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Biomedical subjects

M Andersson

Publications and source records attributed to M Andersson.

At least 73 records · Page 4Linked to original sources

Ultrahigh molar mass component detected in ethylhydroxyethyl cellulose by asymmetrical flow field-flow fractionation coupled to multiangle light scattering.

Asymmetrical flow field-flow fractionation (flow FFF) was connected to multiangle light scattering (MALS) and refractive index (RI) detectors for characterization of the molar mass distribution and molecular radius of a cellulose derivative, ethylhydroxyethyl cellulose (EHEC). Experimental conditions were optimized to allow study of a wide range of molar mass including even ultrahigh molar mass (UHM) components. The weight-average molar mass was 3.1 x 10(5) g x mol(-1) representing a very broad range (of molar mass) from 4.0 x 10(4) to 10(7) g x mol(-1), which corresponds to from <20 to 200 nm rms radius. The light scattering signal showed the presence of an UHM component, possibly an aggregate of extreme size, i.e., approximately 10(8) g x mol(-1) with a hydrodynamic diameter of 0.35 microm. Careful choice of the pore size in in-line filters is necessary in order to minimize MALS detector noise without removing the UHM component. Flow FFF-MALS-RI was demonstrated to be uniquely suited to detect the presence of UHM components.

Cellulose↗

A novel automated fluorometric assay to evaluate sperm viability and fertility in dairy bulls.

The artificial insemination (AI) industry is in need of an objective and rapid, but inexpensive method to evaluate frozen thawed bull semen ejaculates. This study presents a new fluorescence method that uses an automatized fluorometer and fluorophore stain propidium iodide that stains only those cells with damaged membranes. The fluorescence of the semen sample and the totally killed subsample were measured simultaneously, and viability was calculated. Every semen batch was analyzed before use in AI. For fertility evaluation, the nonreturn rates (NR%) obtained from 92,120 inseminations with the analyzed batches were recorded from 166 bulls (436 batches). This study confirms a 3.9% better NR% for the Finnish Holstein-Friesian breed than for Finnish Ayrshire. There was a clear seasonality in NR%: it differed (5.3%) significantly, being best in summer to autumn (June to October) and lowest in winter (January to March). The fluorometer method was fast and easy. The correlation between the total number of viable spermatozoa in an insemination dose and field fertility was low but significant (r = 0.051, P = 0.016), suggesting that the plasma membrane integrity evaluation can serve as a cost-beneficial quality control method of frozen-thawed semen at bull stations.

Animals↗

[Incidence of malignant mesothelioma in Denmark and expected number of future cases among men].

INTRODUCTION: The aim was to analyse incidence rates and to predict the future number of cases of malignant mesothelioma in Denmark. METHODS: We analysed the 1912 cases of malignant mesothelioma reported to the Danish Cancer Register, 1943-1993, in order to describe the current incidence rates. The relative risks of synthetic birth cohorts were estimated by a Poisson regression model and used to predict the future number of cases in males. RESULTS: The incidence rate increased to 1.33 per 100,000 person years in men in 1983-1987, and to 0.51 in women in 1973-1977. According to a Poisson regression model, the risk in birth cohorts in males peaked in the 1940-1944 cohort and decreased to 0.57 in the 1950-1954 cohort. The age-specific incidence rate peaked at 246 per 100,000 person years in the age group of 80-84. The future annual number of mesothelioma cases is expected to peak around 2015 with 93 cases in men born before 1955. DISCUSSION: The fit of the model was not ideal, but with careful interpretation of the results we conclude that a further increase in the number of mesothelioma cases can be expected, and the effect of regulating the environmental exposure to asbestos cannot be expected within the next 10-15 years.

Adult↗

Mutations and allelic loss of p53 in primary tumor DNA from potentially cured patients with colorectal carcinoma.

PURPOSE: To compare p53 alterations in survivors and nonsurvivors after surgery for colorectal cancer. PATIENTS AND METHODS: Twenty-nine potentially cured patients with colorectal carcinoma, without recurrent disease for more than 6 years after their primary surgery, were selected to match a group of 41 colorectal cancer patients with early metastatic spread to the liver. All patients were screened for mutations in the p53 gene, exons 5 to 9, by denaturing gradient gel electrophoresis and subsequent sequencing. RESULTS: The frequency of p53 mutations was significantly different in cured patients (60%) compared with patients with early relapse (41%, P <.05). A significant difference was found in the distribution of mutations, indicating that potentially cured patients had a different proportion of mutations in conserved regions of p53 (P =.02). This difference was explained by a significantly different frequency of mutations in exon 8 (40% v 15%, P =.03), which is part of the conserved region V. All mutations in region V were codon 273 mutations in cured patients, whereas three of four mutations were located in codon 273 in patients with metastatic disease. Allelic loss of p53 (loss of heterozygosity [LOH]) was demonstrated in 26% of the cured patients and in 39% of patients with metastatic disease (P =.36). The combination of mutation and LOH of p53 was the same (17%) in both groups. CONCLUSION: A large number of p53 mutations in colorectal cancer do not promote disease progression. Some mutations, particularly within conserved regions, may even counteract negative functional effects of other p53 structural alterations. A complete loss of p53 function was not related to survival or progression after curative operation of colorectal carcinoma.

Adult↗

[Untreated breast cancer in Denmark 1978-1995].

INTRODUCTION: The lack of registration of women who have received no or alternative treatment for breast cancer has been criticised. No distinction is made in the Danish Cancer Register between these patients and those who only receive palliative treatment for other reasons, such as old age, advanced disease, and competing illnesses. We have estimated the number of women in this group of patients, who, in reality, had not received any treatment with the intent to cure under the health care system, and whether a meaningful analysis of survival for these patients is feasible. METHOD: All women with breast cancer diagnosed during the years 1978-1995 were extracted from the Cancer Register, and we isolated those who had been registered as having had no or only palliative treatment and who had survived for a minimum of 45 days after diagnosis. A search was made in the Danish Breast Cancer Co-operative Group register for unreported treatment and the residual group was followed up individually. RESULTS: Out of 49.058 women with histologically or cytologically verified breast cancer, the Cancer Register listed 840 women with no registered treatment of their disease. Of these, there were 103 cases of carcinoma in situ. A match with the DBCG register revealed that 188 women had nevertheless been operated on. Among the remaining 549 women, 99 were truly untreated, and for 77 of these the reasons given were another or advanced disease or old age. Only 22 women had initially declined treatment for no specific reason. Five of these had later decided on subsequent curative treatment, which leaves 17 women in the category "breast cancer untreated at her own request" ("untreated breast cancer at own will"). Nine are dead, five had their tumour excised at biopsy, and the remaining three are alive with tumours diagnosed by fine needle aspiration biopsy (1) or thru-cut biopsy (2) after 7.7 and 4 years, respectively. CONCLUSION: This report has shown that a survival analysis based on the Cancer Register of untreated breast cancer in relation to treated breast cancer is not meaningful. A true estimation of survival after untreated versus treated breast cancer can only be achieved through a randomised study, which would be unethical.

Age Factors↗

Domestication effects on foraging strategies in fowl.

Birds of two different breeds differing in degree of domestication were studied to reveal any differences in foraging strategies between them. The breeds were wild-type birds (crossing between red jungle fowl (Gallus gallus) and Swedish bantam (Gallus gallus domesticus) and domestic birds (Swedish bantam), breeds representing an increasing level of domestication. Bantam birds have not been selected for any specific characteristics. The birds were allowed to forage in an experimental pen containing two separate food patches, which depleted as a function of being exploited, to see how well the different breeds were able to assess costs and benefits as the distance between patches were changed (short distance between patches compared to long distance between patches). Both breeds behaved in accordance with some general predictions of optimal foraging theory, i.e. moved between patches, left patches before these were empty and stayed for a shorter time in more depleted patches. Wild-type birds responded more than domestic birds to an increase of distance between patches, by spending longer average time in patch when there was a long distance between them compared to when there was a short distance. The wild-type birds adopted what seemed to be a more costly foraging strategy, moving more between patches than the domestic birds without ingesting more feed. During domestication, in the protected environment provided by man, individuals using less costly behavioural strategies may have gained increased fitness over those spending more energy on foraging. Although domestic birds still possessed the ability to respond adaptively to environmental conditions, the differences between the wild-type and the domestic breed might be a result of the reduction of the natural selection pressure which accompanies domestication.

Journal Article↗

The fine specificity of the myelin oligodendrocyte glycoprotein autoantibody response in patients with multiple sclerosis and normal healthy controls.

Antibodies directed against the extracellular immunoglobulin (Ig)-like domain of the myelin oligodendrocyte glycoprotein (MOG(Igd)) mediate demyelination in experimental autoimmune encephalomyelitis (EAE) and are implicated in the immunopathogenesis of multiple sclerosis (MS). In this study we investigated the epitope specificity of MOG(Igd)-specific autoantibodies immunopurified from MS patients (n=17) and normal healthy controls (HD; n=9). ELISA, using a panel of synthetic MOG(Igd) peptides, revealed that the epitope specificity of this response was heterogeneous in both groups. The most frequently recognised epitopes were located in amino acid sequences (a.a.) 1-26 (13/17) and 63-87 (15/17) in MS patients, and 14-39 (6/9) and 63-87 (6/9) in HDs, but there was no association between MS and any particular peptide specificity. We therefore investigated the ability of the immunopurified antibodies to recognise native MOG(Igd) expressed on at the membrane surface by FACS. Unexpectedly, antibodies fulfilling this essential criterion for a demyelinating antibody response were detected only in one of the MS samples. These results indicate that the epitope specificity of the human B cell response to MOG is not only heterogeneous, but may only mediate demyelination in a limited subset of MS patients.

Adolescent↗

P53 mutations in primary tumors and subsequent liver metastases are related to survival in patients with colorectal carcinoma who undergo liver resection.

BACKGROUND: The appearance of p53 mutations in colorectal carcinoma was determined, independent of differentiation and tumor stage of the primary tumors, in relation to the survival of patients who were scheduled to undergo liver resection. METHODS: Tumor material was analyzed for p53 mutations in primary colorectal tumors and subsequent liver metastases from 41 consecutive patients who were scheduled to undergo surgical liver resection. DNA sequencing and immunohistochemical staining of p53 protein within tumor nuclei were performed. RESULTS: Primary tumors displayed p53 mutations within exons 5-9 in 41% of patients. No mutations were found in exons 4, 10, or 11. Forty-one percent of metastatic lesions had the same single mutation that was found in the primary tumor, whereas 11% of metastatic lesions had one additional mutation within exons 5-9; 22% had mutations only in their liver metastases, whereas corresponding primary tumors displayed wild-type p53. None of the patients had mutated p53 in their primary tumor and wild type in their metastases. Survival after undergoing liver resection was correlated negatively (P < 0.05-0.01) with Duke Stages A-D classification of the primary tumors, tumor differentiation, and radicality (> 0.7-0.8 mm) of resected liver metastases. CONCLUSIONS: The presence of p53 mutations in patients with metastatic lesions was related significantly (P < 0.003) to better survival after the patients underwent liver resection compared with patients with wild type p53 in their metastatic lesions. This finding was not related to covariates, such as Duke classification, tumor differentiation, type of liver metastasis, or metastatic radicality during resections. Explanations for this unexpected finding remain unclear, although the authors speculate that occult tumor cells with p53 mutations may be less responsive to growth factor(s) exposure during hepatic regeneration after resection.

Adult↗

Abnormal microheterogeneity of haptoglobin in serum from dogs with various diseases.

Changes in the patterns of glycosylation of canine haptoglobin have recently been demonstrated by isoelectric focusing and immunoblotting. Fucosylated fractions of haptoglobin were identified by selective binding of a fucose-specific lectin. In this study, similar changes were found in the serum of 86 of 137 dogs with various inflammatory, autoimmune and neoplastic diseases. Major changes, including fucosylation, were observed in 40 of the dogs and were most frequent in association with autoimmune haemolytic anaemia. All 40 cases had markedly increased concentrations of haptoglobin and decreased concentrations of haemoglobin. Minor changes were found in the other 46 dogs, whereas no changes in glycosylation were detected in the serum of 40 healthy dogs.

Animals↗

Influence of the solute hydrophobicity on the enantioselective adsorption of beta-blockers on a cellulase protein used as the chiral selector.

Adsorption isotherm data were acquired at different eluent pH values for the enantiomers of several beta-blockers on cellobiohydrolase I on silica gel. They fit well to the biLangmuir model, allowing the determination of the equilibrium constants and the monolayer capacities for chiral and nonselective adsorption. The adsorption of the S-enantiomers (eluted second) is exothermic at low pH, endothermic at high pH, and athermal in a narrow pH range depending on the beta-blocker. This transition pH range is lower for S-alprenolol than for the more hydrophobic S-propranolol, although their endothermic adsorption originates from hydrophobic interactions. This surprising observation is explained by the relative values of the isotherm coefficients. S-Alprenolol seems to have a more pronounced endothermic behavior than S-propranolol because the nonselective interactions of both compounds with the stationary phase are exothermic but their contribution to retention, relative to that of the endothermic chiral interactions, is less important for alprenolol. The order of increasing energy of the chiral interactions is the same as that of hydrophobicity, propranolol>alprenolol>metoprolol.

Adrenergic beta-Antagonists↗

Interference with CD28, CD80, CD86 or CD152 in collagen-induced arthritis. Limited role of IFN-gamma in anti-B7-mediated suppression of disease.

We have investigated interference with co-stimulation by administering mAbs towards CD28, CD80, CD86, and CD152 in mice immunized for the development of collagen-induced arthritis (CIA). Anti-CD80 and anti-CD86 treatment inhibited disease score and incidence, whereas anti-CD28 treatment led only to a delayed disease onset. Administration of anti-CD152 had no effect. The CII-specific Ab-response was suppressed by the co-stimulatory blockade, with a stronger effect on IgG1 than on IgG2a. The CII-driven T cell proliferation, on the other hand, was not affected. Furthermore, T cells primed in the presence of either anti-B7 or anti-CD28 produced markedly increased amounts of IFN-gamma in response to CII. To investigate whether this increase in IFN-gamma was related to disease suppression, IFN-gamma-deficient mice were immunized with CII, treated with anti-B7 and followed for the development of arthritis. As in the wild-type mice, administration of anti-B7 to IFN-gamma-deficient mice led to a reduced disease incidence and severity as well as reduced anti-CII IgG titers. Collectively, these data stress the importance of co-stimulation for the delivery of B cell help rather than for production of Th1 cytokines. We also demonstrate that the enhanced production of IFN-gamma observed after B7-blockade is not accountable for the anti-B7 mediated inhibition of CIA.

Abatacept↗

Alterations in cortical and basal ganglia levels of opioid receptor binding in a rat model of l-DOPA-induced dyskinesia.

Opioid receptor-binding autoradiography was used as a way to map sites of altered opioid transmission in a rat model of l-DOPA-induced dyskinesia. Rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathways sustained a 3-week treatment with l-DOPA (6 mg/kg/day, combined with 12 mg/kg/day benserazide), causing about half of them to develop dyskinetic-like movements on the side of the body contralateral to the lesion. Autoradiographic analysis of mu-, delta-, and kappa-opioid binding sites was carried out in the caudate-putamen (CPu), the globus pallidus (GP), the substantia nigra (SN), the primary motor area, and the premotor-cingulate cortex. The dopamine-denervating lesion alone caused an ipsilateral reduction in opioid radioligand binding in the CPu, GP, and SN, but not in the cerebral cortex. Chronic l-DOPA treatment affected opioid receptor binding in both the basal ganglia and the cerebral cortex, producing changes that were both structure- and receptor-type specific, and closely related to the motor response elicited by the treatment. In the basal ganglia, the most clear-cut differences between dyskinetic and nondyskinetic rats pertained to kappa opioid sites. On the lesioned side, both striatal and nigral levels of kappa binding densities were significantly lower in the dyskinetic group, showing a negative correlation with the rats' dyskinesia scores on one hand and with the striatal expression of opioid precursor mRNAs on the other hand. In the cerebral cortex, levels of mu and delta binding site densities were bilaterally elevated in the dyskinetic group, whereas kappa radioligand binding was specifically increased in the nondyskinetic cases and showed a negative correlation with the rats' dyskinesia scores. These data demonstrate that bilateral changes in cortical opioid transmission are closely associated with l-DOPA-induced dyskinesia in the rat. Moreover, the fact that dyskinetic and nondyskinetic animals often show opposite changes in opioid radioligand binding suggests that the motor response to l-DOPA is determined, at least in part, by compensatory adjustments of brain opioid receptors.

Animals↗

Progesterone receptor antagonists Org 31710 and RU 486 increase apoptosis in human periovulatory granulosa cells.

OBJECTIVE: To investigate if progesterone receptor (PR)-mediated effects are involved in regulating the susceptibility to apoptosis in LH receptor-stimulated human luteinizing granulosa cells. DESIGN: Laboratory study. SETTING: Göteborg University and an in vitro fertilization laboratory of a university hospital. PATIENT(S): Women undergoing oocyte retrieval for in vitro fertilization after ovulation induction with gonadotropins. INTERVENTION(S): Luteinizing granulosa cells were isolated from follicular aspirates after oocyte removal. The cells were treated with or without RU 486 (1 microM-100 microM), Org 31710 (1 microM-100 microM), progesterone (1 nM-10 microM), dexamethasone (0.5 microM-100 microM), dihydrotestosterone (1 nM-25 microM), RU 486 (10 microM-100 microM) + dexamethasone (50 microM), and picrotoxin (1 microM-100 microM) and were cultured under serum-free conditions. MAIN OUTCOME MEASURE(S): Measurement of caspase-3 activity; detection of internucleosomal DNA fragmentation using gel electrophoresis and fluorospectrophotometry; progesterone analysis of spent medium. RESULT(S): Addition of the PR antagonists RU 486 or Org 31710 in vitro to human luteinizing granulosa cells caused an increase in caspase-3 activity and a dose-dependent increase in internucleosomal DNA fragmentation. No effect on DNA fragmentation was seen after addition of dexamethasone, dihydrotestosterone, or picrotoxin. CONCLUSION(S): Nuclear PR-mediated effects are involved in regulating the susceptibility to apoptosis in LH receptor-stimulated human luteinizing granulosa cells.

Caspase 3↗

Pharmacological properties of cannabinoid receptors in the avian brain: similarity of rat and chicken cannabinoid1 receptor recognition sites and expression of cannabinoid2 receptor-like immunoreactivity in the embryonic chick brain.

The pharmacological properties of brain cannabinoid receptors were investigated in brains of 35 day-old chickens, since little is known about the avian cannabinoid system. The cannabinoid1 receptor-selective antagonist ligand [3H]SR 141716A bound to chicken brain membranes with K(D) and Bmax values of 0.92+/-0.28 nM and 790+/-58 fmol/mg protein, respectively. The binding was inhibited by CP 55,940 with a pI50 value of 7.63+/-0.14 and by a series of compounds with the order of potency CP 55,940>R(+)WIN 55,212-2>R-1 methanandamide approximately DAK. S(-)WIN 55,212-3 and AM404 were without inhibitory effect at 1 microM. Similar results were found for rat brain membranes. For both rat and chicken brain membranes, addition of the non-hydrolysable GTP analogues Gpp[NH]p and GTPgammaS shifted the CP 55,940 inhibition curve to the right, consistent with an intact coupling to G-proteins in the preparations. Fatty acid amidohydrolase in chicken brain membranes was less sensitive to inhibition by phenylmethylsulphonyl fluoride and arachidonoyl serotonin than its rodent equivalent. However, when fatty acid amidohydrolase activity in the preparations was reduced by use of a lower assay membrane concentration, anandamide was found to inhibit the binding of [3H]SR 141716A to chicken membranes with a pI50 value of 6.39+/-0.16. Using a novel antibody raised to amino acids 346-359 from the C-terminal tail of the human cannabinoid2 receptor, it was found that embryonic chick brain tissue (and embryonic chick neurones in primary culture) expressed a approximately 53 kDa immunoreactive band. This immunoreactivity, which was prevented by preincubation of the antibody with the immunising peptide, was also seen in cells expressing the recombinant human cannabinoid, receptor, but was not seen in adult chicken brain homogenates or in rat cerebellar homogenates. However, a "classical" cannabinoid2-receptor component of [3H]WIN 55212-2 binding (i.e. a fraction inhibited by low concentrations of the cannabinoid2-receptor-selective antagonist SR 144528) was not found.

Amidohydrolases↗

Persistent changes in striatal gene expression induced by long-term L-DOPA treatment in a rat model of Parkinson's disease.

Current knowledge of the molecular changes induced by dopamine denervation and subsequent treatment with L-DOPA is based on studies performed on relatively acute and young animal models of parkinsonism. It is highly warranted to ask how well these models simulate the state of chronic denervation and sustained L-DOPA pharmacotherapy which are typical of advanced Parkinson's disease. This study investigates the effects of time postdenervation and L-dopa treatment duration on the striatal expression of opioid precursor mRNAs and FosB/DeltaFosB-related proteins. Unilaterally 6-hydroxydopamine-lesioned rats were treated with therapeutical doses of L-DOPA for one year (long-term group) or a few weeks (short-term group). Age-matched lesioned rats received injections of vehicle or bromocriptine, an antiparkinsonian compound which does not produce dyskinesia when administered de novo. The lesion-induced up-regulation of preproenkephalin mRNA expression persisted at more than one year postlesion, and was unaffected by the pharmacological treatments applied. L-DOPA, but not bromocriptine, induced high striatal levels of FosB/DeltaFosB immunoreactivity and prodynorphin mRNA, and these did not differ between short-term and long-term L-DOPA-treated rats. The present data provide the first demonstration that L-DOPA maintains high striatal levels of fosB and prodynorphin gene expression during a prolonged course of treatment, which simulates the clinical practice in Parkinson's disease more closely than the short-treatment paradigms studied thus far.

Animals↗