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Biomedical subjects

I Nilsson

Publications and source records attributed to I Nilsson.

At least 73 records · Page 4Linked to original sources
PubMed1997

Anionic phospholipids are determinants of membrane protein topology.

The orientation of many membrane proteins is determined by the asymmetric distribution of positively charged amino acid residues in cytoplasmic and translocated loops. The positive-inside rule states that loops with large amounts of these residues tend to have cytoplasmic locations. Orientations of constructs derived from the inner membrane protein leader peptidase from Escherichia coli were found to depend on the anionic phospholipid content of the membrane. Lowering the contents of anionic phospholipids facilitated membrane passage of positively charged loops. On the other hand, elevated contents of acidic phospholipids in the membrane rendered translocation more sensitive to positively charged residues. The results demonstrate that anionic lipids are determinants of membrane protein topology and suggest that interactions between negatively charged phospholipids and positively charged amino acid residues contribute to the orientation of membrane proteins.

Alkaline Phosphatase↗
PubMed1997

Molecular mechanism of membrane protein integration into the endoplasmic reticulum.

As proteins are integrated into the membrane of the endoplasmic reticulum, some hydrophilic polypeptide segments are transported through the translocation channel, others remain in the cytosol, and hydrophobic transmembrane sequences are released into the lipid phase. We have addressed the molecular mechanism by which these events occur. We demonstrate that both the lumenal and the cytosolic domains of a membrane protein are synthesized while the ribosome is membrane bound, so that even cytosolic domains come in contact with the translocation channel. We also find that, before translation of the protein is terminated, transmembrane sequences can laterally exit the translocation channel and enter the lipid environment. These results have significant implications for the folding and assembly of membrane proteins.

Animals↗
PubMed1997

Comparison of toremifene and tamoxifen in post-menopausal patients with advanced breast cancer: a randomized double-blind, the 'nordic' phase III study.

The study was planned to compare, in a prospective double-blind randomized trial, the efficacy and safety of toremifene (TOR) and tamoxifen (TAM) in post-menopausal patients with advanced breast cancer who have not had prior systemic therapy for advanced disease. Four hundred and fifteen post-menopausal patients with oestrogen receptor (ER)-positive or ER-unknown advanced breast cancer were randomly assigned to receive daily either 60 mg TOR or 40 mg TAM. The patients were stratified to measurable and non-measurable but evaluable groups. They were assessed for response to therapy, time to progression (TTP), time to treatment failure (TTF), response duration, overall survival and drug toxicity. Two hundred and fourteen patients were randomized into TOR and 201 into TAM treatment. The response rate (complete + partial) was 31.3% for TOR and 37.3% for TAM (P = 0.215). The 95% confidence interval (CI) for the 6% difference was -15.1% to 3.1%. The median TTP was 7.3 months for TOR and 10.2 months for TAM (P = 0.047). The 95% CI for the hazard ratio of 0.80 was 0.64-1.00. A percentage of the TOR patients (9.8%) and the TAM patients (18.9%) discontinued the treatment prematurely (P = 0.011) for various reasons. Consequently, the median TTF of 6.3 vs 8.5 months did not differ significantly (P = 0.271). The hazard ratio was 0.89 and the subsequent 95% CI 0.73-1.09. The median overall survival was 33.0 months for TOR and 38.7 months for TAM (P = 0.645). The hazard ratio was 0.94 with 95% CI of 0.73-1.22. The transient difference in TTP may be related to an imbalance in ER content of the tumours. When only patients with ER-positive tumours were considered (n = 238), no difference between two treatments was seen (P = 0.578). TAM was associated with an overall slightly higher frequency of adverse drug reactions than TOR (44.3 vs 39.3%) and a higher discontinuation rate due to these events (3.5% vs 0.9%). Treatment-emerged moderate dizziness (P = 0.026) and cataracts (P = 0.026) were more frequent among TAM than among TOR patients. In conclusion, TOR (60 mg day(-1)) and TAM (40 mg day(-1)) are equally effective and safe in the treatment of advanced post-menopausal ER-positive or ER-unknown breast cancer.

Adult↗
PubMed1997

Bernard-Soulier syndrome Karlstad: Trp 498-->Stop mutation resulting in a truncated glycoprotein Ib alpha that contains part of the transmembranous domain.

In Bernard-Soulier syndrome, a hereditary bleeding disorder, the platelets are deficient in the glycoprotein (GP) Ib-IX-V complex, a major receptor for the von Willebrand factor. The components of the complex are encoded by separate genes. Patients with this syndrome have a variable expression level of the receptor protein on platelets depending on the specific genetic abnormality. We describe a patient with life-long bleeding symptoms, who is homozygous for a unique stop mutation. Trp 498-->Stop in the GPIb alpha gene, resulting in a truncated GPIb alpha polypeptide chain. In contrast to previously reported truncated forms of GPIb alpha, this form contains a portion of the transmembranous domain as well as the juxtamembranous cysteines engaged in a disulphide bond with GPIb beta. Flow cytometry with GPIb alpha antibodies demonstrated the presence of GPIb on the patient's platelets, although in reduced amounts compared to normal controls. GPIX was similarly detectable. Immunoblotting demonstrated that the patient synthesized a truncated GPIb alpha of the expected size of 130 K, which was, however, sensitive to proteolysis. These studies show that GPIb alpha lacking the intracytoplasmic tail can be expressed at the platelet surface provided elements of the transmembranous domain are present.

Aged↗
PubMed1997

To meet with a stroke: patients' experiences and aspects seen through a screen of crises.

The aim of this study was to elucidate the experiences of stroke victims during the course of disease and the first few months after discharge. Ten individuals, recently having suffered their first manifest stroke with lasting neurological symptoms, narrated their experiences and gave their views at two different appointments during the first few months after discharge. A deductive approach was applied, on the basis of the theory of developmental crises. The analyses of the interviews were performed using a phenomenological hermeneutic method inspired by the philosophy of Ricoeur. The analyses disclosed phenomena signifying developmental crises in all the cases, though the crises profiles were marked by the sequelae the individuals suffered after stroke and by the age-specific stages of which they were in the middle. The solution of the crises was from being reached within the period of data collection, as the interviews were performed relatively early after home-coming and the individuals were in the middle of grasping their new situation. The phenomenon "to meet with a stroke' seems to challenge the whole of the individual's being. The study calls attention to the need for awareness of this matter, which should be indicated to a much greater extent in nursing care and education than has been done until to date.

Activities of Daily Living↗
PubMed1997

Immunoblot assay for serodiagnosis of Helicobacter pylori infections.

An immunoblot assay for the serological diagnosis of Helicobacter pylori infection was evaluated. Serum samples from patients whose gastric biopsy specimens were known to be positive or negative for H. pylori on culture were used to establish interpretive criteria for the immunoblot assay. A panel of sera from patients with diseases other than H. pylori infection and sera from healthy blood donors were included to validate these criteria. All sera were initially assessed in an enzyme immunoassay (Ge-EIA), based on acid glycine-extracted cell surface proteins of H. pylori NCTC 11637. The same antigen extract was used in the immunoblot assay. In addition, the Ge-EIA and the immunoblot assay were compared with a commercially available EIA (Seradyn, Color Vue Pylori). Bands of 110/120 kDa and/or two of five low-molecular-mass proteins (26, 29, 30, 31, and 33 kDa, in any combination) showed a strong correlation with the H. pylori culture-positive patients (97.5%) compared to the correlation obtained with the EIA results (Ge-EIA, 87.5%; Seradyn EIA, 92.5%), and the antibody responses to these proteins were considered specific reactions. In 37 of 40 serum samples from culture-negative patients and also in sera from patients with other disorders, a moderate antibody reactivity to the medium-size proteins (43 to 66 kDa) was observed, and these were considered not valuable for a specific immunoblot assay. Among sera from culture-positive patients, 39 of 40 serum samples were defined to be immunoblot positive, and from among sera from culture-negative patients, 3 of 40 serum samples were defined to be immunoblot positive. The use of sera from patients with negative cultures for H. pylori as negative controls may decrease the sensitivity due to sampling error and false-negative culture results. Immunoblot assay-positive results were detected among 10% of sera from patients with other diseases, whereas they were detected among 42.5% of sera by the Ge-EIA and 47.5% of sera by the Seradyn-EIA. The higher number of EIA-positive sera in this group reflects a possible cross-reactivity (false-positive EIA result). Of the blood donors, representing asymptomatic but possibly colonized subjects, 24% were immunoblot positive. In conclusion, our data indicate that immunoblotting is more sensitive as well as more specific than EIA. Moreover, it permits detection of antibody responses to specific antigens, e.g., the cytotoxin-associated CagA protein, which may have pathological implications.

Adult↗
PubMed1996

Calnexin can interact with N-linked glycans located close to the endoplasmic reticulum membrane.

Calnexin is a central component of the 'quality control' system in the endoplasmic reticulum (ER). Calnexin binds to monoglycosylated oligosaccharides on incompletely folded soluble and membrane proteins in the lumen of the ER and prevents exit from the organelle. We have previously found that the oligosaccharide transferase enzyme can add glycosyl moieties to a membrane protein when the acceptor site is as close as 12-13 residues away from the nearest transmembrane segment (J. Biol. Chem. 268, 5798). We now show that calnexin can bind to oligosaccharides located this close to the membrane, suggesting that its binding site is held at a similar distance from the membrane as is the active site of the oligosaccharide transferase. We further show that calnexin can bind efficiently to glycosylated but not to non-glycosylated forms of a bacterial inner membrane protein, suggesting that it does not have a general affinity for non-glycosylated proteins.

Animals↗
PubMed1996

Serum antibodies against Borrelia afzelii, Borrelia burgdorferi sensu stricto and the 41-kiloDalton flagellin in patients from a Lyme borreliosis endemic area: analysis by EIA and immunoblot.

To evaluate the possible importance of antigenic heterogeneity in the serological diagnosis of Lyme borreliosis a study was performed using antigens from various Lyme Borrelia strains. Serum samples from 102 patients with clinical signs of the infection, all living in an endemic area in southern Sweden, were evaluated by four enzyme immuno assays (EIA). The sera were initially tested for the immunoglobulin G response to antigens from a local Borrelia afzelii strain (ACA1). Serum samples from healthy blood donors residing in the same region were used to define seropositivity in the ACAI-EIA. Immunoblotting was performed with the ACAI antigen and the reactive bands were analysed. A serum was defined as positive when at least four of the Borrelia specific polypeptides (OspC, OspA, OspB, p39, p41 [flagellin], p83, p94, 110kDa) were stained. The same sera were then analysed in three other IgG enzyme immunoassays, one based on antigens from Borrelia burgdorferi sensu stricto B31, and another on pooled protein fractions from strains B31 and ACAI. In the third EIA, sera were analysed for antiflagellin reactivity (B, afzelii strain DK-1). An inconstant immune response was demonstrated in the EIAs and the seropositivity varied between 30-47% when low positive values were excluded, and between 38-73% if all values were included. Fifty sera (50/102) met the criteria for a positive immunoblot, but positive immunoblots were detected with both low positive and negative sera independent of antigen used in the EIAs. Antigens of the local B. afzelii strain were found to detect a higher number of seropositive individuals, which suggests that the antibody reactivity to Lyme Borrelia increases when antigens from a strain endemic in a particular geographical region are used. Data from this study suggest that EIA alone seems insufficient for the serodiagnosis, and antigenic heterogeneity of Lyme Borrelia spp. influences the performance of serum antibody tests. The reliability of serological assays could be increased when the serum antibodies against antigens of Borrelia spp. predominant in the local geographical region are measured.

Antigens, Bacterial↗
PubMed1996

Age at acquisition of Helicobacter pylori infection: comparison of a high and a low prevalence country.

Helicobacter pylori (HP) is now generally accepted as the main aetiological agent in chronic active gastritis and peptic ulcer. Infection with HP is widespread, but the routes of transmission are still unclear. Several studies have shown increasing prevalence of antibodies against HP with age. In developing countries, age at peak incidence of seroconversion is probably considerably lower than in developed countries. We performed a cross-sectional study to determine the age at maximum incidence of seroconversion to HP in a high-prevalence country (Ethiopia) and in a low-prevalence country (Sweden). Sera from 242 Ethiopian children, aged 2-14 years and from 295 Swedish children aged 1-15 years were analysed using an enzyme linked immunosorbent assay (ELISA) for detecting immunoglobulin G (IgG) antibodies. In Ethiopia, a comparison was made of a local and a reference strain for preparation of the antigen, but there was little difference in outcome. A comparison between antigen prepared from the reference strain and the pooled antigen used in the Swedish study also showed little difference. The sharpest rise in seroprevalence was found in the age range 2-4 years. Among 4-year-olds, some 60% had already seroconverted, and among 12-year-olds almost 100% had done so. In Sweden, the sharpest rise appeared between the ages of 9 and 10 years. Above 10 years of age seroprevalence was around 20%. Infection with HP is acquired in early childhood in Ethiopia, but somewhat later, although still before the teens, in Sweden. To determine properly the risk factors for infection with HP, possible exposure must be assessed around the age of seroconversion, since seropositivity may remain for a long time but environmental factors may have changed since primary infection.

Adolescent↗
PubMed1995

Presence of the intermediate filaments cytokeratins and vimentin in the rat corpus luteum during luteal life-span.

The presence of the intermediate filament (IF) proteins cytokeratins and vimentin in corpus luteum (CL) and other parts of the ovary from adult pseudopregnant rats was investigated using immunohistochemistry and immunoblot analysis. To induce pseudopregnancy, female rats were mated with sterile male rats. The mating procedure induces a prolonged luteal life-span of 13 +/- 1 days. Positive staining for cytokeratin could be seen in CL, in the theca layer of follicles, and the ovarian surface epithelium with the broad-spectrum monoclonal antibody cocktail AE1/AE3. Weak staining was also seen in CL with antibodies against cytokeratins 8 and 18. A similar distribution was also seen for vimentin, which furthermore was detected in blood vessels. No changes in staining intensity was seen in CL of different luteal age. The strong staining for vimentin in CL was confirmed by immunoblot analysis, where one main band of 57 kDa was observed from day 1 to day 19 of pseudopregnancy. Expression of the IF proteins investigated seems to start in the newly formed CL and the continuous expression indicates that they are not directly regulated by luteal steroids.

Animals↗
PubMed1995

Role of bile in regulation of gut motility.

Bile empties into the duodenum not only after a meal but also in the interdigestive state. In man, interdigestive biliary emptying is related to fasting motor activity, the migrating motor complex (MMC), in the stomach and small bowel and generally occurs during phase 2 preceding a gastroduodenal phase 3 activity (activity front). It seems that the main regulatory peptide to initiate phase 3 is motilin. During a period with 13 phase 3 activities of MMC, 18 episodes of gall-bladder emptying and 19 motilin peaks were observed. Such a peak of plasma motilin usually took place 25 +/- 11 min after onset of biliary emptying. In conclusion, data indicate that motilin is released to the circulation by the biliary output and induces phase 3 of MMC. The induced phase 3 propels bile acids along the gut to promote their absorption in the distal intestine. The choleretic action of recycling of bile acids may cause subsequent episodes of biliary emptying with motilin release by the action of the enterohepatic circulation of bile acids. In such a manner the MMC may be withheld as a recycling motility pattern.

Animals↗
PubMed1995

Inhibition of the migrating motor complex by duodenal drainage in man.

The effect of varying bile acid output on fasting small intestinal motility was investigated in healthy male volunteers. Biliary output was manipulated by jejunal infusion of isotonic mannitol, which resulted in increased output, and by prolonged drainage of duodenal contents, which resulted in decreased output. Intestinal motility was measured by manometric recordings performed at four levels in the proximal small intestine. A marker dilution technique was used to measure pancreatico-biliary output. There were three experimental groups: duodenal drainage, non-drainage and control. Both duodenal drainage and non-drainage groups underwent jejunal saline infusion, followed by mannitol infusion. The control group did not receive drainage or infusions. In the drainage group, 0.41 (0.13-0.68) activity fronts of the migrating motor complex (MMC) per hour were recorded during saline infusion, but only 0.06 (0-0.19) activity fronts per hour were observed during mannitol infusion. In the non-drainage group, 0.71 (0.61-0.81) activity fronts per hour were observed during saline infusion and 0.50 (0.18-0.82) activity fronts per hour were recorded during mannitol infusion. In the control group, 0.58 (0.33-0.84) activity fronts per hour were recorded during the first 4-h session and 0.58 (0.45-0.71) activity fronts per hour during the second session. There was no difference between the number of activity fronts per hour observed in the control group and those observed in the saline infusion of the drainage group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Ovarian levels of epidermal growth factor receptor mRNA in the rat--a postovulatory decrease.

Members of the epidermal growth factor (EGF) family have many different effects on ovarian cells including a strong inhibition of estradiol-17 beta production. An increased binding of the EGF family to its receptor is seen at the time of ovulation. The aim of the present study was to measure the mRNA levels of the EGF receptor in the preovulatory follicle and to see if the levels are still high after functional luteolysis. The mRNA of the EGF receptor was measured in whole ovaries, follicles and corpora lutea. Pregnant mare serum gonadotrophin (PMSG) stimulated rats were used to get defined follicles. To achieve luteolytic corpora lutea on day 11, the adult female pseudopregnant rat model was used. Determination of the EGF receptor mRNA was performed with solution hybridization analysis, using a 768 bp long probe of the human EGF receptor (2318-3085). A two-fold increase in the mRNA levels of the EGF receptor was registered between 09.00 and 21.00 h during the proestrus day in the preovulatory follicle. Concurrently, serum estradiol-17 beta levels decreased from 420 +/- 65 to 79 +/- 6 pM. High levels of EGF receptor proteins in the preovulatory follicle were verified by immunohistochemistry. The levels of EGF receptor mRNA was decreasing from 25.4 +/- 4.4 fmol mg-1 in the corpus luteum on day 1 to 7.6 +/- 9.9 fmol mg-1 on day 11. Thus, the high amounts of EGF receptor in the ovary during the late preovulatory period might be involved in the regulation of ovarian estradiol-17 beta production.

Animals↗
PubMed1995

Epidemiology and treatment of post-stroke depression.

Depression is a common and serious complication after stroke. According to epidemiological studies, at least 30% of stroke patients experience depression, both early and late after stroke. However, in clinical practice only a minority of the patients are diagnosed and even fewer are treated. There are several studies confirming the magnitude of the problem but the main conclusion which can be drawn from the few treatment studies published is that tricyclic antidepressants cannot be recommended for the treatment of post-stroke depression, mainly because of the high frequency of contraindications and adverse effects. Until now there has only been 1 double-blind, placebo-controlled treatment study from which some general conclusions can be drawn. The study evaluated a selective serotonin reuptake inhibitor (citalopram) and concluded that the drug was well tolerated and effective for the treatment of post-stroke depression. However, when treatment was initiated very early, both the treatment group and the placebo group improved equally during the first 7 weeks after stroke. This finding could indicate diagnosis difficulties during the first few weeks after stroke. A recent study, although small, comparing the combination of drugs with either noradrenergic (desipramine plus mianserin) or noradrenergic and serotonergic effects (imipramine plus mianserin) for post-stroke depression, indicated that drugs with the dual effect may be more effective. Many more double-blind placebo-controlled treatment studies and studies comparing the efficacy and adverse effects of various antidepressants in patients with post-stroke depression need to be conducted. According to 3 small studies, electroconvulsive therapy (ECT) seems to be quite well tolerated and therefore ECT may also be considered in the treatment of post-stroke depression. Future studies should also address the long term efficacy of treatment for post-stroke depression.

Aged↗
PubMed1994

Nonrandom numerical aberrations of chromosomes 7, 9, and 10 in DNA-diploid bladder cancer.

Double-target in situ hybridization technique (ISH) was applied to 37 cases of bladder cancer to detect numerical aberrations of chromosomes 7, 9, 10, and 11 by centromeric DNA probes. Of 33 evaluable cases, 29 (88%) demonstrated chromosome aberrations. In 17 cases with diploid pattern as measured by flow-cytometric DNA analysis (FCM), 15 (88%) demonstrated chromosome aberrations. Of these, trisomy 7, monosomy 9, and trisomy 10 were detected in three, three, and one case, respectively, as a single chromosome aberration. In 14 (88%) of 16 cases with an aneuploid DNA pattern, chromosome aberrations for two or more chromosomes were demonstrated. A significant correlation was observed between grade of chromosome aberrations and tumor grade (p < 0.01, Fisher's test), between number of spots for chromosome 7 and peak value in FCM (p = 0.015, by Spearman rank order test). In eight cases, chromosome aberrations in the tumor were compared with the corresponding pattern in the grossly normal and histologically benign mucosa. Trisomy 10 and monosomy 9 were detected as chromosome numerical aberrations in the histologically normal mucosa, consistent with aberrations in the corresponding patients. We conclude that trisomy 7, monosomy 9, and trisomy 10 may be early events in the evolution of bladder cancer.

Carcinoma, Transitional Cell↗