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Biomedical subjects

G Andersson

Publications and source records attributed to G Andersson.

At least 109 records · Page 6Linked to original sources
PubMed1997

Comparative studies of rat recombinant purple acid phosphatase and bone tartrate-resistant acid phosphatase.

The tartrate-resistant acid phosphatase (TRAP) of rat osteoclasts has been shown to exhibit high (85-94%) identity at the amino acid sequence level with the purple acid phosphatase (PAP) from bovine spleen and with pig uteroferrin. These iron-containing purple enzymes contain a binuclear iron centre, with a tyrosinate-to-Fe(III) charge-transfer transition responsible for the purple colour. In the present study, production of rat osteoclast TRAP could be achieved at a level of 4.3 mg/litre of medium using a baculovirus expression system. The enzyme was purified to apparent homogeneity using a combination of cation-exchange, hydrophobic-interaction, lectin-affinity and gel-permeation chromatography steps. The protein as isolated had a purple colour, a specific activity of 428 units/mg of protein and consisted of the single-chain form of molecular mass 34 kDa, with only trace amounts of proteolytically derived subunits. The recombinant enzyme had the ability to dephosphorylate bone matrix phosphoproteins, as previously shown for bone TRAP. Light absorption spectroscopy of the isolated purple enzyme showed a lambda max at 544 nm, which upon reduction with ascorbic acid changed to 515 nm, concomitant with the transition to a pink colour. EPR spectroscopic analysis of the reduced enzyme at 3.6 K revealed a typical mu-hydr(oxo)-bridged mixed-valent Fe(II)Fe(III) signal with g-values at 1.96, 1.74 and 1.60, proving that recombinant rat TRAP belongs to the family of PAPs. To validate the use of recombinant PAP in substituting for the rat bone counterpart in functional studies, various comparative studies were carried out. The enzyme isolated from bone exhibited a lower K(m) for p-nitrophenyl phosphate and was slightly more sensitive to PAP inhibitors such as molybdate, tungstate, arsenate and phosphate. In contrast with the recombinant enzyme, TRAP from bone was isolated predominantly as the proteolytically cleaved, two-subunit, form. Both the recombinant enzyme and rat bone TRAP were shown to be substituted with N-linked oligosaccharides. A slightly higher apparent molecular mass of the monomeric form and N-terminal chain of bone TRAP compared with the recombinant enzyme could not be accounted for by differential N-glycosylation. Despite differences in specific post-translational modifications, the recombinant PAP should be useful in future studies on the properties and regulation of the mammalian PAP enzyme.

Acid Phosphatase↗
PubMed1997

Gender and diurnal effects on specific open-field behavioral patterns in the portacaval shunted rat.

Hepatic encephalopathy (HE) is a frequently observed neuropsychiatric syndrome with unknown pathogenesis in patients suffering from chronic liver failure. The portacaval shunted (PCS) rat has been extensively used as an experimental model for HE and for studying the effects of portal-systemic shunting. Previous behavioral studies on PCS rats have shown a number of abnormalities but there is no consensus about which abnormalities are characteristic. We therefore made a thorough descriptive study of 100 male and female PCS rats and sham-operated controls four to six weeks after the shunting procedure in an open field. The frequency, duration and average time sequence of various kinds of defined spontaneous behavioral patterns were investigated during both night and day in order to assess behavioral differences between PCS rats and sham-operated controls. The results indicate differences especially regarding motor exploratory behaviors such as forward locomotion and rearing. There were also differences in eating and sniffing behaviors. Our results show that the overall behavioral alteration seen in PCS rats compared to sham-operated controls is that of hypoactivity.

Animals↗
PubMed1997

Role of the X2 box in activated transcription from the DRA promoter in B cells.

We investigated the function of the evolutionary conserved X2 box in the promoter of the HLA-DRA gene from the human major histocompatibility complex (MHC) in resting and activated B cells. NF-X2, which contains members of the AP-1/ATF/CREB families of transcription factors, interacts with the X2 box (5'-TGCGTCA-3') from positions -97 to -91 in the DRA promoter. In resting Raji cells, little to no binding to the X2 box was observed. In sharp contrast, in B cells treated with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), strong interactions between the X2 box and NF-X2 containing c-Fos were observed. As determined by transient expression and RNA analyses, the activation of protein kinase C (PKC) also increased rates of transcription from the wild-type DRA promoter but not from a DRA promoter bearing clustered point mutations in the X2 box. Since the co-expression with a dominant negative c-Fos abolished the responsiveness to TPA, we conclude that activated transcription of the DRA gene depends on interactions between the X2 box and NF-X2, which contains c-Fos.

Animals↗
PubMed1997

Behavioural hearing tactics: a controlled trial of a short treatment programme.

Nineteen elderly hearing impaired subjects participated in an experimental treatment study and received either behavioural hearing tactics or served as untreated controls. Treatment was supplied in the form of a self-help treatment manual supplied with telephone contacts during 4 consecutive weeks. The treatment manual included applied relaxation, communication strategies training, advice to relatives, information, and coping skills. Assessments (pre-post) were conducted in a structured interview measuring coping behaviour. In order to evoke behavioural compensation small acoustic provocations were included in the interview. Pre-post assessments also included questionnaires, daily registered hearing problems, and hours of daily hearing aid use. Results showed significant beneficial effects in favour of the treatment in terms of self-assessed problems and behaviour change.

Adaptation, Psychological↗
PubMed1997

Stress and symptoms of Menière's disease: a time-series analysis.

Meniere's disease is an inner ear disease in which the symptom cluster of hearing loss, tinnitus, and dizziness is found along with attacks of vertigo and nausea. In this study, 20 subjects diagnosed with Meniere's disease completed daily measures of stress and symptoms during periods ranging between 45 and 351 days (M = 193.5). Data were analyzed by means of time-series analysis (ARIMA), and the temporal associations were investigated by lagged correlations. The results showed concurrent (same day) associations between stress and symptoms, but individual differences were found regarding which symptoms were associated with stress. Although stress is linked with symptom perception, this study does not support the role of stress as a precursor of symptoms in Meniere's disease.

Adult↗
PubMed1997

In vivo administration of the 5-HT1A receptor agonist 8-OH-DPAT interferes with brain GABA(A)/benzodiazepine receptor complexes.

In the present study the influence of in vivo administration, or in vitro addition, of the prototypic 5-HT1A receptor agonist 8-OH-DPAT on in vitro characteristics of GABA(A)/benzodiazepine receptor complexes was examined. In vivo administration of 8-OH-DPAT at a dose (32 microg/kg, s.c. -10') that has been reported to produce anxiolytic-like effects in the elevated plus-maze doubled the Kd for in vitro binding of 3H-flunitrazepam to rat cortical membranes (Bmax was unchanged) and enhanced GABA-stimulated (3, 10, 30 and 100 microM) 36Cl- influx in corticohippocampal synaptoneurosomes. In synaptoneurosomes from vehicle treated rats, diazepam (1, 3 and 10 microM) potentiated GABA-stimulated (3 microM) 36Cl- influx. No such effect was observed in tissue from 8-OH-DPAT treated rats, in which the GABA-stimulated (3 microM) 36Cl- influx was similar to that caused by GABA + diazepam in tissue from vehicle treated rats. When added in vitro, 8-OH-DPAT failed to alter basal or GABA-stimulated 36Cl- uptake. In vivo administration of a low "anxiolytic" dose of 8-OH-DPAT thus appears to interfere with GABA(A)/benzodiazepine receptor complexes, whereas in vitro application does not. The underlying mechanism remains to be elucidated but could involve in vivo release of positive modulators of GABA(A)/benzodiazepine receptor complexes, e.g. GABA, endozepines or neurosteroids.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Central vs. peripheral spontaneous behavioral abnormalities in experimental hepatic encephalopathy.

The most common behavioral disturbance reported in experimental chronic hepatic encephalopathy (HE) refers to changes in spontaneous activities in an open field in the portacaval-shunted (PCS) rat. A major problem at present is that not all of these findings of abnormal PCS behavior are in agreement. We, therefore, investigated the total, central, and peripheral locomotor and rearing activities in an open field 2 and 6 months after PCS surgery. The results revealed that, 2 months after surgery, locomotor and rearing activities were lower in PCS rats compared to controls. At 6 months, a partial remission of the behaviors had occurred. Clearly though, as pointed out by the peripheral behavioral recordings, the hypoactivity persisted and, interestingly, central locomotor activity as higher in PCS rats than in controls. This novel finding may be attributed to the special study of central vs. peripheral components of the spontaneous open-field behavior in experimental chronic HE. Our observations may also help explain some of the seemingly discrepant results available in the literature.

Animals↗
PubMed1997

Linomide enhances apoptosis in CD4+CD8+ thymocytes.

Linomide, a quinoline-3-carboxamide, has a pleiotropic immune modulating capacity and inhibits development as well as progression of disease in animal models of autoimmunity. Linomide treatment of mice resulted in a dramatic, dose-dependent decrease of the thymic cell number shortly after the start of administration. Flow cytometric analysis revealed that the major thymocyte subset, the early immature type CD4+CD8+ thymocytes, were reduced in number by 75%, mature CD4+CD8- or CD4-CD8+ thymocytes were less sensitive to treatment. The polyclonal T cell activator Con A (Concanavalin A) was used together with IL-2 to evaluate the potential proliferative responsiveness of ex vivo thymocytes. Thymocytes from mice treated with Linomide exhibited a more vigorous proliferation than control cultures. An effect shown to not only be due to the enrichment of mature thymocytes in the cultures from Linomide treated animals, but also when purified, mature thymocytes (CD4+CD8- and CD4-CD8+) were cultured with Con A and IL-2, these cells responded with a significantly enhanced proliferation. In vivo Linomide treatment did not result in increased plasma concentrations of corticosterone and treatment of adrenalectomized mice resulted in a reduction of thymocytes which was comparable to the effect in intact mice, indicating that glucocorticoids (GC) are not major mediators of Linomide-induced thymocyte deletion. In addition to this, and supporting a glucocorticoid independent mode of action, Linomide treatment of thymocytes in vitro resulted in a significant increase in the number of apoptotic cells, specifically in the CD4+CD8+ subset, implicating apopotosis as one component in the course of thymocyte reduction. In addition to this, in vivo treatment with Linomide resulted in an identical pattern to that seen in vitro in that there was significantly increased apoptosis only in the CD4+CD8+. These data indicate that Linomide modifies thymocyte development using a glucocorticoid independent pathway and results in the increased apoptosis of the CD4+CD8+ subset.

Adjuvants, Immunologic↗
PubMed1997

The influence of cigarette consumption and smoking machine yields of tar and nicotine on the nicotine uptake and oral mucosal lesions in smokers.

The purpose of this investigation, which has been performed as two studies, was to evaluate the association between the daily exposure to nicotine (measured as cigarette smoking machine yields) and the actual uptake of nicotine by cigarette smokers, as well as the association between oral mucosal changes and the exposure to cigarette smoke. In Study 1, consumption data, soft tissue changes and nicotine intake were measured in 47 habitual smokers using cigarettes with tar and nicotine yields within the ranges 9.3-12.2 and 0.72-1.16 mg per cigarette, respectively. The subjects were divided into three groups based on daily cigarette consumption; group averages (standard deviation) were 10.8 (2.2), 17.9 (1.9) and 28.4 (6.1) cigarettes per day. The group averages of tar deliveries from their usual brands of cigarettes were 11.1, 11.0 and 10.5 mg per cigarette, and group averages of nicotine deliveries were 1.05, 1.05 and 1.06 mg per cigarette, respectively. In Study 2, the same data were measured in a group of 77 habitual smokers with an average individual consumption of 11-21 cigarettes per day. The participants in Study 2 were divided into three groups according to tar delivery from their usual brands to cigarettes, with group averages of tar being 6.4 (1.2), 11.0 (1.2) and 16.0 (1.1) mg per cigarette, and of nicotine being 0.70 (0.12), 1.05 (0.12) and 1.34 (0.08) mg per cigarette, respectively. The average consumption of all three groups was within the range 17.1 to 17.9 cigarettes per day. The daily exposures to nicotine and tar were measured as the smoking machine yields multiplied by the number of cigarettes smoked per day. Nicotine uptake was determined by monitoring nicotine and its seven main metabolites in 24-h urine samples. In Study 1 there were significant differences between the three groups in the total amount of nicotine and metabolites excreted in the 24-h urine. The average nicotine uptake was 14.9, 24.4 and 35.4 mg per day, respectively. In Study 2, the 24-h excretion of nicotine and metabolites was about the same in all three groups and averaged 24.5 mg per day. The nicotine uptake was significantly correlated to the number of cigarettes smoked per day but not to the smoking machine yields of tar and nicotine per cigarette. The average prevalences for each of the different oral mucosal lesions (leukoedema, smoker's palate and hairy tongue) were found to increase with increasing consumption and nicotine uptake (Study 1); they were also independent of tar and nicotine yields from the cigarettes smoked (Study 2). These results indicate that the actual uptake of nicotine by smokers could not be estimated from the smoking machine yields. Reduction in exposure to smoke components may best be accomplished if smokers are encouraged to smoke fewer lower-yield cigarettes and to avoid smoking more of each cigarette.

Adult↗
PubMed1997

Aerobic and anaerobic work capacities and leg muscle characteristics in elite orienteers.

Aerobic and anaerobic work capacities, leg muscle structure and metabolic characteristics of m. vastus lateralis (NT), m. rectus femoris (RG) and mm. gastrocnemii (NT and RG) were analysed in five male and seven female elite orienteers from the Swedish National team (NT) and a reference group (RG) of eight male and 10 female upcoming orienteers, all in optimal shape at the end of a competitive season. Maximal oxygen uptake was 78.4 ml/kg/min for NT men (range 75-81) and 67.8 ml/kg/min for NT women (range 62-71), for both groups significantly higher (P < 0.001) than for RG. Maximal serum lactate was 13.3 mmol/l for NT men (range 10-17) and 11.7 mmol/l for NT women (range 8.4-14), which did not differ from RG. No significant correlation was found between maximal oxygen uptake and maximal serum lactate. For NT females only maximal oxygen uptake was significantly related to running economy (P < 0.01). Muscle biopsies showed a high content of type I fibres in m. vastus lateralis as well as in m. gastrocnemius mediale. M. vastus lateralis (NT) had a higher proportion of type I fibres, capillaries per fibre as well as CS, HAD and LDH 1-2 enzymes compared with m. rectus femoris (RG) (P < 0.001-< 0.001), the latter muscle showing a more anaerobic profile. NT males and females had a higher metabolic potential in m. gastrocnemius mediale than RG (P < 0.001). Our results reflect an obligate high and narrow range of aerobic and anaerobic work capacities for successful performance in international elite orienteering. It remains to be shown how these laboratory data are related to individual performance in authentic orienteering competitions.

Adult↗
PubMed1997

Presence of retroelements reveal the evolutionary history of the human DR haplotypes.

Comparison of intron sequences has been a successful tool for drawing major conclusions about the evolutionary relationship of DRB genes. This complex family of genes is discussed in this review as well as a proposed model for the evolution of HLA-DR haplotypes. The model is based both on phylogenetic analysis of intron sequences as well as presence of ERV9 LTR elements located at identical position in intron 5 of a number of DRB genes. According to this model, two main evolutionary branches of DR haplotypes exist. The DR53 haplotype represents one branch, and the second branch contains the DR51, DR52, DR1, and DR8 haplotypes. After the divergence of the DR53 haplotype, an ERV9 LTR element was inserted in a primordial gene. Consequently, all DRB1 genes as well as the DRB3 gene within haplotypes of the second branch, contain this LTR element. In addition, conserved regulatory sequence motifs are found present within these LTR elements that might regulate DRB gene expression. Novel haplotypes are generated by recombinations and the maintenance of the DR haplotype variation as well as the frequent genetic rearrangements observed might be evolutionary advantageous.

Animals↗
PubMed1997

Prior treatments in a group of tinnitus sufferers seeking treatment.

BACKGROUND: Tinnitus is a common problem for which many treatments have been proposed and implemented. Patients tend to seek renewed treatment after treatment failure. The aim of this descriptive study was to describe a group of consecutive tinnitus patients in terms of prior treatments received. METHODS: Sixty-nine tinnitus patients seeking treatment were asked about prior treatments and completed the short Tinnitus Effect Questionnaire (TEQ). Four groups were obtained: No treatment (n = 24), acupuncture (n = 19), relaxation (n = 13), and other treatments (n = 13). Six subscales were derived from the TEQ measuring helplessness, capacity for rest, acceptability of change, emotional effects, hearing speech and sounds, and ability to ignore. The groups were compared with multivariate analyses of covariance and Tukey's post-hoc tests. RESULTS: Results showed minor differences between the groups, the exception being that the untreated group showed more acceptability for change. CONCLUSIONS: Clinicians should be aware of the fact that patients may have tried at least one treatment when entering the audiology clinic. Controlled studies are needed in order to avoid the spread of nonspecific and non-effective treatments in the management of tinnitus.

Acupuncture Therapy↗
PubMed1997

Evaluation of quality of life and symptoms after translabyrinthine acoustic neuroma surgery.

OBJECTIVE: This study aimed to describe the consequences of acoustic neuroma surgery in terms of symptoms and quality of life. STUDY DESIGN: This study was a retrospective case review. SETTING: The surgery was conducted in Uppsala, Sweden. PATIENTS: A consecutive sample of acoustic neuroma patients operated on between 1988 and 1994. INTERVENTION: All patients had been operated on with the translabyrinthine technique. MAIN OUTCOME MEASURES: A questionnaire was constructed including questions about the surgery and symptoms. The House and Brackmann scale was used for grading facial function and the Brackmann and Bars scale was used for self-assessment of facial function. RESULTS: Follow-up data were collected by a postal questionnaire sent out and returned by 141 patients, which yielded a 90% response rate. Normal to moderately impaired facial function (House I-III) was evident in 85.2% of patients, although residual facial problems were reported. Most considered hearing to be worse after surgery (80%), and tinnitus was found in 60% of the sample. Balance problems (45%), dizziness (19%), and headache/pain (22%) were also reported. Work ability was affected in 23%, and 37% reported a continued need for medical consultations, mainly because of facial problems and pain. Most (89%) were pleased with the preoperative information. CONCLUSIONS: This study showed that few patients with acoustic neuroma had experienced negative social consequences after surgery. Although not linked to the operation, residual symptoms were reported that may necessitate further rehabilitation.

Adult↗
PubMed1996

Complementation of divergent mga genes in group A Streptococcus.

The gene (mga4) encoding the positive regulatory protein, Mga4, was cloned and sequenced from an M type 4 strain (AP4) of Streptococcus pyogenes. The deduced amino acid (aa) sequence of this "divergent Mga' shows 88% identity to the prototype Mga1 in its N-terminal half, which contains all three of the predicted helix-turn-helix domains. However, one of the predicted receiver domains of Mga1, which is at its C terminus, is not conserved in the Mga4 aa sequence. Nevertheless, a mutation in mga1 was found to be complemented for activation of the gene encoding M protein (emm) by mga4 in trans. This suggests that the aa residues of the C-terminal predicted receiver domain are not critical for activation of emm transcription.

Amino Acid Sequence↗
PubMed1996

Bone sialoprotein coated on glass and plastic surfaces is recognized by different beta 3 integrins.

Integrins have important roles in mediating cell-matrix interactions, essential for cell migration and signaling. In bone, integrins are suggested to play a role through their ability to mediate cell attachment to bone matrix proteins. In the present study, the subunit composition of integrins binding bone sialoprotein and osteopontin coated on either glass or plastic surfaces was analyzed using cells isolated from bone. Thus, integrin antibodies to alpha v beta 3, alpha IIb beta 3, alpha v, alpha IIb, and beta 3 and the peptides GRGDSP and KQAGDV were used to define the integrins involved in the attachment in vitro of a preparation of multinucleated cells expressing the enzyme tartrate-resistant acid phosphatase. Binding to osteopontin coated on either glass or plastic surfaces was mediated via the alpha v beta 3 integrin. Interestingly, the isolated cells bound to bone sialoprotein coated on plastic via the alpha v beta 3 integrin, but used a different integrin, alpha IIb beta 3, when the protein was coated on glass. It appears that bone sialoprotein when coated on glass and plastic, respectively, changes conformation, thereby altering the contact surface and subsequently the binding specificity. Alternatively, the protein contains two different binding sites, selectively exposed on glass or plastic as a result of different protein binding. The results demonstrate that bone sialoprotein contains domains, or can change conformation, such that it can interact with either the alpha IIb beta 3 or the alpha v beta 3 integrin. Whether the integrins were located on the multinucleated cells proper or on platelets bound to these cells could not be unequivocally concluded. The possible presence of platelets should, however, be considered when interpreting data from the isolated osteoclast system.

Acid Phosphatase↗
PubMed1996

Evolutionary relationship between human major histocompatibility complex HLA-DR haplotypes.

HLA-DR haplotypes of the human major histocompatibility complex are organized in five different groups. They can be identified based on the serological specificity expressed by the polymorphic DRB1 locus and by the presence of a characteristic set of DRB genes. The nucleotide sequences of introns 4 and 5 of the two DRB genes (DRB1(*)01 and DRB6(*)01 ) from a DR1 haplotype and the three DRB genes (DRB1(*)15, DRB6(*)15 , and DRB5(*)15 ), from a DR51 haplotype were determined. This study identified endogenous retroviral long terminal repeat elements (ERV9 LTR) located at identical positions in intron 5 of the DRB1 genes in both the DR1 and DR51 haplotypes. Phylogenetic analyses revealed a close evolutionary relationship between these two haplotypes. The DRB5 gene, unique for the DR51 haplotype, may have been lost by a recent gene deletion event creating the DR1 haplotype. A model for the evolution of the human DR haplotypes involving separate duplication and contraction events is presented.

Base Sequence↗
PubMed1996

The effects of lesions in the mesencephalic raphe systems on male rat sexual behavior and locomotor activity.

Lesions were produced in the median and the dorsal raphe nuclei of the rat, and the effects of these injuries on various behaviors were studied. The median raphe lesions had facilitatory effects on the male rat sexual behavior, as evidenced by a decrease in the number of intromissions prior to ejaculation, as well as shortening of the ejaculation latency and the postejaculatory interval. No effects were seen on the masculine sexual behavior after lesions in the dorsal raphe nucleus. The median raphe lesions drastically increased the locomotory activity whereas the dorsal raphe lesions did not. Treatment with FG5893, a 5-HT1A agonist/5-HT2A receptor antagonist, increased the locomotor activity of the dorsal-raphe-lesioned rats but did not affect the median-raphe-lesioned animals. These results suggest that the dorsal and the median raphe nuclei play different roles in the neural regulation of the sexual behavior and locomotor activity of the male rat. The median raphe nucleus appears to exert a modulatory influence upon these behaviors, which probably is mediated by serotonergic neural pathways.

Animals↗