Biomedical subjects

M Nilsson

Publications and source records attributed to M Nilsson.

At least 55 records · Page 3Linked to original sources

PubMed2002

Molecular cytogenetic mapping of recurrent chromosomal breakpoints in tenosynovial giant cell tumors.

Tenosynovial giant cell tumor (TGCT) is the most common benign tumor of synovium and tendon sheath. Cytogenetic data indicate that 1p11-13 is the region most frequently involved in structural rearrangements. With the aim of eventually identifying the genes associated with TGCT development, we have investigated 1p11-13 breakpoints using fluorescence in situ hybridization (FISH) analysis, with a panel of yeast artificial chromosome (YAC) probes covering 1p11-21. Twenty-six tumors were analyzed by G-banding, and 24 of these showed a breakpoint in 1p11-13. The cytogenetic findings add to previous observations that, among a variety of translocations involving 1p11-13, chromosome 2 is the most common translocation partner, with a breakpoint in 2q35-37. This aberration was found in eight cases. Other recurrent translocation partners, found in two or three cases, were 5q22-31, 11q11-12, and 8q21-22. Material from 21 tumors was available for FISH analysis, which revealed that the breakpoints clustered to one region spanned by two YAC probes, 914F6 and 885F12 located in 1p13.2, in 18 cases. Bacterial artificial chromosome probes were used to map the recurrent breakpoint on chromosome 2. In four of seven cases there was a breakpoint within the sequence covered by probe 260J21, where the RDC1 gene is located, a gene reported to fuse with HMGIC in lipomas with a 2;12 translocation.

Adolescent↗

PubMed2002

Monitoring the setting of calcium-based bone cements using pulse-echo ultrasound.

We present a new technique, based on pulse-echo ultrasound, for monitoring the entire setting process of injectable bone cement. This research has been motivated by the lack of satisfying standards. The main problem with existing standards is the subjectivity, which leads to poor reproducibility. Because of this the results are not comparable between different research groups. A strong advantage with the proposed technique is that if low-intensity ultrasound is used, it provides a non-destructive analysis method. Once the cement paste has been applied to the measurement cell, no manipulation is needed throughout the entire setting process. The problem of the ultrasound affecting the setting of certain cement materials has been investigated, and solutions are discussed. The propagation of ultrasound is temperature-dependent, and therefore a technique for automatic compensation for temperature variations is discussed briefly. The testing was performed on alpha-calcium sulfate hemihydrate (CSH) and mixtures of CSH and alpha-tricalcium phosphate (alpha-TCP). The results show that the acoustic properties of the cement are strongly correlated with the setting time, the density, and the adiabatic bulk modulus. The measured initial and final setting times agree well with the Gillmore needles standard. An important difference compared to the standards, is that the technique presented here allows the user to follow the entire setting process on-line.

Journal Article↗

PubMed2002

Body mass and reflux oesophagitis: an oestrogen-dependent association?

BACKGROUND: There is widespread belief that obesity is associated with gastro-oesophageal reflux disease, but the scientific evidence is weak and contradictory. Our aim is to evaluate the relation between body mass and reflux oesophagitis. METHODS: A population-based case-control study of endoscopically verified case subjects with reflux oesophagitis, and of randomly selected, control subjects matched for age, sex and area of residence. Subjects were classified within three body mass index (BMI) categories: BMI <25 (normal in the WHO classification), BMI 25-30 (overweight) and BMI >30 (obese). Odds ratios (OR) with 95% confidence intervals (CI) were the measures of association. RESULTS: Of 179 matched case-control pairs included in the study, 71 pairs were female. In males, no association between overweight and/or obesity and the risk of reflux oesophagitis was found. In females, there was a strong association between increasing BMI and the risk of reflux oesophagitis, with an OR of 2.9 (95% CI: 1.1-7.6) in the BMI 25-30 group and 14.6 (95% CI: 2.6-80.9) in the BMI >30 group (P value for trend = 0.0007). The association between obesity and oesophagitis was further strengthened by the use of oestrogen replacement medication. CONCLUSIONS: The study discloses a strong and dose-dependent association between body mass and reflux oesophagitis in women as opposed to no association among men. This association might be caused by increased oestrogen activity in overweight and obese females.

Adult↗

PubMed2001

Alpha 1-adrenergic modulation of metabotropic glutamate receptor-induced calcium oscillations and glutamate release in astrocytes.

Astrocytic responses to activation of metabotropic glutamate receptors group I (mGluRs I) and alpha(1)-adrenoreceptors in cultured cells have been assessed using spectral analyzes and calcium imaging. Concentration-dependent changes were observed after stimulation with the mGluR I agonist (S)-3,5-dihydroxyphenylglycine (DHPG). These responses changed from a regular low frequency signal with sharp peaks at 1 microm to a pronounced stage of irregularity at 10 microm. After stimulation with 100 microm the signal was again homogenous in shape and regularity but occurred at a higher frequency. In contrast, the spectral properties after stimulation with the alpha(1)-adrenoreceptor agonist phenylephrine, exhibited considerable variation for all investigated concentrations. DHPG-induced increases in [Ca(2+)](i) were also associated with astroglial glutamate release, whereas no release was observed after noradrenergic stimulation. Both DHPG-mediated calcium signaling and glutamate release were inhibited by preincubation with 10 or 100 microm phenylephrine. Collectively, the present investigation provides new information about the spatial-temporal characteristics of astroglial intracellular calcium responses and demonstrates distinct differences between noradrenergic and glutamatergic receptors regarding intracellular calcium signaling and coupling to glutamate release. The noradrenergic modulation of DHPG-induced responses indicates that intracellular astroglial processes can be regulated in a bi-directional feedback loop between closely connected astrocytes and neurons in the central nervous system.

Animals↗

PubMed2001

The mitochondrial genomes of the iguana (Iguana iguana) and the caiman (Caiman crocodylus): implications for amniote phylogeny.

The complete mitochondrial genomes of two reptiles, the common iguana (Iguana iguana) and the caiman (Caiman crocodylus), were sequenced in order to investigate phylogenetic questions of tetrapod evolution. The addition of the two species allows analysis of reptilian relationships using data sets other than those including only fast-evolving species. The crocodilian mitochondrial genomes seem to have evolved generally at a higher rate than those of other vertebrates. Phylogenetic analyses of 2889 amino-acid sites from 35 mitochondrial genomes supported the bird-crocodile relationship, lending no support to the Haematotherma hypothesis (with birds and mammals representing sister groups). The analyses corroborated the view that turtles are at the base of the bird-crocodile branch. This position of the turtles makes Diapsida paraphyletic. The origin of the squamates was estimated at 294 million years (Myr) ago and that of the turtles at 278 Myr ago. Phylogenetic analysis of mammalian relationships using the additional outgroups corroborated the Marsupionta hypothesis, which joins the monotremes and the marsupials to the exclusion of the eutherians.

Alligators and Crocodiles↗

PubMed2001

RNA-templated DNA ligation for transcript analysis.

Ligase-mediated gene detection has proven valuable for detection and precise distinction of DNA sequence variants. We have recently shown that T4 DNA ligase can also be used to distinguish single nucleotide variants of RNA sequences. Here we describe parameters that influence RNA-templated DNA ligation by T4 DNA ligase. The reaction proceeds much more slowly, requiring more enzyme, compared to ligation of the same oligonucleotides hybridized to the corresponding DNA sequence. The reaction is inhibited at high concentrations of ATP and NaCl and both magnesium and manganese ions can support the reaction. We define reaction conditions where 80% of RNA target molecules can template a diagnostic ligation reaction. Ligase-mediated RNA detection should provide a useful mechanism for sensitive and accurate detection and distinction of RNA sequence variants.

Bacteriophage T4↗

PubMed2001

Vitamin B12 in primary health care and geriatrics--attitudes, knowledge and competence.

OBJECTIVES: The objective of the study was to test attitudes, knowledge and competence of Swedish general practitioners and geriatricians concerning B12-associated problems in 1998. METHODS: Postal questionnaires were sent to a random sample of 485 GPs and a total sample of 613 geriatricians. The response rates were 70% in the GP group and 69% in the geriatrician group. The questionnaire contained 24 statements to be evaluated by a visuo-analogue scale. RESULTS: There were small numerical differences between the two physician groups. The geriatricians were more aware of risk groups for B12 deficiency. GPs were less categorical concerning low hit rate in the laboratory testing of clinical conclusions. There were statistical differences in both directions for statements on pitfalls in laboratory diagnostics. GPs were somewhat less prone to give risk groups prophylactic B12 therapy. CONCLUSIONS: GPs and geriatricians appeared to be familiar with the current debate on B12-associated problems, suggesting that health care quality will be unaffected by patient transfer from hospital care to primary health care.

Aged↗

PubMed2001

Junctional proteins and Ca2+ transport in the rat odontoblast-like cell line MRPC-1.

A transcellular bulk flow of Ca2+ ions through the odontoblast layer is of central importance during dentinogenesis. For this, specialized mechanisms may exist, which by a concerted action, gate Ca2+ into the proximal end of the cells and extrude the ions towards the mineralization front. To elucidate these mechanisms, an in vitro model would be useful. Mature odontoblasts are, however, post-mitotic cells and cannot be propagated in cell culture. The aim of the present study was, therefore, to characterize the odontoblast-like rat cell line MRPC-1(1) with regard to transcellular Ca2+ transport, barrier function, and intercellular junctions when cultured on membranes in Transwell chambers. The MRPC-1 cells grew as epithelial-like cells in a continuous bilayer separated by a thin collagenous matrix and with intercellular junctional complexes. They exhibited properties of a low-resistance epithelium, maintained a Ca(2+)-dependent diffusion barrier, and exhibited a functional diversity between the two cell layers. MRPC-1 cells expressed ZO-1, occludin, E-, and N-cadherins in addition to alpha-, beta-, gamma- and p120cat catenins, thereby demonstrating some traits in common with, but also differences from, epithelial cells and major differences from fibroblasts. The transcellular Ca2+ flux was inhibitable by nifedipine unidirectionally, giving evidence for an active intracellular Ca2+ transport through voltage-gated channels of the L-type. Similarities with native odontoblasts indicate that MRPC-1 cells may be useful for in vitro studies of transcellular Ca2+ transport mechanisms of importance for the calcification process.

Animals↗

PubMed2001

A behavioural pattern analysis of hypoglutamatergic mice--effects of four different antipsychotic agents.

In a hypoglutamatergic rodent model, we have observed certain behaviours that might have relevance for the cognitive impairments seen in autism and schizophrenia. Thus, hypoglutamatergic mice show defective habituation, impaired attention, a meagre behavioural repertoire and a general behavioural primitivization. The aim of the present study was to characterise and quantify changes in movement pattern in mice rendered hypoglutamatergic by means of MK-801 treatment, using an automated video tracking system. Further, the effects of four different antipsychotic drugs, the classical neuroleptic haloperidol, the atypical antipsychotic clozapine, the DA D2/5-HT2A antagonist risperidone and the selective 5-HT2A-receptor antagonist M100907, were compared with respect to effects on NMDA antagonist-induced movement pattern alterations. We found that each receptor antagonist had a unique effect on the MK-801-induced behavioural primitivization. Haloperidol was unable to affect the monotonous behaviour induced by MK-801, while risperidone, clozapine and M100907 produced movement patterns of high intricacy.

Animals↗

PubMed2001

Activation of beta-adrenoceptors opens calcium-activated potassium channels in astroglial cells.

In the present study, effects of the alpha(2)- and beta-adrenoceptor agonists clonidine and isoproterenol on astrocytes in astroglial/neuronal cocultures from rat cerebral cortex were evaluated. The calcium- and potassium-sensitive dyes fura-2 and potassium-binding benzofuran isophtalate (PBFI) were used to study alterations in intracellular concentrations of calcium ([Ca(2+)](i)) and potassium ([K(+)](i)), respectively, while the perforated patch clamp technique was used to analyze transmembrane currents. Exposure to isoproterenol or clonidine elicited an immediate increase in [Ca(2+)](i) that was totally abolished in calcium-free extracellular media. Isoproterenol also decreased [K(+)](i), but clonidine did not. The reduction in [K(+)](i) was inhibited in Ca(2+)-free media. As evaluated with the perforated patch technique, isoproterenol (10(-6)-10(-4) M) induced a slowly developing and long lasting outward current that also was totally abolished in calcium-free buffer. This current was blocked by external tetraethylammonium (TEA, 10 mM) and charybdotoxin (ChTX, 10 nM), but was not affected by apamin (50 nM). The current-to-voltage (I-V) relationships for the isoproterenol-induced currents showed a markedly negative reversal potential, -96 mV+/-7, (mean+/-S.D., n=5). These results suggest that the stimulation of astroglial beta-adrenoceptors by isoproterenol opens calcium-activated potassium channels (K((Ca))). Preincubation with forskolin significantly increased the isoproterenol-induced currents compared with controls, indicating that the opening of astroglial K((Ca)) channels after beta-adrenergic stimulation not only depends on [Ca(2+)](i) but also synergistically involves the cAMP transduction system to which beta-adrenoceptors are known to be positively coupled.

Adrenergic alpha-2 Receptor Agonists↗

PubMed2001

More keys to padlock probes: mechanisms for high-throughput nucleic acid analysis.

With the impending availability of total information about nucleic acid sequences in humans and other organisms, tools to investigate these sequences on a large scale assume increasing importance. Methods currently in use, however, cannot offer the required combination of high-throughput, sensitivity and specificity of detection. Padlock probes, circularizing oligonucleotides, may provide a means to detect, distinguish, quantitate and also locate very large numbers of DNA or RNA sequences. Recent developments in areas such as the biochemistry of ligation and characterization of ligases, methods to replicate circularized probes and the development of assays based on these principles augment the potential of padlock probes.

Biotechnology↗

PubMed2001

Similarities and differences between free 211At and 125I- transport in porcine thyroid epithelial cells cultured in bicameral chambers.

The transport and accumulation of free 211At and 125I- were investigated in thyrocytes cultured as monolayers in bicameral chambers under the influence of thyroid-stimulating hormone, stable iodide, ouabain and perchlorate. The results indicate that there are similarities and differences in the transport mechanisms of free 211At and 125I-. These results will be valuable in the development of radiation protection when handling and using 211At-labeled radiopharmaceuticals, and for the potential use of free 211At in radiation therapy of poorly differentiated thyroid cancer.

Animals↗

PubMed2001

The anesthetic onset and duration of a new lidocaine/prilocaine gel intra-pocket anesthetic (Oraqix) for periodontal scaling/root planing.

BACKGROUND: A new non-injection anesthetic, lidocaine/prilocaine gel (Oraqix, AstraZeneca) in a reversible thermosetting system, has been developed to provide local anesthesia for scaling/root planing (SRP). The aim of this study was to determine the anesthetic onset and duration of the gel for SRP in patients with periodontitis. METHODS: 30 patients were randomized to either 30 s, 2 min, or 5 min of treatment with the gel prior to SRP of a tooth. The gel was applied to periodontal pockets with a blunt applicator. On completion of the SRP of each tooth (2-3 teeth treated/patient), the patients rated their pain on a 100-mm visual analogue scale (VAS). RESULTS: The median VAS pain score was 7.5 mm in the 30-s group, 28.5 mm in the 2-min group, and 15.5 mm in the 5-min group, with a significant difference between the 30-s and 2-min groups (p=0.03). In 2 patients in the 5-min group, but none in the other groups, the SRP was interrupted due to pain. The mean duration of anesthesia measured as pain on probing were 18.1, 17.3, and 19.9 min in the 30-s, 2-min, and 5-min groups, respectively. There were no reports of numbness of the tongue, lip, or cheek, neither were there any adverse local reactions in the oral mucosa. The gel was easy to apply and did not interfere with the SRP procedure. CONCLUSION: Oraqix provides anesthesia after an application time of 30 s, with a mean duration of action of about 17 to 20 min.

Administration, Topical↗

PubMed2001

The level of the mitochondrial mutation A3243G decreases upon ageing in epithelial cells from individuals with diabetes and deafness.

We have in a longitudinal study determined the proportion of the mitochondrial A3243G mutation in DNA obtained from cervical cell samples collected from three individuals affected with mitochondrial diabetes and hearing loss during a period of up to 18 years. Using the minisequencing method we were able to sensitively determine the proportion between mutant and normal mitochondrial DNA. Our results demonstrate a constant decrease in the levels of the pathogenic mutation in mitotic tissues of affected individuals with time.

Adult↗

PubMed2001

Chitosan as a nonviral gene delivery system. Structure-property relationships and characteristics compared with polyethylenimine in vitro and after lung administration in vivo.

Chitosan is a natural cationic linear polymer that has recently emerged as an alternative nonviral gene delivery system. We have established the relationships between the structure and the properties of chitosan-pDNA polyplexes in vitro. Further, we have compared polyplexes of ultrapure chitosan (UPC) of preferred molecular structure with those of optimised polyethylenimine (PEI) polyplexes in vitro and after intratracheal administration to mice in vivo. Chitosans in which over two out of three monomer units carried a primary amino group formed stable colloidal polyplexes with pDNA. Optimized UPC and PEI polyplexes protected the pDNA from serum degradation to approximately the same degree, and they gave a comparable maximal transgene expression in 293 cells. In contrast to PEI, UPC was non toxic at escalating doses. After intratracheal administration, both polyplexes distributed to the mid-airways, where transgene expression was observed in virtually every epithelial cell, using a sensitive pLacZ reporter containing a translational enhancer element. However, the kinetics of gene expression differed - PEI polyplexes induced a more rapid onset of gene expression than UPC. This was attributed to a more rapid endosomal escape of the PEI polyplexes. Although this resulted in a more efficient gene expression with PEI polyplexes, UPC had an efficiency comparable to that of commonly used cationic lipids. In conclusion, this study provides insights into the use of chitosan as a gene delivery system. It emphasises that chitosan is a nontoxic alternative to other cationic polymers and it forms a platform for further studies of chitosan-based gene delivery systems.

Cell Line↗

PubMed2001

Effect of food on the pharmacokinetics of budesonide controlled ileal release capsules in patients with active Crohn's disease.

AIM: To study the influence of food on the systemic availability of budesonide in patients with active Crohn's disease. METHODS: Eight patients with an established diagnosis of Crohn's disease each received 9 mg budesonide controlled ileal release (CIR) capsules (Entocort capsules) orally on two separate occasions: once in a fasting state and once after a heavy breakfast. For reference, deuterium-labelled ((2)H(8)) budesonide, 0.5 mg, was given intravenously. Plasma concentrations of budesonide and (2)H(8)-budesonide were determined for 12 h, and their pharmacokinetic parameters were calculated. RESULTS: Average systemic availability of budesonide during fasting conditions was 10.7%, area under the curve was 27.5 nmol/L x h and peak plasma concentration was 4.1 nmol/L. Corresponding postprandial values were 13.2%, 27.0 nmol/L x h and 3. 8 nmol/L. Food increased the mean absorption time from 4.5 to 6.8 h (P=0.0012). Body clearance of budesonide was about 25% higher after eating (P=0.0015). CONCLUSIONS: Food had little influence on systemic availability and peak plasma concentrations of budesonide administered in CIR capsules. Absorption was retarded postprandially, likely due to delayed gastric emptying. Budesonide in CIR capsules can be administered at the same dose regardless of prandial status in patients with Crohn's disease.

Administration, Oral↗

PubMed2001

Prognostic significance of risk group stratification in elderly patients with acute myeloid leukaemia.

Prognostic factors were studied in a series of 211 acute myeloid leukaemia (AML) patients over 60 years of age, treated at a single centre. The patients were allocated into three risk groups based on cytogenetics, occurrence of antecedent haematological disorder and leucocyte count. Only 3% had low-risk features, 39% had intermediate- and 58% had adverse-risk features. Complete remission (CR) was achieved in 43% of all patients. In multivariate analyses, the number of cycles needed to achieve CR and the risk group were significantly associated with the duration of CR. Median survival time for the entire cohort of patients was only 107 d. Advanced age, low induction treatment intensity, treatment during earlier years and adverse-risk group were associated with shorter overall survival times. Risk group classification may help selection of elderly patients with a good chance of benefiting from intensive treatment to actually receive such treatment, while sparing others with a low probability of survival benefit from toxic treatment. Low intensity induction treatment reduces the chance of obtaining complete remission, produces inferior survival times and should consequently be avoided when the aim is to obtain complete remission. In elderly AML patients, introducing age and re-evaluation of intermediate and good prognosis patients regarding response to induction treatment may improve the risk group classification.

Acute Disease↗

PubMed2001

Prediction of diabetes with body mass index, oral glucose tolerance test and islet cell autoantibodies in a regional population.

OBJECTIVE: Our aim was to test the hypothesis that a combination of markers for Type 1 diabetes (glutamate decarboxylase and IA-2 autoantibodies) and for Type 2 diabetes [oral glucose tolerance test (OGTT) and body mass index (BMI)], would predict clinical diabetes in a regional population. DESIGN: A population-based follow-up cohort study. SETTING: Participants visited the primary health care centre in Lycksele, Sweden in 1988-92. PARTICIPANTS: A cohort of 2278 subjects (M/F 1149/1129) who were studied at follow-up in 1998. At base line there were 2314 subjects (M/F 1167/1147) who participated in the Västerbotten Intervention Program on their birthday when turning either 30, 40, 50 or 60 years of age. Main outcome measurements. A clinically diagnosed diabetes at follow-up when the medical records were reviewed for diagnosis of diabetes. At base line, the participants were subjected to a standard OGTT and their BMI determined along with the autoantibodies. RESULTS: At follow-up, 42/2278 (1.8%, 95% CI 1.2-2.3) (M/F 23/19) had developed diabetes: 41 subjects were clinically classified with Type 2 and one with Type 1 diabetes. There was no significant relation between autoantibody levels at base line and diabetes at follow-up. Stepwise multiple logistic regression showed that the odds ratio for developing diabetes was 10.8 (95% CI 6.3-18.9) in subjects in the fourth quartile of BMI (BMI > 27) compared with 7.8 (95% CI 4.8-12.6) in the fourth quartile of 2-h plasma glucose (>7.5 mmol L(-1)) and 7.2 (95% CI 4.8-11.4) in the fourth quartile of the fasting plasma glucose (>5.6 mmol L(-1)). CONCLUSION: Islet cell autoantibodies did not predict diabetes at follow-up. BMI measured at base line was as effective as 2-h plasma glucose and fasting plasma glucose to predict diabetes in this adult population.

Adult↗