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Biomedical subjects

M Nilsson

Publications and source records attributed to M Nilsson.

At least 217 records · Page 12Linked to original sources
PubMed1992

Polarized efflux of iodide in porcine thyrocytes occurs via a cAMP-regulated iodide channel in the apical plasma membrane.

The intracellular regulation of thyrotropin-stimulated iodide efflux was studied in polarized porcine thyrocytes grown as a continuous, tight monolayer in bicameral culture chambers. From a previous study using this system we know that thyrotropin rapidly increases iodide efflux in the apical but not basal direction of the polarized epithelium. [125I]-iodide efflux in apical direction was stimulated by thyrotropin in a concentration-dependent manner (1-10 U/l), whereas efflux in basal direction was unchanged at any thyrotropin dose. Thyrotropin-induced elevation of intracellular cAMP showed a corresponding concentration dependence. The selective stimulation of apical efflux by thyrotropin was evident also when re-uptake of iodide released in basal direction was blocked by perchlorate. The effect of thyrotropin on apical efflux was mimicked by 8-bromo-cAMP and forskolin, whereas agents known to activate the Ca2+/phosphatidylinositol cascade (epidermal growth factor) and protein kinase C (phorbol ester) or increase cytosolic [Ca2+] (A23187) were inactive. We conclude that the selective stimulation by thyrotropin of apical iodide efflux, corresponding to efflux in luminal direction in intact follicles, occurs via cAMP-regulated iodide channels present in the apical domain of the plasma membrane.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1992

Subtraction radiography of interradicular bone lesions.

Subtraction and conventional radiography were evaluated for their diagnostic potential to assess interradicular bone lesions in the mandibular premolar region. Both conventional radiographs and subtraction images were interpreted by 10 observers. The receiver-operating characteristic (ROC) technique was used to compare the two techniques. The diagnostic validity was higher for the subtraction technique, both for lesions confined to cancellous bone and for lesions including the cortical bone, than for the conventional technique. For bone defects confined to cancellous bone the diagnostic accuracy was lower than those reported from periapical bone lesions irrespective of whether subtraction or conventional radiography was used. We conclude that subtraction radiography improves the detectability of bone lesions, shallow ones in particular. Lesions in the interradicular bone are more difficult to detect than those in the periapical bone.

Alveolar Process↗
PubMed1992

The microwave oven in temporal bone research.

The microwave oven has recently been introduced in morphological research. It can be used for virtually all procedures in histological processing; fixation, dehydration, embedding, staining, immunotechniques, and the techniques used for electron microscopy. Here we report that the microwave oven histoprocedures also have several advantages in temporal bone research on animals. The microwave oven has been tested for (i) fixation, (ii) decalcification, (ii) staining of semithin plastic sections. The microwave oven procedures are time-saving and results in an excellent preservation of the tissues. The microwave histoprocessing should also be applicable to temporal bone research in human.

Animals↗
PubMed1991

Adrenergic and 5-HT2 receptors on the same astroglial cell. A microspectrofluorimetric study on cytosolic Ca2+ responses in single cells in primary culture.

Noradrenaline (NA) or 5-hydroxytryptamine (5-HT) evoked cytosolic Ca2+ mobilization in single type 1 astrocytes in primary culture from the cerebral cortex of newborn rat. The Ca2+ indicator dye fura-2/AM was used in a microspectrofluorimetric system to visualize fluctuations in the intracellular Ca2+ concentration. Activation of the adrenergic receptors alpha 1, alpha 2 and beta, or activation of the 5-HT2 receptors elicited different responses of Ca2+ mobilization with different types of Ca2+ spikes or oscillations. Principally, 4 different types of Ca2+ responses could be obtained: a sharp spike, which declined back to baseline; an initial sharp spike, which declined to a smaller but sustained Ca2+ elevation; an initial sharp spike which declined and showed low amplitude oscillations; and a sharp spike which declined back to baseline with baseline oscillations. Applications of the alpha 2 adrenoceptor agonist clonidine to individual astroglial cells evoked Ca2+ transients mostly in young cultures (cultivated for 7-10 days), while applications of the alpha 1 adrenoceptor agonist phenylephrine evoked Ca2+ transients mostly in older cultures (17-21 days of cultivation). Applications of the beta adrenoceptor agonist isoproterenol evoked Ca2+ transients in both young and older cultures, however, more frequent in older cultures. The alpha 2 and beta receptor responses were dependent on external Ca2+ levels. The NA-evoked Ca2+ responses were seen in cultivated cells at all ages, but were more frequent in older cultures. Approximately 50% of the astroglial cells in 8 day old cultures responded to 5-HT with a cytosolic Ca2+ mobilization and 80% of the cells in 21 day old cultures responded.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

[Effect of alfa-2b interferon on prognostic parameters and clinical events in HIV positive patients in the LAS/ARC stage].

A number of in vivo and in vitro results suggest that interferons have an antiretroviral effect on HIV. To check this, 15 HIV-positive patients who had no full-blown AIDS, were treated with recombinant interferon alpha 2b (5 mill. IU s. c. three times a week) over a period of six months. Twelve to 16 weeks after the initiation of treatment, an increase in CD 4 lymphocytes (+16%), NK cells (+16%), lymphocytes stimulation by con A (+ 176%), neopterin (+66%), and beta-2-microglobulin (+19%) was observed. By the end of the study, all these parameters had slightly decreased again. In all patients with CD4 lymphocytes greater than 0.2 c/nl, we observed a decrease in p24 antigen levels, but in patients with CD4 lymphocytes less than 0.2 c/nl, an increase. It would thus seem that any antiretroviral effect of IFN (as shown by the p24 antigen parameter) is more pronounced in patients with superior immune parameters.

AIDS-Related Complex↗
PubMed1991

Analysis of polyomavirus enhancer-effect on DNA replication and early gene expression.

The polyomavirus enhancer is located adjacent to the origin of DNA replication and the transcriptional promoters. It has a cis-acting essential function in the initiation of both viral DNA synthesis and early transcription. The enhancer is activated by the binding of protein factors to specific sites in DNA. Mutants with deletions of the A- or the B-segment of the enhancer were constructed. In mouse 3T6 cells, the transcription of the viral early region was significantly decreased by deletion of the A-segment, but not by deletion of the B-segment. In contrast, the two deletions had a similar, moderately negative effect on viral DNA synthesis. However, the presence of DNA with a wild-type enhancer in doubly transfected cells resulted in very strong interference with the replication, but not with the transcription, of deletion mutant DNA. DNA of the deletion mutants were subjected to site-directed mutagenesis of the remaining enhancer segment. Three non-viable mutants were isolated. All three had base-pair changes in the A-segment affecting immediately adjacent binding sites of cellular protein factors. The mutants had lost the enhancer activity on the early promoter, but only one of them with multiple base substitutions had lost the capacity of DNA replication. Together, the results suggest that different aspects of enhancer function determine the activity in initiation of transcription and replication.

Amino Acid Sequence↗
PubMed1991

Analogues of parathyroid hormone modified at positions 3 and 6. Effects on receptor binding and activation of adenylyl cyclase in kidney and bone.

Predictive and spectroscopic methods were used to develop a model of the structures of the 1-34 peptides of parathyroid hormone (PTH) and the PTH-related protein (PTHrP). Circular dichroism (CD) studies of bovine PTH-(1-34) and human PTHrP-(1-34)amide in the presence of trifluoroethanol suggest the presence of 24-26 alpha-helical residues. For both peptides, interactions between amino- and carboxyl-region alpha-helices are predicted to result in a hydrophobic core with externally facing hydrophilic residues that include probable determinants of receptor binding and activation. Two such residues, Ser3 and Gln6, are conserved in all known members of the PTH/PTHrP family. We have synthesized 13 novel analogues of bovine PTH-(1-34) monosubstituted at positions 3 and 6 and have determined their biological activities in renal and bone cell radioreceptor and adenylyl cyclase assays. Position 3 analogues displayed biological activity that was reduced in direct proportion to the volume of the substituent side-chain. Position 6 analogues also displayed reduced biological activity, but no simple correlation with side-chain volume or hydrophobicity was evident. The analogues fully displaced labeled PTH from binding sites in renal membranes and bone cells, but [Phe3]bPTH-(1-34), [Tyr3]bPTH-(1-34), [Phe6] bPTH-(1-34), and [Ser6]bPTH-(1-34) were only partial agonists in one or both adenylyl cyclase assays. Of these, [Phe3]bPTH-(1-34) and [Phe6]bPTH-(1-34) were tested for antagonist activity and were found to inhibit the activation of adenylyl cyclase in response to bPTH-(1-34) or hPTHrP-(1-34)amide. These results indicate that positions 3 and 6 contribute important determinants of PTH receptor binding and activation. Modification at these positions represents a novel approach to the development of antagonists of PTH action.

Adenylyl Cyclases↗
PubMed1991

Post-antibiotic effect of beta-lactam antibiotics on gram-negative bacteria in relation to morphology, initial killing and MIC.

The in vitro post-antibiotic effect (PAE) of cefepime, cefotaxime, ceftazidime and imipenem on reference strains of Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas aeruginosa and Serratia marcescens were evaluated by bioluminescence assay of bacterial ATP. In parallel with the PAE determination, initial killing and morphology studies were performed. Imipenem produced greater than 1 h PAE on all strains tested, cefepime and cefotaxime on four strains and ceftazidime only on one of the strains tested. The length of the PAE on different strains did not correlate in the same way to MIC. Imipenem induced greater than 1 h PAE at 1/4-2 MIC while the cephalosporins caused greater than 1 h PAE at 4-256 x MIC. A PAE exceeding 1.2h was seen concomitantly with spheroplasts but there was not necessarily strong (greater than or equal to 99%) initial killing at the same time. The PAE duration at greater than or equal to 99% initial killing varied between 2.0 h and 5.0 h. When the cephalosporins produced less than 1 h PAEs, this was seen concomitantly with production on filaments and weak initial killing. The bioluminescence method was not jeopardized by filament formation and no negative PAE was found in contrast to the viable count method. The study showed that neither a certain multiple of MIC, the presence of spheroplasts nor strong initial killing can predict the length of PAE for beta-lactam antibiotics on gram-negative bacteria.

Anti-Bacterial Agents↗
PubMed1991

Wish to transfer to other jobs among long-term care workers.

This study is based on questionnaires that were sent to the homes of health care personnel working in geriatric care (N = 583) and acute care (N = 328). The purpose was to investigate differences between these groups of personnel regarding job assignment, intention to transfer to another job, attitudes towards demented patients, and the experience of burnout. The results showed that more persons working in acute care were self-assigned to their jobs than those working in geriatric care. More persons in geriatric care stated a wish to transfer to another job in the health care field than those in acute care. The personnel who constantly work with demented patients showed the most positive attitudes towards this group of patients. A larger proportion of personnel with high burnout scores wanted to transfer to another job, compared to those with low burnout scores.

Aged↗
PubMed1991

Staff burnout in dementia care--relations to empathy and attitudes.

Sixty nursing staff in geriatric and psychogeriatric care (RNs, LPNs and nurse's aides) were selected to be studied on two occasions with an interval of one year regarding the relationships between their experience of burnout, empathy and attitudes towards demented patients. A semistructured interview was performed on the second occasion to learn more about their work experience and to relate the ratings of burnout, empathy and attitudes to their experience at work. The staff's experience of burnout changed from a mean score of 2.7 in 1987 to 2.5 in 1988. Their empathic ability was moderately high and increased from 398 (m) in (1987) to 450 (m) in 1988. The attitudes of staff remained unchanged from 1987 to 1988 and no differences were found regarding the staff's age, place of work or time at present place of work. As for the staff's empathy, there was no difference with respect to sex, category of staff or place of work. RN's showed the most positive attitudes towards demented patients both in 1987 and 1988 and differed compared to the nurse's aides and LPN's. Burnout correlated with lower empathy and less positive attitudes in the staff. Regression analysis showed that 'experience of feed-back at work' and 'time spent at present place of work' were the most important factors when explaining burnout among the staff. Staff with high empathy experienced "a close contact with the patient" as the most stimulating factor at work while staff with low empathy experienced "improvement of the patient's health" and "contact with colleagues" as the most stimulating factors. The importance of counteracting burnout in the care of demented patients is stressed.

Adolescent↗
PubMed1991

Heterogeneity among astroglial cells with respect to 5HT-evoked cytosolic Ca2+ responses. A microspectrofluorimetric study on single cells in primary culture.

The effect of 5-hydroxytryptamine (5HT) on cytoplasmic Ca2+ concentration was examined at the single cell level in astroglial enriched primary cultures from newborn rat cerebral cortex. Type 1 astroglial cells were identified and the Ca2+ indicator dye fura 2/AM was used in a microspectrofluorimetric system. Pharmacological studies indicated that the Ca2+ responses were mediated by 5HT2 receptors. Four different patterns of 5HT evoked cytosolic Ca2+ responses were identified including two different types of spike patterns and two types of Ca2+ oscillations (low amplitude and base-line spiking behaviour). In addition, cells with spontaneous Ca2+ oscillations were of two types, those responding to 5HT and those not responding to 5HT. The different responses were identified already on day 7 in culture and were followed up to day 21 with a concomitant increase in the number of responding cells, although the response patterns did not differ during culture. The triggering 5HT concentration was 1 microM. The results suggest that subpopulations of astrocytes exist with respect to 5HT2-evoked cytosolic Ca2+ mobilization.

Animals↗
PubMed1991

Synergistic post-antibiotic effect of amikacin and beta-lactam antibiotics on Enterococcus faecalis.

The in-vitro post-antibiotic effect (PAE) of amikacin alone and in combination with ceftazidime, ceftriaxone and piperacillin was studied for two strains of Enterococcus faecalis using a bioluminescent assay of bacterial ATP. The two strains of E. faecalis were resistant to amikacin, ceftazidime and ceftriaxone but sensitive to piperacillin. The bacterial cultures were incubated with the beta-lactam antibiotics for 1 h and concentrations of amikacin between 2-64 mg/l were then added. Thereafter, incubation continued with the combinations for one more hour. After dilution, regrowth was monitored by measuring bacterial ATP every hour. Increasing concentrations of amikacin (2-64 mg/l), ceftazidime (8-32 mg/l) and ceftriaxone (32-128 mg/l) resulted in little or no PAE (0-0.3 h) on these strains. PAEs of 0.5 to 1.6 h resulted from exposure to piperacillin (4-32 mg/l). In combination amikacin and piperacillin increased the PAE to 5.5 h. A synergistic PAE was also seen when the enterococci were exposed to amikacin combined with ceftazidime or ceftriaxone in concentrations close to the MICs of the latter antibiotics.

Amikacin↗
PubMed1991

Synergic post-antibiotic effect of amikacin in combination with beta-lactam antibiotics on gram-negative bacteria.

The post-antibiotic effect (PAE) of amikacin alone and in combination with ceftazidime, ceftriaxone and piperacillin was studied for two strains each of Pseudomonas aeruginosa and Serratia marcescens using a bioluminescent assay of bacterial ATP. Two models were used for combining beta-lactam antibiotics and amikacin: in one model the cultures were incubated with 32 mg/L of ceftazidime, 128 mg/L of ceftriaxone or 32 mg/L of piperacillin for 1 h. Different concentrations of amikacin (0.5-64 mg/L) were then added. Incubation of the combinations continued for one more hour. The antibiotics were eliminated by dilution. In the second model tested, one strain of S. marcescens was simultaneously exposed to amikacin and a beta-lactam antibiotic for 2 h. The PAEs produced by the drugs in combination were longer than the sum of the individual effects of the drugs when they were used alone. Results were equally good with both models. A synergic PAE was also found with amikacin concentrations close to the MIC in combination with low concentrations of ceftazidime, ceftriaxone and piperacillin.

Amikacin↗
PubMed1991

Enhancer effect of bovine papillomavirus E2 protein in replication of polyomavirus DNA.

In polyomavirus, both transcription from the early promoter and viral DNA replication initiated at the origin of DNA replication is controlled by binding of proteins to the enhancer region. We have developed a simple model system to study the role of an enhancer binding factor in the initiation of polyomavirus DNA replication. A reporter plasmid was constructed which has the enhancer region replaced by two binding sites for a transcription factor, the E2 protein encoded by bovine papillomavirus type 1. Co-transfection of COP 5 cells which express polyomavirus large T-antigen, with the reporter plasmid and an E2 expression plasmid, resulted in E2-dependent stimulation of replication of the reporter plasmid. The activity of several E2 mutants was also analysed. Mutant proteins with decreased activity in transcriptional trans-activation, resulting from impaired DNA binding or other defects, were found to have quantitatively similar reductions of activity in viral DNA replication. The results suggest that the E2 protein activates transcription and polyomavirus DNA replication by similar mechanism(s).

Antigens, Polyomavirus Transforming↗
PubMed1991

Relationship between 99Tcm-MDP uptake and bone mineral density in patients with prostatic carcinoma.

Seventeen men with prostatic carcinoma were investigated with quantitative bone scintigraphy and quantitative computed X-ray tomography before orchiectomy and up to 6 months after this operation. The uptake of 99Tcm-labelled methylene disphosphonate (99Tcm-MDP) and bone mineral density (BMD) were determined for each vertebra from Th10 to L4. Ten patients had normal scintigrams. No change in MDP uptake or BMD was seen after 6 months in these patients. Of the seven patients with abnormal scintigrams, one patient had a clinical sign of progression with an increase in both MDP uptake and BMD. The remaining six patients showed stable or improved clinical status. For their abnormal vertebrae a decrease in MDP uptake was seen, while BMD varied in different ways after 6 months. For the normal vertebrae in these patients with metastatic involvement, no change in MDP uptake was seen. However, the BMD values showed a decrease, indicating a generalized increase in bone resorption at sites distant from the metastases.

Aged↗
PubMed1991

Thyrocyte migration and histiotypic follicle regeneration are promoted by epidermal growth factor in primary culture of thyroid follicles in collagen gel.

The effect of epidermal growth factor (EGF) on the morphology of porcine thyroid follicles cultured in collagen gel was studied by light and electron microscopy. Treatment with EGF (10 ng/ml) for 1-4 days induced a progressive migration of thyrocytes radiating from the mother follicles into the collagen lattice. Migrating cells were often connected with junctional complexes, thus forming small follicles containing microlumina, in which the limiting portion of the plasma membrane expressed microvilli. Autoradiography of [3H]thymidine incorporation in EGF-treated cultures showed that more than 80% of nuclei in mother follicles and migrating cells were labeled after 4 days. TSH (2 mU/ml) given simultaneously with EGF did not influence the effect of EGF on multiplication, migration, and formation of microfollicles. TSH given for 12 h after 4 days of exposure to EGF was able to induce luminal dilation of mother follicles, but caused no change in the appearance of microlumina. It is concluded that thyrocytes in collagen gel retain epithelial characteristics during prolonged stimulation with EGF, in spite of a migrating response. The whole sequence of events, starting with the intact follicle, i.e. multiplication, migration of thyrocytes, and formation of new follicles, could, thus, be visualized to occur in response to a single mitogen, EGF. EGF might be involved in the generation of new follicles in the intact gland.

Animals↗
PubMed1991

Non-polarized cell surface expression of HLA-A,B,C and HLA-DR antigens in Graves' thyroid follicle cells.

The intrathyroidal distribution and cell surface location of HLA-A,B,C and HLA-DR antigens was studied in polarized thyroid follicle cells from Graves' (n = 11) and normal (n = 3) thyroid tissue, using light and electron microscopy. Cryosections and isolated, open follicle segments were incubated with monoclonal antibodies against HLA-A,B,C and HLA-DR antigens and with patient sera containing autoantibodies against the microsomal antigen/thyroperoxidase. Immunoreactivity for HLA-A,B,C and HLA-DR on isolated thyroid follicle cells was frequently detected in Graves' disease, but absent in normal glands. There was a large variation in the immunolabelling between follicles as well as between different glands. Both HLA-A,B,C and HLA-DR immunoreactivity were detected on the apical and the basal surface of the follicle cells. Microsomal antigen/thyroperoxidase immunoreactivity was restricted to the apical cell surface. In contrast to normal tissue, HLA-DR positive cells with a dendritic or macrophage-like morphology were frequent in Graves' tissue. These cells adhered directly to the basal surface of isolated follicle segments. We conclude that HLA antigens are, unlike thyroid-specific plasma membrane constituents, expressed in a non-polarized manner at the surface of the follicular epithelium. These observations might have implications on the immune recognition of thyroidal autoantigens in Graves' disease.

Adult↗