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Biomedical subjects

A Nilsson

Publications and source records attributed to A Nilsson.

At least 91 records · Page 5Linked to original sources

TNF gene polymorphism and its relation to intracerebral production of TNFalpha and TNFbeta in AD.

OBJECTIVE: To analyze the extent of tumor necrosis factor-alpha (TNFalpha) and TNFbeta gene polymorphism in patients with AD and to relate it to intrathecal levels of these cytokines. METHODS: Analyses of TNFalpha and TNFbeta gene polymorphism were performed using PCR in 52 patients with AD and in 25 control subjects, and the levels of corresponding cytokines were analyzed using ELISA. RESULTS: Patients with AD displayed significantly higher intrathecal levels of TNFalpha, but not TNFbeta, compared with the control subjects. The levels of these cytokines did not differ significantly in patients displaying different alleles of the TNF gene. CONCLUSIONS: Results indicate that increased intrathecal production of TNFalpha in AD is preferentially controlled by environmental stimuli rather than genetic makeup.

Aged↗

Association and linkage studies of CRH and PENK genes in bipolar disorder: a collaborative IGSLI study.

Corticotropin-releasing hormone (CRH) and proenkephalin (PENK) are hypothalamic peptides involved in the stress response and hypothalamic-pituitary axis regulation. Previous research has implicated these peptides in the pathogenesis of affective disorders. In this study we investigated two polymorphisms located in the genes that code for CRH and PENK by means of association and linkage analyses. A total of 138 bipolar patients and 108 controls were included in the association study. In addition, 24 families were available for linkage analysis, including six families of probands with documented periodic positivity of dexamethasone suppression tests (DST) during remission. We found no association of bipolar disorder with either gene. Similarly, we did not find any evidence of linkage (P = 0.56 for CRH and 0.52 for PENK) in the entire sample or in the subsample of families of DST positive probands. In conclusion, our study does not support the hypothesis that genes coding for CRH or PENK contribute to the genetic susceptibility to bipolar disorder. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:178-181, 2000.

Adult↗

Cadmium levels in kidney cortex in Swedish farmers.

The cadmium levels in kidney cortex (K-Cd) did not differ statistically between 10 nonsmoking farmers from the south of Sweden, who had a high intake of locally produced food and who were affected by acid precipitation (as indicated by low pH in the drinking water from their private wells) and 10 farmers less affected (medians: K-Cd, 18 vs. 14 microg/g; water pH, 5.2 vs. 7.8). Neither did 10 farmers selected because of "high" blood cadmium (B-Cd) differ from 10 with "low" [medians: K-Cd, 15 vs. 9 microg/g; B-Cd, 2.6 vs. 1.3 nmol/L (0.29 vs. 0.14 microg/L)]. In all 40 farmers, there was an increase of urinary cadmium levels (U-Cd) with decreasing drinking water pH (r(s) = -0.32, P = 0.045). Further, K-Cd increased with rising B-Cd (r(s) = 0.33, P = 0.037), and both B-Cd (r(s) = 0.73, P = 0.0005), and U-Cd (r(s) = 0.74, P = 0.0005) rose with increasing age. Further, there was an association between U-Cd and B-Cd (r(s) = 0.68, P = 0.0005). We could not demonstrate with certainty any effect of the acid precipitation on the cadmium retention in the farmers, although the association between U-Cd and drinking water pH deserves further study.

Adult↗

Powdering floor polish and mucous membrane irritation in secondary school pupils.

OBJECTIVES: Acrylate-styrene copolymer polish has been used to protect the surface of linoleum flooring since the 1960s. Problems with powdering of floor polish were observed at an early stage. In a secondary school in Linköping, Sweden, this phenomenon occurred in the winter of 1994-1995 and the pupils frequently reported irritative symptoms from the eyes and airways. This study was undertaken to assess the potential effect of powdering floor polish on the mucous membranes of the eyes and respiratory tract. METHODS: Repeated questionnaire-based surveys were conducted with identical questions in the spring of 1995 (during the powdering period) and in the autumn of 1995 (after the polish was removed). The questions dealt with irritative symptoms from the nose, eye, throat and lower respiratory tract. RESULTS: A preventive effect related to the removal of polish was found for irritative symptoms in all locations mentioned above, but was particularly clear for the lower respiratory tract (prevalence rate ratio = 0.37, 95% CI = 0.23-0.59). CONCLUSIONS: The results of this study indicate that the powdering of floor polish may cause irritative symptoms from the eyes and airways in school children.

Acrylates↗

Polyglutamine coding genes in bipolar disorder: lack of association with selected candidate loci.

BACKGROUND: Several studies have suggested that expanded trinucleotide repeats, particularly CAG, may have a role in the etiology of BD. Results obtained with the repeat expansion detection technique (RED) have indicated that bipolar patients have an excess of expanded CAG repeats. However, it is not clear which loci account for this difference. METHODS: Using lithium-responsive bipolar patients in order to reduce heterogeneity, we investigated five loci that are expressed in the brain and contain translated CAG repeats. A sample of 138 cases and 108 controls was studied. Genotypes were coded quantitatively or qualitatively and repeat distributions were compared. RESULTS: No difference was found in allele distribution between cases and controls for any of the loci studied. In one locus - L10378 - patients had a tendency to present shorter alleles (28.1 versus 27.9 repeats; t=2.55, df=205, P=0.011), however, this difference disappeared after correction for multiple testing. LIMITATIONS: The study has limitations common to most candidate gene association studies, that is, limited number of loci investigated and limited power to detect loci that account for a small proportion of the total genetic variability. CONCLUSIONS: Our results suggest that the loci investigated have no major role in the genetic predisposition to bipolar disorder.

Adult↗

Protective effect of pregnancy in women with lithium-responsive bipolar disorder.

BACKGROUND: Recent psychiatric literature, while indicating a high incidence of postpartum depression, contains a few clinical reports which support our observations that women with episodic bipolar disorder often remain well without treatment during pregnancy. Our retrospective study statistically examines the clinical course of 28 women with RDC typical bipolar disorder, type I, who became pregnant prior to receiving successful lithium prophylaxis. METHODS: We derived all data from the International Group for the Study of Lithium-treated Patients (IGSLI) database of excellent lithium responders. Data were compared both intraindividually, using data from three 9-month periods - immediately prior to pregnancy, pregnancy and postpartum - and interindividually, using never-pregnant women as controls. RESULTS: Intraindividual data show that women with typical bipolar disorder, type I, experience significantly fewer and shorter recurrences during pregnancy than either before or after. Interindividual comparisons indicate that the recurrence risk during pregnancy is markedly lower than the clinical course would predict. Moreover, the few recurrences observed during pregnancy all took place in the last 5 weeks. LIMITATIONS: Limiting cases to lithium responsive patients could have reduced heterogeneity and perhaps generalizability. CONCLUSIONS: The findings, nonetheless, indicate a marked improvement of the clinical course of typical bipolar disorder, type I, lithium-responsive, during pregnancy. Exploring the underlying protective mechanisms may lead to new understanding of the pathophysiology of mood disorders and to new approaches to treatment and prevention.

Adult↗

Effects of phospholipids on sphingomyelin hydrolysis induced by intestinal alkaline sphingomyelinase: an in vitro study.

Digestion of dietary sphingomyelin (SM) is catalyzed by intestinal alkaline sphingomyelinase (SMase) and may have important implications in colonic tumorigenesis. Previous studies demonstrated that the digestion and absorption of dietary SM was slow and incomplete and that the colon was exposed to SM and its hydrolytic products including ceramide. In the present work, we studied the influences of glycerophospholipids and hydrolytic products of phosphatidylcholine (PC; i.e., lyso-PC, fatty acid, diacylglycerol, and phosphorylcholine) on SM hydrolysis induced by purified rat intestinal alkaline SMase in the presence of 10 mM taurocholate. It was found that various phospholipids including PC, phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylethanolamine (PE), and phosphatidic acid (PA) inhibit alkaline SMase activity in a dose-dependent manner, with the degree of inhibition being in the order PA > PS > PI > PC > PE. Similar inhibition was also seen in a buffer of pH 7.4, which is close to the physiologic pH in the middle of the small intestine. When the effects of hydrolytic products of PC were studied, lyso-PC, oleic acid, and 1,2-dioleoyl glycerol also inhibited alkaline SMase activity, whereas phosphorylcholine enhanced SMase activity. However, in the absence of bile salt, acid phospholipids including PA, PS, and PI mildly stimulated alkaline SMase activity whereas PC and PE had no effect. It is concluded that in the presence of bile salts, glycerophospholipids and their hydrolytic products inhibit intestinal alkaline SMase activity. This may contribute to the slow rate of SM digestion in the upper small intestine.

Journal Article↗

A mutual inhibitory effect on absorption of sphingomyelin and cholesterol.

Several studies have shown that there is a strong physical interaction between cholesterol and sphingomyelin (SM). The critical factor is thought to be the high degree of saturation in the very long acyl chains of SM. In this study we examined the effects of SM on cholesterol absorption in the rat and compared them with those of phosphatidylcholine (PC). Cholesterol absorption was studied by use of the dual-isotope plasma ratio method. We also studied the effect of sterols on the fecal excretion of undigested SM and its metabolites after a single oral meal of (3)H-dihydrosphingosine-labeled SM. When cholesterol was given dissolved in soybean oil, without addition of SM or other phospholipids, absorption was 68 +/- 12% in the rat intestine. As a general feature the absorption was less efficient from the cholesterol/phospholipid dispersions. In dispersions with cholesterol and SM, the lowest cholesterol absorption (9 +/- 2%) was seen with a cholesterol:SM molar ratio of 1:1. With dispersions of cholesterol and different PC substrates the absorption of cholesterol was lower with saturated PC (16 +/- 8%) than with soybean-PC (22 +/- 4%) or dioleoyl PC (23 +/- 8%). Uptake of SM in the rat intestine was reduced by sterols. For example, percentage recovery of (3)H radioactivity in fecal lipids was 38 +/- 8% when SM was given with cholesterol and 16 +/- 3% without any sterol. One third of the radioactivity in feces was present as ceramide. Sitostanol had the same effect on uptake of SM as cholesterol. This study shows that when rats are fed mixtures of SM and cholesterol the intestinal uptake of both lipids is decreased. By feeding mixtures of SM and sterols the exposure of the colon to ceramide can be increased.

Journal Article↗

Wheezing following lower respiratory tract infections with respiratory syncytial virus and influenza A in infancy.

We examined the incidence of subsequent wheezing in 292 children, hospitalized for influenza A or respiratory syncytial virus (RSV) lower respiratory tract infection, during two consecutive seasons (November-December, 1993 and March-April, 1995). Questionnaires concerning episodes of wheezing and known risk factors for wheezy bronchitis were mailed to parents 1 year after hospitalization. Sixty per cent of parents reported two or more episodes of wheezing following either influenza A or RSV. Hospitalization as a result of wheezing was necessary in 15% of the patients. The severity of the primary infection, as indicated by the need for treatment in the intensive care unit (ICU), was correlated with later wheezing. No additional significant risk factors predicting later wheezing could be identified.

Asthma↗

Recombining germline-derived CDR sequences for creating diverse single-framework antibody libraries.

We constructed a single-chain Fv antibody library that permits human complementarity-determining region (CDR) gene fragments of any germline to be incorporated combinatorially into the appropriate positions of the variable-region frameworks VH-DP47 and VL-DPL3. A library of 2 x 109 independent transformants was screened against haptens, peptides, carbohydrates, and proteins, and the selected antibody fragments exhibited dissociation constants in the subnanomolar range. The antibody genes in this library were built on a single master framework into which diverse CDRs were allowed to recombine. These CDRs were sampled from in vivo-processed gene sequences, thus potentially optimizing the levels of correctly folded and functional molecules, and resulting in a molecule exhibiting a lower computed immunogenicity compared to naive immunoglobulins. Using the modularized assembly process to incorporate foreign sequences into an immunoglobulin scaffold, it is possible to vary as many as six CDRs at the same time, creating genetic and functional variation in antibody molecules.

Germ-Line Mutation↗

Total daily energy expenditure and pattern of physical activity measured by minute-by-minute heart rate monitoring in 14-15 year old Swedish adolescents.

OBJECTIVE: To assess total daily energy expenditure (TDEE) and patterns of physical activity among Swedish male and female adolescents and to relate the amount and intensity of physical activity to existing recommendations (energy expenditure equal to or above 12.4 kJ/kg/day or accumulation of 30 min/day in moderate physical activity equal to 4.5 times sedentary energy expenditure or more). DESIGN: TDEE, physical activity level (PAL=TDEE/BMR), energy expenditure (EE) and time spent in different intensities of physical activity were assessed by using minute-by-minute heart rate monitoring in combination with laboratory measured sedentary energy expenditure (SEE) and peak oxygen uptake. SETTING: Department of Physical Education and Health, Orebro University, and Department of Clinical Physiology, Orebro Medical Centre Hospital, Sweden. SUBJECTS: Eighty-two 14-15 y old adolescents (42 boys, 40 girls) from the city of Orebro, randomly selected through a two-stage sampling procedure. RESULTS: TDEE was 12.8 MJ/day and 10.0 MJ/day for boys and girls respectively (P<0.001) and PAL was 1.74 and 1.67 (NS). Forty-four percent and 47%, respectively, of TDEE referred to EE in physical activity, of which 70% for both genders referred to light physical activity (corresponding to <4.5 times SEE). Eleven boys and 14 girls had an EE lower than 12.4 kJ/kg/day and/or did not accumulate 30 min/day in physical activity >/=4.5 SEE. Those (n=20) with the highest PAL values (>2.01 and 1.81, respectively) spent 149 min/day at a >/=4.5 SEE intensity level compared to 40 min/day for those (n=30) with the lowest PAL values (<1.55 and 1.45, respectively). CONCLUSIONS: Swedish adolescent boys and girls are similarly physically active. The major amount of time devoted to physical activity refers to light physical activity. At least thirty percent of adolescents seem not to achieve appropriate levels of physical activity considered to be beneficial for health. SPONSORSHIP: Orebro County Council, The Public Health Committee of Stockholm County Council, Sweducation Foundation.

Adolescent↗

Psychiatric ill health and distribution of body fat mass among female immigrants in Sweden.

Given the association between psychiatric factors and obesity, the aims of the present study were to identify these variables among native Swedish as well as immigrant women, and to compare the prevalence of psychiatric ill health in women of foreign ethnicity with Swedish women. Information on melancholia, life satisfaction, sleeping problems, and use of psychoactive drugs as well as alcohol and smoking habits was obtained from questionnaires in a randomly selected population (n = 1464, participation rate 78%, aged 40 y). Height, body weight and circumferences of waist and hip were self-measured, so allowing calculations of the body mass index (BMI) and the waist to hip ratio (WHR) to be made. Among those who responded 246 (21.9%) were immigrants, divided into the following demographic clusters Nordic countries; Rest of Europe; and Non-European. Among native Swedes, use of psychoactive drugs and melancholy were associated with both BMI and WHR. BMI-associated with use of antidepressants in women from Nordic countries with a short duration of stay, and in subjects with a long duration of residence, was related to life satisfaction. Among subjects from the Rest of Europe, the use of hypnotics was negatively related to BMI, and life satisfaction was positively associated with WHR. Among Non-Europeans with a long duration of residence, BMI was positively connected to the use of anxiolytics and, negatively, to life satisfaction. Furthermore, melancholy was positively associated with WHR (borderline, P=0.086) in Non-Europeans. Subjects from Nordic countries were characterised by a relatively low use of psychoactive drugs and infrequent insomnia. In contrast, subjects from the Rest of Europe with short duration of stay showed a relatively extensive use of psychoactive drugs, and the Non-European group with short duration of stay experienced frequent insomnia, and a low degree of life satisfaction as well as high degree of melancholy. The association between psychiatric factors and obesity is not uniform across ethnic groups, suggesting a combination of genetic predisposition and psychosocial vulnerability. The high prevalence of psychiatric ill health among some ethnic groups should be a matter of public health concern.

Adipose Tissue↗

Allopurinol in addition to 5-aminosalicylic acid based drugs for the maintenance treatment of ulcerative colitis.

BACKGROUND: To investigate the value of combined treatment with allopurinol and 5-aminosalicylic (5-ASA) based drugs as maintenance treatment for ulcerative colitis (UC). METHODS: 199 patients with UC in remission but with active disease during the preceding 3 years were included. Allopurinol 100 mg twice daily or placebo was added to the 5-ASA based maintenance treatment. Clinical and endoscopic follow up was performed after 1, 6 and 12 months. RESULTS: Intention-to-treat analysis after 6 and 12 months showed similar results in both groups. A log-rank test showed that 77% in the allopurinol compared to 59% in the placebo group were still in remission after 6 months (P=0.0083) and 62% and 53% after 12 months, respectively (P=0.0936). This was mainly due to a higher than expected number of relapses during the first 3 months in the placebo group. After the first 3 months, the rate of relapse in each group was similar. CONCLUSIONS: It appears possible that allopurinol in combination with 5-ASA is better than 5-ASA alone for a 6-month, but not a 12-month period. This has to be verified in further dose-ranging studies.

Adult↗

Reduced formation of phosphatidic acid upon B-cell receptor triggering of mouse B-lymphocytes lacking Bruton's tyrosine kinase.

Btk deficient (BtkM) mouse B-lymphocytes do not proliferate when stimulated with anti-immunoglobulin (anti-Ig) antibodies. In order to characterize the molecular basis of this unresponsiveness we have compared early signal transduction pathways triggered by ligating the B cell antigen receptor (BCR) of purified resting B cells from normal C57BL/6 (wild-type) and BtkM mice on C57BL/6 background. BCR-induced signalling events that occur during the first few minutes of activation, such as bulk tyrosine phosphorylations, mitogen-activated protein kinase (MAPK) activation, PI3-kinase dependent PKB/Akt kinase phosphorylation/activation and PLCgamma2 tyrosine phosphorylation are comparable in wild type and BtkM B cells. However, the initial extracellular calcium influx is reduced and the BCR-induced accumulation of phosphatidic acid (PA) display a more transient profile in the BtkM cells. BCR ligation did not induce detectable phosphatidyl-choline PLD activity, suggesting that the reduced PA is owing to a reduction in the phospho-inositide hydrolysis. These findings further support the notion that the proliferative defect of Btk deficient mouse B cells in response to anti-immunoglobulin stimulation stems from a failure to sustain phospholipase-dependent signalling.

Agammaglobulinaemia Tyrosine Kinase↗

Two- to 9-year outcome after autologous chondrocyte transplantation of the knee.

Autologous cultured chondrocyte transplantation was introduced in Sweden in 1987 for the treatment of large (1.5-12.0 cm2) full thickness chondral defects of the knee. The clinical, arthroscopic, and histologic results from the first 101 patients treated using this technique are reported in this study. Patients were assessed retrospectively using three types of endpoints: patient and physician derived clinical rating scales (five validated and two new); arthroscopic assessment of cartilage fill, integration, and surface hardness; and standard histochemical techniques. Ninety-four patients with 2- to 9-years followup were evaluable. Good to excellent clinical results were seen in individual groups as follows: isolated femoral condyle (92%), multiple lesions (67%), osteochondritis dissecans (89%), patella (65%), and femoral condyle with anterior cruciate ligament repair (75%). Arthroscopic findings in 53 evaluated patients showed good repair tissue fill, good adherence to underlying bone, seamless integration with adjacent cartilage, and hardness close to that of the adjacent tissue. Hypertrophic response of the periosteum or graft or both was identified in 26 arthroscopies; seven were symptomatic and resolved after arthroscopic trimming. Graft failure occurred in seven (four of the first 23 and three of the next 78) patients. Histologic analysis of 37 biopsy specimens showed a correlation between hyalinelike tissue (hyaline matrix staining positive for Type II collagen and lacking a fibrous component) and good to excellent clinical results. The good clinical outcomes of autologous chondrocyte transplantation in this study are encouraging, and clinical trials are being done to assess the outcomes versus traditional fibrocartilage repair techniques.

Activities of Daily Living↗