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Biomedical subjects

A Nilsson

Publications and source records attributed to A Nilsson.

At least 19 recordsLinked to original sources

Use of dynamic step response for control of fed-batch conversion of lignocellulosic hydrolyzates to ethanol.

Optimization of fed-batch conversion of lignocellulosic hydrolyzates by the yeast Saccharomyces cerevisiae was studied. The feed rate was controlled using a step response strategy, in which the carbon dioxide evolution rate was used as input variable. The performance of the control strategy was examined using both an untreated and a detoxified dilute acid hydrolyzate, and the performance was compared to that obtained with a synthetic medium. In batch cultivation of the untreated hydrolyzate, only 23% of the hexose sugars were assimilated. However, by using the feed-back controlled fed-batch technique, it was possible to obtain complete conversion of the hexose sugars. Furthermore, the maximal specific ethanol productivity (q(E,max)) increased more than 10-fold, from 0.06 to 0.70 g g(-1) h(-1). In addition, the viability of the yeast cells decreased by more than 99% in batch cultivation, whereas a viability of more than 40% could be maintained during fed-batch cultivation. In contrast to untreated hydrolyzate, it was possible to convert the sugars in the detoxified hydrolyzate also in batch cultivation. However, a 50% higher specific ethanol productivity was obtained using fed-batch cultivation. During batch cultivation of both untreated and detoxified hydrolyzate a gradual decrease in specific ethanol productivity was observed. This decrease could largely be avoided in fed-batch cultivations.

Cellulose↗

Cerebrospinal fluid response to structured treatment interruption after virological failure.

OBJECTIVE: Structured antiretroviral treatment interruption (STI) has been advocated as a therapeutic strategy for HIV-1 infection. We report initial observations of cerebrospinal fluid (CSF) HIV-1 infection in five patients undergoing serial lumbar punctures (LPs) during STI undertaken following virological failure. DESIGN AND METHODS: In this prospective observational study we quantified HIV-1 RNA concentrations and assessed both phenotypic drug susceptibility profiles and genotypic antiviral drug resistance mutations in CSF and plasma during the period of treatment interruption. CSF white blood cells were also counted, and patients' neurological status monitored. RESULTS: In four of the patients, CSF HIV-1 concentration increased more rapidly than that of the plasma, with consequent reduction in the ratio between plasma and CSF viral loads (pVL : cVL). Three individuals developed robust, though asymptomatic CSF lymphocytic pleocytosis. In all patients the predominant HIV-1 quasispecies shifted simultaneously in CSF and plasma from a drug-resistant to a more drug-susceptible phenotype with identical and simultaneous changes in genotypes associated with drug resistance. CONCLUSIONS: STI may be accompanied by previously unrecognized changes in tissue viral exposures and lymphocyte traffic. Hence, despite 'virological failure' as evidenced by persistent plasma viremia, ongoing antiretroviral treatment prior to its interruption appeared to suppress CSF HIV-1 infection (indeed more effectively than that of plasma) and restrain lymphocyte traffic into the CSF. Simultaneous change of resistance mutations in CSF and plasma was likely due to re-emergence and overgrowth of pre-existing strains with ready exchange of virus between these two compartments, either facilitated by or provoking a local CSF lymphocytosis.

Adult↗

Soluble CD23 in cerebrospinal fluid: a marker of AIDS-related non-Hodgkin's lymphoma in the brain.

BACKGROUND: AIDS-related non-Hodgkin's lymphoma (NHL) includes systemic lymphomas, often with brain involvement, and primary central nervous system (CNS) lymphomas. OBJECTIVE: To examine if measurement of soluble CD23 (sCD23) in cerebrospinal fluid (CSF) is useful in the diagnosis and follow-up of AIDS-related NHL. METHOD: sCD23 was measured by enzyme-linked immunosorbent assay and EBV DNA by nested polymerase chain reaction for a group of 134 patients. The NHL group included 14 patients with primary HIV-1 CNS lymphoma, 12 patients with brain involvement of systemic HIV-1 NHL and 10 patients with systemic HIV-1 NHL without brain involvement. These were compared with HIV-1-infected patients with cerebral toxoplasmosis (19), progressive multifocal leukoencephalitis (PML; 8) and AIDS-related dementia (17) and with asymptomatic HIV-1 carriers (54) and uninfected individuals (50). The levels of sCD23 were compared with the presence of Epstein-Barr virus (EBV) DNA in CSF. RESULTS: Significantly higher levels of sCD23 were found in the CSF of the patients with brain lymphoma than in those with systemic NHL (P < 0.002) or with cerebral toxoplasmosis, PML and AIDS-related dementia (P < 0.0001). The sensitivity and specificity of sCD23 in CSF as a marker for detection of brain NHL were 77% and 94%, respectively. High levels of sCD23 were found in CSF from patients with brain NHL independently of the presence (18 out of 26) or absence (8 out of 26) of EBV DNA. CONCLUSIONS: The sCD23 in CSF of HIV-1-infected patients may represent an additional, non-invasive marker for diagnosis of brain involvement in AIDS-related NHL.

Biomarkers↗

DNA-dependent protein kinase is inhibited by trifluoperazine.

The DNA-dependent protein kinase (DNA-PK) is a serine/threonine nuclear kinase, important for the repair of DNA double strand breaks (DSB). Cells defective in DNA-PK show increased sensitivity to ionising radiation and different DNA-damaging drugs, such as cisplatinum. Increased sensitivity to cisplatinum has previously been noted in the presence of phenothiazines. We tested a panel of phenothiazines and one thioxanthen for any influence upon the activity and expression of DNA-PK in a nonsmall cell lung cancer cell line, U-1810. The activity of DNA-PK was completely inhibited in cell lysate and in purified enzyme by 200 microM TFP. DNA-PKcs and Ku86 cleavage were evident in U-1810 cells after 30 min incubation with 100 microM TFP, along with changes in the cells consistent with apoptosis. Our study suggests that phenothiazines and thioxanthens, acting through DNA-PK, have the potential to enhance the effects of DNA damaging agents.

Blotting, Western↗

Electronic structure effects from hydrogen bonding in the liquid phase and in chemisorption: an integrated theory and experimental effort.

A closely integrated theoretical and experimental effort to understand chemical bonding using X-ray spectroscopic probes is presented. Theoretical techniques to simulate XAS (X-ray absorption spectroscopy), XES (X-ray emission spectroscopy), RIXS (resonant inelastic X-ray scattering) and XPS (X-ray photoelectron spectroscopy) spectra have been developed and implemented within a density functional theory (DFT) framework. In combination with new experimental techniques, such as high-resolution XAS on liquid water under ambient conditions and XES on complicated surface adsorbates, new insight into e.g. hydrogen-bonded systems is obtained. For the (3x2) overlayer structure of glycine/Cu(110), earlier work has been extended to include adsorbate-adsorbate interactions. Structures are optimized for large cluster models and for periodic boundary conditions. It is found that specific features in the spectra arise from hydrogen-bonding interactions, which thus have important effects at the molecular-orbital level. XAS on liquid water shows a pronounced pre-edge feature with significant intensity, while the spectrum of ice shows only little intensity in this region. Theoretical spectrum calculations, based on instantaneous structures obtained from molecular-dynamics (MD) simulations, show that the pre-edge feature in the liquid is caused by water molecules with unsaturated hydrogen bonding. Some aspects of the theoretical simulations will be briefly discussed.

Journal Article↗

[National Diabetes Registry. A teaching pedagogical instrument for quality assurance].

The National Diabetes Registry of Sweden presents results from its third year of registration. Quality of care data from more than 41,000 patients with diabetes treated at medical and children's departments as well as primary health care centers are compared with national goals concerning metabolic and blood pressure control, and information is provided concerning the prevalence of lipid treatment, nephropathy, smoking etc. The national HbA1c goal of 6.5% is reached by 30% of patients treated at medical departments and by 50% in primary health care. Concerning patients with onset before 30 years of age, this goal is reached by 25%, which indicates that the national goal is difficult to reach and that individual goals must be set for individual patients.

Adolescent↗

Artefacts in sonography and Doppler.

A working knowledge of the most common artefacts in sonography is essential in order to avoid not only misdiagnosis of artefacts as pathology but also failure to detect pathology "in disguise". The basic artefacts affecting all sonography and some of the ones particular to Doppler and contrast ultrasound are discussed.

Artifacts↗

Heart rate as an indicator of the intensity of physical activity in human adolescents.

The aims of this study were, in a group of adolescents, firstly to identify the absolute heart rates (HR) and the percentages of maximal heart rates (HRmax) corresponding to 40%, 60% and 80% of peak oxygen uptake (PVO2), secondly to identify absolute and relative (%PVO2) oxygen uptakes (VO2) corresponding to HR of 120, 140 and 160 beats.min-1, and thirdly to examine a possible effect of fatness and fitness on the relationship between HR and VO2. The subjects were 127 (60 boys, 67 girls) adolescents with a mean age of 14.8 (SD 0.3) years. The HR and VO2 were measured by means of an incremental exercise test to exhaustion. Linear regressions were performed for the HR-VO2 and VO2-HR relationships using absolute and relative (%HRmax, %PVO2) data for each individual. From these regressions, target HR and VO2 were computed. Average target HR corresponding to 40%, 60% and 80% of PVO2 were: 119 (SD 9), 145 (SD 9), 171 (SD 8), and 120 (SD 10), 146 (SD 8), 172 (SD 8) beats.min-1 for boys and girls, respectively. Average VO2 corresponding to HR of 120, 140 and 160 beats.min-1 were: 22 (SD 5), 30 (SD 5), 38 (SD 6) and 18 (SD 4), 24 (SD 4), 31 (SD 4) mlO2.kg-1.min-1 for boys and girls, respectively. An analysis of covariance showed a significant fitness effect (P < 0.001) for predicted VO2 at all HR studied. The results suggest that the use of absolute HR to define exercise intensity levels when assessing young people's physical activity using HR monitoring detracts from the validity of the interpretation of the data.

Adolescent↗

Physical activity in relation to aerobic fitness and body fat in 14- to 15-year-old boys and girls.

The purpose of this study was to examine the strength of the relationship between different variables of physical activity and aerobic fitness and body fat in adolescent boys and girls. Activity energy expenditure (AEE), time spent in a sedentary state, and time spent engaged in moderate and vigorous physical activity (MVPA, > or = 50% peak oxygen uptake, VO2peak) were assessed by the minute-by-minute heart rate monitoring method in 82 randomly selected 14- to 15-year olds (42 boys, 40 girls). Body fat was determined by measuring skinfold thicknesses. VO2peak was measured by indirect calorimetry. Somatic maturity level was determined by percentages of adult (i.e. 18 years) height attained at examination. AEE was related to aerobic fitness for both genders (boys, r = 0.30, P = 0.056; girls, r = 0.45, P = 0.003). For boys, there was a significant relationship between maturity level and VO2peak (r = 0.48, P < 0.001). For both genders, body fat was significantly and negatively related to VO2peak (r = -0.48 and r = -0.43, P < 0.01). Body fat and maturity explained 47% of the variation in VO2peak in boys, whereas AEE and body fat explained 22% of the variation in VO2peak in girls. No significant associations between physical activity variables and the data on body fat were observed. The total amount of physical activity (AEE) was related to VO2peak, at least in adolescent girls. Although VO2peak seems to be influenced by the maturity level in adolescent boys, the data support the promotion of a daily active lifestyle among young people.

Adipose Tissue↗

Evidence for specific ceramidase present in the intestinal contents of rats and humans.

A neutral ceramidase activity stimulated by bile salt was previously identified in the intestinal content. Recently, bile salt stimulated lipase (BSSL) was found to have ceramidase activity. It is unknown whether the ceramidase activity previously found is attributable to BSSL. To address this question, we compared the behaviors of high quaternary aminoethyl (HQ) anion exchange chromatography, the distributions, the stability, and the responses to lipase inhibitor between ceramidase and pancreatic BSSL. The proteins from whole small intestinal contents of humans and rats were precipitated by acetone and dissolved in 20 mM Tris buffer pH 8.2. These proteins had neutral ceramidase activity but not BSSL activity against p-nitrophenyl acetate. When the proteins were subject to HQ chromatography, two peaks of ceramidase activity were identified, which had acid and neutral pH optima, respectively. Neither of them had BSSL activity against p-nitrophenyl acetate. Western blot using BSSL antiserum failed to identify BSSL protein in the fractions with high neutral ceramidase activity. In rat intestinal tract, pancreatic BSSL activity was high in the duodenum and declined rapidly in the small intestine, whereas neutral ceramidase activity was low in the duodenum and maintained a high level until the distal part of the small intestine. In addition, orlistat, the inhibitor of lipase, abolished human BSSL activity against p-nitrophenyl acetate and slightly reduced its activity against ceramide but had no inhibitory effect on ceramidase activity isolated by HQ chromatography. In conclusion, we provide the evidence for a specific ceramidase other than pancreatic BSSL present in the intestinal content. The enzyme may play important roles in digestion of dietary sphingolipids.

Amidohydrolases↗

Distribution and properties of neutral ceramidase activity in rat intestinal tract.

Ceramide plays an important role in regulating cell proliferation and apoptosis. Recent studies indicate that generation of ceramide in the intestine from sphingomyelin hydrolysis may be implicated in colon cancer development. The enzymes that catalyze the further hydrolysis of ceramide in the intestine have, however, not been well investigated. Our data reveal the existence of a ceramidase (EC 3.5.1.23) in rat intestinal mucosa with an optimal pH of 7.0. One milligram of mucosal protein is able to hydrolyze 44.0+/-9.6 nmol of ceramide in 1 hr. The activity is low in the proximal duodenum and increases to a plateau in the proximal jejunum. The activity is then similar throughout the small intestine, until it declines in the distal part of ileum. Some activity is also detectable in the colon. The activity increases slightly in the presence of monomeric bile salt concentrations and sharply at the critical micellar concentration. Similar patterns were observed for both primary (taurocholate) and secondary (taurodeoxycholate) bile salts. The addition of Triton X-100 enhances the ceramidase activity at optimal bile salt concentration. The reaction is linear with time for the first 20 min and the hydrolytic rate declines slowly thereafter. Finally, the activity shows a considerable resistance against tryptic degradation, as 71% of the ceramidase activity remained when the homogenates were preincubated with high concentrations of trypsin. Intestinal mucosa also has a ceramide synthesis activity, with a distribution pattern generally paralleling ceramide hydrolysis activity. In conclusion, intestinal neutral ceramidase has a distinct distribution pattern and bile salt dependence, which enables it to collaborate with intestinal sphingomyelinase in hydrolysis of sphingomyelin.

Amidohydrolases↗

PET with 11C-deuterium-deprenyl and 18F-FDG in focal epilepsy.

OBJECTIVES: This study compares positron emission tomography (PET) using 11C-deuterium-deprenyl (DED) with PET using 18F-fluorodeoxyglucose(18F-FDG) for examining epileptogenic regions in patients with focal epilepsy. MATERIAL AND METHODS: Twenty-three patients undergoing evaluation for epilepsy surgery were subjected to PET with DED. Fourteen patients had mesial temporal lobe epilepsy (TLE) and 9 patients had seizures of neocortical origin. In addition, 6 healthy control subjects were examined. Pixel-by-pixel analysis was used to generate graphical images of tracer distribution volume (intercept) and the accumulation rate (slope). Asymmetries with respect to relative intercept and slope were compared in patients with temporal lobe epilepsy (TLE), in patients with extra-temporal lobe epilepsy (exTLE), and in the control subjects. The results were compared with 18F-FDG-PET. RESULTS: Among the patients with TLE, significant differences between the epileptogenic and the contralateral lobe were found with DED intercept and FDG-uptake. No significant differences were found with DED slope. The exTLE and the control groups showed no significant differences between sides or lobes. CONCLUSIONS: This study indicates that PET with 11C-deuterium-deprenyl is a useful method for identifying TLE and is equivalent to PET with 18F-FDG in this sense. The method has little localizing value in seizures originating from neocortical structures.

Adolescent↗

HPV-related cancer susceptibility and p53 codon 72 polymorphism.

Conflicting results regarding the association of a polymorphism at codon 72 of the p53 tumour suppressor gene and susceptibility to develop human papilloma virus (HPV)-associated cervical cancer have been published over the last year, implicating differences in ethnic background, sample origin, sample size and/or detection assay. The material for this study was collected in the identical geographical region as for 2 previous reports with contradictory results regarding the association of codon 72 genotype with squamous cell cancer (SCC). We have used an alternative detection assay, based on pyrosequencing technology, that interrogates the variable position by the accuracy of DNA polymerase. In addition to cervical clinical specimens from SCC, HPV16- and HPV18-infected adenocarcinoma cases as well as cervical intraepithelial neoplasia (CIN) were investigated. No significant association was found between p53 codon 72 genotype and the risk to develop adenocarcinoma, SCC or CIN in the Swedish population.

Adenocarcinoma↗

Transrectal catheter drainage of deep abdominal and pelvic abscesses using combined ultrasonography and fluoroscopy.

OBJECTIVE: To describe our experience with transrectal drainage of deep abdominal or pelvic abscesses guided by ultrasonography and fluoroscopy. DESIGN: Open study. SETTING: Teaching hospital, Sweden. SUBJECTS: Eight seriously ill patients with deep abdominal or pelvic abscesses. INTERVENTION: Ultrasonographic and fluoroscopic transrectal drainage. MAIN OUTCOME MEASURES: Clinical follow-up. RESULTS: Eight patients (2 septic, 2 with high fever, and 2 with moderate fever) were effectively and safely drained without general anaesthesia. Their condition improved considerably within hours after drainage. Three patients had recurrent abscesses as a result of the underlying disease. The drainage overcame the sepsis in two patients and allowed a later elective operation. CONCLUSIONS: Transrectal ultrasonographic and fluoroscopic drainage is an effective and safe method for treatment of deep abdominal or pelvic abscesses in seriously ill patients.

Abdominal Abscess↗

Physical activity assessed by activity monitor and doubly labeled water in children.

PURPOSE: To validate the Computer Science and Application's (CSA) activity monitor for assessment of the total amount of physical activity during two school-weeks in 9-yr-old children and to develop equations to predict total energy expenditure (TEE) and activity energy expenditure (AEE) from activity counts and anthropometric variables. METHODS: A total of 26 children (15 boys and 11 girls, mean age 9.1 +/- 0.3 yr) were monitored for 14 consecutive days. TEE was simultaneously measured by the doubly labeled water method. Averaged activity counts (counts.min(-1)) were compared with data on: 1) TEE, 2) AEE = TEE minus basal metabolic rate (BMR; estimated from predictive equations), and 3) daily physical activity level (PAL = TEE/BMR). RESULTS: Physical activity determined by activity counts was significantly related to the data on energy expenditures: TEE (r = 0.39; P < 0.05), AEE (r = 0.54; P < 0.01), and PAL (r = 0.58; P < 0.01). Multiple stepwise regression analysis showed that TEE was significantly influenced by gender, body composition (body weight or fat free mass), and activity counts (R(2) = 0.54--0.60). AEE was significantly influenced by activity counts and gender (R(2) = 0.45). There were no significant differences between activity counts and PAL in discriminating among activity levels with "low" (PAL < 1.56), "moderate" (1.57 < or = PAL > or = 1.81), and "high" (PAL > 1.81) intensity. CONCLUSION: Activity counts from the CSA activity monitor seems to be a useful measure of the total amount of physical activity in 9-yr-old children. Activity counts contributed significantly to the explained variation in TEE and was the best predictor of AEE.

Activities of Daily Living↗

Experimental study of structure-borne sound transmission loss of mechanical joints.

A mechanical joint is one of the most effective ways to reduce the transmission of structure-borne sound. In order to increase the transmission loss, heavily damped joints are often used, which, in many cases, will reduce the structure integrity and hence can only be used in limited cases. In this study attention is focused on a type of resonant joint, i.e., a joint which will increase the transmission loss but will not reduce the structure integrity. The study is based on experiments in a one-dimensional structure. It is found that by adjusting the overlap of the joint, the transmission loss of 30 dB can be obtained at a certain frequency range without adding any dissipative materials. The mechanism of this high transmission loss is the cantilever-type resonance. The resonant frequency can be predicted precisely. The influence of extra dissipative material is investigated. The performance of the same joint in a finite structure is also examined by using the concept of vibrational insertion loss. When there is a certain damping in a finite system, a rather high insertion loss can still be achieved by using the above-mentioned joint, but the resonant frequency is shifted to higher end. It seems that the effective length of the cantilever is shortened by the finiteness.

Journal Article↗

Characterization of the annexin I gene and evaluation of its role in type 2 diabetes.

In a previous study, we identified suggestive linkage between type 2 diabetes and a locus on chromosome 9p13-q21. This region contains the gene annexin I (ANXA1), encoding a protein suggested to be involved in both insulin secretion and insulin action. In this study, we sequenced the exon/intron boundaries of the human ANXA1 gene and performed mutation screening in 41 individuals from the initial linkage study. We identified five single nucleotide polymorphisms A58G, A401G, intronic variance sequence (IVS)8-28A/G, IVS11 +31A/G, and IVS12-11T/G, which were further tested for association to diabetes in 197 parent/offspring trios using the transmission disequilibrium test. No significant association with type 2 diabetes was observed, although the common A allele of the +58A/G variant gave a 22:12 transmission distortion (P = 0.12). This variant was further genotyped in 481 case and control subjects, but no difference in allele, genotype, or haplotype frequencies were observed between the groups. Further, a novel polymorphic (CA)(15-25) repeat in intron 11 was genotyped in the subjects included in the initial linkage study. No improvement of the original finding was observed. We therefore concluded that the ANXA1 gene is unlikely to harbor variants that contribute to risk of type 2 diabetes.

Alleles↗