Search PubMed⌕ Search

Biomedical subjects

S Eriksson

Publications and source records attributed to S Eriksson.

At least 235 records · Page 13Linked to original sources
PubMed1994

Gene technology-based antimetabolite design: the use of an in vitro protein expression system to facilitate antimetabolite design for virally-induced human diseases and malignant conditions.

A precondition for the chemotherapeutic treatment of a variety of virally-induced human diseases and malignant conditions is a highly selective interaction of the drug molecule to be used with it's biological target. To ensure the development of novel, effective drugs, it is essential that the biological target is well characterised with regard to it's structure and activity. Such characterisation relies upon adequate amounts of pure target being available. One of the most important enzymatic importers for antimetabolites is the enzyme thymidine kinase. In this article an in vitro protein expression system is described which facilitates the production of milligram amounts of pure and biologically active thymidine kinase, from a number of important biological sources. Results have shown that the in vitro produced enzyme has the exact biochemical propeties of the in vivo enzyme. Thus the in vitro protein expression system is an ideal vechicle to facilitate an in depth investigation of the enzyme's biological properties.

Journal Article↗
PubMed1994

Autoimmune liver disease in patients with primary Sjögren's syndrome.

Forty-five patients with primary Sjögren's syndrome were studied for evidence of autoimmune liver disease. Twenty-nine patients had normal liver function tests, normal IgM and a normal test for antimitochondrial antibodies and smooth muscle antibodies. Among the remaining 16 patients, abnormal liver function tests were found in 12 (27% of all patients); eight of these patients had biochemical cholestasis. Elevated plasma IgM (> 2 g/l) was observed in nine patients, three with normal liver function tests, while antimitochondrial antibodies were positive in six patients, one with normal liver function tests, and smooth muscle antibodies were found in three. Based on these findings and percutaneous liver biopsy, a diagnosis of primary biliary cirrhosis was established in four patients and autoimmune chronic active hepatitis in two. The present study showed that abnormal liver function tests in patients with primary Sjögren's syndrome are frequent and may indicate associated autoimmune liver disease. These data further emphasize the systemic nature of autoimmune disorders.

Adult↗
PubMed1994

Phosphorylation of 2-chlorodeoxyadenosine (CdA) in extracts of peripheral blood mononuclear cells of leukaemic patients.

2-Chlorodeoxyadenosine (CdA) is an antileukaemic agent used in treatment of hairy cell leukaemia (HCL) and chronic lymphocytic leukaemia of B- and T-cell type (B-CLL and T-CLL). The aim of this study was to elucidate the interpatient variability of CdA phosphorylation and its relation to response to CdA treatment. In extracts of peripheral blood mononuclear cells of patients with B-CLL (n = 39), CdA phosphorylation was significantly higher than in HCL (n = 19) when calculated per protein (391 +/- 155 pmol CdA phosphorylated/mg protein/min versus 288 +/- 166 pmol/mg/min, P < 0.001), but was the same when calculated per cell (12 +/- 5.9 pmol/10(6) cells/min versus 14 +/- 5.9 pmol/10(6) cells/min) due to a larger cell volume in HCL. In T-CLL (n = 6), CdA phosphorylation was significantly lower than in B-CLL, both when calculated per protein (128 +/- 68 pmol/mg/min, P < 0.001) or per cell (5.7 +/- 2.7 pmol/10(6) cells/min, P < 0.05). This low CdA phosphorylation in T-CLL was unexpected because normal B- and T-lymphocytes contain equal amounts of CdA phosphorylation. With B-CLL, 21 patients who responded (complete and partial response) to CdA treatment showed a significantly higher CdA phosphorylation than 13 patients not responding to CdA treatment (456 +/- 170 pmol/mg/min versus 309 +/- 97 pmol/mg/min, P < 0.01). We conclude that the level of CdA phosphorylation is correlated with the response of leukaemias to CdA treatment.

Cladribine↗
PubMed1994

An interaction between Gemfibrozil and alpha 1-antitrypsin.

Previous studies have demonstrated such hydrophobic compounds as cholesterol and lithocholic acid, to interact with alpha 1-antitrypsin (alpha 1-AT). We observed a similar interaction between the anionic, hydrophobic lipid-lowering drug Gemfibrozil and alpha 1-AT in a deficient (PiZZ) patient, affecting the physicochemical and antiproteinase properties of the inhibitor protein. Gemfibrozil treatment in non-PiZ patients also resulted in a reduction of alpha 1-AT activity which could be reproduced in vitro.

Drug Interactions↗
PubMed1994

Strong link between the alpha 1-antitrypsin PiZ allele and Wegener's granulomatosis.

OBJECTIVES: To ascertain whether a relationship exists between the PiZ alpha 1-antitrypsin (alpha 1AT) variant and antineutrophil cytoplasm antibodies (ANCA)-positive vasculitis in a large group of Swedish patients, and whether analysis for the presence of the PiZ variant might be useful for diagnostic or prognostic purposes. DESIGN: Retrospective cross-sectional study. SETTING: The Department of Internal Medicine, Malmö General Hospital, and the Department of Nephrology, University of Lund, Sweden. SUBJECTS AND MAIN OUTCOME MEASURES: Serum samples from 105 proteinase 3-ANCA-positive patients were analysed using an ELISA with a monoclonal antibody specific for the PiZ-gene product. Complete clinical data were retrieved for 84% (88/105) of the patients, for diagnosis and survival analysis. RESULTS: We identified 17 heterozygotes and one homozygote (P < 0.0001). All 88 patients with available clinical data were considered to have some form of microscopic vasculitis including 66 (75%) diagnosed as having Wegener's granulomatosis (WG), of whom 15 (23%) were PiZ heterozygotes (odds ratio 6.0, 95% confidence interval 3-10). There were no significant differences between PiZ carriers and noncarriers in sex distribution, mean age at onset of disease, interval between onset and inclusion in the study, or in median duration of follow-up (P > 0.2 for all comparisons). During follow-up, 38% (6/16) of the PiZ heterozygotes died, compared with 17% (11/66) of noncarriers of the variant (P= 0.02), which suggests that PiZ heterozygosity may be a marker of poor prognosis. PiZ heterozygotes with systemic vasculitis would not appear to be identifiable by their pretreatment plasma alpha 1AT concentrations, as all such patients in the present study had concentrations within or above the normal range. CONCLUSION: We conclude that heterozygotes for the PiZ variant of the alpha 1AT gene are at greater risk of than the general population of developing WG. Knowledge of such a genetic factor may not only aid our understanding of the mechanism involved in this illness but may also serve as significant prognostic factor in following the course of the disease.

Adolescent↗
PubMed1994

Abdominal aortic aneurysms and alpha 1-antitrypsin deficiency.

The incidence of abdominal aortic aneurysms (AAAs) has been reported to be increased in heterozygous (PiMZ) and homozygous (PiZZ) alpha 1-antitrypsin (alpha 1 AT) deficiency. We report a further case of AAA in a PiSZ alpha 1AT-deficient female with primary biliary cirrhosis (PBC). Moreover, to assess the risk of AAA in patients with PiZZ alpha 1AT deficiency, we conducted a retrospective study based on 30 consecutive autopsied adult cases of severe alpha 1AT deficiency identified during the period 1963-1993 in the city of Malmö, Sweden, during which autopsies were performed in 49,548, or 58.4%, of all residents in the city who died. From the homozygote frequency in the general population, 50 of these would be expected to have alpha 1AT deficiency. The disease had been diagnosed in 35, and autopsies had been performed in 30 adults. Each autopsied case was matched with four controls selected from the same autopsy register, and the Mantel-Haenszel odds ratio (ORmh) was calculated. We found one case of AAA amongst the 30 PiZZ individuals autopsied, and one case amongst 120 autopsied controls (ORmh = 2.65, 95% confidence limits, 0.47-15.0; P = 0.273). We found no significant evidence of the relationship between AAA and the PiZZ polymorphism, although previously reported by others. At least in severe alpha 1AT deficiency, any coexistence of the PiZZ phenotype and AAA would seem to be fortuitous.

Aged↗
PubMed1994

Hypertension and thirst outlasting renal vasoconstriction as effects of a brief evaluation of systemic angiotensin II in sheep.

The influence of 10 min intracarotid (i.c.) and intravenous (i.v.) infusions of angiotensin II (Ang II; 20 pmol kg-1 min-1) on carotid blood pressure (cBP) and renal blood flow (RBF) was studied in unanaesthetized ewes without and with pre-treatment with the alpha 1- and beta-adrenoceptor blocker labetalol. RBF was also monitored during 30 min intracerebroventricular (ICV) infusions of Ang II at 2 pmol kg-1 min-1. The i.c. infusions of Ang II induced about 50 mmHg rise in cBP. A steep decline occurred during 5 min post-infusion, followed by a much slower reduction with the cBP remaining above control level at 40 min post-infusion. The pressure elevation induced by i.v. Ang II was less pronounced but exhibited a similar pattern. Labetalol significantly reduced the pressor response to i.c. as well as i.v. Ang II. The i.c. and i.v. infusions of Ang II conspicuously reduced the RBF regardless of whether the ewes were labetalol-treated or not. At 5 min after the infusions RBF had returned to control level. The ICV infusions did not influence the RBF. Ang II i.c. elicited thirst in 50% of the ewes with the urge to drink remaining at 40 min post-infusion. The dipsogenic response was not reduced by labetalol pretreatment. The results imply that no cerebral component contributes to the reduction in RBF induced by systemic Ang II. However, a centrally mediated action seems to be the cause of the long-lasting post-infusion cBP elevation and dipsogenic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1994

Restriction and enhancement of human immunodeficiency virus type 1 replication by modulation of intracellular deoxynucleoside triphosphate pools.

Human immunodeficiency virus type 1 (HIV-1) replication is shown to be sensitive to the intracellular concentration of deoxynucleoside triphosphate substrates. Addition of thymidine to established cell lines resulted in a dramatic reduction of virus production. The effect could be substantially alleviated by addition of deoxycytidine, which, alone, enhanced viral titers by a factor of 2 to 3. Hydroxyurea treatment abolished HIV-1 replication in peripheral blood mononuclear cells and could be reversed by deoxyadenosine. These data show that HIV-1 replication occurs under suboptimal DNA precursor conditions.

CD4 Antigens↗
PubMed1994

Longitudinal changes in craniomandibular dysfunction in an elderly population in northern Sweden.

Longitudinal changes and cohort differences in craniomandibular dysfunction (CMD) were studied in a 79-year-old cohort (n = 65) and in 70-year-old cohorts in 1981 (n = 62) and 1990 (n = 60) by means of interview and clinical examination. Although the frequency of reported CMD symptoms decreased, many clinical signs of CMD increased during the 9-year observation period. Women reported more symptoms and showed more signs of CMD than men, and a great many of the clinical signs registered in 1981 still persisted in 1990. The 70-year-old cohort studied in 1990 showed a lower frequency of reported symptoms of CMD and of temporomandibular joint pain on palpation and a higher frequency of muscle pain and mandibular deviation than the 70-year-olds examined in 1981.

Age Factors↗
PubMed1994

Prevalence and clinical significance of gliadin antibodies in healthy children and adults.

Coeliac disease (CD) is associated with the presence of gliadin antibodies (GA) (IgG and IgA), often used as a screening test for CD. Using a modified micro-enzyme-linked immunosorbent assay for GA, we studied the prevalence of GA in three healthy groups: children (mean age, 12 years), adult blood donors (mean age, 38 years), and healthy women (mean age, 57 years). We also studied the clinical characteristics of the blood donors. On the basis of findings in 27 untreated CD patients, cut-off levels of IgG and IgA antibody titres were chosen to yield a test with relatively low sensitivity (56%) but high specificity (100%). Analysis of IgM antibodies did not improve the sensitivity. Of the 384 12-year-old children, both IgG and IgA GA positivity was found in 15 (3.91%), a rate significantly greater than that in the blood donors (22 of 1537, 1.43%; p < 0.001) or in the middle-aged women (11 of 944, 1.17%; p < 0.0001). Of the 22 GA-positive healthy blood donors, 13 underwent small-bowel biopsy, but only 1 of the specimens manifested histologic changes compatible with CD. The other 12 had normal specimens, including a normal intraepithelial lymphocyte count. The estimated frequency of CD among the blood donors was thus 1 of 1500, a figure consistent with those previously published. We conclude that GA occur frequently in the Swedish population but that their prevalence decreases with increasing age. As a screening test for CD in healthy individuals, the GA titre is of poor predictive value.

Adult↗
PubMed1994

Unsuspected coeliac disease in chronic 'cryptogenic' liver disease.

BACKGROUND: Earlier reports have suggested that a relationship exists between chronic liver disease and coeliac disease (CD). Gliadin antibodies (GA) have been used to screen for CD. METHODS: Using a micro-enzyme-linked immunosorbent procedure, we analysed sera from 327 consecutive patients with chronic liver disease for GA (IgA and IgG) and evaluated their clinical significance. RESULTS: GA were detected in 19 patients (6%), a prevalence six times greater than that found in healthy blood donors. In 9 of the 19 patients the liver disease had been classified as cryptogenic. The occurrence of GA was independent of the degree of hepatocellular impairment. A diagnosis of CD was confirmed in 5 of the 10 patients who underwent small-bowel biopsy. CONCLUSIONS: Our findings suggest the prevalence of CD in patients with chronic liver disease to be at least 1.5%--that is, 15 times higher than in the general population. They also suggest that the possible presence of CD should be considered in cases of chronic 'cryptogenic' liver disease.

Adult↗
PubMed1994

The diagnostic value of repetitive preoperative analyses of C-reactive protein and total leucocyte count in patients with suspected acute appendicitis.

BACKGROUND: Studies have shown that C-reactive protein (CRP) and total leucocyte count (WBC) in suspected acute appendicitis analysed only on admission gave valuable information to guide the surgeon. The aim of this study was to investigate the usefulness of CRP and WBC measured repetitively before operation. METHODS: During a 1-year period 227 patients were studied before emergency appendicectomy. CRP and WBC were analysed every 4th h. The upper limits of the reference intervals used were 9.0 x 10(9)/l for WBC and 10 mg/l for CRP. RESULTS: Of the 227 appendicectomized patients, 170 (75%) had acute appendicitis. Sixty-six of the patients were tested on two or more occasions every 4th h. Forty-six of these patients had appendicitis; repetitive tests showed a continuing rise in CRP values but a continuing decrease in WBC. The negative appendicectomy rate among these 66 patients was 30%, which theoretically would have fallen to 19% if patients with normal results had not been subjected to surgery. CONCLUSIONS: Repeated laboratory tests for CRP and WBC should be performed in patients with suspected acute appendicitis requested to stay for further observation. If these test results are normal, the surgeon should preferably refrain from operating but consider other differential diagnoses.

Acute Disease↗
PubMed1994

Long-term consequences with regard to clinical outcome and cost-effectiveness of episodic treatment with omeprazole or ranitidine for healing of duodenal ulcer.

The clinical outcome and cost-effectiveness of episodic treatment of duodenal ulcer with omeprazole and ranitidine were evaluated over a 5-year period. The analysis was based on data from published clinical trials comparing healing rates obtained with omeprazole and with ranitidine, as well as on data from the literature on ulcer recurrence and other clinical events. Patients with an active duodenal ulcer were treated until healed or for a maximum of 24 weeks. Maintenance therapy was instituted in patients with ulcers that were very slow to heal and in patients with frequent relapses after cessation of treatment. Patients who experienced frequent relapses while receiving maintenance therapy, and those whose ulcer had not healed after 24 weeks of continuous treatment, were defined as candidates for surgery. A statistical model was set up and a random number generator used to generate a sequence of clinical events, month by month, over a 5-year period for each patient in a large cohort. Episodic treatment with omeprazole was shown to be more effective in avoiding maintenance treatment and surgery when compared with episodic treatment with ranitidine. Patients who received episodic treatment with omeprazole also spent more time in remission from disease. Using current Swedish cost data, it was found that episodic treatment with omeprazole was more cost-effective than episodic treatment with ranitidine.

Cost-Benefit Analysis↗
PubMed1994

Parentage testing and linkage analysis in the horse using a set of highly polymorphic microsatellites.

Ten (TG)n positive clones, isolated from an equine genomic library and sequenced, contained 12-19 uninterrupted TG repeats. Primers for polymerase chain reaction (PCR) were synthesized and nine of these (TG)n loci (HTG7-15) were successfully amplified and utilized in this study together with five previously reported equine microsatellite loci (HTG2-6). The PCR products were analysed by polyacrylamide gel electrophoresis followed by automated laser fluorescence detection or autoradiography. All microsatellites showed polymorphism and stable Mendelian inheritance. Differences in microsatellite variability between horse breeds were detected. A linkage analysis comprising HTG2-15, one coat colour gene and 16 genetic blood markers enabled addition of HTG2 to linkage group U2 and a new linkage group (U6) was established comprising the loci HTG7 and HTG12. Close linkage was excluded within a set of eight microsatellites. The estimated probability of exclusion in four breeds for a parentage test based on these eight loci varied between 0.96 and 0.99.

Animals↗
PubMed1993

Deoxycytidine and 2',3'-dideoxycytidine metabolism in human monocyte-derived macrophages. A study of both anabolic and catabolic pathways.

In the present study we have explored the catabolism of dCyd and 2',3'-dideoxycytidine (ddC) in mature monocyte-derived macrophages (M/M) and focused on its relation to the accumulation of intracellular anabolites. We found that dCyd catabolism in M/M was significant in 1-week old cultures (15% of 0.5 microM dCyd, 0.5 nmole/million cells, catabolized within one hour of incubation) and further increased in more mature 3-week and 5-week old cultures (> 85% catabolized within one hour). Dihydrouracil (DHU) was irreversibly formed as end product of the dCyd catabolism, with dUrd and Ura as intermediate metabolites. Intracellularly, dCyd nucleotides were detected up to three hours of incubation, with dCTP maintained at steady levels between one and three hours. However, after twelve hours of incubation DHU was the only detectable intracellular as well as extracellular metabolite. In contrast to what was observed with dCyd, we found that ddC was resistant to catabolism, with no detectable catabolites formed within twenty-four hours of incubation. Therefore ddC anabolism was unopposed by catabolic pathways and consequently intracellular anabolites of ddC accumulated throughout twenty-four hours of incubation. Based on these results, we propose that lack (or inhibition) of catabolism is at least as important as efficient anabolic phosphorylation for obtaining therapeutic effects of pyrimidine nucleoside analogs.

Biotransformation↗
PubMed1993

Endothelial cells release casein kinase II--like activity capable of phosphorylating fibrinogen in response to thrombin.

Rat liver endothelial cells cultivated in the absence of serum and activated with thrombin released up to 10% of the total protein kinase activity into the cell medium using casein or fibrinogen as the phosphate acceptor protein. The activity was partly inhibited by heparin, indicating that it was of the casein kinase II type. The release of kinase started directly after the addition of thrombin (2 NIH U/ml) to the media with two maxima; one after about 10 min and the second after around 30 min. The phosphorylating activity of media from cells incubated for longer times was less dependent on thrombin-induction which probably indicated the start of destruction of the cells. The results reported suggest that phosphorylation of fibrinogen could occur in the blood under acute phase conditions.

Animals↗