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Biomedical subjects

G Andersson

Publications and source records attributed to G Andersson.

At least 55 records · Page 3Linked to original sources

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↗

Morphological and functional features of clasts in low phosphate, vitamin D-deficiency rickets.

Focusing on resorption processes, we have extended our previous studies on chondroclasts and osteoclasts in normally developing tissues, using a model of nutritionally induced vitamin D-deficiency rickets. To analyze the resorption process, we investigated the matrix-resorbing cells in this modified and poorly mineralized tissue regarding morphological features and expression of tartrate-resistant acid phosphatase (TRAP) at the subcellular level. Our goal was to test the hypotheses that initiation of resorption is impaired with unmineralized matrix, and that such alterations involve changes in the subcellullar distribution of TRAP, implicating a role for this enzyme in the resorption process. Our results reveal distinctly different morphological appearances of clast-like cells in rickets compared with normal osteoclasts and chondroclasts. Ordinary resorption structures of osteoclasts and chondroclasts at the cell-matrix border, i.e., ruffled borders and clear zones, are profoundly altered in favor of a less well-defined intermediate zone. TRAP distribution at the subcellullar level is also clearly different from that in osteoclasts and chondroclasts from normal rodents, with impaired secretion; consequently, the enzyme is unable to function in the matrix outside the ruffled border. Our ultrastructural observations demonstrate that in rickets, the clasts are incapable of degrading the poorly mineralized cartilage and bone efficiently. Rachitic clasts seem to be recruited to the matrix surface and interaction between cell and matrix is also initiated, but definitive resorption structures at the cell-matrix border are not normally developed. Whether resorption is inhibited by the mere lack of mineral or mineral-associated proteins, or by other mechanisms remains to be settled.

Acid Phosphatase↗

Cellular distribution of estrogen receptor beta in neonatal rat bone.

Estrogens affect bone metabolism, and ovariectomy of rats results in marked bone loss caused by stimulation of osteoclastic bone resorption. Estrogen receptors (ER) have been demonstrated in osteoblasts and bone marrow stromal cells, but their presence in osteoclasts is controversial. Until recently, only one type of ER (now renamed ERalpha) had been identified. After the discovery of a novel ER subtype (ERbeta), it became necessary to re-investigate the ER expression in human and rodent bone. In the present study we examined the expression of ER mRNA in neonatal rat bone. Expression of ER alpha and beta mRNA (RT-PCR) was evident in femurs of 3-week-old male and female rats. In situ hybridization histochemistry of femural bones with digoxigenin labelled riboprobes, as well as radioactively labeled riboprobes, revealed that ERbeta mRNA was predominantly expressed in osteoblasts covering the metaphyseal bone trabecular surface. The presence of ERbeta mRNA in osteoblasts of rat bone suggests that ERbeta is involved in the mechanism of action of estrogens in bone.

Animals↗

Tinnitus and cognitive interference: a stroop paradigm study.

The aim of this study was to investigate cognitive interference caused by tinnitus by means of a modified version of the Stroop color-word test. In a mixed-design study, the performances of tinnitus patients (n = 23) and healthy controls with normal hearing (n = 23) were compared on three versions of the Stroop test: the original version, a modified version including physical-threat words, and a tinnitus version for which tinnitus words (descriptors of tinnitus; e.g., peep) were derived empirically. Matched control conditions (words) were included for all three versions, yielding a total of six screens that were presented on a computer. Participants in the control group were matched with the patients for age and gender. Main dependent measures were performance on the Stroop tests in terms of total time for completing each test. Also included were the Tinnitus Questionnaire (TQ), the Beck Depression Inventory (BDI), the state version of the Spielberger Trait State Anxiety Inventory (STAI-S), and a subtest from the Wechsler Adult Intelligence Scale measuring verbal ability. Results showed that tinnitus patients performed significantly slower on all six test conditions. The classical Stroop color-word interference was replicated in both groups. Also, an effect for physical-threat words was found for both groups. Our expected tinnitus word interference could not be established. Patients scored significantly higher than controls on the BDI and the STAI, but these measures did not correlate with the Stroop results. In conclusion, the results indicate that tinnitus patients have impaired cognitive performance overall, as measured by these variations of the Stroop paradigm, but hearing impairment cannot be excluded as a possible confounder.

Adult↗

Regional cerebral blood flow during tinnitus: a PET case study with lidocaine and auditory stimulation.

Brain imaging of tinnitus has suggested central correlates of tinnitus perception. This study presents positron emission tomographic (PET) measurements of regional cerebral blood flow (rCBF) in a female tinnitus patient with bilateral left dominant tinnitus. Lidocaine infusion (75 mg during 5 min (0.2 mg/kg/min)) resulted in a 75% reduction of tinnitus and a temporary abolition of the dominant tinnitus in her left ear. Regional CBF was measured in four conditions: i) at rest while concentrating on tinnitus, ii) following maximum effect of lidocaine, iii) during sound stimulation, and iv) the following day at rest while concentrating on tinnitus. Subtraction analyses showed that tinnitus was associated with increased rCBF in the left parieto-temporal auditory cortex, including the primary and secondary auditory cortex with a focus in the parietal cortex (Brodmann areas 39, 41, 42, 21, 22). Activations were also found in right frontal paralimbic areas (Brodmann areas 47, 49 and 15). Sound stimulation resulted in bilateral activation of auditory areas. It is suggested that tinnitus is processed in primary, secondary and integrative auditory cortical areas. Tinnitus perception may involve areas related to auditory attention, while emotional processing relates to temporofrontal paralimbic areas.

Acoustic Stimulation↗

Effect of cooling suit treatment in patients with multiple sclerosis evaluated by evoked potentials.

The aim of the present study was to determine whether any significant alterations of evoked potentials could be detected after treatment of patients with multiple sclerosis with a cooling suit. All patients had previously experienced a positive effect of this treatment. Six patients were investigated with visual, sensory and motor evoked potentials and six further patients with only motor evoked potentials. All patients had relevant clinical lesions. The mean values for the group of patients were similar before and after cooling, but a few individuals showed a substantial improvement of motor evoked potentials after cooling, with increased amplitude and/or shortened central motor conduction time. There was also a weak, but significant, correlation between temperature decrements and the reduction of central motor conduction time. However, since the central motor conduction times of most patients were only slightly affected, this effect could explain only a small part of the beneficial effect of cooling. Effects on cognition and executive ability or improvement of spasticity may be of greater importance.

Adult↗

Time-series analysis of the relationship between dizziness and stress.

Ten individuals with dizziness participated in a longitudinal study on the relationship between stress and dizziness. The participants rated dizziness and stress on visual analogue scales twice daily for a period of 28 days (in all 56 data points). The ratings of stress included physical stress, mental stress, emotional stress, and the presence of stressful events. The data was analysed by means of time-series analysis (ARIMA), and the temporal associations investigated by lagged correlations. Results showed concurrent associations between dizziness and mental and emotional stress. However, individual differences were observed indicating complex and diverse patterns of association between different forms of stress and dizziness.

Adult↗

Oral mucous membrane flora in patients using saliva substitutes.

UNLABELLED: Salivary substitutes are sometimes valuable for elderly people and radiotherapy patients, and may be used indefinitely. It is possible that this change in the ecology may effect the oral flora. OBJECTIVE: To analyse the presence of micro-organisms on oral mucous membranes during use of saliva substitutes. DESIGN: Cross-over single-blind study. SETTING: Clinic for Maxillofacial Surgery, Malmö University Hospital and Department of Oral Microbiology, Malmö University. SUBJECTS: 19 patients with low salivary secretion who had been radiated for cancer in the head and neck region. INTERVENTION: Two saliva substitutes: linseed extract and a carboxymethyl cellulose preparation (Salinum and MAS-84) were used for 3 week periods. MEASUREMENTS: Microbial samples taken, processed and analysed. RESULTS: No differences were observed when comparing baseline values with the results after the saliva substitutes and no significant differences between the use of different agents. CONCLUSION: The study suggests that use of linseed extract and carboxymethyl cellulose preparation during periods of weeks does not influence flora commonly related to caries, periodontitis or infections in the oral mucous membranes.

Adult↗

A controlled trial of self-help treatment of recurrent headache conducted via the Internet.

The Internet can reach a large number of people at a low cost and offers the opportunity for 2-way communication. The present study was designed to evaluate the effects of applied relaxation and problem solving in the treatment of recurrent headache when implemented via the Internet and E-mail. A group of 102 headache sufferers were randomized to 2 conditions: a 6-week treatment condition or a waiting-list control. The dropout was proportionately large (56%), and at the end of the study there were 20 participants in the treatment condition and 25 participants in the control condition. Results showed statistically significant reductions in headache for the treated participants. In 50% of these, the reduction was clinically significant. The Internet has the potential to serve as a complement in the treatment of recurrent headache and deserves further study.

Adult↗

Longitudinal follow-up of occupational status in tinnitus patients.

In this study, the long-term outcome of tinnitus patients was studied in terms of changes in occupational status from admission to follow-up for an average duration of 5 years. A consecutive series of 189 tinnitus patients seen between the years 1988 and 1995 were sent a postal questionnaire booklet; 146 provided usable responses (a 77% response rate). Results showed a significant change in occupational status, which was explained partly by retirement because of old age. Few were unemployed at follow-up, and relatively few were on sick leave. These data suggest that tinnitus patients may be less of a demand for the sickness benefit system in Sweden, but it may reflect also that tinnitus is not accepted as a cause for sick absenteeism.

Adult↗

Tartrate-resistant purple acid phosphatase is synthesized as a latent proenzyme and activated by cysteine proteinases.

Purple acid phosphatases (PAPs) are binuclear acid metallohydrolases also referred to as tartrate-resistant acid phosphatases (TRAPs) or type 5 acid phosphatases. The cDNA sequences of TRAP/PAP enzymes from different species and organs indicate that these enzymes are translated as monomeric polypeptides of approx. 35 kDa, contrasting with the predominantly two-subunit structure observed in purified enzyme preparations. In the present study we have compared certain structural and enzyme-kinetic properties of recombinant rat PAP (monomeric) with those of the native rat bone TRAP/PAP enzyme (two-subunit), and examined effects on these parameters by cleaving the monomeric recombinant PAP with the serine proteinase trypsin or the cysteine proteinases papain or cathepsin B. Cleavage with trypsin resulted in a moderate activation of the recombinant enzyme and shifted the pH optimum to a slightly more basic value (5.0-5.5). Cleavage with papain resulted in complete activation and conferred similar properties to those of the bone PAP variant with regard to pH optimum (5.5-6.0) and sensitivity to reducing agents, as well as in the sizes of the subunits. Substrate specificity studies showed that the two-subunit bone PAP was considerably more active than the monomeric recombinant rat PAP towards a variety of serine-, threonine- and tyrosine-phosphorylated substrates. Of these substrates, bovine milk osteopontin seemed to be the most readily dephosphorylated substrate. In conclusion, the results suggest that the monomeric form of PAP represent a latent proenzyme with low enzymic activity towards both tyrosine- and serine/threonine-containing phosphorylated substrates. Besides being implicated in the catabolism of the extracellular matrix, members of the cysteine proteinase family might also exert a regulatory role in degradative processes involving the PAP enzymes by converting the newly synthesized PAPs to enzymically active and microenvironmentally regulated species.

Acid Phosphatase↗

Crystal structure of a mammalian purple acid phosphatase.

Tartrate-resistant acid phosphatase (TRAP) is a mammalian di-iron- containing enzyme that belongs to the family of purple acid phosphatases (PAP). It is highly expressed in a limited number of tissues, predominantly in bone-resorbing osteoclasts and in macrophages of spleen. We have determined the crystal structure of rat TRAP in complex with a phosphate ion to 2.7 A resolution. The fold resembles that of the catalytic domain of kidney bean purple acid phosphatase (KBPAP), although the sequence similarity is limited to the active site residues. A surface loop near the active site is absent due to proteolysis, leaving the active-site easily accessible from the surrounding solvent. This, we believe, gives a structural explanation for the observed proteolytic activation of TRAP. The current structure was determined at a relatively high pH and without any external reducing agents. It is likely that it represents an oxidized and therefore catalytically inactive form of the enzyme.

Acid Phosphatase↗

Altered open-field behavior in experimental chronic hepatic encephalopathy after single venlafaxine and citalopram challenges.

RATIONALE: Latent or manifest chronic hepatic encephalopathy (HE) symptomatology often includes affective symptoms. It is therefore warranted to investigate the functional outcome of novel antidepressants when chronic HE prevails. OBJECTIVE: Portacaval shunt (PCS) in rats is a widely used experimental model for chronic HE, a neuropsychiatric syndrome accompanying liver dysfunction. HE is believed to arise from a primary alteration in neurotransmission in the CNS. PCS has been reported to increase the metabolism of serotonin in the brain, and thus the central serotonin nerve of PCS rats may contain more serotonin than normal. However, the functional relevance of this serotonergic alteration in terms of affecting behavioral performance of PCS rats has been only rarely studied. METHODS: Locomotor and rearing activities were recorded in PCS and sham-operated control rats. A single subcutaneous challenge with saline versus either the mixed serotonin/noradrenaline reuptake inhibitor venlafaxine (10 mg x kg(-1)) or the selective serotonin reuptake inhibitor citalopram (5 mg x kg(-1)) were performed. RESULTS: The PCS-saline injected rats showed reduced locomotor and rearing activity compared with sham-saline treated rats. While no significant differences could be observed following the venlafaxine challenge to controls, the PCS-venlafaxine challenged rats displayed reduced behavioral activity as compared to PCS-saline treated rats. The PCS-citalopram rats, however, displayed increased activity compared with the PCS-saline rats while, again, no effect of the citalopram challenge to controls was found. CONCLUSIONS: The present study show altered but opposite behavior in PCS rats, when challenged with either venlafaxine or citalopram, compared to PCS control rats. These findings therefore support the contention that caution should be advocated when CNS monoamine active drugs are used in liver-impaired subjects until better delineation of the combined pharmacodynamic and pharmacokinetic outcome for each such drug in this condition has been made.

Analysis of Variance↗