Biomedical subjects

I Nilsson

Publications and source records attributed to I Nilsson.

At least 55 records · Page 3Linked to original sources

PubMed1999

Insertion of a bacterial secondary transport protein in the endoplasmic reticulum membrane.

The sodium ion-dependent citrate carrier of Klebsiella pneumoniae (CitS) contains 12 hydrophobic potential transmembrane domains. Surprisingly, an alkaline phosphatase fusion study in Escherichia coli has suggested that only 9 of these domains are embedded in the membrane, and 3 are translocated to the periplasm (van Geest, M., and Lolkema, J. S. (1996) J. Biol. Chem. 271, 25582-25589). To provide independent data on the topology and mode of membrane insertion of CitS, we have investigated its insertion into the endoplasmic reticulum (ER) membrane. By using in vitro translation of model proteins in the presence of dog pancreas microsomes, each of the putative transmembrane segments of CitS was assayed for its potency to insert into the ER membrane, both as an isolated segment as well as in the context of COOH-terminal truncation mutants. All 12 segments were able to insert into the membrane as Ncyt-Clum signal anchor sequences. In a series of COOH-terminal truncation mutants, the segments inserted in a sequential way except for one segment, segment Vb, which was translocated to the lumen. Hydrophobic segments VIII and IX, which, according to the alkaline phosphatase fusion study, are in the periplasm of E. coli, form a helical hairpin in the ER membrane. These observations suggest a topology for CitS with 11 transmembrane segments and also demonstrate that the sequence requirements for signal anchor and stop transfer function are different.

Alkaline Phosphatase↗

PubMed1999

A new bone dust packer for use in neurosurgery.

A new tool for the packing of bone dust has been developed. The instrument compresses a mixture of bone dust and saline into suitable cylindrical plugs, fitting neatly into craniotomy burrholes. The skullbone at the craniotomy area will heal neatly also assuring the best healing possibilities for the overlying skin. The cosmetic results are excellent as no skin dents or cavities will be formed over the burrholes.

Adult↗

PubMed1999

Helicobacter pylori infection in Ethiopian children: a cohort study.

Risk factors for infection with Helicobacter pylori (HP) were investigated in a cohort study of 121 seronegative children in Ethiopia aged 2-4 y, who had previously participated in a case-control study. Blood samples were drawn at inclusion in the cohort study and again after 12 and 30 months. At 12 months the parents were also interviewed about putative risk factors for infection, using a structured questionnaire. Analyses were made by comparing risk factors in seropositive and seronegative children. The seroconversion rate during the first year was 31% (27/87) and during the following 18 months 34% (17/50; corresponding to an annual incidence of 24%). After a period of 30 months, 58% (14/24) of the children who were 24-29 months old at inclusion in the study had seroconverted, compared with 40% (4/10) of those who were 30-35 months old, 73% (22/30) of those who were 36-41 months old and 31% (4/13) of those who were 42 months old or more. These results indicate that peak age for HP infection is below 6 y in this cohort in Ethiopia, and might also reflect a pattern of repeated seroconversion and sero-reversion in early childhood. Independent predictors of HP-seroconversion were the variables 'drinking-water', comparing water from a well with water from rivers or pipes (RR = 1.46, 95% CI 1.0-2.15) and 'antibiotic treatment' (RR = 1.84, 95% CI 1.16-2.92).

Child, Preschool↗

PubMed1999

Division of Listeria monocytogenes serovar 1/2a strains into two groups by PCR and restriction enzyme analysis.

Altogether, 100 strains of Listeria monocytogenes serovar 1/2a isolated from humans, animals, food, and the environment were typed by a combination of PCR and restriction enzyme analysis (REA). A PCR product of 2,916 bp, containing the downstream end of the gene inlA (955 bp), the space between inlA and inlB (85 bp), and 1,876 bp of the gene inlB, was cleaved with the enzyme AluI, and the fragments generated were separated by gel electrophoresis. By this method two different cleavage patterns were obtained. Seventy of the 100 strains shared one restriction profile, and the remaining 30 strains shared the second one. No relation was found between the types differentiated by PCR-REA and the origins of the strains.

Animals↗

PubMed1999

Crisis phenomena after stroke reflected in an existential perspective.

The study gains a deeper understanding of crisis phenomena emerging after stroke and focuses on these phenomena viewed in an existential perspective. Ten stroke victims narrated their experiences of their new life situation in open-ended interviews, conducted during the first few months after discharge. The participants were analyzed using a phenomenological-hermeneutic approach. This analysis disclosed an extremely distressing situation related to the individuals' struggle to manage in various dimensions of life. The phenomena were intertwined in a complex way and the critical interpretation involved a transcendence to the existential dimension of life. The situation was metaphorically depicted as "a struggle in the darkness" in a "boundary situation," where the issues ultimately touched on life and death, fate and future, meaning and meaninglessness. The study indicates the significance of existential issues pervading the seemingly concrete struggle to manage life after stroke.

Aged↗

PubMed1999

Effect of anticoagulation on renal function and protein excretion in experimental acute ischemic renal failure.

Female Sprague-Dawley rats underwent right nephrectomy and 40 min left renal artery occlusion (RAO). After 15 min of reflow, polyethylene glycol 1000 (PEG1000) was infused to induce osmotic diuresis and to enable glomerular filtration rate (GFR) measurements. Urine was collected during a 90 min period, and the concentrations of PEG1000, albumin, IgG, IgM and fibrin(ogen)/degradation products (FIB) were assessed both in plasma and urine by radial immuno diffusion technique Groups of rats were subjected to saline + RAO, warfarin + RAO or sham-operation. GFR as measured by PEG1000 clearance averaged 0.61, 0.036 and 0.094 mL/min/100g BW/kidney in sham-operated, saline + RAO and warfarin + RAO rats, respectively. Urinary excretion of albumin and IgG increased substantially in both ischemic groups. IgM was not detected in any of the urine samples. FIB excretion was lowest in the saline + RAO group, possibly due to retention of FIB-containing obstructions in the tubules. Rats subjected to warfarin + RAO had significantly higher excretion of FIB. This result suggests that warfarin does not prevent the glomerular sieving of macromolecules in the glomerular filter, but reduces tubular obstruction by preventing fibrin formation, which may explain its positive effect on GFR.

Acute Kidney Injury↗

PubMed1998

Proline-induced disruption of a transmembrane alpha-helix in its natural environment.

alpha-Helix formation in globular proteins has been studied both theoretically and experimentally for decades, while a lack of both high-resolution structures and suitable experimental techniques has hampered the study of helices in membrane proteins. We have developed a new experimental approach, glycosylation mapping, where the active site of the lumenally exposed endoplasmic reticulum enzyme oligosaccharyl transferase is used as a point of reference against which the position of a transmembrane segment in the membrane can be measured. Here, we report an initial analysis of the helix-breaking properties of proline residues inserted in a transmembrane helix. We find that proline residues can break a transmembrane helix, but only when inserted near the end, and only when the helix is sufficiently long. The glycosylation mapping technique may be generally useful for determining the position of transmembrane helices in the membrane.

Amino Acid Sequence↗

PubMed1998

Positively and negatively charged residues have different effects on the position in the membrane of a model transmembrane helix.

We have studied the effects of single charged residues on the position of a model transmembrane helix in the endoplasmic reticulum membrane using the glycosylation mapping technique. Asp and Glu residues cause a re-positioning of the C-terminal end of the transmembrane helix when placed in the one to two C-terminal turns but not when placed more centrally. Arg and Lys residues, in contrast, have little effect when placed in the two C-terminal turn but give rise to a more substantial shift in position when placed 9-11 residues from the helix end. We suggest that this difference between the effects of positively and negatively charged residues can be explained by the so-called snorkel effect, i.e. that the very long side-chains of Arg and Lys can reach up along the transmembrane helix to allow the terminal, charged moiety to reside in the lipid headgroup region while the Calpha of the residue is positioned well below the membrane/water interface.

Amino Acid Sequence↗

PubMed1998

Breaking the camel's back: proline-induced turns in a model transmembrane helix.

We have constructed model membrane proteins with hydrophobic segments of the general composition Leu29Val-Leun where n=10 and 20, and have analyzed their transmembrane topology when inserted into microsomal membranes. These hydrophobic segments span the membrane once, even though they are twice as long as normal transmembrane helices. Strikingly, a single proline residue introduced near the center of the Leu39Val hydrophobic stretch induces the formation of two transmembrane segments separated by a tight turn. These results have implications for our understanding of membrane protein assembly in the endoplasmic reticulum, and for the development of techniques for predicting membrane protein topology.

Amino Acid Sequence↗

PubMed1998

The dual-tube microsurgical suction instrument.

A dual-tube suction instrument intended for both macro- and microsurgery has been developed. A detachable air-tight inner tube is fitted into a conventional suction instrument; extending the ordinary sucking tube. The inner tube can easily be fitted, as well as removed from the other tube; a particular advantage in case the inner tube becomes obstructed. On removal of the inner tube the outer tube becomes cleaned and is at once, ready for re-use. Since the suction instrument does not have to be removed from the suction hose, valuable time is saved, enabling permanent sucking capacity.

Equipment Design↗

PubMed1998

Helicobacter pylori and the relation to other risk factors in patients with acute bleeding peptic ulcer.

BACKGROUND: The influence of ulcer risk factors is well known in chronic peptic ulcer disease. In this study the risk factors were investigated in patients with peptic ulcer complicated by an acute bleeding episode. METHOD: In 106 consecutive patients with acute bleeding peptic ulcer, age, previous history of ulcer disease, presence of dyspeptic symptoms, smoking habits, consumption of nonsteroidal anti-inflammatory drugs (NSAIDs), and haemoglobin concentration at admission were recorded. Helicobacter pylori infection was detected by means of two serologic tests in samples obtained at admission for the acute bleeding episode. RESULTS: Three-quarters of both gastric ulcer and duodenal ulcer patients were shown to have H. pylori antibodies. NSAID use and smoking habits were similar in patients with and without H. pylori antibodies. CONCLUSIONS: The results indicate that H. pylori infection, NSAID use, and smoking habits act as largely independent risk factors in patients with acute bleeding peptic ulcer.

Acute Disease↗

PubMed1998

Risk factors for infection with Helicobacter pylori--a study of children in rural Ethiopia.

The public health impact of Helicobacter pylori (HP) infection is gradually becoming obvious, the bacterium now being implicated as an aetiologic agent in a variety of gastric diseases. Transmission routes still remain unknown, although single risk factors, such as domestic crowding (especially bed-sharing) in childhood and low parental socioeconomic status, have been pointed out in studies from developed countries. In an attempt to study the risk factors in a developing country, we performed a case control study of 242 randomly selected children aged 2-4 y in Butajira rural area in Ethiopia. Blood samples were drawn and a questionnaire administered. The total prevalence of IgG antibody to HP among the children in the region was 48% (116/242). Several risk factors such as: crowding, water, animals, sanitation, etc. correlated strongly to seropositivity in a univariate analysis. After controlling for possible confounding, independent predictors of seropositivity were: living in town (OR = 2.15, p = 0.001), increasing age (OR = 1.71, p = 0.060), and being a Muslim (OR = 1.54, p = 0.005). It could not be excluded that a bad water supply in town could explain the difference in seroprevalence between town and village. These results indicate that, in developing countries, factors relating to community and religion might be as important risk factors for infection with HP in children as characteristics of the family or the home.

Antibodies, Bacterial↗

PubMed1998

Hepatocyte growth factor (HGF) in patients with pneumonia: a comparison between survivors and non-survivors.

Hepatocyte growth factor (HGF) is a multifunctional growth factor. After lung injury HGF is secreted in the lung and promotes reconstruction of the damaged organ. We measured, retrospectively, the serum HGF concentrations collected on admission in 55 patients with bacterial pneumonia, using an enzyme-linked immunosorbent assay (ELISA). The patients were divided into 3 groups: Group 1 was survivors with normal liver function (n = 14), Group 2 was survivors with abnormal liver function (n = 31) and Group 3 was non-survivors (n = 10). Median concentrations of HGF were elevated in Groups 1 and 2; and no statistically significant difference between these 2 groups was found. Group 3 had a median HGF concentration within the reference range, significantly lower than both Group 1 and Group 2. In addition LDH was significantly higher in non-survivors as compared with survivors. The combination of LDH and HGF concentrations discriminated between survivors and non-survivors (sensitivity 0.90 and specificity 0.96). The results support the hypothesis that increased levels of HGF might be a natural part of the healing process of lung injury, irrespective of liver involvement, and that patients without increased HGF levels, especially those with concomitant liver function impairment, may have a poor prognosis.

Aged↗

PubMed1998

Effects of intravenous regional administration of methylprednisolone plus mepivacaine in rheumatoid arthritis.

To evaluate the subjective and objective response to intravenous regional administration of a glucocorticoid (IVRAG) on rheumatoid arthritis (RA), twenty RA-patients received, in a randomised, double-blind crossover and placebo-controlled fashion, either 50 mg methylprednisolone in mepivacaine 0.25% or mepivacaine (placebo) in one hand only using a Bier-block technique. The other hand was given the opposite. One week later the procedure was repeated but the previous placebo hand was now treated with the glucocorticoid. About 50% of the patients experienced a subjective improvement at 1 and 6 weeks. After one week a significant reduction was recorded in grip diastasis with no difference between the glucocorticoid and the placebo. In the other outcome measures (grip strength, handvolume, rest pain, and movement provoked pain) no differences were recorded between the glucocorticoid and placebo. At six weeks a significant reduction in grip diastasis and movement provoked pain as well as a significant increase in grip strength were noted. Hand volume was unchanged. IVRAG is a safe, easy and well-tolerated technique. The beneficial results are probably due to both a systemic and a regional effect. The findings of benefit in both hands at the end of one week seem to suggest that mepivacaine can give some short term improvement.

Adult↗

PubMed1998

CagA protein seropositivity in a random sample of adult population and gastric cancer patients in Estonia.

OBJECTIVE: The prevalence of antibodies to CagA protein, associated with the risk of developing gastric cancer (GC), was studied in an Estonian adult population with a high prevalence of Helicobacter pylori (HP) infection and in a group of GC patients. DESIGN: In a representative sample of a random adult population from the South Estonian town of Karksi-Nuia, containing 199 subjects (86 M, 113 F, mean age 42.4) and in 45 (22 M, 23 F, mean age 64.5) consecutive patients with gastric adenocarcinoma, recruited during the periods 1986-87 and 1995-96 in the Hospital of Oncology, University of Tartu, anti-CagA IgG antibodies were determined by enzyme-linked immunosorbent assay (ELISA) using a recombinant fragment of CagA protein. The occurrence of anti-CagA IgG in ELISA was compared with immunoblot results for 141 subjects. RESULTS: Seropositivity to acid glycine extracted cell surface proteins of HP was 85% in the population and 91% in GC patients (p = 0.39). Anti-CagA IgG antibodies were present in 63% of the population and in 87% of GC patients (p = 0.004). The highest prevalence of anti-CagA IgG in the population sample occurred in the age group 20-29 (76%). A comparison of anti-CagA positivity evaluated by using ELISA and immunoblot showed an agreement of results in 80% of cases. CONCLUSION: HP seropositivity was similarly high in the Estonian random adult population sample and in GC patients, however, the prevalence of anti-CagA IgG was significantly higher in GC patients. Moreover, persons aged 20-29 years in the population possess the highest prevalence of anti-CagA IgG and should be given further attention with respect to the development of GC later in life.

Adenocarcinoma↗

PubMed1998

Hormonal regulation of liver fatty acid-binding protein in vivo and in vitro: effects of growth hormone and insulin.

Liver fatty acid-binding protein (LFABP) is an abundant protein in hepatocytes that binds most of the long chain fatty acids present in the cytosol. It is suggested to be of importance for fatty acid uptake and utilization in the hepatocyte. In the present study, the effects of bovine GH (bGH) and other hormones on the expression of LFABP and its messenger RNA (mRNA) were studied in hypophysectomized rats and in vitro using primary cultures of rat hepatocytes. One injection of bGH increased LFABP mRNA levels about 5-fold after 6 h, but there was no effect of this treatment on LFABP levels. However, 7 days of bGH treatment increased both LFABP mRNA and LFABP protein levels 2- to 5-fold. Female rats had higher levels of LFABP than male rats. Hypophysectomy of female rats, but not that of male rats, decreased LFABP levels markedly. Treatment of hypophysectomized rats with bGH for 7 days as two daily injections or as a continuous infusion increased LFABP levels to a similar degree. This finding indicates that the sex difference in the expression of LFABP is not regulated by the sexually dimorphic secretory pattern of GH. Neither insulin nor insulin-like growth factor I treatment of hypophysectomized rats for 6-7 days had any effect on LFABP mRNA or LFABP levels. In vitro, bGH dose-dependently increased the expression of LFABP mRNA, but only in the presence of insulin. Insulin alone had a marked dose-dependent effect on LFABP mRNA levels and was of importance for maintaining the expression of LFABP mRNA during the culture. Incubation with bGH increased LFABP mRNA levels within 3 h. GH had no effect on LFABP mRNA levels in the presence of actinomycin D, indicating a transcriptional effect of GH. Incubation with glucagon in vitro decreased LFABP mRNA levels markedly, indicating that glucagon, in contrast to GH, has an effect opposite that of insulin on LFABP mRNA expression. It is concluded that GH is an important regulator of LFABP in vivo and in vitro. In contrast to the effect of GH on insulin-like growth factor I mRNA, the presence of insulin was a prerequisite for the effect of GH on LFABP mRNA expression in vitro. The results emphasize the role of GH in the regulation of hepatic fatty acid metabolism.

Animals↗

PubMed1998

Cloning and characterization of 5'-end alternatively spliced human cholecystokinin-B receptor mRNAs.

We report here the cloning and characterization of a 5'-end alternatively spliced human cholecystokinin-B (CCK-B) receptor mRNA. The 5'-end of this CCK-B receptor transcript (termed CCK-BRtx) consisted of exon Ia, present in the ordinary full-length CCK-B receptor mRNA (CCK-BRwt), and exon Ib, present in a previously described 5'-end alternatively spliced CCK-B receptor mRNA (CCK-BRt). A short open reading frame preceded the AUG translation initiation codon of the CCK-BRtx. Transfection of COS-7 cells with the CCK-BRtx or CCK-BRt cDNAs did not lead to the appearance of peptidergic and non-peptidergic binding sites. Cell free in vitro translation yielded proteins of approximately 44 kDa (CCK-B receptor) and 40 kDa (CCK-BRt receptor) whereas no 40 kDa product was detected from the cloned CCK-BRtx cDNA. Instead, a protein product of approximately 9 kDa was visualized, the size corresponding to the predicted protein encoded by the short open reading frame. The alternatively spliced CCK-B receptor transcripts were concomitantly expressed with the ordinary full-length CCK-B receptor mRNA in the brain, pancreas, and stomach. The possibility that such transcripts are translated in vivo into truncated CCK-B receptors is discussed.

Alternative Splicing↗

PubMed1998

Effects of melagatran, a new low-molecular-weight thrombin inhibitor, on thrombin and fibrinolytic enzymes.

Melagatran, a new, competitive and rapid inhibitor of thrombin with a molecular mass of 429 Da is described. Melagatran is well tolerated when administered in very high doses, and the oral bioavailability in the dog is relatively high. The aim of the study was to determine, in the preclinical setting, the degree of selectivity against the fibrinolytic system required for entering the clinical development phase. Melagatran was compared with two structurally similar thrombin inhibitors, inogatran and H 317/86. The potent inhibition of thrombin by melagatran was demonstrated by a low inhibition constant (Ki) for thrombin (0.002 micromol/l) and prolongation of clotting time to twice the control value in coagulation assays at low concentrations (0.010, 0.59 and 2.2 micromol/l for thrombin time, activated partial thromboplastin time and prothrombin time, respectively). Furthermore, thrombin-induced platelet aggregation was inhibited at the same concentration (IC50-value 0.002 micromol/l) as the Ki-value for thrombin. In two assays of global fibrinolysis, inhibition was observed at a concentration of 1.1 micromol/l in a euglobulin plasma fraction model, while no inhibition was observed at a concentration of < or = 10 micromol/l in a plasma model. In an in vivo model of endogenous fibrinolysis in the rat, inhibition of fibrinolysis was observed at > or = 1.0 micromol/l. In all assays, except the Ki-ratio determinations, the compounds could be graded with regard to selectivity against the fibrinolytic system: inogatran > melagatran > H 317/86. For melagatran, inhibition of fibrinolysis was not observed at concentrations below the upper limit of the proposed therapeutic plasma concentration interval (< 0.5 micromol/l). Thus, melagatran seems to have a sufficient selectivity against the fibrinolytic system, while H 317/86 was considered to be insufficient for clinical development.

Administration, Oral↗