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Biomedical subjects

S Eriksson

Publications and source records attributed to S Eriksson.

At least 19 recordsLinked to original sources
PubMed2000

Rapid inhibition by sodium azide of the phosphoinositide-mediated calcium response to serotonin stimulation in human platelets: preservation in Alzheimer's disease.

The effect of sodium azide (NaN(3)) upon platelet Ca(2+) signalling has been investigated. A 60 s preincubation with 1 mM NaN(3) reduced the Ca(2+) response to 1 microM serotonin without a corresponding reduction in the responses to 52 mU/ml thrombin or 70 microM beta-amyloid(25-35) (A beta(25-35)). The effect of NaN(3) upon the response to serotonin, which was not blocked by either glutathione ethyl ester (GTEE) or dithiothreitol (DTT), was similar in platelets obtained from patients with Alzheimer's disease and from age- and gender-matched controls. After a preincubation time of 5 min was used, the Ca(2+) response to thrombin was greatly reduced by 1 mM NaN(3), but not by 50 microM 4-hydroxynonenal (HNE, 50 microM). Platelet levels of HNE and malondialdehyde were not significantly affected by up to 30 min of incubation with NaN(3) at room temperature. It is concluded that the rapid effect of NaN(3) upon the Ca(2+) response to serotonin in human platelets is not mediated by an inhibition of cytochrome c oxidase, and is due to an action proximal to phosphoinositide-specific phospholipase C.

Adult↗
PubMed2000

Expression of human mitochondrial thymidine kinase in Escherichia coli: correlation between the enzymatic activity of pyrimidine nucleoside analogues and their inhibitory effect on bacterial growth.

Mitochondrial thymidine kinase (TK2) phosphorylates pyrimidine nucleosides to monophosphates and is expressed constitutively through the cell cycle in all cells. Because of the overlap of its substrate specificity with that of the cytosolic thymidine kinase (TK1) and deoxycytidine kinase (dCK), it has been difficult to determine the role of TK2 in activating nucleosides used in chemotherapy. In this report, we described the construction of a recombinant Escherichia coli strain which could be used to test if TK2 activity is limiting for the toxicity of nucleosides. Enzymes of bacterial origin which are involved in thymidine and deoxyuridine anabolism and catabolism were eliminated, and the cDNA for human TK2 was introduced. In the crude extract of the engineered E. coli, the level of thymidine kinase was, after induction of TK2 expression, several hundred fold higher than in the control strain. Several pharmacologically interesting nucleoside analogues, including 3'-azidothymidine, 2',3'-didehydro-2',3'-dideoxythymidine, and 2', 3'-dideoxy-beta-L-3'-thiacytidine, were tested for their effects on the growth of this recombinant strain. For a comparison, the phosphorylation of these compounds was determined with purified recombinant TK1, TK2, and dCK. A correlation was observed between the phosphorylation of several of these compounds by TK2 and their effects on bacterial growth. These results demonstrate that activation of growth-inhibiting pyrimidine nucleosides can be catalyzed by TK2, and together with recombinant E. coli strains expressing other cellular nucleoside kinases, this whole-cell bacterial system may serve as a tool to predict the efficacy and side effects of chemotherapeutic nucleosides.

Cell Division↗
PubMed2000

Depth motion sensitivity functions.

Functions reliably describing perception of motion in depth have been established experimentally by using psychophysical methods of size and distance estimations and threshold measurements. The stimuli were generated with a new hybrid technique yielding an image refresh rate of 1667 Hz. In this way it was possible to generate rapid expansions and contractions of the moving checkerboard pattern constituting the stimulus for depth motion perception. The results showed that perceived size constancy as well as depth impression varied with oscillation frequency. Under the conditions of slow motions (oscillation frequencies around 2 Hz), perfect size constancy was obtained. Above that limit, size constancy systematically decreased, and with oscillation frequencies of about 5 Hz the perceived size constancy was close to zero when small-sized patterns were used. Under the conditions of wide field stimulation (when the pattern subtended 66 degrees of visual angle), the cut-off limit increased to 16 Hz. Since the perception of depth motion amplitudes as well as perceived velocities of the visual object are related to perceived size constancy, the findings have certain implications for theoretical explanations of depth motion perception.

Depth Perception↗
PubMed2000

Cytotoxicity, cell-cycle perturbations and apoptosis in human tumor cells by lipophilic N4-alkyl-1-beta-D-arabinofuranosylcytosine derivatives and the new heteronucleoside phosphate dimer arabinocytidylyl-(5'-->5')-N4-octadecyl-1-beta-D-arabinofuranosylcytosi ne.

The arabinofuranosylcytosine (AraC) derivative N4-octadecyl-1-beta-D-arabinofuranosylcytosine (NOAC) and its (5'-->5')-heterodinucleoside phosphate analog NOAC-AraC were compared with AraC for cytotoxicity, cell-cycle dependence, phosphorylation by deoxycytidine (dC) kinase and apoptosis induction in native, AraC- or NOAC-resistant HL-60 cells. NOAC was cytotoxic in all cells with three to seven-fold lower IC50 concentrations than those of NOAC-AraC or AraC. In contrast to NOAC-AraC, the lipophilic monomer NOAC overcame AraC resistance, inducing apoptosis in more than 80% of native and AraC-resistant HL-60 cells. This suggests that NOAC-AraC may be cleaved intracellularly only at very slow rates to AraC and NOAC or to the 5'-monophosphates, whereas NOAC exerts different mechanisms of action from AraC. In vitro the dimer was cleaved by phosphodiesterase or human serum to NOAC, AraC and AraC monophosphate. In contrast to AraC, N4-alkylated AraC derivatives with alkyl chains ranging from 6-18 C atoms were not substrates for dC kinase. Furthermore, treatment of the multidrug-resistant cell lines KB-ChR-8-5 and KB-V1 with the N4-hexadecyl-AraC derivative NHAC did not induce P-170 glycoprotein expression, suggesting that the N4-alkyl-AraC derivatives are able to circumvent MDR1 multidrug resistance. The in vivo activity of liposomal NOAC in a human acute lymphatic leukemia xenograft model confirmed the antitumor activity of this representative of the N4-alkyl-arabinofuranosylcytosines.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Bacterial adaptation to host innate immunity responses.

Several recent reports show that different bacterial components trigger innate and inflammatory responses in host organisms. In parallel, selected bacterial virulence factors have been identified that interfere with corresponding responses. In many cases, this involves interference with host proinflammatory signal transduction pathways, whereas in selected cases bacterial virulence factors interfere with host antibacterial mechanisms. This indicates that bacteria, besides activating cellular responses, also have the capacity to directly interact with branches of the innate defence.

Adaptation, Physiological↗
PubMed2000

Acrylamide: a cooking carcinogen?

Exposure to acrylamide (AA) has been monitored by mass spectrometric detection of the adduct, N-(2-carbamoylethyl)valine (CEV), to the N-termini of hemoglobin (Hb), according to the N-alkyl Edman method. In these studies, a conspicuous background level, about 40 pmol/g of globin, of apparently the same adduct was regularly observed in Hb from persons without known exposure to AA. For testing of the hypothesis that this adduct originates from AA formed in cooking, rats were fed fried animal standard diet for 1 or 2 months. These animals exhibited a strong increase of the level of the studied Hb adduct, compared to control rats fed unfried diet. By gas chromatography/tandem mass spectrometry, the identity with CEV was confirmed by the concordance of the product ion spectrum of the studied adduct with that of a verified standard and by interpretation of the fragment ions. Further support of the chemical structure, at the same time pinpointing AA as the causative reactive factor, was obtained through the demonstration that AA is formed in the heating of the feed and that the level of AA in the fried feed is compatible with the measured levels of the CEV adduct. The raised CEV adduct levels observed in experimental animals are of a magnitude that is similar to the background level in nonsmoking humans. These data render it likely that cooking of food is a major source of the background dose of AA also in humans. An evaluation of cancer tests of AA and available data for its metabolism leads to the estimation that the background dose of AA is associated with a considerable cancer risk.

Acrylamide↗
PubMed2000

Mitochondrial and submitochondrial localization of human deoxyguanosine kinase.

Deoxyguanosine kinase and thymidine kinase 2 are responsible for catalysing the first step in the salvage of deoxynucleosides in mitochondria. These enzymes also play an important role in activating several antiviral and anticancer nucleoside analogs, which may lead to unwanted side-effects when the resulting nucleotides are incorporated into the mitochondrial genome. We studied deoxyguanosine kinase in submitochondrial fractions from human placental mitochondria. It was localized in the mitochondrial matrix fraction by Western blotting using a purified polyclonal antibody. This antibody was also used in an immunohistochemical in situ experiment with human embryonic kidney 293 cells, in which the deoxyguanosine kinase antibody colocalized with a mitochondrion-specific fluorescent probe and there was no significant cytosolic staining.

Cell Fractionation↗
PubMed2000

Prevalence and clinical spectrum of chronic viral hepatitis in a middle-aged Swedish general urban population.

BACKGROUND: Although abundant data are available regarding the prevalence of chronic hepatitis B or C virus (HBV, HCV) among both blood donors and patients with liver diseases, corresponding data for the general population are scarce. Accordingly, this study was designed to investigate the prevalence and clinical spectrum of HBV and HCV in a general Swedish middle-aged urban population. METHODS: Demographic data and blood samples were collected from subjects enrolled in a prospective study of cancer development in the city of Malmö (population 250,000). The participation rate in the preliminary examination was 46.2%. From 12,445 individuals born between 1926 and 1945 and included in the study, a statistically representative subsample of 6103 persons was selected. Blood samples were available from 5533 of these. The mean age of the subjects in the series was 58.5 +/- 5.9 years, and 59% were women. The HBV markers used were anti-HBc and HBsAg. HCV antibodies were detected with a third generation anti-HCV ELISA, followed by immunoblotting (RIBA 3) if the test was positive. Immunoblot-reactive samples were analysed for HCV-RNA by polymerase chain reaction and genotyped. In all patients with signs of chronic HBV or HCV, epidemiological data were evaluated and liver biopsies obtained. RESULTS: Of the series as a whole (n = 5533), 4.2% (n = 211) tested positive for anti-HBc and 0.2% (n = 10) for HBsAg. RIBA 3 analysis showed 0.37% (18/5533) to be anti-HCV-positive, of whom 83% (15/18) were HCV-RNA-positive. Apart from two (both from HBsAg carriers) with normal histology, all liver biopsies manifested various degrees of inflammation and fibrosis. Among anti-HCV-positives, median grade was 6 and median stage 1 (Knodell score). CONCLUSION: The prevalence of both chronic HBV and HCV is low in the Swedish general urban middle-aged population. Nonetheless, the long-term effects on the population and the health care system may be significant.

Female↗
PubMed2000

Alpha1-antitrypsin deficiency may be a risk factor for duodenal ulcer in patients with Helicobacter pylori infection.

BACKGROUND: Most individuals with Helicobacter pylori infection in Western countries have no evidence of peptic ulcer disease (PUD). We therefore assessed the PiZ deficiency variant of the major plasma protease inhibitor alpha1-antitrypsin (alpha1AT) as a risk factor for PUD in H. pylori-infected individuals. METHODS: The cohort comprised 100 patients with endoscopically or surgically proven PUD (30 patients with duodenal ulcer (DU) and 70 patients with gastric ulcer (GU)) and 162 age- and sex-matched controls with PUD-negative endoscopic findings and no history of PUD. Plasma samples were screened for alpha1AT deficiency (PiZ) with an enzyme-linked immunosorbent assay (ELISA) and phenotyped by isoelectric focusing. H. pylori infection was evaluated with an IgG ELISA technique. RESULTS: Among the 262 patients 17 (6.5%) were positive for the PiZ alpha1AT deficiency, a frequency of the same magnitude as in the Swedish general population (4.7%). Of the PiZ carriers 76% (13 of 17) had H. pylori antibodies compared with 61% (151 of 245) of the non-PiZ carriers (NS). The prevalence of DU tended to be higher in H. pylori-positive PiZ carriers than in non-PiZ carriers (15.4%, 4 of 26 versus 0 of 4). Furthermore, among patients with DU a high PiZ allele frequency (13.3%, 4 of 30) was found compared with the general population (4.7%) (odds ratio (OR), 3.2; 95% confidence interval (CI), 1.09-8.94; P = 0.02). All DU patients carrying the PiZ allele were positive for H. pylori. In addition, four of five PiZ carriers with H. pylori infection and PUD had DU. CONCLUSIONS: The PiZ allele may be a contributing factor in the development of DU in H. pylori-positive individuals.

Duodenal Ulcer↗
PubMed2000

The effect of dimethyl sulphoxide on the induction and repair of double-strand breaks in human cells after irradiation with gamma-rays and accelerated ions: rapid or slow repair may depend on accessibility of breaks in chromatin of different compactness.

PURPOSE: The repair of double-strand breaks (dsb) in mammalian cells is characterized by a rapid phase with a half-life of less than half an hour and a slower phase that lasts for many hours. The proportion of slow repair increase with LET and it has been suggested that the slow repair component consists of more complex damage and is more deleterious to the cells. To see if removal of OH radicals could remove part of the damage in complex dsb and make them easier to repair, human cells were irradiated in the presence of dimethyl sulphoxide (DMSO). METHODS: Induction and repair of dsb were studied by neutral elution in human VH10 cells exposed to y-rays, helium ions (mean LET 40 keV/microm) and 80 and 125 keV/microm monoenergetic nitrogen ions in the presence and absence of 2 M DMSO. RESULTS: Incubation of cells exposed to gamma-rays, 40 keV/microm helium and 80 keV/microm N ions demonstrated that scavenging of OH radicals by DMSO removed most of the rapid repair component. The response to DMSO was less marked after 125 keV/microm nitrogen ions, where about half of the rapid repair was resistant to DMSO. CONCLUSIONS: It is unlikely that the complexity of dsb is responsible for the slow repair because the removal of OH radicals did not make the breaks easier to repair. Instead, it is suggested that rapid and slow repair can be explained on the basis of how different parts of the chromatin are accessible to repair enzymes.

Cells, Cultured↗
PubMed2000

Reducing negative appendectomy: evaluation of ultrasonography and computer tomography in acute appendicitis.

OBJECTIVE: To study the sensitivity and the specificity for ultrasonography and computed tomography in patients with suspected appendicitis, and their value to the clinician. MAIN OUTCOME MEASURES: The negative appendectomy rate and the sensitivity and the specificity for ultrasonography and computed tomography in patients with suspected appendicitis. RESULT: The diagnostic accuracy was 88% (men 95%, women 80%). Two hundred and thirty-nine patients were examined by ultrasonography preoperatively. The sensitivity for ultrasonography was 0.82 and the specificity was 0.97. Forty-nine patients were examined by computed tomography preoperatively. The sensitivity for computer tomography was 0.88 and the specificity was 0.95. CONCLUSIONS: We conclude that ultrasound and computed tomography investigations on patients with suspected appendicitis are of great value. Computed tomography seems to have a higher sensitivity than ultrasound and a high specificity. In fertile women, where unnecessary surgery is best avoided, we believe that computed tomography investigation or ultrasound examination are better alternatives to surgical intervention.

Adult↗
PubMed2000

Serum antibodies to Helicobacter hepaticus and Helicobacter pylori in patients with chronic liver disease.

BACKGROUND: Bile tolerant helicobacter species such as H hepaticus and H bilis have frequently been reported to cause hepatitis in mice and other rodents. AIMS: To investigate the possible pathogenic role of these and other helicobacter species in chronic liver disease in humans. METHODS: Serum samples from 144 patients with various chronic liver diseases, 30 patients with primary sclerosing cholangitis (PSC), and 48 healthy blood donors were analysed for antibodies against H hepaticus murine strain CCUG 33637 and H pylori strain CCUG 17874. Cell surface proteins of H hepaticus were extracted by acid glycine buffer and used in an enzyme immunoassay (EIA) and immunoblot (IB). RESULTS: 56 of 144 (39%) patients with chronic liver diseases and six of 30 (20%) with PSC showed increased antibody concentrations in the H hepaticus EIA; in the H pylori EIA the numbers were 58% and 13% respectively. Compared with the healthy blood donors the antibody reactivity against the two helicobacter species was not increased (46% and 48% respectively). Patient serum samples retested by the H hepaticus EIA after absorption with sonicated H pylori cells remained positive in 12 of 37 (33%) serum samples. Distinct antibody reactivity to 55-65 kDa proteins was observed by H hepaticus IB, after the absorption step, and was considered specific for H hepaticus. These 12 serum samples were from patients with chronic alcoholic liver disease. CONCLUSIONS: Antibodies to H hepaticus, often cross reacting with H pylori, occur frequently in patients with chronic liver diseases, with no clear cut relation to specific diagnostic groups. The pathogenic significance of these findings is not known.

Adult↗
PubMed2000

Myrosinase: gene family evolution and herbivore defense in Brassicaceae.

Glucosinolates are a category of secondary products present primarily in species of the order Capparales. When tissue is damaged, for example by herbivory, glucosinolates are degraded in a reaction catalyzed by thioglucosidases, denoted myrosinases, also present in these species. Thereby, toxic compounds such as nitriles, isothiocyanates, epithionitriles and thiocyanates are released. The glucosinolate-myrosinase system is generally believed to be part of the plant's defense against insects, and possibly also against pathogens. In this review, the evolution of the system and its impact on the interaction between plants and insects are discussed. Further, data suggesting additional functions in the defense against pathogens and in sulfur metabolism are reviewed.

Amino Acid Sequence↗
PubMed2000

Dual-label time-resolved immunofluorometric assay of free and total prostate-specific antigen based on recombinant Fab fragments.

BACKGROUND: Recombinant Fab fragments are attractive as reagents for novel sandwich immunoassays, but no such assays have been described. We developed a dual-label two-site immunoassay based entirely on recombinant Fab fragments and compared it to the same assay with intact monoclonal antibodies. METHODS: The capture Fab fragment, which binds free prostate-specific antigen (PSA) and PSA in complex with alpha(1)-antichymotrypsin on an equimolar basis, is site-specifically biotinylated and attached to the solid phase in streptavidin-coated microtitration wells. The Fab fragment that detects only free PSA is site-specifically labeled with a fluorescent europium chelate, and the Fab fragment that detects both free and serpin-complexed PSA in an equimolar fashion is labeled with a fluorescent terbium chelate. Time-resolved fluorescence is used to measure both europium and terbium signals in one well. RESULTS: The detection limits of the assay (mean + 3 SD of zero calibrator) were 0.043 and 0.28 microgram/L, respectively, for free and total PSA. The within-run and day-to-day CVs were 2-11% and 4-10%, respectively. Mean recoveries were 93% and 98% in female and male sera, respectively. Compared with the commercial ProStatus PSA Free/Total Assay, the intercepts of the regression equations (r >0. 99) were not significantly different from zero, and the slopes were 0.95-1.01. In one female serum sample, PSA was falsely increased with the monoclonal assay but was undetectable with the recombinant assay. CONCLUSIONS: The performance of this novel assay based on recombinant components is comparable to a conventional assay based on monoclonal antibodies. The more complete control of the essential characteristics of site-specifically derivatized recombinant Fab fragments will be valuable for the design of miniaturized and multianalyte assay concepts where correct antibody orientation, density, and capacity as well as uncompromised binding affinity are required.

Antibodies, Monoclonal↗