues (nTRAP) and addition of oxidizing agents completely inactivated both bone and nTRAP. The IC(50) for three known oxyanion inhibitors of TRAP/PAP was similar for bone and nTRAP with the same rank order of potency (molybdate > tungstate > phosphate). This indicates that the redox-sensitive binuclear iron center characteristic of mammalian PAPs is present also in nTRAP. Western blots of partially purified nTRAP revealed a band with the expected size of 35 kD. The expression of TRAP in the trigeminal ganglion, brain, and spinal cord was confirmed at the mRNA level by RT-PCR. In situ hybridization histochemistry demonstrated TRAP mRNA expression in small ganglion cells of the trigeminal ganglion, in alpha-motor neurons of the ventral spinal cord, and in Purkinje cells of the cerebellum. TRAP-like immunoreactivity was encountered in the cytoplasm of neuronal cell bodies in specific areas of both the central and the peripheral nervous system. Together, the data demonstrate that active TRAP/PAP is expressed in certain parts of the rat nervous system.

Acid Phosphatase↗
PubMed2001

Female estrogen receptor beta-/- mice are partially protected against age-related trabecular bone loss.

Recently, it has been shown that inactivation of estrogen receptor beta (ER-beta) by gene targeting results in increased cortical bone formation in adolescent female mice. To study the possible involvement of ER-beta in the regulation of the mature skeleton, we have extended the analyses to include 1-year-old ER-beta knockout mice (ER-beta-/-). Male ER-beta-/- mice did not express any significant bone phenotypic alterations at this developmental stage. However, the increase in cortical bone parameters seen already in the adolescent female ER-beta-/- mice was maintained in the older females. The aged female ER-beta-/- mice further exhibited a significantly higher trabecular bone mineral density (BMD) as well as increased bone volume/total volume (BV/TV) compared with wild-type (wt) mice. This was caused by a less pronounced loss of trabecular bone during adulthood in female ER-beta-/- mice. The growth plate width was unaltered in the female ER-beta-/- mice. Judged by the expression of the osteoclast marker tartrate-resistant acid phosphatase (TRAP) and cathepsin K (cat K; reverse-transcription-polymerase chain reaction [RT-PCR]) as well as the serum levels of C-terminal type I collagen cross-linked peptide, bone resorption appeared unaffected. However, an increase in the messenger RNA (mRNA) expression levels of the osteoblast marker core-binding factor alpha1 (Cbfa1) suggested an anabolic effect in bones of old female ER-beta-/- mice. In addition, the mRNA expression of ER-alpha was augmented, indicating a role for ER-alpha in the development of this phenotype. Taken together, the results show that ER-beta is involved in the regulation of trabecular bone during adulthood in female mice and suggest that ER-beta acts in a repressive manner, possibly by counteracting the stimulatory action of ER-alpha on bone formation.

Animals↗
PubMed2000

The GB virus C/hepatitis G virus replicates in hepatocytes without causing liver disease in healthy blood donors.

Thirty-seven persons were identified with GB virus C (GBV-C) single infection by polymerase chain reaction screening of 1254 healthy blood donors. Of 33 donors who returned for clinical examination, 17 underwent liver biopsy. Clinical, biochemical, and histologic evaluation did not reveal any signs of liver disease. Liver biopsies of 15 donors were analyzed by in situ hybridization with GBV-C RNA probes and immunologic staining for the GBV-C envelope 2 protein. GBV-C replication was identified in the cytoplasm of hepatocytes of 10 (67%) donor livers but in none of 7 liver biopsies of chronic hepatitis B virus carriers negative for serum GBV-C RNA. Thus, there was no evidence of liver disease in GBV-C-infected healthy blood donors despite viral replication in hepatocytes.

Adult↗
PubMed2000

Job exposures as correlates of recovery in population-based rehabilitation intervention for work-related low back disorders.

PURPOSE: Evaluating the impact of population-based rehabilitation interventions for work-related low back disorders (WR-LBD) requires job exposure factors to be considered as time-varying covariates. The role of job factors in recovery has not been well-established as most studies are based upon clinic samples, not working populations. This report represents the initial exploration of variables to be included in modeling job exposures as time-varying covariates of a study of work-place based rehabilitation intervention.METHODS: The study sample consisted of 162 hourly production employees from two automotive plants with work-related low back disorder not due to external trauma. Data reported herein were collected at baseline from an on-going large randomized clinical trial of rehabilitation for WR-LBD. Low back pain as measured by the North American Spine Society Baseline Form was examined in relation to: self-reported job factors from the Job Content Questionnaire and job risk category for low back disorder determined by the Lumbar Motion Monitor (LMM), an electronic goniometer which transmits back motion signals to a computer for analysis.RESULTS: Low back pain, with and without leg pain, was not found to be associated with hours worked in the previous week, job shift, perceptions of the pace of the job, or job risk of low back disorder as measured by the LMM. Low back pain was significantly (p < 0.05) correlated with perceptions of: how hard the work was, how much physical effort was required, how hectic the job was, whether or not there was sufficient time to do the job, and how much concentration and physical effort were required for the job.CONCLUSIONS: Self-report of perceptions of job strain may be as important, if not more important, than current quantitative factors thought to influence recovery from work-related low back pain.

Journal Article↗
PubMed2000

Estrogen receptor specificity in the regulation of skeletal growth and maturation in male mice.

Androgens may regulate the male skeleton directly through a stimulation of androgen receptors or indirectly through aromatization of androgens into estrogen and, thereafter, through stimulation of estrogen receptors (ERs). The relative importance of ER subtypes in the regulation of the male skeleton was studied in ERalpha-knockout (ERKO), ERbeta-knockout (BERKO), and double ERalpha/beta-knockout (DERKO) mice. ERKO and DERKO, but not BERKO, demonstrated decreased longitudinal as well as radial skeletal growth associated with decreased serum levels of insulin-like growth factor I. Therefore, ERalpha, but not ERbeta, mediates important effects of estrogen in the skeleton of male mice during growth and maturation.

Animals↗
PubMed2000

Changes in polyamine metabolism during glucocorticoid-induced programmed cell death in mouse thymus.

When mice are injected with dexamethasone, cortical thymocytes are deleted through programmed cell death (PCD). We have used this in vivo model system to investigate the kinetics of PCD and cell proliferation in relation to polyamine metabolism for 16 h after injection of dexamethasone. As a marker for PCD, we used the appearance of a sub-G(1)peak in the DNA histogram. When a sub-G(1)peak appeared at 4 h after dexamethasone treatment, the activity of the polyamine catabolic enzyme spermidine/spermine N(1)-acetyltransferase (SSAT) was significantly increased and the activity of the polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase (AdoMetDC) was significantly decreased compared to the activities found in the thymi of control mice. Despite the significant changes in the activities of SSAT and AdoMetDC, the only change in the polyamine pool during the experimental period was that of putrescine. Presumably the complexity of this in vivo system masks changes in the spermidine and spermine pools that were expected in relation to the increased SSAT activity and decreased AdoMetDC activity.

Acetyltransferases↗