Biomedical subjects

A Nilsson

Publications and source records attributed to A Nilsson.

At least 37 records · Page 2Linked to original sources

PubMed2004

Ultrafast molecular dissociation of water in ice.

Using x-ray emission and photoemission spectroscopies to measure the occupied valence levels in a thin crystalline ice film, we resolve the ionization-induced dissociation of water in ice on a femtosecond time scale. Isotope substitution confirms proton transfer during the core-hole lifetime in spite of the nonresonant excitation. Through ab initio molecular dynamics on the core-ionized state, the dissociation and spectrum evolution are followed at femtosecond intervals. The theoretical simulations confirm the experimental analysis and allow for a detailed study of the dissociative reaction path.

Biophysical Phenomena↗

PubMed2004

X-ray emission spectroscopy of (2 square root of 3 x 2 square root of 3)R30 degrees CO/Ru(0001): comparison to c(2x2)CO/Ni(100) and c(2x2)CO/Cu(100).

The atom specific electronic structure of (2 square root of 3 x 2 square root of 3)R30 degrees CO on hcp Ru(0001) has been determined with resonantly excited x-ray emission spectroscopy. We find that the general features of the local adsorbate electronic structure are similar to the situation of CO adsorbed on the fcc metals Ni(100) and Cu(100). The interpretation of the surface chemical bond of (2 square root of 3 x 2 square root of 3)R30 degrees CO/Ru(0001) based on the direct application of the local, allylic model from on-top adsorption on the fcc(100) surfaces Ni(100) and Cu(100) explains many aspects of the surface chemical bond. However, also nonlocal contributions like adsorbate-adsorbate interaction and the deviation from upright on-top adsorption on the Ru(0001) surface influence observables like the heat of adsorption and the Me-CO bond strength.

Journal Article↗

PubMed2004

Genotypic and phenotypic differences between Arabian and Scandinavian women with gestational diabetes mellitus.

AIMS/HYPOTHESIS: Gestational diabetes mellitus is a heterogeneous disorder characterised by impaired insulin secretion and action. Our aim was to study whether autoimmunity, variations in genes affecting insulin secretion and action, or both, contribute to the development of gestational diabetes and whether the pathogenesis of the disease differs between women with a Scandinavian or Arabian background. METHODS: We studied a total of 500 unrelated women with gestational diabetes (400 Scandinavian and 100 Arabian) and 550 unrelated pregnant non-diabetic control women (428 Scandinavian and 122 Arabian) matched for ethnicity. RESULTS: Arabian women with gestational diabetes were 50% more insulin resistant for the same BMI compared with Scandinavian women with the disease (homeostasis model assessment [HOMA-IR]; 3.2+/-0.3 vs 2.2+/-0.2, p=0.02). Both Scandinavian (4.2% vs 0.9%, p=0.008) and Arabian (4.6% vs 0.0%, p=0.03) women with gestational diabetes had a higher frequency of GAD antibodies (GAD65Ab) than the matched controls. The frequency of HLA-DQB1 risk genotypes was slightly higher in Scandinavian women with gestational diabetes than in the Scandinavian controls (46.3% vs 38.8%, p=0.03) but no significant difference was found between the Arabian women with gestational diabetes and the Arabian controls (47% vs 51.6%, p=0.47). There were no significant differences in the frequency of the insulin gene variable number of tandem repeat ( INS VNTR) alleles and genotypes or the peroxisome proliferator-activated receptor-gamma 2 ( PPAR gamma 2-Pro12Ala) polymorphism between the women with gestational diabetes and the control women either in Arabian or in Scandinavian women. CONCLUSIONS/INTERPRETATION: Gestational diabetes mellitus was associated with the presence of GAD65Ab in both study groups. Scandinavian women with gestational diabetes may share some genetic features with Type 1 diabetes. In addition, Arabian women with gestational diabetes are more insulin resistant than Scandinavian women with gestational diabetes and with the same BMI.

Adult↗

PubMed2004

The structure of the first coordination shell in liquid water.

X-ray absorption spectroscopy and x-ray Raman scattering were used to probe the molecular arrangement in the first coordination shell of liquid water. The local structure is characterized by comparison with bulk and surface of ordinary hexagonal ice Ih and with calculated spectra. Most molecules in liquid water are in two hydrogen-bonded configurations with one strong donor and one strong acceptor hydrogen bond in contrast to the four hydrogen-bonded tetrahedral structure in ice. Upon heating from 25 degrees C to 90 degrees C, 5 to 10% of the molecules change from tetrahedral environments to two hydrogen-bonded configurations. Our findings are consistent with neutron and x-ray diffraction data, and combining the results sets a strong limit for possible local structure distributions in liquid water. Serious discrepancies with structures based on current molecular dynamics simulations are observed.

Chemical Phenomena↗

PubMed2004

Bioavailability of selenium from bovine milk as assessed in subjects with ileostomy.

OBJECTIVE: To assess the absorption of dietary selenium in humans, especially of milk selenium. DESIGN: : 1-day meal studies in subjects with ileostomy. SETTING: Hospital outpatient clinics. SUBJECTS: Three subjects in the pilot study and nine subjects in the main study (eight men/ four women). INTERVENTION: Different beverages, 1 l/day, were given in addition to basal diets (soft drink, 1 week; low-fat milk, 3 weeks; fermented low-fat milk, 3 weeks and soft drink, 1 week). Ileostomy effluents were collected during the last 2 days in each of the four periods. RESULTS: On days when the subjects were given 1 l of low-fat milk, the estimated fractional absorption of total dietary selenium was 65.5 (2.3)% (mean (s.d.), n=18), which was similar to the value when fermented low-fat milk was given (64.1 (3.2)%). However, both the calculated amount of milk selenium absorbed (10.9 (2.4) vs 9.4 (1.7) microg selenium) and its fractional absorption (73.3 (16.1) vs 64.1 (11.2)%, n=18) were significantly higher for milk than for fermented milk. CONCLUSIONS: Selenium from milk and other sources is well absorbed in subjects with ileostomy. The real absorption may be even higher than the values shown.

Adult↗

PubMed2004

Microorganisms and volatile organic compounds in airborne dust from damp residences.

Airborne dust samples from damp (n = 9) and control (n = 9) residences were analyzed for microorganisms (molds and bacteria), bacterial markers (3-hydroxy fatty acids and muramic acid), and adsorbed volatile organic compounds (VOCs). The number of mold species was greater in the damp residences than in the controls (23 vs.18) and nine mold species were found only in damp residences. The levels of 3-hydroxy fatty acids and muramic acid correlated better in damp residences than in controls, indicating that damp conditions affect the bacterial flora of airborne dust. Identifications made by culture and microscopy of the major molds found, i.e. Aspergillus, Cladosporium, and Penicillum, coincided with the identification of VOCs known to be produced by these species. A number of additional VOCs irritating to the skin, eyes, or respiratory tract were also found. The results from this pilot study illustrate the diversity of microorganisms and VOCs present in the indoor environment and suggest that analysis of airborne dust may help to assess human exposure to microorganisms and chemical compounds.

Air Pollution, Indoor↗

PubMed2004

Monitoring of long-term thiopurine therapy among adults with inflammatory bowel disease.

BACKGROUND: The immunosuppressive effects of thiopurine drugs are mainly mediated through their intracellular metabolism into active 6-thioguanine nucleotide (6-TGN) metabolites, which are incorporated into DNA. Erythrocyte 6-TGN (E-6TGN) levels have been proposed as an instrument for monitoring treatment. The aim of the study was to use erythrocyte E-6TGN, methylated mercaptopurine (MeMP) metabolites, and thiopurine methyltransferase (TPMT) measurements in a clinical setting to determine the clinical outcome in relation to thiopurine metabolism. METHODS: Fifty-five adult patients with inflammatory bowel disease were included in a prospective study and followed for 6 months. Metabolite levels were measured and correlated to outcome and AZA/6-MP dose. RESULTS: The E-6TGN level was significantly related to the TPMT genotype (P = 0.008). Patients in disease remission had higher E-6TGN levels than patients with disease activity both at baseline (P < 0.05) and after 6 months (P = 0.02). Active disease was more frequent among subjects with E-6TGN < or = 125 nmol/mmol Hb at baseline (P = 0.04), but not at 6 months. AZA/6-MP drug dose was positively correlated to E-MeMP levels (r = 0.48; P < 0.001) and E-MeMP/E-6TGN ratio (r = 0.41; P = 0.002). Dose changes were positively correlated with the changes in E-MeMP levels (P = 0.01) and E-MeMP/E-6TGN ratio (P = 0.03). CONCLUSIONS: E-6TGN level was the only factor in this study related to disease activity, while there was no relationship between AZA/6-MP dose and E-6TGN levels. This finding illustrates the clinical usefulness of E-6TGN monitoring in the evaluation of treatment intensity.

Adolescent↗

PubMed2004

Lipid oxidation in frozen, mechanically deboned turkey meat as affected by packaging parameters and storage conditions.

Mechanically deboned turkey meat (MDTM) was stored in different packaging materials (film produced with natural antioxidant (alpha-tocopherol) or synthetic antioxidant) at -20 degrees C for 12 mo in a vacuum, modified atmosphere, or air. One-half of the samples were thawed at 4 degrees C for 24 h after 1 mo of storage and then refrozen. Oxidative rancidity was evaluated during storage by measuring the development of 2-thiobarbituric acid reactive substances (TBARS), and hexanal, a volatile oxidation product. Vacuum- and modified atmosphere-packaged samples had lower TBARS values and hexanal content than air-packaged samples with corresponding treatments. Hexanal content and TBARS values increased with storage time, and the highest levels were obtained after 6 mo of storage. The largest increase was obtained with presence of oxygen. Mechanically deboned turkey meat stored in packages where a natural antioxidant (alpha-tocopherol) was used in production of one of the PE layers, had, in almost every instance, the lowest TBARS values and hexanal content when stored in vacuum or modified atmosphere. However, this difference was not statistically significant. Neither TBARS values nor hexanal content showed dependency of the temperature profile (frozen or frozen/thawed/refrozen) during storage.

Aldehydes↗

PubMed2004

Adverse biochemical and physiological effects of prostacyclin in experimental brain oedema.

BACKGROUND: Prostacyclin (PGI2) and its stable analogues are known to reduce capillary hydraulic permeability. This study explores the biochemical and physiological effects of i.v. infusion of low-dose PGI2 in an experimental model of vasogenic brain oedema. METHODS: Twenty-seven anaesthetized and mechanically ventilated piglets with brain oedema induced by intrathecal injection of lipopolysaccharide (LPS) were used. Five of the animals received a continuous infusion of PGI2 (1 ng kg(-1) min(-1)) i.v. Four microdialysis catheters were placed in the brain to measure interstitial concentrations of glucose, lactate, and glycerol. Mean arterial pressure (MAP), intracranial pressure (ICP) and temperature were monitored continuously. Low-dose infusion of PGI2 started 1 h before the LPS injection and was constant during the study period. RESULTS: Intracranial pressure increased significantly in animals treated with PGI2. The increase in ICP was associated with significant cerebral biochemical changes: decrease in glucose, increase in lactate, increase in lactate/glucose ratio and increase in glycerol. CONCLUSION: In LPS-induced brain oedema i.v. infusion of low-dose PGI2 caused a further increase in ICP and a perturbation of energy metabolism, indicating cerebral ischemia and degradation of cellular membranes.

Animals↗

PubMed2003

Wnt-signalling pathway in ovarian epithelial tumours: increased expression of beta-catenin and GSK3beta.

Beta-catenin is involved in both cell-cell adhesion and in transcriptional regulation by the Wingless/Wnt signalling pathway. Alterations of components of this pathway have been suggested to play a central role in tumorigenesis. The present study investigated, by immunohistochemistry and immunoblotting, the protein expression and localisation of beta-catenin, adenomatous polyposis coli (APC), glycogen synthase kinase 3beta (GSK3beta) and lymphocyte enhancer factor-1 (Lef-1) in normal human ovaries and in epithelial ovarian tumours in vivo and in vitro. Immortalised human ovarian surface epithelium and ovarian cancer cell cells (OVCAR-3) expressed beta-catenin, APC, GSK3beta and Lef-1. Nuclear staining of beta-catenin and Lef-1 were demonstrated only in OVCAR-3 cells. There were significant increases of beta-catenin and GSK3beta, while APC was reduced in ovarian cancer compared to the normal ovary. Beta-catenin and Lef-1 were coimmunoprecipitated in ovarian tumours, but not in the normal ovary. Nuclear localisation of beta-catenin or Lef-1 could not be demonstrated in the normal ovary or in the ovarian tumours. The absence of nuclear localisation of beta-catenin could be due to an increased binding to the cadherin-alpha-catenin cell adhesion complex. In fact, we have earlier reported an increased expression of E-cadherin in ovarian adenocarcinomas. In summary, this study demonstrates an increase in the expression of components of the Wingless/Wnt pathway in malignant ovarian tumours. The increase suggests a role for this signalling pathway in cell transformation and in tumour progression. However, it remains to be demonstrated whether it is an increased participation of beta-catenin in transcriptional regulation, or in the stabilisation of cellular integrity, or both, that is the crucial event in ovarian tumorigenesis.

Adenocarcinoma↗

PubMed2003

Bonding of saturated hydrocarbons to metal surfaces.

The adsorption of octane on Cu(110) was studied by x-ray absorption and x-ray emission spectroscopy, in combination with spectrum calculations in the framework of density functional theory, as a model system for alkane adsorption on transition metals. Significant electron sharing between the adsorbate and metal surface and involvement of both bonding and antibonding C-H molecular orbitals in the molecule-metal bond was found. The calculations were extended to the case of octane adsorbed on Ni(110), and the position of the metal d band was found to be important for the bonding. The results were generalized to show that this is important for the efficiency as an alkane dehydrogenation catalyst.

Journal Article↗

PubMed2003

A pharmacoscintigraphic evaluation of oral budesonide given as controlled-release (Entocort) capsules.

AIMS: To investigate the gastrointestinal pharmacokinetics of controlled-release (Entocort) and standard budesonide capsules. METHODS: Six Crohn's disease patients and eight healthy controls were given controlled-release capsules containing budesonide and an inert 111In label, following breakfast. In the patients, a standard capsule containing deuterium-labelled budesonide was given simultaneously. In the controls, on a separate occasion, the controlled-release capsules were given in the fasting state. Gastrointestinal transit was recorded by a gamma camera. Plasma budesonide and deuterium-labelled budesonide were used to estimate drug release, and urine cortisol was used to assess systemic effects. RESULTS: Budesonide delivery to the ileo-colonic region was significantly greater after the intake of the controlled-release capsules [69%; 95% confidence interval (CI), 54-84] than after the standard capsules (30%; 95% CI, 15-45) (P = 0.005). Fasting had little impact on uptake. The transit and pharmacokinetics of budesonide were similar in both subject groups, although systemic availability was higher in patients (21%; 95% CI, 13-33) than in controls (12%; 95% CI, 10-14) (P = 0.009). Urinary cortisol was, however, similar in both groups. CONCLUSIONS: A major fraction of budesonide is released in the ileum and throughout the colon, the intended target for the controlled-release formulation. The prandial state has little effect on budesonide uptake.

Administration, Oral↗

PubMed2003

Low frequency of plasma nerve-growth factor detection is associated with death of memory B lymphocytes in HIV-1 infection.

Nerve growth factor (NGF) regulates B cell activation and differentiation and is an autocrine survival factor for memory B lymphocytes. We have reported recently that the number of memory B cells is reduced during HIV-1 infection. In this study we evaluated whether alteration in the NGF supply was involved in memory B cell loss in HIV-1-infected subjects. High rate of cell death in vitro was observed in memory B cells from HIV-1-infected individuals compared to uninfected donors (26.2 +/- 2.5%versus 7.9 +/- 1.4%, P < 0.001). The increased expression of Fas on memory B cells from infected subjects did not enhance the susceptibility of the cells to Fas-mediated apoptosis in vitro. The frequency of NGF detection in plasma from HIV-1-infected subjects was significantly lower than in healthy donors (33.6%versus 63.6%, P < 0.001). Also, the median plasma NGF in HIV-1-infected individuals was significantly lower than in uninfected controls (5 versus 14 pg/ml, respectively, P < 0.01). Interestingly, the plasma NGF level was correlated directly 1 to the percentage of memory B cells (P < 0.05). HIV-1-infected subjects with a low number of peripheral memory B cells had a reduced incidence of plasmatic NGF (7.4%) compared to patients with a normal level of memory B cells (37%, P < 0.01). Moreover, the addition of recombinant NGF (1 micro g/ml) to cultures of purified B cells reduced cell death of memory B cells from HIV-1-infected subjects from 24.04 +/- 3.0% to 17.4 +/- 1.3% (P < 0.01). HIV-1-infected individuals also carried higher levels of natural anti-NGF autoantibodies compared to uninfected subjects. In conclusion, we found that memory B cells from HIV-1-infected individuals are primed for cell death. Our study suggests an association between low frequency of plasma NGF detection and the increased cell death of memory B lymphocytes observed during HIV-1 infection. Low levels of NGF in plasma may be due to reduced supply or to NGF binding to natural anti-NGF autoantibodies.

Autoantibodies↗

PubMed2003

Low and high LET radiation-induced apoptosis in M059J and M059K cells.

PURPOSE: To investigate and compare the ability of DNA-dependent protein kinase (DNA-PK)-deficient and -proficient cells to undergo apoptosis after exposure to low and high linear energy transfer (LET) radiation. MATERIALS AND METHODS: A human glioma cell line M059J lacking the catalytic subunit of DNA-PK (DNA-PKcs) and its DNA-PKcs-proficient counterpart, M059K, were exposed to 1 and 4 Gy of accelerated nitrogen ions (14N, 140 eV nm(-1), 8-12 Gy min(-1)) or 60Co gamma-rays (0.2 eV nm(-1), 0.7 Gy min(-1)). The induction of apoptosis was studied up to 144 h post-irradiation using two different methods: morphological characterization of apoptotic cells after fluorescent staining and cell size distribution analysis to detect apoptotic bodies. In parallel, protein expression of DNA-PKcs and poly(ADP-ribose) polymerase (PARP) as well as DNA-PK and caspase-3 activity were investigated. RESULTS: Low and high LET radiations (4 Gy) induced a time-dependent apoptotic response in both cell lines. Low LET radiation induced a significantly elevated apoptotic response in M059J as compared with M059K cells at 144 h post-irradiation. Following high LET radiation exposure, there was no difference between the cell lines at this time. PARP cleavage was detected in M059J cells following both low and high LET irradiation, while only high LET radiation induced PARP cleavage in M059K cells. These cleavages occurred in the absence of caspase-3 activation. CONCLUSIONS: M059J and M059K cells both display radiation-induced apoptosis, which occur independently of caspase-3 activation. The apoptotic course differs between the two cell lines and is dependent on the quality of radiation.

Apoptosis↗

PubMed2003

Determinants of serum triglycerides and high-density lipoprotein cholesterol in traditional Trobriand Islanders: the Kitava Study.

OBJECTIVES: To analyse variables explaining the variation between serum triglycerides (TGs) and high density lipoprotein cholesterol (HDL-C) in a non-western population characterized by unfavourable TG and HDL-C levels despite marked leanness, low blood pressure and low fasting serum insulin. The study subjects included yraditional Pacific Islanders from Kitava, Trobriand Islands, Papua New Guinea and a population in Sweden. METHODS: The study was designed as a cross-sectional survey. Fasting serum lipoproteins and apolipoproteins, insulin, blood pressure and anthropometric measurements were analysed in 122 male and 47 female Kitavans aged 20-86 years and in a control population of 729 healthy men and women aged 20-66 from Uppsala. Main outcome measures were determinants of TG and HDL-C using a simple and multiple linear regression analysis. RESULTS: A negative association was found between TGs and HDL-C in Kitava (r = -0.38. p < 0.0001) and Sweden (r = -0.46, p < 0.0001), while TGs were positively associated with non-HDL-C and ApoB in both groups. In contrast to what was found in the Swedish subjects, TG and HDL-C levels were not associated with body mass index, waist circumference, glucose, insulin or systolic blood pressure in the Kitavans. CONCLUSION: Despite an apparent absence of cardiovascular disease and the metabolic syndrome in the Kitavans, the relationship between TGs and HDL-C was similar to that observed in Caucasians, while neither of the variables was associated with markers of insulin sensitivity in the Kitavans. Whether the findings can be explained by normal physiology or partially reflect the high intake of carbohydrates and saturated fat in Kitava is uncertain.

Adult↗

PubMed2002

Structure and bonding of water on Pt(111).

We address the adsorption of water on Pt(111) using x-ray absorption, x-ray emission, and x-ray photoelectron spectroscopy along with calculations in the framework of density functional theory. Using the direct relationship between the electronic structure and adsorbate geometry, we show that in the first layer all the molecules bind directly to the surface and to each other through the in-layer H bonds without dissociation, creating a nearly flat overlayer. The water molecules are adsorbed through alternating metal-oxygen (M-O) and metal-hydrogen (M-HO) bonds.

Journal Article↗

PubMed2002

On-line estimation of sugar concentration for control of fed-batch fermentation of lignocellulosic hydrolyzates by Saccharomyces cerevisiae.

A feed control strategy, based on estimated sugar concentrations, was developed with the purpose of avoiding severe inhibition of the yeast Saccharomyces cerevisiae during fermentation of spruce hydrolyzate. The sum of the fermentable hexose sugars, glucose and mannose, was estimated from on-line measurements of carbon dioxide evolution rate and biomass concentration by use of a simple stoichiometric model. The feed rate of the hydrolyzate was controlled to maintain constant sugar concentration during fed-batch fermentation, and the effect of different set-point concentrations was investigated using both untreated and detoxified hydrolyzates. The fed-batch cultivations were evaluated with respect to cellular physiology in terms of the specific ethanol productivities, ethanol yields, and viability of the yeast. The simple stoichiometric model used resulted in a good agreement between estimated sugar concentrations and off-line determinations of sugar concentrations. Furthermore, the control strategy used made it possible to maintain a constant sugar concentration without major oscillations in the feed rate or the sugar concentration. For untreated hydrolyzates the average ethanol productivity could be increased by more than 130% compared to batch fermentation. The average ethanol productivity was increased from 0.12 to 0.28 g/g h. The productivity also increased for detoxified hydrolyzates, where an increase of 16% was found (from 0.50 to 0.58 g/g h).

Journal Article↗

PubMed2002

Cardiovascular prevention before admission reduces mortality following acute myocardial infarction in patients with diabetes.

OBJECTIVES: Previous studies have shown that patients with diabetes mellitus have an increased mortality after suffering from acute myocardial infarction (AMI). Patients with diabetes have several risk factors for cardiovascular disease. Our objective was to quantify the prevalence of pharmacological cardiovascular prevention at admission and relate such treatment to short and long-term mortality following AMI in patients with and without diabetes. DESIGN AND SUBJECTS: All patients discharged from the Department of Internal Medicine at Helsingborg Hospital in 1996 and 1997 with a principal diagnosis of AMI were included in the study. Patients were divided into two groups according to the presence or absence of diabetes. Cardiovascular risk factors, on-going medication, type of ward following admission, peak creatine kinase MB mass (CKMB) and immediate treatment were registered. Information about death was obtained from the national register. Kaplan-Meier analysis was performed for life-expectancy. RESULTS: A total of 673 patients with AMI were registered, of which 117 (17.4%) had diabetes. No differences in 30 days (17.1% vs. 15.3%) or 1-year (24.8% vs. 27.4%) mortality were seen between the diabetes and control groups, whereas the 2-year mortality was significantly higher in the diabetes group (40.2% vs. 29.1%). Cardiovascular risk factors occurred more often in the diabetes group and the use of aspirin, ACE-inhibitors, statins and diuretics was significantly more frequent. In patients treated with aspirin, in combination with either statin or angiotensin converting enzyme (ACE)-inhibitor, or both, no differences were seen in 30 days, 1 or 2-year mortality between groups. CONCLUSION: In contrast to earlier studies we did not find an increased 30 days and 1-year mortality in patients with diabetes suffering from AMI. This discrepancy was linked to a higher frequency of pharmacological cardiovascular prevention, a finding supporting the hypothesis that survival of a diabetes patient after AMI could be affected by factors operating before the infarction.

Aged↗